Myocardial protection during aortic valve replacement

J THORAC

CARDIOVASC SURG

82:837-847, 1981

Myocardial protection during aortic valve replacement Comparison of different methods by intraoperative coronary sinus blood sampling and postoperative serial serum enzyme determinations Ninety-seven patients undergoing isolated aortic valve replacement were studied during operation by simultaneous blood sampling from the coronary sinus and radial artery and, after operation, by serial determinations of myocardial enzymes. Myocardial protection was accomplished by selective coronary perfusion (SCP) in 26 patients, crystalloid potassium cardioplegia (CPC) in 38, single-dose blood cardioplegia (SBC) in IS, and continuous blood cardioplegia (CBC) in 18 patients, The CBC method consisted of a slow pulsatile infusion of 15° C cold oxygenated blood from the heart-lung machine (with 16 mmoles of K+ and 16 mmoles of Mg :" per liter added) selectively into the left coronary artery during aortic cross-clamping. The intraoperative blood samples were analyzed for Po 2 , oxygen saturation, oxygen content, Pco.; pH, lactate, pyruvate, glucose, potassium, and myoglobin; the postoperative blood samples for creatine kinase (CK), its isoenzyme (CK-MB) , and aspartate aminotransferase (ASAT, equivalent to serum glutamic oxaloacetic transaminase). Myocardial biopsy specimens were taken from the left ventricle on induction and termination of cardioplegia in the blood cardioplegia groups and analyzed for adenosine triphosphate (ATP), creatine, and creatine phosphate. In the SCP group, one patient (4 %) died of left ventricular failure resulting from ischemic myocardial damage and three ( 12%) needed inotropic support postoperatively. In the three cardioplegia groups (71 patients), there were no deaths and none of the patients needed inotropic support. The metabolic studies showed that SCP failed to protect the myocardium completely despite adequate coronary flow. Ten minutes after bypass, the heart was still producing lactate. The pattern of metabolic changes was similar in the three cardioplegia groups and was characterized by an early washout of lactate and other metabolic products, decreased oxygen extraction, potassium, myoglobin, and enzyme release. The CK-MB serum activity peaked between 2 and 4 hours after reperfusion. If the three cardioplegia methods were compared by the metabolic and enzymatic parameters, the CBC method was the best. The metabolic disturbances were significantly smaller and normalized more quickly during reperfusion. Blood samples from the coronary sinus during the continuous cardioplegic perfusion showed that the heart extracted oxygen despite its relaxed state and the low temperature (15° to 18° C). The myocardial biopsy specimens also showed significantly less ATP and CP decrease in the CBC patients than in the other patients.

Christian L. Olin, M.D. (by invitation), Vollmer Bomfim, M.D. (by invitation), Rutger Bendz, M.D. (by invitation), Lennart Kaijser, M.D. (by invitation), Stellan J. Strom, M.D. (by invitation), and Christer H. Sylven, M.D. (by invitation), Stockholm, Sweden Sponsored by Viking O. Bjork, M.D., Stockholm, Sweden From the Thoracic Surgical Clinic, the Departments of Physiology and Internal Medicine, Karolinska Hospital, and the Departments of Clinical Chemistry and Internal Medicine, St. Erik's Hospital, Stockholm, Sweden. Read at the Sixty-first Annual Meeting of The American Association for Thoracic Surgery, Washington, D. C., May 11-13, 1981. Address for reprints: Christian Olin, M.D., Department of Thoracic Surgery, University Hospital, 221 85 Lund, Sweden. 0022-5223/81/120837+11$01.10/0

Left ventricular failure resulting from ischemic myocardial damage is a major cause of mortality and morbidity following aortic valve replacement. At least seventy percent of perioperative deaths are directly or indirectly related to this complication. 1-3 A few of the surviving patients will have chronic cardiac disability because of persisting myocardial failure." 5 Therefore,

© 1981 The C. V. Mosby Co.

837

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Olin et al.

Table I. Some preoperative patient data (values are given as mean ± SEM) Sex No. of patients

Age (yr)

M

SCP

26

58 ± I

CPC

38

SBC

CBC

Group

I

F

Diagnosis

No.

17

9

55 ± 2

29

9

15

59 ± 2

13

2

18

56 ± 4

12

6

AS AI AS + AI AS AI AS + AI AS AI AS + AI AS AI AS + AI

16 5 5 14 II 13 6 5 4 6 4 8

Heart volume" (mllm" BSA)

542 ± 20 586 ± 23 600 ± 44 595 ± 50

Legend: SCP, Selective coronary perfusion. CPC, Hypotbennie crystalloid potassium cardioplegia. SBC, Single-dose blood cardioplegia. CBC, Continuous blood cardioplegia. AS, Aortic stenosis. AI, Aortic insufficiency. AS + AI, Aortic stenosis and insufficiency. BSA, Body surface area. *Detennined according to Kjellberg. Lonnroth, and Rudhe'' (1951).

Table II. Characteristics of the cardioplegic solution used in the crystalloid potassium cardioplegia group (CPC group) 130 20

Na" (mmole/L) K+ (mmole/L)

Cat" (mmole/L) Mgt" (mmole/L)

2 I 110

CI- (mmole/L) Acetate- (mmole/L) pH Osmolality (mOsrnlL) Temperature

30 7.0 280

eC)

5-10

subjected to aortic valve replacement. Another aim was to compare different methods of myocardial protection by quantitative assessment of the metabolic disturbances they caused. It was then necessary to estimate the degree of ischemic trauma on the heart during aortic cross-clamping. This was achieved by combining the duration of cross-clamping with the mean left ventricular temperature into an index, the "time-temperature index" (TTl). This index is a useful tool when comparative studies of various cardioplegic procedures are undertaken.

Patients and methods Table III. Characteristics of the sanguineous cardioplegic solutions used in the single-dose blood cardioplegia group (SBC) and the continuous blood cardioplegia group (CBC) _ _ _ _1

P02 (kPa)

Oxygen content (mVL) Hematocrit (%) K+ (mmole/L)

SBC infusion

CBC perfusion _

96 ± 3 73 ± 4 20 ± I 20

95 ± 5

7.8 ± 0.1

96 ± 9 22 ± I 20 16 7.4 ± 0.1

5-10

10-20

Mg"" (mmole/L) pH Temperature

eC)

great attention must be paid to the technique of intraoperative myocardial protection, particularly in patients with limited myocardial function, in order to improve the results of operation. The purpose of the present study was to define the "normal" pattern of myocardial metabolism in patients

Ninety-seven patients undergoing isolated aortic valve replacement were studied. They were divided into four separate groups according to the method of myocardial protection. Twenty-six patients were operated upon with selective coronary perfusion (SCP), 38 with crystalloid potassium cardioplegia (CPC) , 15 with single-dose blood cardioplegia (SBC), and 18 patients with continuous blood cardioplegia (CBC). Some preoperative data are given in Table I. Only patients with normal coronary arteries for their age were included. Ninety-five percent had either a selective coronary artery study or an aortogram to exclude the presence of significant coronary artery disease. Surgical management. The anesthetic technique employed was essentially the same in the four groups. The heart was exposed through a median sternotomy. Venous blood was drained by a single large-bore cannula in the right atrium. The arterialized blood from the heart-lung machine was returned through a No.8 Sarns cannula in the ascending aorta. An AGA-Bj6rk heart-

Volume 62 Number 6

Myocardial protection during AVR

839

December. 1961

inf usionr:-. tine _. ._ .. coronary perfusion connuIo - ·

Fig. 2. Insulating pad for cold cardioplegia(Shiley Laboratories, Irvine, Calif.). The smallersize is used for children. The pads are made of compressed plastic foam and can be easily cut in the required size and shape.

coronary sinus catheter

Fig. 1. Diagram of the system used for continuous blood cardioplegia. The blood bag contains oxygenated blood with extrapotassium and is usedonlyfor induction of cardioplegia. lung machine with a disposable Shiley oxygenator was used for cardiopulmonary bypass. In the SCP group, the heart-lung machine was primed with 400 ml of acid-citrate-dextrose blood and 2,000 ml of Ringer's acetate solution. In the three cardioplegia groups, the prime consisted only of 2,000 ml of Ringer's acetate. In general , the SCP group was operated upon with perfusion hypothermia to 30° C, whereas the others were operated upon at a temperature of 25° to 26° C .

Myocardial protection. Selective coronary perfusion . Blood for coronary perfusion was taken from a side line of the arterial line, which was branched into two separate lines, one for each perfusion cannula. For the left coronary artery, a straight No. 2 plastic cannula with a self-expanding rubber balloon (Polystan, Copenhagen, Denmark) was employed and for the right, a No. I angled cannula of the same type . With this system, an average flow of 250 ml/min through the left and 130 ml/min through the right coronary artery was obtained. 6 In all groups, after onset of cardiopulmonary bypass,

the left ventricle was vented through the apex with a soft plastic catheter. The temperature of the heart was reduced by a short period of perfusate cooling. The aorta was cross-clamped and opened. The coronary arteries were probed and cannulated (only the left in the cardioplegia groups). The cannulas were held in position by stay sutures and were left in place as long as possible, A Bjork-Shiley tilting disc valve was used for valvular replacement in all patients. Cardioplegia . The composition and characteristics of the various cardioplegic solutions are given in Tables II and III . In the CPC group , cold Ringer's acetate solution (5° to 10° C) with 16 mmoles of K + added per liter was used . In the SBC group, blood was taken from the heart-lung machine, stored in plastic bags, and cooled in a refrigerator. Before use, buffer and 16 mmoles of K+ per liter were added . In the CBC group, oxygenated blood was taken directly from the heartlung machine and cooled by a spiral coil immersed in ice water (Fig . I) . Before entering the heart, the blood was modified by the addition of 16 mmoles of K + and 16 mmoles of Mg t" per liter. Usually, a flow rate of 20 to 30 ml/min was used and the perfusion was made pulsatile by omitting one of the rolls in the roller pump and by adding a one-way valve in the distal part of the line. Before this cardioplegic perfusion was begun, the heart was cooled and arrested with the same method as the SBC group . Local cooling consisted of " soft" ice (made by lightly freezing Ringer's solution) packed around the heart. The heart was insulated from the pericardium by a specially designed plastic pad (Fig . 2). In the SBC group, soft ice was applied several times .

The Journal of

840

Olinetal.

Thoracic and Cardiovascular Surgery

'C40 31 36 34 32

30

Mvoc-rdlal temp

~1'L---r---r------,---__r_--"----"--"",,,,,-""r---r-110

;V

1

IOml_ poet ICC

o,m)/l 100

10

O. cont.A-Ydlff O'----~--__r_--..----,.--....,....--.,._-___.-___..',<_~~

.. Fig. 3. Myocardial temperature and myocardial oxygen extraction during selective coronary perfusion. Vertical lines indicate standard error of the mean. ECC, Extracorporeal circulation. A-V, Arteriovenous.

Table IV. Surgical events

Group

SCP CPC

SBC CBC

No. of patients 25 38 15 18

Aortic crossclamp time (min) 77 61 65 56

± 3* ± 2

± 3 ± 2

ECC time

(min) 89 87 88 74

± 3 ± 3 ± 3 ± 3

ECC temp. (0C)

30 ± 2 25 ± 2 26 ± 2 26 ± 2

Legend: SCP, Selective coronary perfusion. CPC, Hypothermic crystalloid potassium cardioplegia.

Mean myocardial temp. (0C) 31 ± 20 ± 14 ± 18 ±

TTl

(OC

x min x 4)

2

1 1 1

1,052 ± 48 740 ± 60 995 ± 44

sac, Single-dose blood cardioplegia. cac, Continuous blood

cardioplegia. ECC, Extracorporeal circulation. TTl, Time-temperature index. 'Left coronary perfusion 70 ± 3 minutes; right coronary perfusion (22 patients) 56 ± 5 minutes.

Details of the operative cardioplegic procedures have been previously reported. 6-12

Intraoperative measurements. Temperature. Body temperature was measured in the upper part of the esophagus and rectum. In the SCP group, myocardial temperature was measured through a thin thermistor in the coronary sinus. In the three cardioplegia groups, myocardial temperature was monitored through a thin thermistor probe in the posterior wall of the left ventricle. In the CBC group, the temperature of the cardioplegic perfusate was measured by a thermistor probe inserted into the perfusion line. Pressures. In the SCP group, pressures were measured in the radial artery, right atrium, and in the left coronary perfusion line. In the cardioplegia groups, pressures were measured in the radial artery and right

and left atria. In the CBC group, pressure was also measured in the cardioplegic perfusion line. Flows. In the SCP group, blood flow was measured separately in the left and right coronary perfusion cannulas with the aid of an electromagnetic flowmeter (Nycotron, Drammen, Norway). Blood sampling. Blood samples were simultaneously taken from the radial artery and the coronary sinus. The coronary sinus catheter was introduced through the right atrial wall before bypass. The position of the tip was confirmed by external palpation and was so placed that the catheter collected blood mainly from the left ventricle. In the CBC group, a specially designed, round-tipped catheter permitted sampling during the continuous cardioplegic perfusion. In the SCP group, blood samples were taken on six

Volume 82

Myocardial protection during AVR

Number 6

84 1

December, 1981

a-cs 0.- content difference mltl Myocardial oxygen extraction 120 ,

.. continuous blood • single dose blood o asanguineous

..........,. ECC 0

j

0

pre ECC

10

J

30

aortic clamp release

sc min.

Fig. 4. Myocardial oxygen extraction following cardioplegia with different types of cardioplegic solutions. a-cs, Arterial-coronary sinus. ECC, Extracorporeal circulation.

different occasions simultaneously with the pressure and flow recordings: before bypass, after onset of coronary perfusion (usually 3 to 5 minutes after aortic cross-clamping), 10,30, and 60 minutes thereafter, and 10 minutes after termination of bypass. In the three cardioplegia groups, blood samples were taken on five different occasions: before bypass, immediately after release of the aortic cross-clamp, and 10, 30, and 60 minutes thereafter. In addition, venous blood samples were taken at regular intervals postoperatively for enzyme determinations in all four groups. Myocardial biopsy specimens. In the SBC and CBC groups, myocardial biopsy specimens were taken from the apex of the left ventricle immediately after induction of cardioplegia and shortly before release of the aortic cross-clamp. Postoperative care and hemodynamic monitoring. Postoperatively, the patients were usually sedated by intravenous morphine and diazepam and ventilated by a respirator for the first 20 hours. Systolic arterial pressure and mean right and left atrial pressures were routinely monitored during that period. A twelve-lead electrocardiogram was taken on all patients for the first 3 postoperative days and read by experienced cardiologists. Analytical methods. Oxygen saturation was measured spectrophotometrically and oxygen tension by polarographic methods. Oxygen content was calculated from the oxygen saturation and tension together with the hemoglobin concentration. Glucose, lactate, and pyruvate in blood, glucogen,

lactate, adenosine triphosphate (ATP) , creatine phosphate, and total creatine in myocardial tissue were analyzed by enzymatic fluorometric methods. Creatine kinase (CK) and its isoenzyme CK-MB were analyzed according to Oliver;!" and Mercer." Myoglobin was measured by radioimmunoassay. 15 Aspartate aminotransferase (ASAT, equivalent to serum glutamic oxaloacetic transaminase) was assayed as recommended by the Scandinavian Society for Clinical Chemistry and Clinical Physiology. For further methodological details, see Kaijser and associates:" and Bomfim.!? Calculations. Myocardial oxygen consumption was calculated from the coronary blood flow and the myocardial arterial-coronary sinus oxygen difference. Mean myocardial temperature was determined by plotting and integrating the left ventricular temperature against time, starting 10 minutes after aortic crossclamping (when myocardial cooling was completed) and ending shortly before release of the cross-clamp. The area under the curve was measured planimetrically and referred to as the "time-temperature index" (TTl). It serves as an index of ischemic myocardial trauma. 9 Cumulative lactate release and cumulative glucose extraction were assessed in the cardioplegia groups by measuring the area between the arterial-coronary sinus concentration curves for the first 60 minutes after reperfusion. A CK-MB activity curve was plotted for each patient. The efficacy of three different methods for the assessment of enzyme release were evaluated: (1) peak CK-MB activity; (2) cumulative 24 hour release, calcu-

The Journal of

842

Olin et al.

Thoracic and Cardiovascular Surgery

3,0

mmoy.

", ....- Lactate art.

00--- Lactate cor. sinus

,

20 pre ECC ...- - - - - - -

30

i

50

ECC - - - - - - -.. ~ pcm ECC

_ - - - - - Cor. perf. ------~

~

Fig. 5. Lactate arterial-coronary sinus difference during selective coronary perfusion. The high coronary sinus lactate concentration immediately after onset of perfusion is explained by the preceding 3 to 5 minute period of myocardial anoxia. ECC, Extracorporeal circulation.

lated as the area under the 24 hour activity curve; and (3) cumulative activity until peak, calculated as the area below the curve until peak and referred to as CK-MB max area. For the ASAT enzyme, only the postoperative 20 hour value was used. Statistical methods. Statistical analysis was made according to Snedecor and Cochran;" Data are presented as mean ± SEM (standard error of the mean), with three levels of significance (p < 0.05, p < 0.01, and p < 0.001). Informed consent. The study was approved by the ethics committee of the hospital. Informed consent was given by each patient. Results and comments Patient-dependent variables. Age was essentially the same in all four groups (Table I). There were comparatively more patients with aortic stenosis in the SCP group; thus the relative heart volume was smaller for this group. Otherwise, there were no differences among the groups. Surgical events. Aortic cross-clamp time was longest (77 minutes) in the SCP group and shortest (56 minutes) in the CBC group (Table IV). This difference probably reflects the difference in operative conditions in the two groups; the SCP method is technically difficult, with two coronary perfusion cannulas and a beating heart, whereas the CBC method is easy, with one cannula, a completely relaxed heart, and no need of repeating local cooling. Mean myocardial temperature

was significantly lower (14° C) in the SBC group than in the other cardioplegia groups. This difference was explained by the more aggressive local cooling in this group combined with the use of the insulating pad. This also led to a lower TTl in this group. In general, we gained the impression that hearts protected with blood cardioplegia (SBC and CBC groups), especially if a low myocardial temperature was attained, were somewhat more difficult to reperfuse and defibrillate, although they functioned extremely well later on. Clinical results. In the SCP group, one patient (4%) died of left ventricular failure. Autopsy showed a large hemorrhagic infarction. Three patients (12%) needed postoperative inotropic stimulation to maintain a satisfactory blood pressure. In the cardioplegia groups, all patients survived operation without complications. None needed inotropic stimulation postoperatively. Postoperative cardiac performance. Systolic arterial pressure was significantly higher in the cardioplegia groups postoperatively, even though several patients needed pharmacologic reduction of the blood pressure. There was no significant difference between the three cardioplegia groups in this respect. Mean right and left atrial pressures were not significantly different. One patient in the SCP group and another in the SBC group needed pacemaker implantation owing to persisting atrioventricular dissociation. Cardiac metabolism. Before bypass, the coronary sinus oxygen saturation and the arterial-coronary sinus

Volume 82

Myocardial protection during AVR

Number 6 December, 1981

843

lactate a- cs difference -I.S

mmol,l

Myocardial lactate release o asanguineous • single dose blood A continuous blood

-1.0

...

.....

III

C-0.5

... '" 0t----'J'--,----.--::::::.....o:;;:-:::::::'i4"--=====::;t> z

..

Q

..'" ...

o

)(

10

-----i

~+0.5

30

60

>---II-'

pre

A

ECC

min.

A ECC

aortic clamp release

Fig. 6. Myocardial lactate release following cardioplegia with different types of cardioplegic solutions. Only heartsprotected with continuous blood cardioplegia displayed normal lactatemetabolism 30 and 60 minutes after cardioplegia. a-cs, Arterial-coronary sinus. ECC, Extracorporeal circulation. oxygen difference were normal in all patients. Myocardial extraction (arterial-coronary sinus difference) of glucose, lactate, and pyruvate was of the same magnitude as in healthy men. 16 , 19 Serum enzymes were within normal limits. Myocardial oxygen extraction. Immediately following onset of SCP, the rate of myocardial oxygen extraction fell dramatically (Fig. 3). This was mainly explained by the reduced temperature and nonworking state of the heart. When the temperature started to rise during rewarming, oxygen extraction gradually increased, but it did not reach prebypass levels during the observation period. In the three cardioplegia groups, the degree of oxygen extraction was very low after cardioplegia (Fig. 4). It slowly rose during reperfusion, but never reached prebypass values. In a comparison of the three methods, the CBC group showed the most rapid recovery; 60 minutes after release of the aortic cross-clamp, the oxygen extraction was significantly higher than in the other groups. Lactate release. Immediately after onset of SCP, there was a marked release of lactate into the coronary sinus (Fig. 5). This was probably due to washout of lactate that had accumulated in the heart during the preceding 3 to 5 minute period of anoxia. It was interesting to find that it took at least 10 to 30 minutes for lactate metabolism to normalize reasonably well, despite adequate coronary blood flow. During rewarming, the coronary sinus concentration of lactate started to rise again, and 10 minutes after termination of bypass (about 15 minutes after release of the aortic crossclamp) the heart was still producing lactate.

Table V. Results of some metabolic calculations

Group

No. of patients

Cumulative lactate release (mmole/L x min)

Cumulative glucose extraction (mmole/L)

CPC SBC CBC

38 15 18

4.2 ± 0.6 5.4 ± 1.0 2.5 ± 0.6

7.9 ± 1.0 6.8 ± 0.9 7.0 ± 0.6

Legend: CPC, Hypothermic crystalloid potassium cardioplegia. sac, Singledose blood cardioplegia.

cac, Continuous blood cardioplegia.

In the three cardioplegia groups, there was a marked release of lactate into the coronary sinus during the first 10 minutes of reperfusion (Fig. 6). In the CBC group, the lactate metabolism had normalized already after 30 minutes with the same degree of extraction of lactate by the heart as before bypass. In the other two cardioplegia groups, the lactate metabolism never returned to normal during the period of observation. Cumulative lactate release was significantly less (p < 0.001) in the CBC group than in the other cardioplegia groups (Table V). Glucose extraction. This was studied only in the cardioplegia patients. A significant degree of glucose extraction by the heart (almost fivefold the normal) was observed during the first 30 minutes of reperfusion. After that time it became less apparent. There was no difference in the cumulative glucose extraction between the groups (Table V). Potassium release. There was no K+ release in the SCP group, during or after bypass. In the cardioplegia groups, on the other hand, there was a rather marked K+ release during the first 10 minutes after reperfusion.

The Journal of

844 Olin et al.

Thoracic and Cardiovascular Surgery

o

CONTINUOUS BLOOD GROUP

171,

j

Ld SINGLE DOSE GROUP

% 100

SO

o 100

SO

o

j

AlP

, CP

, , A

early phase

A

end of cardioplegia

Fig. 7. Relative changes in myocardial adenosine triphosphate (ATP) and creatine phosphokinase (ep) concentrations between induction and end of cardioplegia in patients operated upon withsingle-dose bloodcardioplegia andcontinuous blood cardioplegia.

In the SBC group it was more pronounced immediately after reperfusion, whereas in the others it was more significant to minutes later. There was no appreciable difference between the groups in the total amount of K+ released. Myocardial biopsy specimens. The decrease in myocardial creatine phosphate concentration was significantly lower in the CBC group than in the SBC group (Fig. 7). Enzyme release. CK-MB isoenzyme. In general, the activity peaked early, in most patients already after 3 hours. After 24 hours most of the activity had disappeared (Fig. 8). When the different groups were compared, the SCP group had the highest degree of postoperative CK-MB release (Table VI). Patients with aortic cross-clamp times in excess of 75 minutes as a rule had very high values, whereas those below this limit invariably had low activities. Among the cardioplegia groups, the CBC patients had the lowest release. There was no marked difference between the CPC and the SBC group (Fig. 8). Calculating the CK-MB max area shows that it was about twice as low in the CBC group as in the two other cardioplegia groups (Table VI). Myoglobin release. The arterial-coronary sinus difference of myoglobin is shown in Fig. 9. In general,

myoglobin is a sensitive indicator of ischemia and is released early in patients with acute myocardial infarction.P: 20 During cardiac operations, however, it is also liberated from the skeletal muscles. 20 In order to assess its release from the myocardium under the existing conditions, it is therefore necessary to study the arterial-coronary sinus difference. As can be seen from Fig. 9, there was almost no myoglobin release from the hearts protected with CBC. After 30 minutes, patients operated upon with crystalloid cardioplegia (CPC) had higher myoglobin release than those operated on with SBC. Correlations. Of the surgical events most likely to be associated with a high degree of ischemic myocardial trauma, long aortic cross-clamp time and high mean myocardial temperature are the most important. If these parameters are correlated to possible biochemical markers of myocardial damage, poor correlations are generally obtained (Table VII). This is understandable, as ischemic myocardial damage in this situation is so multifactorial in origin. However, if the aortic cross-clamp time is combined with the mean myocardial temperature into the TTl (see above) and correlated to the CK-MB max area, a linear correlation with a coefficient of 0.80 is obtained. This figure is quite satisfactory considering the numerous variables included in a clinical study of this nature. Discussion Although the clinical results obtained in the present study were satisfactory, the metabolic findings indicated that none of the methods for myocardial protection entirely protected the heart from ischemic myocardial injury. The normal electrocardiograms and the pattern of enzyme release, however, suggested that the injury was of a reversible nature and resembled more temporary cell membrane dysfunction. Comparing the different methods of myocardial protection shows that the CBC method was superior. Not only did it allow a more rapid and complete normalization of the metabolic disturbances, but it also resulted in less postoperative enzyme release. This method theoretically combines cardioplegia with coronary perfusion. Blood samples in to patients from the coronary sinus during the slow continuous cardioplegic perfusion showed that the heart extracted oxygen at a low rate (about I ml/min at 15° C). The disadvantage with this method is that it is technically somewhat more demanding than the other procedures. The method of infusing the cardioplegic solution directly into the left coronary artery after the aorta has been opened has several advantages, especially in pa-

Volume 82 Number 6

Myocardial protection during AVR

December, 1981

CK-MB

SERUM

o o • •

IJ atll 1.2

845

c. perfusion asanguineous single dose blood continuous blood

0.6

o· o

_v_

0 •• •

.::

pre ace

pre op

6

12

aortic clamp release

Fig. 8. Serum CK-MB activity after operation. Patients operated upon with selective coronary perfusion had the highest enzyme release and those with continuous blood cardioplegia the lowest. ECC, Extracorporeal circulation.

Myoglobin a- cs difference mgll

-150

o asanguineous • single dose blood • continuous blood - 75

o +-""""--.....,.I----;:----------,r---------+ eo min. 30 o ~""C'--

pre ECC

-t

aortic clamp release

Fig. 9. Myoglobin release following cardioplegia with different types of cardioplegic solutions. Patients operated upon with continuous blood cardioplegia had almost no release of myoglobin into the coronary sinus. a-cs, Arterial-coronary sinus. ECC, Extracorporeal circulation.

tients with aortic insufficiency. 8 The left ventricle is thoroughly cooled and arrested with a comparably small amount of cardioplegic solution. The excision of the valve can be started as soon as the cannula is in place. Thus variable aortic cross-clamp time will be saved and accidental loss of calcium pieces from the valve into the coronary ostium is avoided. The infusion pressure, however, should not be too high, in order to prevent local trauma by the self-inflating balloon, and the cannula should not be pushed too far into the ostium in the event of an early division of the artery. The right ventricle is usually well cooled by a brief period of

perfusate cooling before cross-clamping in combination with local cooling, and it has always contracted well. In the present study, the coronary sinus could be cannulated in all patients without complications. Patients with left ventricular hypertrophy usually have large coronary arteries and thereby also large coronary sinuses. The tip of the coronary sinus catheter should preferably be rounded and be positioned at least 5 em into the sinus to prevent accidental dislocation. It will then collect blood mainly from the left ventricle, and in the present study it was of particular advantage with respect to the cardioplegic infusions into the left coro-

846

The Journal of Thoracic and Cardiovascular Surgery

Olin et al.

Table VI. Results of serum enzyme determinations

Group SCP CPC SBC CBC

Peak CK activity concentration (JJ1
No. of patients 25 38 15 18

20.4 12.1 15.2 9.7

± ± ± ±

Peak CK-MB activity concentration ( JJ1
2.4 1.2 2.2 1.8

1.44 0.74 0.76 0.54

± ± ± ±

0.35 0.04 0.07 0.05

CK-MBpeak time (hr)

CK-MBmax area (JJ1
ASAT activity at 20 hours (JJ1
± ± ± ±

1.89 ± 0.1 2.10 ± 0.2 0.94 ± 0.1

2.9 ± 0.6 1.3 ± 0.1 1.3 ± 0.1 1.0 ± 0.1

4.0 3.7 3.6 2.7

0.4 0.3 0.3 0.4

SCP, Selective coronary perfusion. CPC, Hypothennic crystalloid potassium cardioplegia. SBC, Single-dose blood cardioplegia. CBC, Continuous blood cardioplegia. CK, Creatine phosphate. CK-MB, Creatine phosphate isoenzyme. ASAT, Aspartate aminotransferase.

Legend:

Table VII. Correlation coefficients between determinants and possible indicators of ischemic myocardial damage Aortic cross-clamp ECC time time CK-MB peak activity CK-MB 24 hr release CK-MB max area Myoglobin peak ASAT max

0.38 0.31 0.61 0.32 0.34

0.32 0.24 0.46 0.44 0.43

Mean myocardial temperature

TTl

0.28 0.34 0.60 0.18 0.19

0.53 0.45 0.80 0.35 0.60

ECC, Extracorporeal circulation. TTl, Time-temperature index. CK-MB, Creatine kinase isoenzyme. ASAT, Aspartate aminotransferase.

Legend:

nary artery. The myocardial temperature was consequently also measured in the lateral or posterior part of the left ventricle. The metabolic changes observed after cardioplegia could be divided into three main types: (1) washout of metabolites that had accumulated during cardioplegia, (2) temporary dysfunction of the cell membrane, and (3) restitution of depleted energy stores. The washout took place during the first 10 to 15 minutes of reperfusion. We, therefore, recommend at least 10 minutes of reperfusion under appropriate pressure before bypass is terminated. Obviously, the cell membrane dysfunction persisted longer. The restitution of depleted energy stores was a much slower process and was not completed during the observation period (60 minutes). The methods used for study of cardiac metabolism in the present investigation are obviously too complicated for use in clinical application. However, determination of the myocardium-specific CK-MB isoenzyme is not too complicated and can be used in clinical practice. It necessitates frequent blood sampling in the early postoperative period and, for the peak of the serum activity curve to be determined adequately, hourly blood sampling for the first 4 hours. In the present study, the peak activity occurred 2 to 4 hours after the end of cross-

clamping. This is in contrast with the findings after acute myocardial infarction, wherein the peak comes 16 to 18 hours after the onset of chest pain. 16 Hence, in order to eliminate the presence of complicating myocardial necrosis after the cardiac operation, occasional blood samples must also be taken later. The CK-MB max area proved to be the best of the different "markers" of ischemic myocardial damage. A correlation coefficient of 0.80 was obtained to the two main determinants of ischemic myocardial injuryduration of aortic cross-clamping and mean myocardial temperature (combined into the TTl). The CK-MB max area reflects the cumulative release of the enzyme, which actually takes place during the first 3 hours provided that the operation is not complicated by myocardial infarction. Furthermore, it will not be adversely influenced by such factors as elimination of the enzyme or fluid shifts. Using metabolic and enzymatic parameters for comparison, CBC was the most efficient method for myocardial protection during aortic valve replacement. The method theoretically combines the advantages of cardioplegia with that of coronary perfusion and is an attractive concept for intraoperative myocardial protection during cardiac operations. Blood samples from the coronary sinus during the slow continuous cardioplegic perfusion showed that the heart extracted oxygen despite its relaxed state and the low myocardial temperature (15° to 18° C). A flow rate of 25 to 30 ml/min was found to be sufficient, but perhaps the perfusion would be even more efficient if made still more pulsatile. The technical assistance of Jane Strand, acknowledged.

R.N., is gratefully

REFERENCES Henze A, Carlsson S, Bjork YO: Mortality and pathology following aortic valve replacement with the Bjork-Shiley tilting disc valve. Scand J Thorac Cardiovasc Surg 7:7-

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2 Barnhorst DA, Oxman HA, Connolly DC, Pluth JR, Danielson GK, Wallace RB, McGoon DC: Isolated replacement of the aortic valve with the Starr-Edwards prosthesis. A 9 year review. J THoRAc CARDIOVASC SURG 70:113-118,1975 3 Levang 0: Aortic valve replacement. A randomized study comparing the Bjork-Shiley and Lillehei-Kaster disc valves. Preoperative haemodynamic evaluation and early results. Scand J Thorac Cardiovasc Surg 12:197-205, 1978 4 Bjork YO, Henze A, Holmgren A: Central haemodynamics at rest and during exercise before and after aortic valve replacement with the Bjork-Shiley tilting disc valve in patients with isolated aortic stenosis. Scand J Thorac Cardiovasc Surg 7: 1-6, 1973 5 Bjork YO, Henze A, Holmgren A: Central haemodynamics at rest and during exercise before and after operation with the Bjork-Shiley tilting disc valve in patients with aortic incompetence. Scand J Thorac Cardiovasc Surg 7: 214-225, 1973 6 Bomfim V, Kaijser L, Olin C: Myocardial protection during aortic valve replacement. Physiological and metabolic effects of selective coronary perfusion on the fibrillating heart. Scand J Thorac Cardiovasc Surg 12:207-212,1978 7 Bjork YO, Bomfim V, Olin C: An isolation pad for cold cardioplegia. Scand J Thorac Cardiovasc Surg 12:177, 1978 8 Olin C, Bomfim V: Myocardial protection during aortic valve replacement. Selective infusion of cold cardioplegic solution into the left coronary artery. Scand J Thorac Cardiovasc Surg 15:221-225, 1979 9 Bomfim V, Kaijser L, Bendz R, Sylven C, Olin C: Myocardial protection during aortic valve replacement. Cardiac metabolism and enzyme release following hypothermic cardioplegia. Scand J Thorac Cardiovasc Surg 14:43-49, 1980 10 Bomfim V, Kaijser L, Bendz R, Sylven C, Olin C: Myocardial protection during aortic valve replacement. Effects of mannitol in the cardioplegic solution on cardiac metabolism and enzyme release. Scand J Thorac Cardiovasc Surg 15:129-133, 1981

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I I Bomfim V, Kaijser L, Bendz R, Sylven C, Olin C: Myocardial protection during aortic valve replacement. Comparison between sanguineous and asanguineous cardioplegic solutions. Scand J Thorac Cardiovasc Surg 15: 135-139, 1981 12 Bomfim V, Kaijser L, Bendz R, Sylven C, Morillo F, Olin C: Myocardial protection during aortic valve replacement. Cardiac metabolism and enzyme release following continuous blood cardioplegia. Scand J Thorac Cardiovasc Surg 15:141-147, 1981 13 Oliver JT: A spectrophotometric method for the determination of creatine phosphokinase and myokinase. Biochern J 61:116, 1955 14 Mercer DW: Separation of tissue and serum creatine kinase isoenzymes by ion-exchange chromatography. Clin Chern 20:36-40, 1974 15 Sylven C, Bendz R: Myoglobin, creatine-kinase and its isoenzyme MB in serum after acute myocardial infarction. Eur J Cardiol 45:5 I5-52 I, 1978 16 Kaijser L, Lassers BW, Wahlqvist ML, Carlsson LA: Myocardial lipid and carbohydrate metabolism in fasting men during prolonged exercise. J Appl Physiol 32:847858, 1972 17 Bomfim V: Myocardial protection during aortic valve replacement. A clinical and laboratory study of intraoperative myocardial metabolism. Scand J Thorac Cardiovasc Surg, Suppl 29, 1981 18 Snedecor GW, Cochran WG: Statistical Methods, Ames, Iowa, 1967, Iowa State University Press 19 Kaijser L, Carlsson LA, Eklund B, Nye ER, Rossner S, Wahlqvist ML: Substrate uptake by the ischaemic human heart during angina induced by atrial pacing, Effect of Acute Ischaemia on Myocardial Function, IT Oliver, OC Julian, KW Donald, eds., Edinburgh and London, 1972, Churchill Livingstone 20 Strom S, Mogensen L, Bendz R: CK-MB kinetics in acute myocardial infarction and after coronary bypass operations. Scand J Thorac Cardiovasc Surg 13:61-66, 1979 21 Kjellberg SR, Lonnroth H, Rudhe V: The effect of various factors on the roentgenological determination of cardiac volumes. Acta Radiol (Stockholm) 35:4 I3-427, 195 I