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Studies of retrograde cardioplegia
J
THORAC CARDIOVASC SURG
1989;97:605-12
Studies of retrograde cardioplegia I. Capillary blood flow distribution to myocardium supplied by open and occluded arteries This study defines the nutritive (i.e., capillary) distribution of blood cardioplegic solutions delivered via retrograde and antegrade techniques to muscle supplied by open and occluded coronary arteries where myocardial segments are in jeopardy of inadequatecardioplegic protection.Open-cbest anesthetizeddogs were studied by mixing radioactive microspheres (15 ± 5 #Lm) with a blood cardioplegic solution and administering cardioplegia either into the coronary sinus or into the proximal aorta with the left anterior descending coronary artery openor occluded (30% ± 2 % area at risk).Nutritiveflow (i.e., percentageof delivered 15 #Lm microspheres trapped in myocardial capillaries) during retrograde infusions averaged 65% versus 87 % withantegrade cardioplegia (p < 0.05).Retrograde and antegrade cardioplegic nutritive flow to aU left ventricular regionswas comparable with the left anterior descending coronary artery open (65 versus 82 m1/100 gm/min, p> 0.05), and both methods provided preferential hyperperfusion of subendocardial muscle (endocardial/epicardial ratios 1.6 and 1.5, respectively). Nutritive flow to muscle supplied by the occluded left anterior descending coronary artery was preserved better by retrograde than antegrade cardioplegia (35 versus 5 m1/100 gm/min, p < 0.05).Preferential subendocardial hyperperfusion was maintained during retrograde cardioplegia (52 m1/100 gm/min, endocardial/epicardial ratio 1.6), but flow was redistributed away from subendocardial muscle with antegrade cardioplegia «2 m1/100 gm/min, endocardial/epicardial, 0.29, p < 0.05). Left ventricular flow was reduced markedly during retrograde infusion with the left anterior descending coronary artery open or occluded (23 and 12 m1/100 gm/min), but septal cooling was superior to antegrade cardioplegia (150 ± 10 C versus 20% ± 3%, p < 0.05) despite near-normal antegrade septal flow (the left anterior descending coronary artery was ligated beyond the first septal branch). Right ventricular nutritive flow was only 7 m1/100 gm/min during retrograde coronary sinus perfusion and was maintained normaUy with antegrade cardioplegia. We conclude that retrograde cardioplegia is (1) superior to antegrade cardioplegia in delivering nutritive flow to areas supplied by occluded arteries, (2) maintains preferential subendocardial flow to subendocardial muscle in jeopardy of inadequate cardioplegic protection during occlusion of the left anterior descending coronary artery, (3) produces exceUent left ventricular septal cooling despite reduced nutritive flow, and (4) is distributed poorly to the right ventricle.
Marshall T. Partington, MD, Christophe Acar, MD, Gerald D. Buckberg, MD, Pierre Julia, MD, Edward R. Kofsky, MD, and Helen I. Bugyi, PhD, Los Angeles, Calif.
Distribution of cardioplegic solution of all cardiac regions is a prerequisite for the safe clinical use of cardioplegia for myocardial protection. Retrograde perFrom the Division of Thoracic Surgery, University of California at Los Angeles Medical Center, Los Angeles, Calif. Supported in part by National Institutes of Health Grant No. HL 16292. Received for publication April 6, 1988. Accepted for publication Oct. II, 1988. Address for reprints: G. D. Buckberg, MD, UCLA Medical Center, Department of Surgery, Los Angeles, CA 90024.
fusion of the coronary venous system, proposed originally by Pratt' in 1898, is one alternative to achieve cardioplegic distribution, especially when coronary stenoses or occlusions are present. Retrograde coronary sinus perfusion has been studied experimentally'? and used clinically,' but there is limited information about the volume of nutritive flow provided by this method of delivery. Capillary perfusion (i.e., nutritive flow) is especially important if oxygenated cardioplegic solutions are used to enhance aerobic metabolism during cardiaplegic induction, maintenance, and reperfusion," Retrograde coronary sinus perfusion in the beating 605
6 0 6 Partington et al.
heart has been shown to provide inadequate flow to completely avoid damage to hearts subjected to acute coronary occlusion."9 Prior studies of retrograde coronary sinus perfusion in beating (working or nonworking) hearts are of interest but are of limited value to the cardiac surgeon who delivers retrograde coronary sinus flow to produce and maintain cardiac arrest, where the myocardial flow and oxygen requirements are reduced markedly.'? Most previous studies designed to evaluate the myocardial distribution of retrograde coronary sinus perfusion under conditions that simulate those used during clinical cardiac operations (i.e., arrested in situ or excised or isolated hearts) employ indirect and qualitative methods. These methods include gel casting of the coronary venous system,' 1 rates of cooling," dye or angiographic techniques," and collection of effluent from different cardiac chambers," but do not allow quantification of nutritive (i.e., capillary) blood flow. The one semiquantitative study of retrograde nutritive flow distribution by Solorzano, Taitelbaum, and Chiu 13 (using radioactive microspheres) suggests that only 26% of microspheres are trapped by retrograde coronary sinus perfusion, but that report provides no data on either absolute flow rates or the distribution of flow between ischemic and nonischemic regions or to the ventricular septum or right ventricle. The present study was undertaken to determine and quantify the distribution of coronary sinus retrograde cardioplegia in hearts arrested under conditions that simulate the clinical use of retrograde and antegrade techniques in patients with and without coronary stenoses. The data will show that (1) 60% to 70% of retrograde coronary ~lnUS cardioplegic perfusion provides nutritive flow to the left ventricle, (2) the intraventricular septum is cooled preferentially by retrograde cardioplegia, despite its receiving only 25% of flow delivered to the area of risk beyond coronary stenoses, (3) left ventricular subendocardial muscle in the area at risk (occluded artery), as well as in areas with open arteries, is perfused preferentially by retrograde techniques, and (4) the right ventricle receives scant retrograde flow via the coronary sinus. Methods Experimental preparation. Fifteen mongrel dogs (25 to 35 kg) were anesthetized with intravenous sodium thiamylal (30 mg/kg), maintained on sodium pentobarbital (2 mg/kg), and placed on positive-pressureendotracheal ventilation with 100% oxygen, All dogs received humane care in compliance with the "Principles of Laboratory Animal Care" formulated by the National Society for Medical Research and the "Guide for the Care and Use of Laboratory Animals" prepared by the National Academy of Sciences and published by the National
The Journal of Thoracic and Cardiovascular Surgery
Institutes of Health (NIH publication No, 80-23, revised 1978). The chest was opened by median sternotomy and the pericardium was incised and cradled. After systemic heparinization (3 mg/kg) cardiopulmonary bypass was started with an 18F arterial cannula in the femoral artery and double venous cannulation of the cavae for venous return. A vent was placed into the left ventricle through an apical stab wound. Myocardial temperature was measured by placing thermistor probes in the left ventricular wall, the area at risk, and in the intraventricular septum (Yellow Springs Instrument Co" Yellow Springs, Ohio). The left anterior descending coronary artery (LAD) was dissected adjacent to its first diagonal branch for subsequent occlusion to produce an eventual area at risk. The azygos vein was ligated, and both venae cavae were snared to allow isolation of the right side of the heart. The right atrium was opened to expose the coronary sinus for subsequent infusion of the retrograde cardioplegia, An 18-gauge needle was placed into the aorta for induction of antegrade cardioplegia with a 6 ° to 10° C blood cardioplegic solution containing potassium chloride, 30 mg/L, which was made cold by being passed through a separate heat exchanger (Shiley BCD Plus, Shiley Incorporated, Irvine, Calif.), All hearts received antegrade cardioplegia (200 ml/rnin) to produce global arrest, which occurred within 30 seconds of starting the cardioplegic infusion. This allowed all flow distribution measurements to be made in the arrested heart under steady state conditions. The LAD was then occluded and 3 ml of gentian violet was injected into the cardioplegic infusion to define the area at risk (unstained muscle). Experimental groups Retrograde cardioplegia. Retrograde cardioplegia was delivered by calibrated roller pump to the arrested heart through a No. 12 Foley catheter inflated 2 to 3 ern within the coronary sinus. In seven of these dogs the LAD occlusion was left in place during the retrograde coronary sinus cardioplegic infusion, and in four others the occlusion was removed so that the distribution of retrograde cardioplegic solution could be assessed without the presence of coronary occlusion. Radioactive microspheres (15 ± 5 /Lm) were injected into the coronary sinus infusion line to determine the distribution of retrograde cardioplegia. Two batches of microspheres were injected simultaneously to be certain of the adequacy of mixing and lack of clumping. The injection port for microspheres was 2 feet proximal to the Foley catheter that had been placed on the coronary sinus, and the infusion was continued for 3 minutes after injection to allow for complete distribution. Infusion pressure was kept at 50 mm Hg and retrograde coronary sinus flow averaged 135 ± 21 ml/rnin and ranged from 90 to 200. Antegrade cardioplegia. Four hearts received only antegrade cardioplegia (150 ml/rnin) at an infusion pressure ranging from 50 to 70 mrn Hg. The pressure was estimated by subtracting the known pressure drop in the delivery system at that flow rate from the pressure recorded in the heat exchanger. In these hearts, the first microsphere injection was made into the cardioplegic line (approximately 2 feet proximal to the aorta) and the cardioplegic infusion was continued for 3 more minutes to allow microspheres to be distributed within the myocardium. A second injection of microspheres was made after LAD occlusion followed by similar 3-minute periods of cardioplegic flow.
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Retrograde cardioplegia, I
April 1989
Microsphere analyses. The total number of microspheres delivered was determined by counting the radioactivity in each injection vial and dividing by the counts per bead by standard techniques of gamma spectrometry. All effluent flow from the aorta, left ventricle, and right side of the heart was collected to analyze for radioactivity to determine how many microspheres escaped trapping by the heart. The microsphere vial, syringe, and injection tubing were analyzed also for radioactivity to determine the number of microspheres retained in the microsphere delivery system to avoid introducing errors in subsequent calculations designed to determine microsphere flow. Hearts were excised immediately after the microsphere injections and subsequent cardioplegic infusions had been completed. Care was taken to avoid any antegrade or retrograde perfusion after cardiac excision to prevent dislodging microspheres trapped during the prior injection. (Our previous pilot study showed that reinstituting antegrade flow after retrograde cardioplegia dislodged approximately 50% to 70% of microspheres that were trapped within the heart during retroperfusion. The hearts were then separated into areas at risk (identified by lack of gentian violet staining), area at nonrisk (posterior left ventricle supplied by unobstructed circumflex artery), intraventricular septum, right ventricular free wall, and atria placed into preweighed vials for subsequent analyses by gamma spectrometry. The vials containing heart muscle from different regions were reweighed and flows were calculated from the equation:
F = Fk X Mu M, u where F, is the cardioplegic flow (antegrade or retrograde) delivered by the calibrated roller pump and M, is the number of microspheres counted in the total heart. M, is either the microspheres in the heart or those in the collected right ventricular, left ventricular, and aortic effluent, and the F, (unknown flow) is that flow determined by solving the aforementioned equation. Nutritive flow is calculated from the microspheres in the heart. Nonnutritive flow is calculated from the microspheres in the effluent. The trapping index" is that proportion of microspheres delivered to the heart that remain in cardiac muscle samples.
Results Results were similar when two batches of microspheres were injected simultaneously and attest to the adequacy of mixing and lack of microsphere clumping during delivery and subsequent distribution. Analysis of the heart, effluent, and injection vial, syringe, and tubing showed that 94% ± 1% of all injected microspheres were recovered from the heart or effluent. Only 6% of microspheres remained in the syringes, stopcock, and delivery system or injection vial. Consequently, all subsequent calculations of flow were based on the actual number of microspheres delivered to the heart (i.e., M, = 94% of the microspheres drawn up for each study). The LAD supplied similar amounts of left ventricle in both instances (31% ± 4% and 33% ± 2%
60 7
100 80
~ LAD OPEN
LAD OCCLUDED
cc/100g/min
60 40 20 0
LV (AR)
~
LV (non AR)
0SEPTUM
C:IiI RV
Fig. 1. Distribution of retrograde cardioplegic flow to area at risk (Ar) supplied by LAD, area at no risk (non Ar) supplied by circumflex coronary artery, and septum and right ventricle (RV).
of left ventricular muscle mass, including the intraventricular septum). Capillary flow versus nonnutritive flow Retrograde cardioplegia. The capillary (i.e., nutritive) flow is determined from the number of 15 ± 5 JLm microspheres given to the heart that were recovered by scintillation counting of the different sections of cardiac muscle. Conversely, the noncapillary flow was determined from the number of microspheres that were shunted away from the capillary bed and recovered in the effluent collected from the right and left sides of the heart. Total cardiac nutritive flow averaged 70% ± 4% of delivered flow during retrograde coronary sinus infusions when both the LAD and circumflex coronary arteries were open and fell to 61% ± 6% when the LAD was occluded adjacent to the first diagonal branch. Conversely, 30% ± 4% and 39% ± 6% of injected microspheres were nonnutritive and thereby bypassed the myocardial capillary bed with the LAD open or occluded. The lowest retrograde coronary sinus nutritive flow occurred always in the right ventricular free wall; flows averaged 7 ± 2 and lO ± 2 ml/IOO gm/rnin, respectively, with the LAD open and occluded (Fig. 1). Retrograde flow to the anterior left ventricular free wall averaged 82 ± 11 ml/IOO gm/rnin when the LAD was open and fell to 35 ± 6 ml/lOO mg/rnin when the LAD was occluded (p < 0.05) (Fig. 2). Retrograde coronary sinus flow to the posterior left ventricle (nonrisk area) was comparable at 66 ± 3 and 56 ± 9 ml/rnin, respectively, when the LAD was either open or occluded. Retrograde cardioplegia was redistributed toward left ventricular subendocardial muscle when the LAD was either occluded or open (endocardial/epicardial [endo/ epi] ratio 1.64 and 1.59, respectively). Retrograde flow to the intraventricular septum was only 23 ± 9 ml/lOO gm/rnin) when the LAD was open
The Journal of
608
Thoracic and Cardiovascular Surgery
Partington et af.
LAD OPEN
100
LAD CLOSED 30
80 cc/100g/min
~
ANT LV SEPTUM
60
...
40 20
o *
Ante p
Retro
..JJ Ante
20 °C
10
Retro
Fig. 2. Nutritive flow to area at risk supplied by LAD with antegrade (ante) and retrograde (retro) cardioplegia. Note: (I) comparable flow with both methods when LAD is patent; (2) superior flow with retrograde method when LAD is occluded.
and fell to 12 ± 4 ml/IOO gm/rnin when the LAD was occluded (P> 0.05). Septal cooling with retrograde cardioplegia was, however, more profound than that achieved after antegrade cardioplegia (15 ° ± 1 ° C versus 20° ± 3° C) despite markedly reduced retrograde capillary flow. Deep septal hypothermia was achieved comparably by retrograde techniques whether the LAD was open or occluded (Fig. 3). Antegrade cardioplegia. Myocardial blood flow was 87% ± 4% nutritive with antegrade cardioplegia, with only 13% of the injected microspheres collected in the effluent. Nutritive flows were comparable in the anterior left ventricle, septum, and circumflex area, averaging 65 ± 2 ml/IOO gm/rnin in these regions when the LAD was open. Antegrade cardioplegic delivery with the LAD occluded resulted in a profound reduction in flow to the anterior left ventricle (to 8% of previous values), so that flow averaged only 5 ± 1 ml/100 gm/rnin. Left ventricular subendocardial muscle was underperfused most severely, with the endo/epi flow ratios falling to 0.29 (from 1.5), and subendocardial perfusion became negligible «2 ml/IOO gm/rnin). Septal flow was reduced only marginally during antegrade cardioplegia, as the first septal artery originated proximal to the LAD occlusion. These restrictions of antegrade flow to muscle in jeopardy of inadequate protection in the area at risk were mirrored in the degree of myocardial hypothermia; anterior left ventricular temperature fell to only 30° ± 1° C despite 1100 ml of 4 ° to 6° cardioplegic infusion, whereas septal temperature fell to 20° ± 3° C (Fig. 3). Antegrade versus retrograde capillary flow. Nutritive flow to the anterior left ventricle supplied by the patent LAD was comparable at 65 ± 5 and 82 ± 11 ml/IOO gm/min, p > 0.05, when cardioplegic delivery was antegrade via the aorta or retrograde via the
0
ANTEGRADE LAD OCCLUDED
[)
RETROGRADE LAD OCCLUDED
Fig. 3. Myocardial temperature recorded by thermistor probe in the anterior left ventricle (L V) and septum during antegrade and retrograde infusions while LAD was occluded. Note: (I) better cooling of the anterior left ventricle with retrograde cardioplegia; (2) better septal cooling with retrograde cardioplegia despite less septal nutritive flow (see text for explanation).
coronary sinus (Figs. 1 and 4). Conversely, capillary flow to the anterior left ventricle in the presence of left atrial occlusion was only 5 ml/100 gm/rnin with antegrade cardioplegia and rose sevenfold to 35 ± 6 ml/100 gm/rnin when the cardioplegic solution was delivered retrogradely via the coronary sinus. The differences in nutritive cardioplegic distribution between the anterior and retrograde techniques of administration during coronary occlusion were most apparent from the regional endocardial and epicardial flow analyses. Antegrade blood cardioplegic flow was distributed preferentially (endo/epi ratio 1.5 ± 0.2) toward subendocardial muscle without coronary occlusion (Fig. 5). Conversely, selective underperfusion of endocardial muscle followed antegrade cardioplegic delivery when there was LAD occlusion; endo/epi ratio fell to 0.29 and endocardial flow fell to <2 ml/100 gm/rnin (p < 0.05). Retrograde cardioplegic flow via the coronary sinus was also distributed preferentially toward endocardial muscle when the LAD was open (endo/epi ratio 1.59 ± 0.25, p < 0.05), and this preferential retrograde subendocardial perfusion persisted during LAD occlusion (endo/epi ratio 1.64 ± 0.13). Consequently, left ventricular subendocardial flow during retrograde cardioplegia with LAD occlusion was 52 ml/rnin (versus 35 ml/min transmural flow) and exceeded antegrade perfusion to this region by thirtyfold, p < 0.05.
Discussion This study shows that retrograde cardioplegia via the coronary sinus provides substantial capillary flow to the left ventricular free wall, even in the presence of
Volume 97 Number 4
Retrograde cardioplegia, I
April 1989
n
60
~
LAD OPEN
2.0
609
LAD CLOSED
ANT LV SEPTUM
40
ENDO/EPI 1.0
cc/100g/min
20
o *
o
ANTEGRADE LAD OPEN
* p
ANTEGRADE RETROGRADE '--LAD OCCLUDED---'
Fig. 4. Nutritive flow (mi/IOO gm/rnin) during antegrade and retrograde cardioplegic infusions to the area at risk supplied by LAD (anteriorleft ventricle (ant LVI) and the left ventricular septum. Note: (I) improved septal flow with antegrade cardioplegia, as the LAD was ligated beyond the first septal artery; (2) superior distribution of retrograde cardioplegia to the anterior left ventricle supplied by the occluded LAD.
coronary occlusion. This nutritive retrograde cardioplegic perfusion is delivered preferentially to the vulnerable subendocardial muscle, whether the LAD is open or occluded, and thereby enhances hypothermic reduction of energy demands. Conversely, antegrade cardioplegic perfusion is redistributed away from the subendocardial muscle in the presence of LAD occlusion and fails to provide the hypothermic myocardial protection to jeopardized muscle. Retrograde capillary flow to the intraventricular septum is low (i.e., 25% of flow to the anterior ventricle), whether the LAD is open or closed, but septal cooling is excellent despite this more limited retrograde perfusion. Several reports document the capacity of retrograde cardioplegia to protect myocardium in jeopardy of having intraoperative damage because of the presence of coronary occlusion5.12.13 or cardiac hypertrophy." Indirect evidence for the adequate distribution of retrograde cardioplegia via the coronary sinus to jeopardized muscle is provided by the preservation of high-energy phosphates, good regional myocardial cooling, and restoration of adequate function of muscle reliant on retrograde cardioplegic protection." Our study quantifies the ability of retrograde cardioplegia to deliver potentially nutritive flow to the capillary bed despite the presence of a coronary occlusion that limits access to antegrade cardioplegia to this area. Previous attempts to evaluate the distribution of retrograde cardioplegia, with the exception of one study, have failed to distinguish between nutritive flow (i.e., capillary flow) and that perfusion which is nonnutritive (i.e.,
Ante
Retro
Ante
Retro
p
Fig. 5. Distribution of antegrade (ante) and retrograde (refro) cardioplegia to anterior left ventricle with LAD patent and occluded. Note: (I) severe redistribution away from left
ventricular subendocardial muscle duringantegrade cardioplegia with LAD occluded; (2) preferential endocardial perfusion with antegrade and retrograde cardioplegia with LAD open; (3) maintained preferential endocardial perfusion with retrograde cardioplegia with LAD occluded.
arteria-sinusoidal, arterial luminal vessels) because of methodologic limitations (i.e., dye studies, gel studies, collected effiuents).ll.15.16 The quantification of capillary flow is especially important with oxygenated cardioplegic solutions that are intended to maximize myocardial oxygen use during cardioplegic induction, maintenance, and reperfusion." Our finding of 60% to 70% trapping of retroperfused microspheres in the myocardium is at variance with the report of Solorzano, Taitelbaum, and Chiu," who concluded that only 26% of injected microspheres are trapped and provide nutritive flow. There are several differences between our study and theirs that may explain these discrepant results. First, we injected microspheres after antegrade cardioplegic arrest, rather than instituting retrograde perfusion to a heart removed rapidly from dogs killed with barbiturate overdose. Differences in vascular and extravascular resistance may have existed (especially if the hearts were beating or fibrillating) that could result in shunting of microspheres away from the capillary bed through the existing rich network of veno-venous anastomoses.' Second, their study used a perfusion pressure of 80 mm Hg, which may have caused edema and increased vascular resistance and favored shunting away from capillary beds. Gott and associates," in 1957, reported that thebesian flow in the right side of the heart rose progressively when retrograde perfusion pressure was increased to this level. We kept perfusion pressure at 50 mm Hg to avoid producing edema and hemorrhage." Third, their report does not state clearly whether the retrograde microsphere infusion was followed by an antegrade infusion of autologous blood that may have dislodged and flushed
6 10
The Journal of Thoracic and Cardiovascular
Partington et al.
Surgery
6
4 cc/100g/min
2
o
I
DEMAND
I
SUPPLY
Fig. 6. Myocardial supply/demand balance during retrograde cardioplegic infusions (assuming reduction of left ventricular temperature to only 22° C) and area of LAD occlusion. Note: (1) low oxygen demands (0.3 mi/IOO gm/ min); (2) abundant oxygen delivery to meet these demands (assuming flow of 35 ml/IOO grn/rnin).
out microspheres that were trapped only loosely in the venous capillary bed. This would lead to a systematic underestimate of retrograde nutritive flow and explain partially the disparity between our results and theirs. Our pilot study showed, for example, that antegrade cardioplegic flow after retrograde cardiolegia dislodged as many as 75% of trapped microspheres and resulted in calculated retrograde nutritive flows that were similar to the proportion of trapped microspheres reported by Solorzano, Taitelbaum, and Chiu." Consequently, we carefully avoided antegrade flow after retrograde cardioplegic administration. The low capillary flows measured in the intraventricular septum and right ventricle are consistent with reports showing that qualitative flow to these regions is deficient by the retrograde method of coronary sinus delivery.ll.l? Our placement of the retrograde coronary sinus balloon catheter within the coronary sinus may have magnified the failure to provide substantial right ventricular flow, since the balloon catheter was positioned beyond the early branches of the coronary sinus, reported by Menasche and colleagues? to drain (or perfuse) the right ventricle. This limitation of retrograde cardioplegic distribution to the right ventricle via the coronary sinus in dogs may be less problematic in man, for the right ventricular free wall is perfused better via retrograde techniques in man than in the dog. I? The failure of retrograde cardioplegia to provide substantial nutritive flow to the intraventricular septum has been attributed to the presence of well-developed thebesian channels, which provide the main drainage of the septum." Our study shows that this reduced capillary septal flow during retrograde cardioplegic delivery is associated with an abrupt and profound degree of
septal hypothermia during retrograde infusion. Septal cooling by retrograde cardioplegia with either an open or closed LAD was better than that after antegrade cardioplegia despite occlusion of the LAD beyond the first septal branch and near normal septal flows with antegrade cardioplegia. This disparity between capillary flow and myocardial cooling during retrograde delivery suggests a drainage pattern whereby cold blood retroperfused via the coronary sinus may bypass the capillary bed and traverse septal veno-venous connections-? (i.e., veno-sinusoidal-thebesian septal channels) and exert cooling without providing abundant nutritive flow. The predominance of visually' observed retrograde drainage occurred directly into the right atrium and right ventricle via thebesian venous channels as reported by Solorzano, Taitelbaum, and Chiu." Eckstein, Hornberger, and San09 in 1958 reported a similar tendency of blood introduced into the coronary sinus to escape without passing through capillaries. The deep level of septal hypothermia may, in fact, allow the limited retrograde septal flow to provide sufficient oxygen to meet metabolic needs of the cold arrested heart. Abnormal septal wall motion has been reported to follow antegrade cardioplegic delivery in patients with coronary disease." Conceivably, septal wall motion studies after retrograde cardioplegic techniques may show fewer abnormalities if the postoperative septal changes are caused by impaired cardioplegic distribution (especially if the septal artery is obstructed). Our previous studies" of myocardial flow distribution show the septum is a pure endocardial structure. The present study shows the endocardium is underperfused preferentially by antegrade cardioplegia (endojepi ratio 0.29, 2 mIj100 gmjmin) and hyperperfused selectively by retrograde cardioplegia (endojepi ratio 1.60, 52 mIj100 gmjmin), even with LAD occlusion. These quantitative data are supportive of qualitative reports showing that retrograde infusions opacify the microvasculature of the left ventricular subendocardial layers more extensively than antegrade infusions.II Nutritive flow to the anterior left ventricle fell from 81 ± 10 mIjmin to 35 mIj100 gm/rnin during retrograde delivery with the LAD occluded, but this blood flow (1) provided excellent cooling of the jeopardized muscle (i.e., 20° ± 4° C versus 30° ± 2° C with antegrade cardioplegia) and (2) delivered abundant oxygen to meet the very low requirements of arrest at 20°C (Fig. 6). The retrograde nutritive flows in our study were comparable to the 39 ± 1 mIjmin flow rate reported by Hochberg and Austen,' who perfused the LAD vein with a vein graft connected to the aorta during acute LAD arterial occlusion.
Volume 97 Number 4
Retrograde cardioplegia. I
April 1989
The inability of retrograde oxygenated blood flow to provide adequately for the oxygen demands of the working heart was reported first by Eckstein, Hornberger, and Sano,? and this finding has been supported subsequently by others.' This limitation of retrograde blood flow has been used, in part, to justify the limited clinical interest in retrograde techniques. This objection is a sound reason to avoid retrograde techniques in the working heart, but is not a valid reason to discard retrograde perfusion techniques during cardiac operations in which oxygen demands are reduced by total vented bypass and lowered further by cardioplegic arrest. The arrested heart requires less than 5% as much oxygen as the beating working heart during hypothermia «20 0 C),22 and our study shows that retrograde techniques provide abundant oxygen to supply arrested cold cardiac muscle when blood cardioplegia is the vehicle for oxygen delivery. The observed flow rate of 35 ml/IOO gm/rnin delivers twentyfold more oxygen than needed to supply the energy demands of the cold arrested heart, and the septal flow of 12 to 23 rnI/lOO gm/rnin may provide satisfactory oxygen supply to meet low demands of cardiac arrest, especially with profound septal hypothermia. We conclude from this study that retrograde coronary sinus perfusion of cardioplegic solutions provides excellent nutritive flow to left ventricular myocardium supplied by open and occluded coronary arteries, and delivers flow selectively to subendocardial muscle even in the presence of coronary occlusion. The limited septal flow delivered retrogradely is associated with preferential and profound septal hypothermia and suggests that septal cooling and protection may be achieved by nonnutritive retrograde flow via veno-venous collaterals. The limited right ventricular flow via retrograde techniques suggests that retrograde cardioplegic techniques may not protect the right ventricle adequately if they are the only method of cardioplegic delivery. We gratefully acknowledge the outstanding supportive efforts of our research associates, Mr. Edward Dolendo and Ms. Nand Stellino, and the typing and organizational efforts of Ms. Judith Miller Becker. REFERENCES 1. Pratt FH. The nutrition of the heart through the vessels of the Thebesius and the coronary veins. Am J Physiol 1898;1:86.
2. Hochberg MS, Austen WG. Selective retrograde coronary venous perfusion. Ann Thorac Surg 1980;29:6:57888.
3. Lolley DM, Hewitt RL, Drapanas T. Retroperfusion of the heart with a solutionof glucose, insulin,and potassium
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during anoxic arrest. J THORAC CARDIOVASC SURG 1974;67:364-70.
4. Poirier RA, Guyton RA, McIntosh CL. Drip retrograde coronary sinus perfusionfor myocardial protection during aortic cross-clamping. J THORAC CARDIOVASC SURG 1975;70:966-73.
5. Bolling SF, Flaherty JT, Bulkley BH, Gott VL, Gardner TJ. Improved myocardial preservation during global ischemia by continuous retrograde coronary sinus perfusion. J THORAC CARDIOVASC SURG 1983;86:659-66. 6. Lolley DM, Hewitt RL. Myocardial distribution of asanguineous solutions retroperfused under low pressure through the coronary sinus. J Cardiovasc Surg 1980; 21:287-94.
7. Menasche P, Kural S, Fauchet M, et al. Retrograde coronary sinus perfusion: a safe alternative for ensuring cardioplegicdelivery in aortic valve surgery. Ann Thorac Surg 1982;34:647-58. 8. Buckberg GD: Strategies and logic of cardioplegic delivery to prevent, avoid, and reverse ischemic and reperfusion damage. J THORAC CARDIOVASC SURG 1987;93: 127-39.
9. Eckstein RW, Hornberger JC, Sano T. Acute effects of elevation of coronary sinus pressure. Circulation 1958; 7:422-36. 10. Buckberg GD, Brazier JR, Nelson RL, Goldstein SM,
McConnell DH, Cooper N. Studies of the effects of hypothermia on regional myocardial blood flow and metabolism during cardiopulmonary bypass. I. The adequately perfused beating, fibrillating, and arrested heart. J THORAC CARDIOVASC SURG 1977;78:87-94. 11. Shiki K, Masuda M, Yonenaga K, Asou T, Tokunaga K. Myocardial distribution of retrograde flow through the coronary sinus of the excised normal canine heart. Ann Thorac Surg 1986;41 :265-71. 12. Masuda M, Yonenaga K, Shiki K, et al. Myocardial protection in coronary occlusion by retrograde cardioplegic perfusion via the coronary sinus in dogs. J THORAC CARDIOVASC SURG 1986;92:255-63. 13. Gundry SR, Kirsh MM. A comparison of retrograde cardioplegia vs antegrade cardioplegia in the presence of coronary artery obstruction. Ann Thorac Surg 1984; 38:124-7. 14. Abd-Elfattah AS, Salter DR, Murphy CE, Goldstein JP, Brunsting LA, Wechsler AS. Metabolic differences
between retrograde and antegrade cardioplegia after reversible normothermic global ischemic injury. Surg Forum 1986;37:267-70. 15. Solorzano J, Taitelbaum G, Chiu RCJ. Retrograde coronary sinus perfusionfor myocardial protection during cardiopulmonary bypass. Ann Thorac Surg 1978;25: 201-8. 16. Hammond GL, Austen WG. Drainage patterns of coro-
nary arterial flow as determined from the isolated heart. Am J Physiol 1967;212:1435-40. 17. Gott VL, Gonzalez JL, Zuhdi MN, Varco RL, Lillehei CWo Retrograde perfusionof the coronary sinus for direct
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vision aortic surgery. Surg Gynecol Obstet 1957;104:31928. 18. Hammond GL, Davies AL, Austen WG. Retrograde coronary sinus perfusion: a method of myocardial protection in the dog during left coronary artery occlusion. Ann Surg 1967;166:39-47. 19. Moir TW, Eckstein RW, Driscol TE. Thebesian drainage of the septal artery. Circ Res 1964;12:212-9. 20. Vignola PA, Boncher CA, Curfman GD, et al. Abnormal interventricular septal motion following cardiac surgery: clinical, surgical, echocardiographic and radionuclide correlates. Am Heart 1 1979;97:27-34.
The Journal of Thoracic and Cardiovascular Surgery
21. Hoffmann lIE, Buckberg GD, Fixler DE, Archie lP. Regional flow in the right and left ventricular free walls and septum during tachycardia, aortic constriction and arteria-venous fistulas. In: Maseri A, ed. Myocardial blood flow in man: methods and significance in coronary disease. Torino: Minerva Medica, 1972:65-78. 22. Bretschneider lH, Hubner G, Knoll D, Lohr B, Nordbeck H, Spreckermann PG. Myocardial resistance and tolerance to ischemia: physiological and biochemical basis. 1 Cardiovasc Surg (Torino) 1975;16:241-60.
Bound volumes available to subscribers Bound volumes of THE JOURNAL OFTHORACIC AND CARDIOVASCULAR SURGERY are available to subscribers (only) for the 1989 issues from the Publisher, at a cost of $55.00 ($72.00 international) for Vol. 97 (January-June) and Vol. 98 (July-December). Shipping charges are included. Each bound volume contains a subject and author index and all advertising is removed. Copies are shipped within 60 days after publication of the last issue of the volume. The binding is durable buckram with the JOURNAL name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact The C.V. Mosby Company, Circulation Department, 11830 Westline Industrial Drive, St. Louis, Missouri 63146-3318, USA; phone (800) 325-4177, ext. 351. Subscriptions must be in force to qualify. Bound volumes are not available in place of a regular JOURNAL subscription.
THORAC CARDIOVASC SURG
1989;97:605-12
Studies of retrograde cardioplegia I. Capillary blood flow distribution to myocardium supplied by open and occluded arteries This study defines the nutritive (i.e., capillary) distribution of blood cardioplegic solutions delivered via retrograde and antegrade techniques to muscle supplied by open and occluded coronary arteries where myocardial segments are in jeopardy of inadequatecardioplegic protection.Open-cbest anesthetizeddogs were studied by mixing radioactive microspheres (15 ± 5 #Lm) with a blood cardioplegic solution and administering cardioplegia either into the coronary sinus or into the proximal aorta with the left anterior descending coronary artery openor occluded (30% ± 2 % area at risk).Nutritiveflow (i.e., percentageof delivered 15 #Lm microspheres trapped in myocardial capillaries) during retrograde infusions averaged 65% versus 87 % withantegrade cardioplegia (p < 0.05).Retrograde and antegrade cardioplegic nutritive flow to aU left ventricular regionswas comparable with the left anterior descending coronary artery open (65 versus 82 m1/100 gm/min, p> 0.05), and both methods provided preferential hyperperfusion of subendocardial muscle (endocardial/epicardial ratios 1.6 and 1.5, respectively). Nutritive flow to muscle supplied by the occluded left anterior descending coronary artery was preserved better by retrograde than antegrade cardioplegia (35 versus 5 m1/100 gm/min, p < 0.05).Preferential subendocardial hyperperfusion was maintained during retrograde cardioplegia (52 m1/100 gm/min, endocardial/epicardial ratio 1.6), but flow was redistributed away from subendocardial muscle with antegrade cardioplegia «2 m1/100 gm/min, endocardial/epicardial, 0.29, p < 0.05). Left ventricular flow was reduced markedly during retrograde infusion with the left anterior descending coronary artery open or occluded (23 and 12 m1/100 gm/min), but septal cooling was superior to antegrade cardioplegia (150 ± 10 C versus 20% ± 3%, p < 0.05) despite near-normal antegrade septal flow (the left anterior descending coronary artery was ligated beyond the first septal branch). Right ventricular nutritive flow was only 7 m1/100 gm/min during retrograde coronary sinus perfusion and was maintained normaUy with antegrade cardioplegia. We conclude that retrograde cardioplegia is (1) superior to antegrade cardioplegia in delivering nutritive flow to areas supplied by occluded arteries, (2) maintains preferential subendocardial flow to subendocardial muscle in jeopardy of inadequate cardioplegic protection during occlusion of the left anterior descending coronary artery, (3) produces exceUent left ventricular septal cooling despite reduced nutritive flow, and (4) is distributed poorly to the right ventricle.
Marshall T. Partington, MD, Christophe Acar, MD, Gerald D. Buckberg, MD, Pierre Julia, MD, Edward R. Kofsky, MD, and Helen I. Bugyi, PhD, Los Angeles, Calif.
Distribution of cardioplegic solution of all cardiac regions is a prerequisite for the safe clinical use of cardioplegia for myocardial protection. Retrograde perFrom the Division of Thoracic Surgery, University of California at Los Angeles Medical Center, Los Angeles, Calif. Supported in part by National Institutes of Health Grant No. HL 16292. Received for publication April 6, 1988. Accepted for publication Oct. II, 1988. Address for reprints: G. D. Buckberg, MD, UCLA Medical Center, Department of Surgery, Los Angeles, CA 90024.
fusion of the coronary venous system, proposed originally by Pratt' in 1898, is one alternative to achieve cardioplegic distribution, especially when coronary stenoses or occlusions are present. Retrograde coronary sinus perfusion has been studied experimentally'? and used clinically,' but there is limited information about the volume of nutritive flow provided by this method of delivery. Capillary perfusion (i.e., nutritive flow) is especially important if oxygenated cardioplegic solutions are used to enhance aerobic metabolism during cardiaplegic induction, maintenance, and reperfusion," Retrograde coronary sinus perfusion in the beating 605
6 0 6 Partington et al.
heart has been shown to provide inadequate flow to completely avoid damage to hearts subjected to acute coronary occlusion."9 Prior studies of retrograde coronary sinus perfusion in beating (working or nonworking) hearts are of interest but are of limited value to the cardiac surgeon who delivers retrograde coronary sinus flow to produce and maintain cardiac arrest, where the myocardial flow and oxygen requirements are reduced markedly.'? Most previous studies designed to evaluate the myocardial distribution of retrograde coronary sinus perfusion under conditions that simulate those used during clinical cardiac operations (i.e., arrested in situ or excised or isolated hearts) employ indirect and qualitative methods. These methods include gel casting of the coronary venous system,' 1 rates of cooling," dye or angiographic techniques," and collection of effluent from different cardiac chambers," but do not allow quantification of nutritive (i.e., capillary) blood flow. The one semiquantitative study of retrograde nutritive flow distribution by Solorzano, Taitelbaum, and Chiu 13 (using radioactive microspheres) suggests that only 26% of microspheres are trapped by retrograde coronary sinus perfusion, but that report provides no data on either absolute flow rates or the distribution of flow between ischemic and nonischemic regions or to the ventricular septum or right ventricle. The present study was undertaken to determine and quantify the distribution of coronary sinus retrograde cardioplegia in hearts arrested under conditions that simulate the clinical use of retrograde and antegrade techniques in patients with and without coronary stenoses. The data will show that (1) 60% to 70% of retrograde coronary ~lnUS cardioplegic perfusion provides nutritive flow to the left ventricle, (2) the intraventricular septum is cooled preferentially by retrograde cardioplegia, despite its receiving only 25% of flow delivered to the area of risk beyond coronary stenoses, (3) left ventricular subendocardial muscle in the area at risk (occluded artery), as well as in areas with open arteries, is perfused preferentially by retrograde techniques, and (4) the right ventricle receives scant retrograde flow via the coronary sinus. Methods Experimental preparation. Fifteen mongrel dogs (25 to 35 kg) were anesthetized with intravenous sodium thiamylal (30 mg/kg), maintained on sodium pentobarbital (2 mg/kg), and placed on positive-pressureendotracheal ventilation with 100% oxygen, All dogs received humane care in compliance with the "Principles of Laboratory Animal Care" formulated by the National Society for Medical Research and the "Guide for the Care and Use of Laboratory Animals" prepared by the National Academy of Sciences and published by the National
The Journal of Thoracic and Cardiovascular Surgery
Institutes of Health (NIH publication No, 80-23, revised 1978). The chest was opened by median sternotomy and the pericardium was incised and cradled. After systemic heparinization (3 mg/kg) cardiopulmonary bypass was started with an 18F arterial cannula in the femoral artery and double venous cannulation of the cavae for venous return. A vent was placed into the left ventricle through an apical stab wound. Myocardial temperature was measured by placing thermistor probes in the left ventricular wall, the area at risk, and in the intraventricular septum (Yellow Springs Instrument Co" Yellow Springs, Ohio). The left anterior descending coronary artery (LAD) was dissected adjacent to its first diagonal branch for subsequent occlusion to produce an eventual area at risk. The azygos vein was ligated, and both venae cavae were snared to allow isolation of the right side of the heart. The right atrium was opened to expose the coronary sinus for subsequent infusion of the retrograde cardioplegia, An 18-gauge needle was placed into the aorta for induction of antegrade cardioplegia with a 6 ° to 10° C blood cardioplegic solution containing potassium chloride, 30 mg/L, which was made cold by being passed through a separate heat exchanger (Shiley BCD Plus, Shiley Incorporated, Irvine, Calif.), All hearts received antegrade cardioplegia (200 ml/rnin) to produce global arrest, which occurred within 30 seconds of starting the cardioplegic infusion. This allowed all flow distribution measurements to be made in the arrested heart under steady state conditions. The LAD was then occluded and 3 ml of gentian violet was injected into the cardioplegic infusion to define the area at risk (unstained muscle). Experimental groups Retrograde cardioplegia. Retrograde cardioplegia was delivered by calibrated roller pump to the arrested heart through a No. 12 Foley catheter inflated 2 to 3 ern within the coronary sinus. In seven of these dogs the LAD occlusion was left in place during the retrograde coronary sinus cardioplegic infusion, and in four others the occlusion was removed so that the distribution of retrograde cardioplegic solution could be assessed without the presence of coronary occlusion. Radioactive microspheres (15 ± 5 /Lm) were injected into the coronary sinus infusion line to determine the distribution of retrograde cardioplegia. Two batches of microspheres were injected simultaneously to be certain of the adequacy of mixing and lack of clumping. The injection port for microspheres was 2 feet proximal to the Foley catheter that had been placed on the coronary sinus, and the infusion was continued for 3 minutes after injection to allow for complete distribution. Infusion pressure was kept at 50 mm Hg and retrograde coronary sinus flow averaged 135 ± 21 ml/rnin and ranged from 90 to 200. Antegrade cardioplegia. Four hearts received only antegrade cardioplegia (150 ml/rnin) at an infusion pressure ranging from 50 to 70 mrn Hg. The pressure was estimated by subtracting the known pressure drop in the delivery system at that flow rate from the pressure recorded in the heat exchanger. In these hearts, the first microsphere injection was made into the cardioplegic line (approximately 2 feet proximal to the aorta) and the cardioplegic infusion was continued for 3 more minutes to allow microspheres to be distributed within the myocardium. A second injection of microspheres was made after LAD occlusion followed by similar 3-minute periods of cardioplegic flow.
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Retrograde cardioplegia, I
April 1989
Microsphere analyses. The total number of microspheres delivered was determined by counting the radioactivity in each injection vial and dividing by the counts per bead by standard techniques of gamma spectrometry. All effluent flow from the aorta, left ventricle, and right side of the heart was collected to analyze for radioactivity to determine how many microspheres escaped trapping by the heart. The microsphere vial, syringe, and injection tubing were analyzed also for radioactivity to determine the number of microspheres retained in the microsphere delivery system to avoid introducing errors in subsequent calculations designed to determine microsphere flow. Hearts were excised immediately after the microsphere injections and subsequent cardioplegic infusions had been completed. Care was taken to avoid any antegrade or retrograde perfusion after cardiac excision to prevent dislodging microspheres trapped during the prior injection. (Our previous pilot study showed that reinstituting antegrade flow after retrograde cardioplegia dislodged approximately 50% to 70% of microspheres that were trapped within the heart during retroperfusion. The hearts were then separated into areas at risk (identified by lack of gentian violet staining), area at nonrisk (posterior left ventricle supplied by unobstructed circumflex artery), intraventricular septum, right ventricular free wall, and atria placed into preweighed vials for subsequent analyses by gamma spectrometry. The vials containing heart muscle from different regions were reweighed and flows were calculated from the equation:
F = Fk X Mu M, u where F, is the cardioplegic flow (antegrade or retrograde) delivered by the calibrated roller pump and M, is the number of microspheres counted in the total heart. M, is either the microspheres in the heart or those in the collected right ventricular, left ventricular, and aortic effluent, and the F, (unknown flow) is that flow determined by solving the aforementioned equation. Nutritive flow is calculated from the microspheres in the heart. Nonnutritive flow is calculated from the microspheres in the effluent. The trapping index" is that proportion of microspheres delivered to the heart that remain in cardiac muscle samples.
Results Results were similar when two batches of microspheres were injected simultaneously and attest to the adequacy of mixing and lack of microsphere clumping during delivery and subsequent distribution. Analysis of the heart, effluent, and injection vial, syringe, and tubing showed that 94% ± 1% of all injected microspheres were recovered from the heart or effluent. Only 6% of microspheres remained in the syringes, stopcock, and delivery system or injection vial. Consequently, all subsequent calculations of flow were based on the actual number of microspheres delivered to the heart (i.e., M, = 94% of the microspheres drawn up for each study). The LAD supplied similar amounts of left ventricle in both instances (31% ± 4% and 33% ± 2%
60 7
100 80
~ LAD OPEN
LAD OCCLUDED
cc/100g/min
60 40 20 0
LV (AR)
~
LV (non AR)
0SEPTUM
C:IiI RV
Fig. 1. Distribution of retrograde cardioplegic flow to area at risk (Ar) supplied by LAD, area at no risk (non Ar) supplied by circumflex coronary artery, and septum and right ventricle (RV).
of left ventricular muscle mass, including the intraventricular septum). Capillary flow versus nonnutritive flow Retrograde cardioplegia. The capillary (i.e., nutritive) flow is determined from the number of 15 ± 5 JLm microspheres given to the heart that were recovered by scintillation counting of the different sections of cardiac muscle. Conversely, the noncapillary flow was determined from the number of microspheres that were shunted away from the capillary bed and recovered in the effluent collected from the right and left sides of the heart. Total cardiac nutritive flow averaged 70% ± 4% of delivered flow during retrograde coronary sinus infusions when both the LAD and circumflex coronary arteries were open and fell to 61% ± 6% when the LAD was occluded adjacent to the first diagonal branch. Conversely, 30% ± 4% and 39% ± 6% of injected microspheres were nonnutritive and thereby bypassed the myocardial capillary bed with the LAD open or occluded. The lowest retrograde coronary sinus nutritive flow occurred always in the right ventricular free wall; flows averaged 7 ± 2 and lO ± 2 ml/IOO gm/rnin, respectively, with the LAD open and occluded (Fig. 1). Retrograde flow to the anterior left ventricular free wall averaged 82 ± 11 ml/IOO gm/rnin when the LAD was open and fell to 35 ± 6 ml/lOO mg/rnin when the LAD was occluded (p < 0.05) (Fig. 2). Retrograde coronary sinus flow to the posterior left ventricle (nonrisk area) was comparable at 66 ± 3 and 56 ± 9 ml/rnin, respectively, when the LAD was either open or occluded. Retrograde cardioplegia was redistributed toward left ventricular subendocardial muscle when the LAD was either occluded or open (endocardial/epicardial [endo/ epi] ratio 1.64 and 1.59, respectively). Retrograde flow to the intraventricular septum was only 23 ± 9 ml/lOO gm/rnin) when the LAD was open
The Journal of
608
Thoracic and Cardiovascular Surgery
Partington et af.
LAD OPEN
100
LAD CLOSED 30
80 cc/100g/min
~
ANT LV SEPTUM
60
...
40 20
o *
Ante p
Retro
..JJ Ante
20 °C
10
Retro
Fig. 2. Nutritive flow to area at risk supplied by LAD with antegrade (ante) and retrograde (retro) cardioplegia. Note: (I) comparable flow with both methods when LAD is patent; (2) superior flow with retrograde method when LAD is occluded.
and fell to 12 ± 4 ml/IOO gm/rnin when the LAD was occluded (P> 0.05). Septal cooling with retrograde cardioplegia was, however, more profound than that achieved after antegrade cardioplegia (15 ° ± 1 ° C versus 20° ± 3° C) despite markedly reduced retrograde capillary flow. Deep septal hypothermia was achieved comparably by retrograde techniques whether the LAD was open or occluded (Fig. 3). Antegrade cardioplegia. Myocardial blood flow was 87% ± 4% nutritive with antegrade cardioplegia, with only 13% of the injected microspheres collected in the effluent. Nutritive flows were comparable in the anterior left ventricle, septum, and circumflex area, averaging 65 ± 2 ml/IOO gm/rnin in these regions when the LAD was open. Antegrade cardioplegic delivery with the LAD occluded resulted in a profound reduction in flow to the anterior left ventricle (to 8% of previous values), so that flow averaged only 5 ± 1 ml/100 gm/rnin. Left ventricular subendocardial muscle was underperfused most severely, with the endo/epi flow ratios falling to 0.29 (from 1.5), and subendocardial perfusion became negligible «2 ml/IOO gm/rnin). Septal flow was reduced only marginally during antegrade cardioplegia, as the first septal artery originated proximal to the LAD occlusion. These restrictions of antegrade flow to muscle in jeopardy of inadequate protection in the area at risk were mirrored in the degree of myocardial hypothermia; anterior left ventricular temperature fell to only 30° ± 1° C despite 1100 ml of 4 ° to 6° cardioplegic infusion, whereas septal temperature fell to 20° ± 3° C (Fig. 3). Antegrade versus retrograde capillary flow. Nutritive flow to the anterior left ventricle supplied by the patent LAD was comparable at 65 ± 5 and 82 ± 11 ml/IOO gm/min, p > 0.05, when cardioplegic delivery was antegrade via the aorta or retrograde via the
0
ANTEGRADE LAD OCCLUDED
[)
RETROGRADE LAD OCCLUDED
Fig. 3. Myocardial temperature recorded by thermistor probe in the anterior left ventricle (L V) and septum during antegrade and retrograde infusions while LAD was occluded. Note: (I) better cooling of the anterior left ventricle with retrograde cardioplegia; (2) better septal cooling with retrograde cardioplegia despite less septal nutritive flow (see text for explanation).
coronary sinus (Figs. 1 and 4). Conversely, capillary flow to the anterior left ventricle in the presence of left atrial occlusion was only 5 ml/100 gm/rnin with antegrade cardioplegia and rose sevenfold to 35 ± 6 ml/100 gm/rnin when the cardioplegic solution was delivered retrogradely via the coronary sinus. The differences in nutritive cardioplegic distribution between the anterior and retrograde techniques of administration during coronary occlusion were most apparent from the regional endocardial and epicardial flow analyses. Antegrade blood cardioplegic flow was distributed preferentially (endo/epi ratio 1.5 ± 0.2) toward subendocardial muscle without coronary occlusion (Fig. 5). Conversely, selective underperfusion of endocardial muscle followed antegrade cardioplegic delivery when there was LAD occlusion; endo/epi ratio fell to 0.29 and endocardial flow fell to <2 ml/100 gm/rnin (p < 0.05). Retrograde cardioplegic flow via the coronary sinus was also distributed preferentially toward endocardial muscle when the LAD was open (endo/epi ratio 1.59 ± 0.25, p < 0.05), and this preferential retrograde subendocardial perfusion persisted during LAD occlusion (endo/epi ratio 1.64 ± 0.13). Consequently, left ventricular subendocardial flow during retrograde cardioplegia with LAD occlusion was 52 ml/rnin (versus 35 ml/min transmural flow) and exceeded antegrade perfusion to this region by thirtyfold, p < 0.05.
Discussion This study shows that retrograde cardioplegia via the coronary sinus provides substantial capillary flow to the left ventricular free wall, even in the presence of
Volume 97 Number 4
Retrograde cardioplegia, I
April 1989
n
60
~
LAD OPEN
2.0
609
LAD CLOSED
ANT LV SEPTUM
40
ENDO/EPI 1.0
cc/100g/min
20
o *
o
ANTEGRADE LAD OPEN
* p
ANTEGRADE RETROGRADE '--LAD OCCLUDED---'
Fig. 4. Nutritive flow (mi/IOO gm/rnin) during antegrade and retrograde cardioplegic infusions to the area at risk supplied by LAD (anteriorleft ventricle (ant LVI) and the left ventricular septum. Note: (I) improved septal flow with antegrade cardioplegia, as the LAD was ligated beyond the first septal artery; (2) superior distribution of retrograde cardioplegia to the anterior left ventricle supplied by the occluded LAD.
coronary occlusion. This nutritive retrograde cardioplegic perfusion is delivered preferentially to the vulnerable subendocardial muscle, whether the LAD is open or occluded, and thereby enhances hypothermic reduction of energy demands. Conversely, antegrade cardioplegic perfusion is redistributed away from the subendocardial muscle in the presence of LAD occlusion and fails to provide the hypothermic myocardial protection to jeopardized muscle. Retrograde capillary flow to the intraventricular septum is low (i.e., 25% of flow to the anterior ventricle), whether the LAD is open or closed, but septal cooling is excellent despite this more limited retrograde perfusion. Several reports document the capacity of retrograde cardioplegia to protect myocardium in jeopardy of having intraoperative damage because of the presence of coronary occlusion5.12.13 or cardiac hypertrophy." Indirect evidence for the adequate distribution of retrograde cardioplegia via the coronary sinus to jeopardized muscle is provided by the preservation of high-energy phosphates, good regional myocardial cooling, and restoration of adequate function of muscle reliant on retrograde cardioplegic protection." Our study quantifies the ability of retrograde cardioplegia to deliver potentially nutritive flow to the capillary bed despite the presence of a coronary occlusion that limits access to antegrade cardioplegia to this area. Previous attempts to evaluate the distribution of retrograde cardioplegia, with the exception of one study, have failed to distinguish between nutritive flow (i.e., capillary flow) and that perfusion which is nonnutritive (i.e.,
Ante
Retro
Ante
Retro
p
Fig. 5. Distribution of antegrade (ante) and retrograde (refro) cardioplegia to anterior left ventricle with LAD patent and occluded. Note: (I) severe redistribution away from left
ventricular subendocardial muscle duringantegrade cardioplegia with LAD occluded; (2) preferential endocardial perfusion with antegrade and retrograde cardioplegia with LAD open; (3) maintained preferential endocardial perfusion with retrograde cardioplegia with LAD occluded.
arteria-sinusoidal, arterial luminal vessels) because of methodologic limitations (i.e., dye studies, gel studies, collected effiuents).ll.15.16 The quantification of capillary flow is especially important with oxygenated cardioplegic solutions that are intended to maximize myocardial oxygen use during cardioplegic induction, maintenance, and reperfusion." Our finding of 60% to 70% trapping of retroperfused microspheres in the myocardium is at variance with the report of Solorzano, Taitelbaum, and Chiu," who concluded that only 26% of injected microspheres are trapped and provide nutritive flow. There are several differences between our study and theirs that may explain these discrepant results. First, we injected microspheres after antegrade cardioplegic arrest, rather than instituting retrograde perfusion to a heart removed rapidly from dogs killed with barbiturate overdose. Differences in vascular and extravascular resistance may have existed (especially if the hearts were beating or fibrillating) that could result in shunting of microspheres away from the capillary bed through the existing rich network of veno-venous anastomoses.' Second, their study used a perfusion pressure of 80 mm Hg, which may have caused edema and increased vascular resistance and favored shunting away from capillary beds. Gott and associates," in 1957, reported that thebesian flow in the right side of the heart rose progressively when retrograde perfusion pressure was increased to this level. We kept perfusion pressure at 50 mm Hg to avoid producing edema and hemorrhage." Third, their report does not state clearly whether the retrograde microsphere infusion was followed by an antegrade infusion of autologous blood that may have dislodged and flushed
6 10
The Journal of Thoracic and Cardiovascular
Partington et al.
Surgery
6
4 cc/100g/min
2
o
I
DEMAND
I
SUPPLY
Fig. 6. Myocardial supply/demand balance during retrograde cardioplegic infusions (assuming reduction of left ventricular temperature to only 22° C) and area of LAD occlusion. Note: (1) low oxygen demands (0.3 mi/IOO gm/ min); (2) abundant oxygen delivery to meet these demands (assuming flow of 35 ml/IOO grn/rnin).
out microspheres that were trapped only loosely in the venous capillary bed. This would lead to a systematic underestimate of retrograde nutritive flow and explain partially the disparity between our results and theirs. Our pilot study showed, for example, that antegrade cardioplegic flow after retrograde cardiolegia dislodged as many as 75% of trapped microspheres and resulted in calculated retrograde nutritive flows that were similar to the proportion of trapped microspheres reported by Solorzano, Taitelbaum, and Chiu." Consequently, we carefully avoided antegrade flow after retrograde cardioplegic administration. The low capillary flows measured in the intraventricular septum and right ventricle are consistent with reports showing that qualitative flow to these regions is deficient by the retrograde method of coronary sinus delivery.ll.l? Our placement of the retrograde coronary sinus balloon catheter within the coronary sinus may have magnified the failure to provide substantial right ventricular flow, since the balloon catheter was positioned beyond the early branches of the coronary sinus, reported by Menasche and colleagues? to drain (or perfuse) the right ventricle. This limitation of retrograde cardioplegic distribution to the right ventricle via the coronary sinus in dogs may be less problematic in man, for the right ventricular free wall is perfused better via retrograde techniques in man than in the dog. I? The failure of retrograde cardioplegia to provide substantial nutritive flow to the intraventricular septum has been attributed to the presence of well-developed thebesian channels, which provide the main drainage of the septum." Our study shows that this reduced capillary septal flow during retrograde cardioplegic delivery is associated with an abrupt and profound degree of
septal hypothermia during retrograde infusion. Septal cooling by retrograde cardioplegia with either an open or closed LAD was better than that after antegrade cardioplegia despite occlusion of the LAD beyond the first septal branch and near normal septal flows with antegrade cardioplegia. This disparity between capillary flow and myocardial cooling during retrograde delivery suggests a drainage pattern whereby cold blood retroperfused via the coronary sinus may bypass the capillary bed and traverse septal veno-venous connections-? (i.e., veno-sinusoidal-thebesian septal channels) and exert cooling without providing abundant nutritive flow. The predominance of visually' observed retrograde drainage occurred directly into the right atrium and right ventricle via thebesian venous channels as reported by Solorzano, Taitelbaum, and Chiu." Eckstein, Hornberger, and San09 in 1958 reported a similar tendency of blood introduced into the coronary sinus to escape without passing through capillaries. The deep level of septal hypothermia may, in fact, allow the limited retrograde septal flow to provide sufficient oxygen to meet metabolic needs of the cold arrested heart. Abnormal septal wall motion has been reported to follow antegrade cardioplegic delivery in patients with coronary disease." Conceivably, septal wall motion studies after retrograde cardioplegic techniques may show fewer abnormalities if the postoperative septal changes are caused by impaired cardioplegic distribution (especially if the septal artery is obstructed). Our previous studies" of myocardial flow distribution show the septum is a pure endocardial structure. The present study shows the endocardium is underperfused preferentially by antegrade cardioplegia (endojepi ratio 0.29, 2 mIj100 gmjmin) and hyperperfused selectively by retrograde cardioplegia (endojepi ratio 1.60, 52 mIj100 gmjmin), even with LAD occlusion. These quantitative data are supportive of qualitative reports showing that retrograde infusions opacify the microvasculature of the left ventricular subendocardial layers more extensively than antegrade infusions.II Nutritive flow to the anterior left ventricle fell from 81 ± 10 mIjmin to 35 mIj100 gm/rnin during retrograde delivery with the LAD occluded, but this blood flow (1) provided excellent cooling of the jeopardized muscle (i.e., 20° ± 4° C versus 30° ± 2° C with antegrade cardioplegia) and (2) delivered abundant oxygen to meet the very low requirements of arrest at 20°C (Fig. 6). The retrograde nutritive flows in our study were comparable to the 39 ± 1 mIjmin flow rate reported by Hochberg and Austen,' who perfused the LAD vein with a vein graft connected to the aorta during acute LAD arterial occlusion.
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Retrograde cardioplegia. I
April 1989
The inability of retrograde oxygenated blood flow to provide adequately for the oxygen demands of the working heart was reported first by Eckstein, Hornberger, and Sano,? and this finding has been supported subsequently by others.' This limitation of retrograde blood flow has been used, in part, to justify the limited clinical interest in retrograde techniques. This objection is a sound reason to avoid retrograde techniques in the working heart, but is not a valid reason to discard retrograde perfusion techniques during cardiac operations in which oxygen demands are reduced by total vented bypass and lowered further by cardioplegic arrest. The arrested heart requires less than 5% as much oxygen as the beating working heart during hypothermia «20 0 C),22 and our study shows that retrograde techniques provide abundant oxygen to supply arrested cold cardiac muscle when blood cardioplegia is the vehicle for oxygen delivery. The observed flow rate of 35 ml/IOO gm/rnin delivers twentyfold more oxygen than needed to supply the energy demands of the cold arrested heart, and the septal flow of 12 to 23 rnI/lOO gm/rnin may provide satisfactory oxygen supply to meet low demands of cardiac arrest, especially with profound septal hypothermia. We conclude from this study that retrograde coronary sinus perfusion of cardioplegic solutions provides excellent nutritive flow to left ventricular myocardium supplied by open and occluded coronary arteries, and delivers flow selectively to subendocardial muscle even in the presence of coronary occlusion. The limited septal flow delivered retrogradely is associated with preferential and profound septal hypothermia and suggests that septal cooling and protection may be achieved by nonnutritive retrograde flow via veno-venous collaterals. The limited right ventricular flow via retrograde techniques suggests that retrograde cardioplegic techniques may not protect the right ventricle adequately if they are the only method of cardioplegic delivery. We gratefully acknowledge the outstanding supportive efforts of our research associates, Mr. Edward Dolendo and Ms. Nand Stellino, and the typing and organizational efforts of Ms. Judith Miller Becker. REFERENCES 1. Pratt FH. The nutrition of the heart through the vessels of the Thebesius and the coronary veins. Am J Physiol 1898;1:86.
2. Hochberg MS, Austen WG. Selective retrograde coronary venous perfusion. Ann Thorac Surg 1980;29:6:57888.
3. Lolley DM, Hewitt RL, Drapanas T. Retroperfusion of the heart with a solutionof glucose, insulin,and potassium
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during anoxic arrest. J THORAC CARDIOVASC SURG 1974;67:364-70.
4. Poirier RA, Guyton RA, McIntosh CL. Drip retrograde coronary sinus perfusionfor myocardial protection during aortic cross-clamping. J THORAC CARDIOVASC SURG 1975;70:966-73.
5. Bolling SF, Flaherty JT, Bulkley BH, Gott VL, Gardner TJ. Improved myocardial preservation during global ischemia by continuous retrograde coronary sinus perfusion. J THORAC CARDIOVASC SURG 1983;86:659-66. 6. Lolley DM, Hewitt RL. Myocardial distribution of asanguineous solutions retroperfused under low pressure through the coronary sinus. J Cardiovasc Surg 1980; 21:287-94.
7. Menasche P, Kural S, Fauchet M, et al. Retrograde coronary sinus perfusion: a safe alternative for ensuring cardioplegicdelivery in aortic valve surgery. Ann Thorac Surg 1982;34:647-58. 8. Buckberg GD: Strategies and logic of cardioplegic delivery to prevent, avoid, and reverse ischemic and reperfusion damage. J THORAC CARDIOVASC SURG 1987;93: 127-39.
9. Eckstein RW, Hornberger JC, Sano T. Acute effects of elevation of coronary sinus pressure. Circulation 1958; 7:422-36. 10. Buckberg GD, Brazier JR, Nelson RL, Goldstein SM,
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