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Feasibility of intraoperative coronary angiography during hypothermie cardioplegic arrest
Feasibility of Intraoperative Coronary Angiography During Hypothermic Cardioplegic Arrest James A. Goldstein, MD, Steven B. Laster, MD, and T. Bruce Ferguson, Jr, MD Division of Cardiology, Department of Medicine, and the Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri
Although intraoperative coronary angioplasty has the potential to enhance revascularization in selected patients undergoing coronary bypass, this technique is only rarely performed, due in part to the lack of angiographic monitoring. Accordingly, to develop angiographic techniques potentially applicable to intraoperative angioplasty, 6 conditioned dogs were placed on full cardiopulmonary bypass, the aorta was cross-clamped, and the heart arrested with cold cardioplegia solution. After 45 minutes of arrest, selective coronary angiography was performed employing catheters introduced through a proximal aortotomy. Small-volume contrast injections resulted in excellent opacification; however, the contrast agent stagnated within the coronary tree.
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he advent of techniques that achieve myocardial revascularization has dramatically altered the prognosis for patients with coronary artery disease. Surgical revascularization has beneficial effects in terms of the symptoms, functional status, and quality of life in patients with chronic stable angina, increases longevity in those with high-risk patterns of coronary artery disease, and may improve left ventricular performance in patients with ischemic left ventricular dysfunction [1-1 11. "Complete" revascularization (ie, restoration of flow to all myocardial regions compromised by stenotic arteries) confers the greatest benefits; conversely, incomplete revascularization is associated with a less optimal outcome [l-131. Unfortunately, owing to anatomic and technical considerations, one significant limitation of coronary artery bypass grafting has been the inability to completely revascularize some patients with coronary artery disease, such as those with stenoses distal to graft anastomotic sites [13]. Some patients are, in fact, deemed "inoperable" due to distal coronary involvement. Such distal stenoses also impart an increased risk of perioperative myocardial infarction [14, 151, and the grafts anastomosed to such vessels are prone to early closure due to sluggish flow related to diminished coronary runoff [14]. Thus, there is a need for adjunctive techniques to optimize the extent of revascularization in patients undergoing surgical revascularization. Intraoperative balloon Accepted for publication Oct 21, 1993 Address reprint requests to Dr Goldstein, Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Ave, Box 8086, St. Louis, MO 63110.
0 1994 by The
Society of Thoracic Surgeons
Fortunately, intracoronary flush injection of the salinecardioplegia solution resulted in immediate and complete contrast washout. After discontinuation of bypass, echocardiography revealed normal left and right ventricular function. Histopathologic analysis of tissue specimens from animals in which contrast was flushed documented the presence of normal coronary arteries and myocardium. These findings demonstrate methods by which intraoperative coronary angiography can be performed in the arrested heart without having adverse effects on either the cardiac function or histologic appearance. These techniques may have application for the performance of intraoperative angioplasty. (Ann Thorac Surg 1994;57:1597-604)
angioplasty (IOBA) offers just such potential [13, 16-24]. However, this procedure is not widely applied, due in part to the lack of application of angiographic monitoring, a technique crucial to the success of catheter-dependent endovascular interventions. All prior attempts at IOBA have been performed without angiographic monitoring, relying instead on the "blind" insertion of dilation catheters [13, 16-24]. Results of the procedure have been assessed, if at all, by inserting a metal probe into the vessel before and after dilation. The initial success of IOBA has been less than that of percutaneous transluminal coronary angioplasty [16-271, and thus there has been less acceptance of this procedure. The application of angiographic monitoring techniques therefore has the potential to enhance the performance of IOBA. Accordingly, this study was undertaken to develop techniques for performing coronary angiography in the heart arrested by cardioplegia and to evaluate its effects on cardiac function and histology.
Material and Methods Six conditioned dogs (weight, 20 to 30 kg) were premedicated with morphine sulfate (0.5 mg/kg, subcutaneously), anesthetized with sodium pentobarbital (30 mg/kg, intravenously), and mechanically ventilated. Subsequent additional doses of pentobarbital were given as necessary to maintain adequate anesthesia. Both femoral arteries and veins were surgically exposed. To measure the aortic and left ventricular pressures, a dual pressure-sensor micromanometer-tipped catheter (Millar Instruments, Houston, TX) was inserted retrogradely through a femoral artery and positioned under fluoroscopic guidance and 0003-4975/94/$7.00
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pressure monitoring. A median sternotomy was performed. Baseline hemodynamic measurements were obtained and two-dimensional echocardiography was performed (Hewlett-Packard Instruments, Palo Alto, CA) employing a transepicardial approach. The azygos vein was ligated and the venae cavae were individually cannulated for the total duration of cardiopulmonary bypass. A femoral artery was cannulated for the purpose of arterial perfusion, and both ventricles were vented through their respective apices. The aorta was dissected free of surrounding tissues. The animals were then placed on full cardiopulmonary bypass and cooled to 30°C. A myocardial thermistor was positioned in the left ventricular subendocardium to monitor the efficacy of cardioplegia infusion. An 8F vascular sheath (shortened to 2 cm) with a sidearm (Cordis Corporation, Miami, FL) was inserted into the aortic root through a proximal aortotomy and secured with sutures. A 6F left coronary angiographic catheter (Schneider [USA], Minneapolis, MN) connected to a three-way manifold was inserted through the sheath and advanced under fluoroscopic guidance so that it was adjacent to, but not within, the orifice of the left main coronary artery. The aorta was then cross-clamped, the heart cooled externally with topical iced saline, and 500 mL of cardioplegia solution (Ringer's lactate solution with a potassium concentration of 25 mEqL at 4°C) was infused through the sidearm of the indwelling aortic sheath. Cardioplegic arrest was maintained for 45 minutes; during this period, additional topical iced saline was administered and cardioplegic solution infused to maintain the myocardial temperature below 15°C. After 45 minutes of arrest, the left coronary catheter was engaged into the left main coronary artery and coronary angiography performed by hand injection using nonionic contrast (Optiray; Mallinckrodt Medical, St. Louis, MO). The volume, rate, and pressure of contrast delivery were adjusted manually to obtain maximal opacification of the left coronary tree. Coronary angiograms were recorded on cineangiographic film at 30 frames per second until the dye cleared, or for a total of 10 seconds, whichever came first. In the first animal studied, contrast was administered without the immediate injection of saline or cardioplegia. After this initial contrast injection, the dye persisted within the coronary tree for 10 minutes; however, the subsequent injection of 5 mL of flush solution (consisting of equal parts saline and cardioplegia solution) resulted in prompt and complete contrast washout from the coronary tree. This injection protocol was repeated in this animal only, with dye persistence similarly documented until saline-cardioplegia flush was performed. In the remaining 5 animals, coronary angiograms were initially performed as described; however, immediately after the injection of contrast agent, the salinecardioplegia flush solution (5 mL) was injected to clear contrast from the coronary tree. This process was recorded on cineangiographic film. In these 5 animals, additional contrast injections were also administered and consisted of nonionic dye diluted with saline to 50% and 25% strength. After each contrast injection, the salinecardioplegia flush solution was injected immediately.
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The catheters were then removed and the aorta was unclamped. After reperfusion and rewarming, the animals were weaned from bypass. Echocardiographic studies and hemodynamic recordings were obtained again 30 minutes after the discontinuation of cardiopulmonary bypass. The animals were then sacrificed and the hearts excised for analysis.
Data Acquisition Coronary angiograms were obtained with standard angiographic equipment (Angioskop; Siemens, Iselin, NJ) and recorded on cineangiographic film at 30 frames per second. Pressures and the echocardiogram were recorded on a direct-writing strip-chart recorder (Gould Instruments, Cleveland, OH). Epicardial echocardiograms were obtained in the short-axis and four-chamber views. Transducer orientation was adjusted to maximize right and left ventricular volumes and to optimize visualization of the endocardium to facilitate analysis of wall motion and thickening. Transducer position was reproduced by placement relative to native and surgical epicardial landmarks. Images were recorded on videotape for quantitative offline analysis with a calibrated microcomputer system (Hewlett-Packard Instruments). All experiments conformed to the "Position of the American Heart Association on Research Animal Use" and were conducted with the approval of the Washington University Committee on Humane Care of Laboratory Animals.
Analysis of Data Qualitative analysis of coronary angiograms was performed by first selecting angiographic frames for clarity at comparable points in the cardiac cycle. Images were then analyzed with respect to the intensity of opacification, and the quality of resolution of the major epicardial arteries and branches was assessed as excellent, good, fair, or poor. The aortic peak systolic and mean diastolic pressures and the left ventricular peak systolic and enddiastolic pressures were measured. Surface electrocardiographic limb leads were analyzed from the strip-chart recordings. The echocardiographic features pertaining to ventricular size and performance were analyzed. Ventricular areas were traced at end-diastole and end-systole in the shortaxis view and fractional area changes were calculated as follows: % fractional area change = (end-diastolic area end-systolic area)/end-diastolic area x 100 (HewlettPackard Instruments data analysis package). Alterations in ventricular diastolic areas were expressed as the percentage change relative to baseline (designated as 100%). Ventricular wall thickness was measured in the midseptum, left ventricular posterior wall, and mid right ventricular free wall at end-diastole and end-systole; the percentage of systolic thickening was calculated as follows: % thickening = (end-systolic thickness - end-diastolic thickness)/end-diastolic thickness x 100. The distance (diameter) between the left ventricular posterior wall and the left interventricular septa1 endocardia1 surface was measured at end-diastole and end-systole and the systolic shortening calculated as follows: % shortening = (end-
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diastolic diameter - end-systolic diameter)/end-diastolic diameter x 100). The diameter between the right ventricular free wall and right septal surface was similarly measured and systolic shortening calculated. For each measurement and under each set of conditions, two separate beats were analyzed and the values averaged. Thin cross-sections of proximal right and left coronary arteries and samples from sections of the right ventricular free wall, interventricular septum, and left ventricular posterior wall were fixed in formalin, stained with hematoxylin-eosin, and examined by light microscopy. Myocardial sections were evaluated for the integrity of crossstriations and myocyte nuclei, and for evidence of myocellular or interstitial edema, contraction bands, hemorrhage, or an inflammatory infiltrate. Histopathologic analysis of the coronary arteries included evaluation of the integrity of the endothelial layer, internal elastic lamina, and vascular smooth muscle.
Statistics Data were expressed as the mean L the standard errors of the mean. Comparisons were made by paired t test. A significant difference was considered to be present at the 95% confidence level.
Results
General Characteristics A total of 8 animals were studied. Two animals were subsequently excluded from analysis. In one, the left main coronary artery could not be selectively cannulated for angiography; in the other, the catheter induced left main coronary artery dissection, resulting in compromise of flow. In the remaining 6 animals that underwent successful study, the mean cardiopulmonary bypass time was 75 & 12 minutes and the mean aortic cross-clamp time was 53 ? 4 minutes. Multiple contrast injections were performed in all animals. In 1 animal, contrast injections were allowed to stagnate indefinitely; in the remaining animals, the contrast medium was promptly flushed from the coronary vasculature with injections of salinecardioplegia solution. Additional injections of diluted contrast material were performed in these latter 5 animals. The mean volume of contrast agent administered per animal, including that necessary to engage the left coronary artery, was 72 k 11 mL (range, 40 to 150 mL), computed as a full-strength equivalent.
Coronary Angiography In all animals, the selective intracoronary injection of 5 mL of full-strength contrast agent resulted in excellent opacification throughout the coronary tree and in the excellent resolution of all primary, secondary, and tertiary coronary branches (Fig 1).In that animal in which contrast injection was not followed by hand flush injection of the salinecardioplegia solution, contrast material persisted within the coronary tree for more than 10 minutes without spontaneous washout. However, flush injections in this and in the remaining animals resulted in immediate and complete washout of contrast material from the coronary
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tree (see Fig 1).Injection of similar volumes of contrast agent diluted to 50% strength also resulted in excellent opacification and resolution of the entire coronary tree, equivalent to that achieved with full-strength contrast medium. However, injection of contrast material diluted to 25% strength resulted in poor coronary opacification and resolution.
Hernodynamic, Electrocardiographic, and Echocardiographic Changes At baseline, before the institution of bypass, all animals were normotensive and in sinus rhythm with a mild sinus tachycardia, and the echocardiographic variables pertaining to left and right ventricular function were normal (Table 1). At 30 minutes after the discontinuation of cardiopulmonary bypass, all animals were in sinus rhythm at an increased rate, but showed no conduction abnormalities. Aortic and left ventricular pressures were not significantly different compared to the baseline values (see Table 1). Echocardiography demonstrated that the left ventricular chamber size was unchanged, the left ventricular posterior wall and interventricular septal systolic thickening was normal to hypercontractile, and the global left ventricular performance (assessed as the fractional area change) was normal or increased in all animals (see Table 1; Fig 2). Right ventricular size and free wall function were normal in 4 of the 6 animals after bypass (see Fig 2). In 2 animals, right ventricular free-wall motion abnormalities were evident in regions where there was gross evidence of intramural hematoma caused by mechanical trauma inflicted during placement of the right ventricular vent. In both instances, there was right ventricular dilatation with paradoxical septal motion but intact septal thickening. However, in both animals, right ventricular free-wall systolic thickening was increased in regions remote from these areas of traumatic injury; employing measurements from these intact regions yielded an increase in the right ventricular free-wall systolic thickening calculated for the entire group of 8 animals (see Table 1). The global right ventricular performance (measured by the fractional area change) was also slightly increased in all 8 animals.
Histopathologic Analysis Histologic examination of specimens obtained from animals that underwent coronary angiography followed by prompt flush injections revealed the presence of normal coronary arteries with an intact endothelium, internal elastic lamina, and vascular smooth muscle layers (Fig 3A). Both the right and left ventricular myocardium was also normal (Fig 3B). However, in the animal subjected to prolonged intracoronary contrast medium stagnation, a vacuolar pattern was evident within the subintimal aspect of the vascular smooth muscle layer, though the endothelial layer and internal elastic lamina of the left coronary artery appeared intact (Fig 3C). However, the myocar-
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Fig 1. lntracoronay injection of fullstrength contrast followed by saline-cardioplegia flush during total cardioplegic arrest. (A) Selective contrast injection results in intense opacification throughout the left coron a y tree (arrows), with high-quality resolution of all primay, seconday, and tertiay coronay branches. (B,C, D ) Frame-by frame sequence documents that prompt flush injection results in immediate contrast washout.
dium in this animal appeared normal (Fig 3D) and the right coronary artery was unaffected.
Considerations Pertinent to the Methods of This Study This study, which was designed to assess the feasibility of intraoperative coronary angiography employing a canine preparation, does not directly address the effects of angiographically monitored intraoperative coronary dilations performed in diseased human hearts. Intracoronary contrast material could have different effects when administered under conditions of cardioplegic arrest in hearts with substantial coronary artery disease and preexistent left ventricular dysfunction. More specifically, the present study did not evaluate the early or late effects of contrast injections on atherosclerotic coronary arteries undergoing balloon dilations. The clinical application of angiographically guided intraoperative angioplasty must also take into account techniques to limit radiation exposure. The management of potential dilation complications, such as coronary dissection, must also be considered. Therefore, caution must be employed when extrapolating the
Table 1. Summa y of Hemodynamic and Echocardiographic Data Variable
Baseline
After Bypass
*
~~
Heart rate (beatdmin) Aortic systolic pressure (mm Hg) Aortic mean diastolic pressure (mm Hg) LV systolic pressure (mm Hg) LV end-diastolic pressure (mm Hg) LV end-diastolic size (% of baseline) LV fractional area change (%) LV posterior wall systolic thickening (%) IVS systolic thickening (%) LV posterior wall-IVS shortening (%) RV end-diastolic size (% of baseline) RV fractional area change (%) RV free-wall systolic thickening (%) RV free wall-IVS shortening (%) a
110 f 18 148 23” 153 t 21 138 2 29 86 2 14 94 f 18 152 t 20 139 t 26 8 2 4 13 2 6 100 96 f 8 33 2 4 50 2 5“ 22 ? 3 34 4” 27 ? 4 35 2 6a 14 ? 2 20 4” 100 91 ? 6 30 2 3 38 2 6 23 ? 4 33 2 6” 21 2 5 18 2 2
*
*
< 0.05.
= interventricular ventricular.
Lv
=
left ventricular;
RV
=
right
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ED
ES
LONG AXIS
SHORT AXIS
Fig 2 . Two-dimensional echocardiographic long-axis and short-axis studies performed in 1 animal 30 minutes after bypass. At end-diastole, left ventricular size is normal. At end-systole, left ventricular posterior wall and interventricular septal thickening and shortening are vigorous (arrows) and the global left ventricular fractional area change is intact. Right ventricular free-wall contraction is intact (arrows) and global right ventricular performance is normal. (ED = end-diastole; ES = end-systole; FW = free wall; LV = left ventricle; RV = right ventricle; VS = interventricular septum.)
present findings to the setting of patients undergoing surgical coronary revascularization.
Comment This experimental study demonstrates techniques by which intraoperative coronary angiography can be performed in the heart arrested with crystalloid cardioplegic solution. Our results show that, under these conditions, the intracoronary injection of contrast medium is well tolerated. These findings may have application in the development of methods for performing angiographically guided intraoperative coronary endovascular interventions in patients undergoing surgical revascularization. The widespread application of percutaneous transluminal coronary angioplasty has altered the spectrum of underlying cardiac disorders in patients referred for surgical revascularization, with a clear trend toward multivessel, multilesion coronary artery disease characterized by more diffuse and distal atherosclerotic involvement and preexistent left ventricular dysfunction [12]. It is precisely such patients who have the greatest need for complete revascularization, and it is just such patterns of coronary involvement that make this goal more difficult to achieve using traditional surgical revascularization approaches alone. Although multiple-grafting techniques and surgical endarterectomy offer potential solutions to
some of these anatomic challenges [28], such techniques are also beset by anatomic and technical limitations. Intraoperative balloon angioplasty offers potential revascularization solutions to some of these frequently encountered anatomic and technical challenges, including lesions distal to intended graft anastomotic sites, compromised prominent septal branches, tandem lesions entrapping significant side branches, and vessels deemed too small or a borderline size for grafting [13, 16-24]. However, previous approaches to IOBA have been hampered, in part, by the lack of angiographic monitoring [16-241. Angiographic monitoring is crucial to the success of catheter-based endovascular interventions: it not only facilitates the safe and efficient positioning and manipulation of the dilation apparatus, but provides the means to assess the acute effects of angioplasty, in particular allowing for the prompt detection of inadequate dilatations and for the delineation of vascular complications needing immediate further intervention. Although lack of angiographic monitoring has undoubtedly contributed to the lesser initial success rates achieved with this procedure compared to those of percutaneous transluminal coronary angioplasty [25-291, when initial intraoperative dilations have been successful, the long-term results appear to be comparable to those for percutaneous transluminal coronary angioplasty, with no evidence of an increased incidence of early closure nor of a greater likelihood of later
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Fig 3 . Histologic specimens from an animal in which the intracoronary injection of contrast material was promptly followed by push injections shows the left coronary artery to be normal (A), with an intact endothelial layer and internal elastic lamina (arrows),as well as normal vascular smooth muscle. The left ventricular myocardium in this animal also appeared intact (B). However, in the animal subjected to prolonged intracoronary contrast stagnation, though the left coronary artery specimen exhibited an intact endothelial layer and internal elastic lamina (C; solid arrows), a patchy vacuolated pattern was evident within the subintimal aspect of the vascular smooth muscle layer (open arrows). The left ventricular myocardium in this animal appeared normal (D).
restenosis [ 13, 16241. Nevertheless, these procedural limitations have contributed to low levels of acceptance and application of IOBA.
Intraoperative Angiography: Techniques and Effects on Cardiac Function Angiographic guidance should facilitate the performance of IOBA. However, technical considerations and physiologic conditions encountered during bypass procedures dictate the need for modifications to traditional angiographic techniques as applied to IOBA. Specifically, coronary perfusion pressure and myocardial contractions, which normally facilitate transcoronary contrast flux, are absent in the cross-clamped arrested heart; therefore, the means of contrast delivery and removal, and the effects of contrast medium on myocardial function, must be considered. Observations from the present study demonstrate that, during hypothermic cardioplegic arrest, highresolution coronary angiograms can be obtained from the selective intracoronary injection of small volumes of dilute contrast agent. However, because of the absent proximal aortic perfusion pressure and myocardial contraction encountered under these conditions, contrast material was
found to stagnate within the coronary tree without any discernible spontaneous efflux of dye. Though noncoronary collateral sources are known to provide variable amounts of coronary flow during cardiopulmonary bypass [30, 311, in the present study these mechanisms furnished no appreciable coronary washout. Fortunately, the hand injection of small volumes of saline-cardioplegic solution as a contrast medium "chaser" resulted in the prompt efflux of contrast agent from the coronary tree. Coronary angiography performed with these techniques was well tolerated. All animals were successfully weaned off cardiopulmonary bypass and showed excellent myocardial function. In those animals in which contrast agent was promptly flushed by intracoronary salinecardioplegia injections, histopathologic analysis revealed no evidence of abnormalities in the myocardium or coronary arteries. However, in the lone animal in which contrast material was allowed to stagnate within the coronary vasculature for a prolonged period, microscopy studies revealed the presence of a vacuolated pattern in the vascular smooth muscle layer of the left coronary artery. However, the vessels were otherwise intact and the myocardium appeared normal. The precise nature of
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these histopathologic alterations is unclear and defining it is beyond the scope of the present study. However, that such changes were not present in the animals in which contrast agent was promptly washed out suggests that they may represent the effects of prolonged intracoronary contrast stagnation, thereby emphasizing the importance of minimizing contrast exposure by using small volumes of contrast agent followed by prompt and brisk washout injections. Our study employed intraoperative coronary angiography to perform and document the immediate results of IOBA, and the angiography was performed during cardioplegic arrest. The safety of intraoperative angiography under conditions of restored aortic perfusion pressure in the beating heart has previously been documented in patients, in whom contrast agent was injected directly into vein grafts for the purpose of assessing graft patency and flow after the completion of graft anastomoses [32].
Clinical Implications The potential benefits of IOBA as an adjunct to achieve more complete revascularization in patients undergoing coronary artery bypass grafting have previously been emphasized [13, 16-24]. Intraoperative balloon angioplasty may confer additional benefits above and beyond its ability to restore perfusion to regions otherwise destined to be incompletely revascularized. For example, the dilation of distal stenoses may enhance intraoperative delivery of cardioplegia and thereby reduce the incidence and extent of perioperative myocardial infarction, increase graft patency by improving graft runoff, and augment collateral flow to unrevascularized regions [13]. In addition, the dilation of secondary and side branches may reduce the need for multiple and segmental grafting, and thereby reduce the aortic cross-clamp time. Intraoperative balloon angioplasty also has the potential to achieve total revascularization, that is, not only the surgical bypass of proximal lesions and dilation of distal stenoses, but also the retrograde dilation of primary proximal lesions [13]. Given the cumulative attrition of saphenous vein grafts over time [ 1 4 , 91, the adjunctive intraoperative dilation of left main coronary artery and other critical proximal lesions could provide a dual coronary supply system that may serve as a flow safety net should graft compromise occur [13]. Although the potential for such proximal dilations to exert deleterious effects on graft patency owing to competitive flow patterns has been refuted by some [13], whether such a revascularization strategy confers short-term or long-term benefits in patients is a hypothesis that requires clinical validation.
Summa y Our findings demonstrate the merit of techniques by which intraoperative coronary angiography can be performed in the cross-clamped heart arrested with cold crystalloid cardioplegia. The selective delivery of intracoronary contrast agent, followed by brisk saline-cardioplegia flush injections, yields high-quality coronary angiograms without adversely affecting cardiac function or histology. Intraoperative coronary angiography thus ap-
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pears feasible and may have application in the performance of IOBA in patients undergoing coronary artery bypass grafting. We wish to express our appreciation to Linda Gallo for her secretarial support.
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25. Gruntzig A, Senning A, Siegenthaler WE. Nonoperative dilatation of coronary artery stenosis: percutaneous transluminal coronary angioplasty. N Engl J Med 1979;301:61-8. 26. Parisi AF, Folland ED, Hartigan P. A comparison of angioplasty with medical therapy in the treatment of single-vessel coronary artery disease. N Engl J Med 1992;326:10-6. 27. Weintraub WS, Jones EL, King SB, Craver J, Douglas JS, Guyton R. Changing use of coronary angioplasty and coronary bypass surgery in the treatment of chronic coronary artery disease. Am J Cardiol 1990;65:18%8. 28. Brenowitz JB, Kayser KL, Johnson WD. Results of coronary artery endarterectomy and reconstruction. J Thorac Cardiovasc Surg 1988;95:1-10. 29. Webb JG, Myler RK, Shaw RE, Anwar A, Murphy MC, Mooney JF. Bidirectional crossover and late outcome after coronary angioplasty and bypass surgery: 8 to 11year followup. J Am Coll Cardiol 1990;16:57-65. 30. Moberg A. Anastomoses between extracardiac vessels and coronary arteries - I - via bronchial arteries. Post-mortem angiography study in adults and newborn infants. Acta Radio1 Diagn 1967;6:177-92. 31. Brazier J, Hottenrott C, Buckberg G. Noncoronary collateral myocardial blood flow. Ann Thorac Surg 1975;19:427-35. 32. Diethrich EB, Kinard SA, Scappatura E, Mitsuoka H, Moiel D. Intraoperative coronary arteriography. Am J Surg 1972; 124815-8.
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Although intraoperative coronary angioplasty has the potential to enhance revascularization in selected patients undergoing coronary bypass, this technique is only rarely performed, due in part to the lack of angiographic monitoring. Accordingly, to develop angiographic techniques potentially applicable to intraoperative angioplasty, 6 conditioned dogs were placed on full cardiopulmonary bypass, the aorta was cross-clamped, and the heart arrested with cold cardioplegia solution. After 45 minutes of arrest, selective coronary angiography was performed employing catheters introduced through a proximal aortotomy. Small-volume contrast injections resulted in excellent opacification; however, the contrast agent stagnated within the coronary tree.
T
he advent of techniques that achieve myocardial revascularization has dramatically altered the prognosis for patients with coronary artery disease. Surgical revascularization has beneficial effects in terms of the symptoms, functional status, and quality of life in patients with chronic stable angina, increases longevity in those with high-risk patterns of coronary artery disease, and may improve left ventricular performance in patients with ischemic left ventricular dysfunction [1-1 11. "Complete" revascularization (ie, restoration of flow to all myocardial regions compromised by stenotic arteries) confers the greatest benefits; conversely, incomplete revascularization is associated with a less optimal outcome [l-131. Unfortunately, owing to anatomic and technical considerations, one significant limitation of coronary artery bypass grafting has been the inability to completely revascularize some patients with coronary artery disease, such as those with stenoses distal to graft anastomotic sites [13]. Some patients are, in fact, deemed "inoperable" due to distal coronary involvement. Such distal stenoses also impart an increased risk of perioperative myocardial infarction [14, 151, and the grafts anastomosed to such vessels are prone to early closure due to sluggish flow related to diminished coronary runoff [14]. Thus, there is a need for adjunctive techniques to optimize the extent of revascularization in patients undergoing surgical revascularization. Intraoperative balloon Accepted for publication Oct 21, 1993 Address reprint requests to Dr Goldstein, Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Ave, Box 8086, St. Louis, MO 63110.
0 1994 by The
Society of Thoracic Surgeons
Fortunately, intracoronary flush injection of the salinecardioplegia solution resulted in immediate and complete contrast washout. After discontinuation of bypass, echocardiography revealed normal left and right ventricular function. Histopathologic analysis of tissue specimens from animals in which contrast was flushed documented the presence of normal coronary arteries and myocardium. These findings demonstrate methods by which intraoperative coronary angiography can be performed in the arrested heart without having adverse effects on either the cardiac function or histologic appearance. These techniques may have application for the performance of intraoperative angioplasty. (Ann Thorac Surg 1994;57:1597-604)
angioplasty (IOBA) offers just such potential [13, 16-24]. However, this procedure is not widely applied, due in part to the lack of application of angiographic monitoring, a technique crucial to the success of catheter-dependent endovascular interventions. All prior attempts at IOBA have been performed without angiographic monitoring, relying instead on the "blind" insertion of dilation catheters [13, 16-24]. Results of the procedure have been assessed, if at all, by inserting a metal probe into the vessel before and after dilation. The initial success of IOBA has been less than that of percutaneous transluminal coronary angioplasty [16-271, and thus there has been less acceptance of this procedure. The application of angiographic monitoring techniques therefore has the potential to enhance the performance of IOBA. Accordingly, this study was undertaken to develop techniques for performing coronary angiography in the heart arrested by cardioplegia and to evaluate its effects on cardiac function and histology.
Material and Methods Six conditioned dogs (weight, 20 to 30 kg) were premedicated with morphine sulfate (0.5 mg/kg, subcutaneously), anesthetized with sodium pentobarbital (30 mg/kg, intravenously), and mechanically ventilated. Subsequent additional doses of pentobarbital were given as necessary to maintain adequate anesthesia. Both femoral arteries and veins were surgically exposed. To measure the aortic and left ventricular pressures, a dual pressure-sensor micromanometer-tipped catheter (Millar Instruments, Houston, TX) was inserted retrogradely through a femoral artery and positioned under fluoroscopic guidance and 0003-4975/94/$7.00
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pressure monitoring. A median sternotomy was performed. Baseline hemodynamic measurements were obtained and two-dimensional echocardiography was performed (Hewlett-Packard Instruments, Palo Alto, CA) employing a transepicardial approach. The azygos vein was ligated and the venae cavae were individually cannulated for the total duration of cardiopulmonary bypass. A femoral artery was cannulated for the purpose of arterial perfusion, and both ventricles were vented through their respective apices. The aorta was dissected free of surrounding tissues. The animals were then placed on full cardiopulmonary bypass and cooled to 30°C. A myocardial thermistor was positioned in the left ventricular subendocardium to monitor the efficacy of cardioplegia infusion. An 8F vascular sheath (shortened to 2 cm) with a sidearm (Cordis Corporation, Miami, FL) was inserted into the aortic root through a proximal aortotomy and secured with sutures. A 6F left coronary angiographic catheter (Schneider [USA], Minneapolis, MN) connected to a three-way manifold was inserted through the sheath and advanced under fluoroscopic guidance so that it was adjacent to, but not within, the orifice of the left main coronary artery. The aorta was then cross-clamped, the heart cooled externally with topical iced saline, and 500 mL of cardioplegia solution (Ringer's lactate solution with a potassium concentration of 25 mEqL at 4°C) was infused through the sidearm of the indwelling aortic sheath. Cardioplegic arrest was maintained for 45 minutes; during this period, additional topical iced saline was administered and cardioplegic solution infused to maintain the myocardial temperature below 15°C. After 45 minutes of arrest, the left coronary catheter was engaged into the left main coronary artery and coronary angiography performed by hand injection using nonionic contrast (Optiray; Mallinckrodt Medical, St. Louis, MO). The volume, rate, and pressure of contrast delivery were adjusted manually to obtain maximal opacification of the left coronary tree. Coronary angiograms were recorded on cineangiographic film at 30 frames per second until the dye cleared, or for a total of 10 seconds, whichever came first. In the first animal studied, contrast was administered without the immediate injection of saline or cardioplegia. After this initial contrast injection, the dye persisted within the coronary tree for 10 minutes; however, the subsequent injection of 5 mL of flush solution (consisting of equal parts saline and cardioplegia solution) resulted in prompt and complete contrast washout from the coronary tree. This injection protocol was repeated in this animal only, with dye persistence similarly documented until saline-cardioplegia flush was performed. In the remaining 5 animals, coronary angiograms were initially performed as described; however, immediately after the injection of contrast agent, the salinecardioplegia flush solution (5 mL) was injected to clear contrast from the coronary tree. This process was recorded on cineangiographic film. In these 5 animals, additional contrast injections were also administered and consisted of nonionic dye diluted with saline to 50% and 25% strength. After each contrast injection, the salinecardioplegia flush solution was injected immediately.
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The catheters were then removed and the aorta was unclamped. After reperfusion and rewarming, the animals were weaned from bypass. Echocardiographic studies and hemodynamic recordings were obtained again 30 minutes after the discontinuation of cardiopulmonary bypass. The animals were then sacrificed and the hearts excised for analysis.
Data Acquisition Coronary angiograms were obtained with standard angiographic equipment (Angioskop; Siemens, Iselin, NJ) and recorded on cineangiographic film at 30 frames per second. Pressures and the echocardiogram were recorded on a direct-writing strip-chart recorder (Gould Instruments, Cleveland, OH). Epicardial echocardiograms were obtained in the short-axis and four-chamber views. Transducer orientation was adjusted to maximize right and left ventricular volumes and to optimize visualization of the endocardium to facilitate analysis of wall motion and thickening. Transducer position was reproduced by placement relative to native and surgical epicardial landmarks. Images were recorded on videotape for quantitative offline analysis with a calibrated microcomputer system (Hewlett-Packard Instruments). All experiments conformed to the "Position of the American Heart Association on Research Animal Use" and were conducted with the approval of the Washington University Committee on Humane Care of Laboratory Animals.
Analysis of Data Qualitative analysis of coronary angiograms was performed by first selecting angiographic frames for clarity at comparable points in the cardiac cycle. Images were then analyzed with respect to the intensity of opacification, and the quality of resolution of the major epicardial arteries and branches was assessed as excellent, good, fair, or poor. The aortic peak systolic and mean diastolic pressures and the left ventricular peak systolic and enddiastolic pressures were measured. Surface electrocardiographic limb leads were analyzed from the strip-chart recordings. The echocardiographic features pertaining to ventricular size and performance were analyzed. Ventricular areas were traced at end-diastole and end-systole in the shortaxis view and fractional area changes were calculated as follows: % fractional area change = (end-diastolic area end-systolic area)/end-diastolic area x 100 (HewlettPackard Instruments data analysis package). Alterations in ventricular diastolic areas were expressed as the percentage change relative to baseline (designated as 100%). Ventricular wall thickness was measured in the midseptum, left ventricular posterior wall, and mid right ventricular free wall at end-diastole and end-systole; the percentage of systolic thickening was calculated as follows: % thickening = (end-systolic thickness - end-diastolic thickness)/end-diastolic thickness x 100. The distance (diameter) between the left ventricular posterior wall and the left interventricular septa1 endocardia1 surface was measured at end-diastole and end-systole and the systolic shortening calculated as follows: % shortening = (end-
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diastolic diameter - end-systolic diameter)/end-diastolic diameter x 100). The diameter between the right ventricular free wall and right septal surface was similarly measured and systolic shortening calculated. For each measurement and under each set of conditions, two separate beats were analyzed and the values averaged. Thin cross-sections of proximal right and left coronary arteries and samples from sections of the right ventricular free wall, interventricular septum, and left ventricular posterior wall were fixed in formalin, stained with hematoxylin-eosin, and examined by light microscopy. Myocardial sections were evaluated for the integrity of crossstriations and myocyte nuclei, and for evidence of myocellular or interstitial edema, contraction bands, hemorrhage, or an inflammatory infiltrate. Histopathologic analysis of the coronary arteries included evaluation of the integrity of the endothelial layer, internal elastic lamina, and vascular smooth muscle.
Statistics Data were expressed as the mean L the standard errors of the mean. Comparisons were made by paired t test. A significant difference was considered to be present at the 95% confidence level.
Results
General Characteristics A total of 8 animals were studied. Two animals were subsequently excluded from analysis. In one, the left main coronary artery could not be selectively cannulated for angiography; in the other, the catheter induced left main coronary artery dissection, resulting in compromise of flow. In the remaining 6 animals that underwent successful study, the mean cardiopulmonary bypass time was 75 & 12 minutes and the mean aortic cross-clamp time was 53 ? 4 minutes. Multiple contrast injections were performed in all animals. In 1 animal, contrast injections were allowed to stagnate indefinitely; in the remaining animals, the contrast medium was promptly flushed from the coronary vasculature with injections of salinecardioplegia solution. Additional injections of diluted contrast material were performed in these latter 5 animals. The mean volume of contrast agent administered per animal, including that necessary to engage the left coronary artery, was 72 k 11 mL (range, 40 to 150 mL), computed as a full-strength equivalent.
Coronary Angiography In all animals, the selective intracoronary injection of 5 mL of full-strength contrast agent resulted in excellent opacification throughout the coronary tree and in the excellent resolution of all primary, secondary, and tertiary coronary branches (Fig 1).In that animal in which contrast injection was not followed by hand flush injection of the salinecardioplegia solution, contrast material persisted within the coronary tree for more than 10 minutes without spontaneous washout. However, flush injections in this and in the remaining animals resulted in immediate and complete washout of contrast material from the coronary
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tree (see Fig 1).Injection of similar volumes of contrast agent diluted to 50% strength also resulted in excellent opacification and resolution of the entire coronary tree, equivalent to that achieved with full-strength contrast medium. However, injection of contrast material diluted to 25% strength resulted in poor coronary opacification and resolution.
Hernodynamic, Electrocardiographic, and Echocardiographic Changes At baseline, before the institution of bypass, all animals were normotensive and in sinus rhythm with a mild sinus tachycardia, and the echocardiographic variables pertaining to left and right ventricular function were normal (Table 1). At 30 minutes after the discontinuation of cardiopulmonary bypass, all animals were in sinus rhythm at an increased rate, but showed no conduction abnormalities. Aortic and left ventricular pressures were not significantly different compared to the baseline values (see Table 1). Echocardiography demonstrated that the left ventricular chamber size was unchanged, the left ventricular posterior wall and interventricular septal systolic thickening was normal to hypercontractile, and the global left ventricular performance (assessed as the fractional area change) was normal or increased in all animals (see Table 1; Fig 2). Right ventricular size and free wall function were normal in 4 of the 6 animals after bypass (see Fig 2). In 2 animals, right ventricular free-wall motion abnormalities were evident in regions where there was gross evidence of intramural hematoma caused by mechanical trauma inflicted during placement of the right ventricular vent. In both instances, there was right ventricular dilatation with paradoxical septal motion but intact septal thickening. However, in both animals, right ventricular free-wall systolic thickening was increased in regions remote from these areas of traumatic injury; employing measurements from these intact regions yielded an increase in the right ventricular free-wall systolic thickening calculated for the entire group of 8 animals (see Table 1). The global right ventricular performance (measured by the fractional area change) was also slightly increased in all 8 animals.
Histopathologic Analysis Histologic examination of specimens obtained from animals that underwent coronary angiography followed by prompt flush injections revealed the presence of normal coronary arteries with an intact endothelium, internal elastic lamina, and vascular smooth muscle layers (Fig 3A). Both the right and left ventricular myocardium was also normal (Fig 3B). However, in the animal subjected to prolonged intracoronary contrast medium stagnation, a vacuolar pattern was evident within the subintimal aspect of the vascular smooth muscle layer, though the endothelial layer and internal elastic lamina of the left coronary artery appeared intact (Fig 3C). However, the myocar-
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Fig 1. lntracoronay injection of fullstrength contrast followed by saline-cardioplegia flush during total cardioplegic arrest. (A) Selective contrast injection results in intense opacification throughout the left coron a y tree (arrows), with high-quality resolution of all primay, seconday, and tertiay coronay branches. (B,C, D ) Frame-by frame sequence documents that prompt flush injection results in immediate contrast washout.
dium in this animal appeared normal (Fig 3D) and the right coronary artery was unaffected.
Considerations Pertinent to the Methods of This Study This study, which was designed to assess the feasibility of intraoperative coronary angiography employing a canine preparation, does not directly address the effects of angiographically monitored intraoperative coronary dilations performed in diseased human hearts. Intracoronary contrast material could have different effects when administered under conditions of cardioplegic arrest in hearts with substantial coronary artery disease and preexistent left ventricular dysfunction. More specifically, the present study did not evaluate the early or late effects of contrast injections on atherosclerotic coronary arteries undergoing balloon dilations. The clinical application of angiographically guided intraoperative angioplasty must also take into account techniques to limit radiation exposure. The management of potential dilation complications, such as coronary dissection, must also be considered. Therefore, caution must be employed when extrapolating the
Table 1. Summa y of Hemodynamic and Echocardiographic Data Variable
Baseline
After Bypass
*
~~
Heart rate (beatdmin) Aortic systolic pressure (mm Hg) Aortic mean diastolic pressure (mm Hg) LV systolic pressure (mm Hg) LV end-diastolic pressure (mm Hg) LV end-diastolic size (% of baseline) LV fractional area change (%) LV posterior wall systolic thickening (%) IVS systolic thickening (%) LV posterior wall-IVS shortening (%) RV end-diastolic size (% of baseline) RV fractional area change (%) RV free-wall systolic thickening (%) RV free wall-IVS shortening (%) a
110 f 18 148 23” 153 t 21 138 2 29 86 2 14 94 f 18 152 t 20 139 t 26 8 2 4 13 2 6 100 96 f 8 33 2 4 50 2 5“ 22 ? 3 34 4” 27 ? 4 35 2 6a 14 ? 2 20 4” 100 91 ? 6 30 2 3 38 2 6 23 ? 4 33 2 6” 21 2 5 18 2 2
*
*
< 0.05.
= interventricular ventricular.
Lv
=
left ventricular;
RV
=
right
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ED
ES
LONG AXIS
SHORT AXIS
Fig 2 . Two-dimensional echocardiographic long-axis and short-axis studies performed in 1 animal 30 minutes after bypass. At end-diastole, left ventricular size is normal. At end-systole, left ventricular posterior wall and interventricular septal thickening and shortening are vigorous (arrows) and the global left ventricular fractional area change is intact. Right ventricular free-wall contraction is intact (arrows) and global right ventricular performance is normal. (ED = end-diastole; ES = end-systole; FW = free wall; LV = left ventricle; RV = right ventricle; VS = interventricular septum.)
present findings to the setting of patients undergoing surgical coronary revascularization.
Comment This experimental study demonstrates techniques by which intraoperative coronary angiography can be performed in the heart arrested with crystalloid cardioplegic solution. Our results show that, under these conditions, the intracoronary injection of contrast medium is well tolerated. These findings may have application in the development of methods for performing angiographically guided intraoperative coronary endovascular interventions in patients undergoing surgical revascularization. The widespread application of percutaneous transluminal coronary angioplasty has altered the spectrum of underlying cardiac disorders in patients referred for surgical revascularization, with a clear trend toward multivessel, multilesion coronary artery disease characterized by more diffuse and distal atherosclerotic involvement and preexistent left ventricular dysfunction [12]. It is precisely such patients who have the greatest need for complete revascularization, and it is just such patterns of coronary involvement that make this goal more difficult to achieve using traditional surgical revascularization approaches alone. Although multiple-grafting techniques and surgical endarterectomy offer potential solutions to
some of these anatomic challenges [28], such techniques are also beset by anatomic and technical limitations. Intraoperative balloon angioplasty offers potential revascularization solutions to some of these frequently encountered anatomic and technical challenges, including lesions distal to intended graft anastomotic sites, compromised prominent septal branches, tandem lesions entrapping significant side branches, and vessels deemed too small or a borderline size for grafting [13, 16-24]. However, previous approaches to IOBA have been hampered, in part, by the lack of angiographic monitoring [16-241. Angiographic monitoring is crucial to the success of catheter-based endovascular interventions: it not only facilitates the safe and efficient positioning and manipulation of the dilation apparatus, but provides the means to assess the acute effects of angioplasty, in particular allowing for the prompt detection of inadequate dilatations and for the delineation of vascular complications needing immediate further intervention. Although lack of angiographic monitoring has undoubtedly contributed to the lesser initial success rates achieved with this procedure compared to those of percutaneous transluminal coronary angioplasty [25-291, when initial intraoperative dilations have been successful, the long-term results appear to be comparable to those for percutaneous transluminal coronary angioplasty, with no evidence of an increased incidence of early closure nor of a greater likelihood of later
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Fig 3 . Histologic specimens from an animal in which the intracoronary injection of contrast material was promptly followed by push injections shows the left coronary artery to be normal (A), with an intact endothelial layer and internal elastic lamina (arrows),as well as normal vascular smooth muscle. The left ventricular myocardium in this animal also appeared intact (B). However, in the animal subjected to prolonged intracoronary contrast stagnation, though the left coronary artery specimen exhibited an intact endothelial layer and internal elastic lamina (C; solid arrows), a patchy vacuolated pattern was evident within the subintimal aspect of the vascular smooth muscle layer (open arrows). The left ventricular myocardium in this animal appeared normal (D).
restenosis [ 13, 16241. Nevertheless, these procedural limitations have contributed to low levels of acceptance and application of IOBA.
Intraoperative Angiography: Techniques and Effects on Cardiac Function Angiographic guidance should facilitate the performance of IOBA. However, technical considerations and physiologic conditions encountered during bypass procedures dictate the need for modifications to traditional angiographic techniques as applied to IOBA. Specifically, coronary perfusion pressure and myocardial contractions, which normally facilitate transcoronary contrast flux, are absent in the cross-clamped arrested heart; therefore, the means of contrast delivery and removal, and the effects of contrast medium on myocardial function, must be considered. Observations from the present study demonstrate that, during hypothermic cardioplegic arrest, highresolution coronary angiograms can be obtained from the selective intracoronary injection of small volumes of dilute contrast agent. However, because of the absent proximal aortic perfusion pressure and myocardial contraction encountered under these conditions, contrast material was
found to stagnate within the coronary tree without any discernible spontaneous efflux of dye. Though noncoronary collateral sources are known to provide variable amounts of coronary flow during cardiopulmonary bypass [30, 311, in the present study these mechanisms furnished no appreciable coronary washout. Fortunately, the hand injection of small volumes of saline-cardioplegic solution as a contrast medium "chaser" resulted in the prompt efflux of contrast agent from the coronary tree. Coronary angiography performed with these techniques was well tolerated. All animals were successfully weaned off cardiopulmonary bypass and showed excellent myocardial function. In those animals in which contrast agent was promptly flushed by intracoronary salinecardioplegia injections, histopathologic analysis revealed no evidence of abnormalities in the myocardium or coronary arteries. However, in the lone animal in which contrast material was allowed to stagnate within the coronary vasculature for a prolonged period, microscopy studies revealed the presence of a vacuolated pattern in the vascular smooth muscle layer of the left coronary artery. However, the vessels were otherwise intact and the myocardium appeared normal. The precise nature of
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these histopathologic alterations is unclear and defining it is beyond the scope of the present study. However, that such changes were not present in the animals in which contrast agent was promptly washed out suggests that they may represent the effects of prolonged intracoronary contrast stagnation, thereby emphasizing the importance of minimizing contrast exposure by using small volumes of contrast agent followed by prompt and brisk washout injections. Our study employed intraoperative coronary angiography to perform and document the immediate results of IOBA, and the angiography was performed during cardioplegic arrest. The safety of intraoperative angiography under conditions of restored aortic perfusion pressure in the beating heart has previously been documented in patients, in whom contrast agent was injected directly into vein grafts for the purpose of assessing graft patency and flow after the completion of graft anastomoses [32].
Clinical Implications The potential benefits of IOBA as an adjunct to achieve more complete revascularization in patients undergoing coronary artery bypass grafting have previously been emphasized [13, 16-24]. Intraoperative balloon angioplasty may confer additional benefits above and beyond its ability to restore perfusion to regions otherwise destined to be incompletely revascularized. For example, the dilation of distal stenoses may enhance intraoperative delivery of cardioplegia and thereby reduce the incidence and extent of perioperative myocardial infarction, increase graft patency by improving graft runoff, and augment collateral flow to unrevascularized regions [13]. In addition, the dilation of secondary and side branches may reduce the need for multiple and segmental grafting, and thereby reduce the aortic cross-clamp time. Intraoperative balloon angioplasty also has the potential to achieve total revascularization, that is, not only the surgical bypass of proximal lesions and dilation of distal stenoses, but also the retrograde dilation of primary proximal lesions [13]. Given the cumulative attrition of saphenous vein grafts over time [ 1 4 , 91, the adjunctive intraoperative dilation of left main coronary artery and other critical proximal lesions could provide a dual coronary supply system that may serve as a flow safety net should graft compromise occur [13]. Although the potential for such proximal dilations to exert deleterious effects on graft patency owing to competitive flow patterns has been refuted by some [13], whether such a revascularization strategy confers short-term or long-term benefits in patients is a hypothesis that requires clinical validation.
Summa y Our findings demonstrate the merit of techniques by which intraoperative coronary angiography can be performed in the cross-clamped heart arrested with cold crystalloid cardioplegia. The selective delivery of intracoronary contrast agent, followed by brisk saline-cardioplegia flush injections, yields high-quality coronary angiograms without adversely affecting cardiac function or histology. Intraoperative coronary angiography thus ap-
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pears feasible and may have application in the performance of IOBA in patients undergoing coronary artery bypass grafting. We wish to express our appreciation to Linda Gallo for her secretarial support.
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