Acute myocardial infarction and ischemic injury during surgery for coronary artery disease Herbert N. Hultgren, M.D. Udipi R. Shettigar, M.D. James F. Pfeifer, M.D. William W. Angell, M.D. Palo Alto and Stanford, Calif.

It is now well recognized that acute intraoperative myocardial infarction is a significant complication of coronary artery surgery. Supporting evidence consists of the appearance of typical ECG signs of acute infarction in the immediate postoperative period accompanied by abnormal elevation of serum enzymes. 1-~ In fatal cases autopsy studies have confirmed the diagnosis of acute infarction. In addition, many patients exhibit abnormalities in T waves and ST segments associated with abnormal enzyme elevations which probably represent lesser degrees of acute infarction with an intramural or subendocardial location. The term "acute ischemic injury" has been applied to such occurrences:l It is the purpose of this study to determine the incidence of acute infarction and acute ischemic injury in the following four operative interventions for coronary artery disease. 1. Internal mammary implants (Vineberg operation) for stable angina. 2. Saphenous vein bypass for stable angina. 3. Saphenous vein bypass grafts for unstable angina or the impending myocardial infarction syndrome. 4. Saphenous vein bypass grafts performed in conjunction with valve replacement surgery or commissurotomy. The present study has the following features From the Cardiology and Cardiovascular Surgery Services, Palo Alto Veterans Administration Hospital and Stanford University Medical School. Received for publication Mar. 23, 1976. Accepted for publication June 25, 1976. Reprint requests: Herbert N. Hultgren, M.D., Chief, Cardiology Service, Veterans Administration Hospital, 3801 Miranda Ave., Palo Alto, Calif. 94304.

146

which permit a valid comparison between the four procedures: 1. All operations were performed by the same operating team using similar techniques of cardiopulmonary bypass and vein bypass grafting. 2. The group of patients studied did not have other surgical procedures performed, such as resection of ventricular aneurysms or endarterectomy. 3. Selection of patients for internal m a m m a r y implants and vein bypass grafts was performed using a standard protocol which excluded patients with persisting evidence of left ventricular failure, left ventricular aneurysm or other features associated with a high operative mortality. 4. Pre- and postoperative evaluation of the electrocardiograms and serum enzymes was carried out by a single group of observers using similar methods and criteria. For those reasons the present study should present a reasonably accurate comparative evaluation of the incidence of myocardial infarction and ischemic injury occurring in the four groups of patients evaluated. Materials and methods Composition of study group. Internal mammary implants. Forty patients were studied. Criteria for selection for surgery was the presence of chronic, stable angina with a duration of at least one year. Persisting symptoms despite medical therapy were present in all patients. None had prior surgical procedures for the relief of angina. Patients with severe hypertension, chronic congestive failure, or left ventricular aneurysm were excluded. Saphenous vein bypass grafts-Stable angina.

August, 1977, Vol. 94, No. 2, pp. 146-153

Infarction in coronary artery surgery One hundred twelve patients. Indications for surgery and exclusions were similar to those in the implant group above. Saphenous vein bypass g r a f t s - U n s t a b l e angina. Sixty-eight patients. Unstable angina was defined by the presence of at least one of the following criteria: (1) Stable angina with a recent increase in se~(erity, (2) Angina of recent onset, (3) Rest angina or acute coronary insufficiency of recent onset, and (4) Angina with recent episodes of Ventricular fibrillation or tachycardia. Prior to surgery recent infarction was excluded b y serial electrocardiograms and serum enzyme determinations. Combined bypass grafts and valve replacement surgery. Seventy-four patients. All patients had significant valvular disease and obstructive coronary artery disease. All had symptomatic valvular lesions of sufficient hemodynamic significance to warrant valve replacement. In addition, significant coronary disease was revealed by arteriography in all patients. Obstructive lesions which decreased luminal diameter by > 50 per cent were considered significant. Diagnostic criteria. Electrocardiograms were recorded on all patients prior to surgery and daily thereafter for seven days. All tracings were reviewed independently by two observers using the following criteria for the diagnosis of acute myocardial infarction or acute ischemic injury which have been previously described: Infarction-Appearance of new, persistent Q waves of.04 second duration or longer or new QS deflections associated with characteristic evolutionary changes in the S T segment a n d T waves. The appearance of transient intraventricular conduction defects was not considered diagnostic of infarction unless new Q waves appeared. True posterior infarction with a new R wave in V, was not observed in any of the postoperative patients. Ischemic injury: (1) Flat ST segment depression of greater than 2 mm. in left ventricular leads, lasting more than 48 hours, (2) deep T wave inversions persisting for more than 48 hours, (3) ventricular arrhythmias, such as ventricular tachycardia or ventricular fibrillation, and (4) absence of new significant Q waves or QS deflections. The following serum enzyme determinations were performed preoperatively and postoperatively on days 1, 2, 3, 6, and 10: serum glutamic

American Heart Journal

oxalacetic transaminase (SGOT), lactic dehydrogenase (LDH), and creatine phosphokinase (CPK). Upper limits prior to operation were considered to b e 4 0 , 350, and 60 units, respectively. Standard analytical methods were employed. 4-6 It is well known t h a t cardiac and coronary surgery will result in an increase in serum enzymes during the immediate postoperative period in the absence of evidence of myocardial infarction or acute ischemic injury. Previous studies from our hospital suggest that acceptable criteria for abnormal rises in serum enzymes in the immediate postoperative period consist of CPK values exceeding 200 units, SGOT values exceeding 90 units and LDH values exceeding 900 units.1. ~6 These values may differ in other hospitals since they are dependent, in part, upon the surgical technique employed including the duration of cardiopulmonary bypass, aortic cross-clamp time and clinical status of the patients. CPK values are not indicated in the tabular summaries since the cardiac fraction was not determined and the correlation of CPK elevations with ECG changes was poor. Results Internal mammary implants. A total of 40 consecutive patients were studied. Thirty-eight were males and two were females. The mean age was 50 years (range 35 to 69 years), All had stable angina of at least six months duration. None had persistent symptoms of left ventricular failure. Thirty-five had treadmill tests and 30 (86 per cent) were positive. Twelve had right heart catheterization studies and none had a pulmonary artery wedge pressure exceeding 16 mm. at rest. Twenty-six (65 per cent) had ECG evidence of prior myocardial infarction. All had coronary arteriography. Severe coronary artery disease involving a t least two major vessels was present in all patients. Surgery was performed from October, 1965, to August, 1971. The surgical technique employed has been previously described. 7 Twenty-seven had single and 13 had double implants. ECG evidence of acute myocardial infarction was observed in the i m m e d i a t e postoperative period in 11 patients (27.5 per cent) and evidence of acute ischemic injury was observed in 12 patients (30 per cent). Serum enzyme data are shown in Table I.

147

H u l t g r e n et al.

I. Number and incidence (%) of ECG abnormalities, SGOT values over 90 units and L D H values over 900 units in 40 patients who had "internal m a m m a r y implants for stable angina pectoris"

Table

ECG abnormalities No. [ % Acute infarction Ischemic injury Neither of above

11 12 17

27.5 30.0 42.0

Abnormal enzymes 90

%

>900

%

5/8* 4/9 0/14

62 44 0

7/8 4/10 0/12

88 40 0

>

*Denominators indicate number of patients where enzymes were determined.

Table II. Number and incidence (%) of ECG abnormalities, S G O T values over 90 units and L D H values over 900 units in 40 patients who had "SVBG for stable angina"

ECG abnormali~es No. ] % Acute infarction Ischemie injury Neither of above

16 25 71

14.3 22.3 63.4

Abnormal enzymes > 90

%

>900

%

14/15" 8/24 10/64

93 33 16

9/12 5/16 3/37

75 31 8

*Denominators indicate number of patients where enzymes were determined.

SGOT levels exceeded 90 units in 9 out of 31 patients (29 per cent) and L D H levels exceeded 900 units in 11 out of 30 pat i ent s (37 per cent). If one examines abnormal elevations of either SGOT or L D H which were observed in 15 patients there were associated ECG signs of either acute infarction or ischemic injury in 11 patients (73 per cent). T he 30-day operative mortality rate in 40 patients was 10 per cent (four deaths): All four deaths were clearly due to intraoperative infarction with characteristic ECG changes in four patients and abnormal rises in SGOT and L D H in three patients. One patient died 36 hours after surgery and no enzymes were obtained.

Saphenous vein bypass grafts for stable angina. A total of 112 consecutive patients with stable angina pectoris were studied. All were males. Th e mean age was 51 years (range 33 to 63 148

years). T he clinical characteristics of these patients were similar to those in the internal m a m m a r y implant series since the criteria of selection for surgery was similar. Forty-one patients had multistage treadmill tests prior to surgery and 27 (66 per cent) had positive tests. In 69 patients the mean ejection fraction was 62 per cent (range 89 to 22 per cent). T h e operative technique employed has been previously described:" None of the patients had procedures other than vein bypass grafts performed. Single grafts' were used in 33 patients, double grafts in 59, and triple grafts were used in 20. T he mean cardiopulmonary bypass time was 103 minutes (range 190 to 31 minutes), and the mean aortic cross clamp time was 17 minutes (range 46 to 5 minutes). Results. ECG evidence of acute myocardial infarction was found in 16 patients (14.3 per Cent) and evidence of acute ischemic injury was found in 25 patients (22.3 per cent). Serum enzyme data are shown in Table II. Abnormal levels of SGOT were noted in 32 out of 103 patients (31 per cent), and abnormal L D H levels were present in 17 out of 65 patients (26 per cent). In 38 patients who had an abnormal elevation of either SGOT or L D H there were 27 (71 per cent) who had ECG signs of acute infarction or ischemic injury. The 30-day operative mortality rate in 112 patients was 2.7 per cent (three deaths). In two patients death was clearly due to extensive myocardial infarction manifested by typiCal ECG changes and abnormal elevations of serum enzymes. Unstable angina. A total of 68 patients was studied. Sixty-five were males and three were females. T he mean age was 54 years (range 35 to 72 years). All had unstable angina with a duration of acute symptoms of one t o 180 days prior to hospital entry. Four general clinical presentations were observed: 1. Stable angina of more t han 6 m ont hs duration with a recent increase in severity (70 per cent). 2. Acute coronary insufficiency or rest a n g i n a (23 per cent). 3. Recent onset of angina within 90 days of hospital entry (8 per cent). 4. Angina with episodes of ventricular tachycardia or ventricular fibrillation (5 per cent). All 68 patients had a~ute, transient electrocar-

August, 1977, Vol. 94, No. 2

Infarction in coronary artery surgery

diographic changes during chest pain compatible with myocardial ischemia. None of the patients had clinical evidence of an acute myocardial infarction as evidenced by the appearance of diagnostic Q waves and evolutionary ST-T wave changes or diagnostic serum enzyme elevations. None of the patients had symptoms of persistent left ventricular failure. Twenty-eight (41 per cent) had ECG evidence of healed myocardial infarction. All patients had coronary arteriography and severe coronary disease involving at least two major coronary vessels was present in all patients. Forty-four patients (65 per cent) had moderate abnormalities in left ventricular contraction and the mean ejection fraction determined in 31 patients was 69 per cent (range 90 to 33 per cent). Surgery was performed between February, 1971, and June, 1975. All patients had saphenous vein bypass grafts without endarterectomy or other procedures. The mean pump bypass time in 57 patients was 132 minutes (range 29 to 235 minutes) and the mean aortic cross clamp time in 42 patients was 30 minutes (range 5 to 75 minutes). Eleven had single grafts, 36 had double grafts, 19 had triple grafts, and two had quadruple grafts. Results. ECG evidence of acute myocardial infarction was observed in the immediate postoperative period in 14 patients {20.6 per cent), and evidence of acute ischemic injury was observed in 12 patients {17.6 per cent). Serum enzyme data are shown in Table III. Abnormal levels of SGOT occurred in 27 of 66 patients (41 per cent) and LDH in 23 out of 64 patients (36 per cent). In 27 patients who had abnormal enzyme levels there were 20 {70.4 per cent) who had ECG signs of infarction or ischemic injury. The 30-day operative mortality rate in 68 patients was 1.5 per cent (one death). This death occurred in the operating room due to inability to maintain a suitable blood pressure after the oper, ation. No autopsy was obtained. Combined bypass grafts and valve replacement surgery. A total of 74 consecutive patients were studied. The mean age was 59 years (range 43 to 81 years). Seventy patients were males and four were females. The primary indication for surgery was valvular heart disease and vein bypass graft surgery was performed because of the presence of significant obstructive lesions of major coi~onary arteries demonstrated by selecAmerican Heart Journal

Table Ill. Number and incidence (5) of ECG

abnormalities, SGOT values over 90 units and LDH values over 900 units in 40 patients who had "SVBG for unstable angina"

Abnormal enzymes

CG abnormalities o. I % Acute infarction Ischemic injury Neither of above

14 12 42

20.6 17.6 62

8 oTf > 90 1 13/14"

7/12 7/40

f, I I. 900 93 58 17.5

12/14

86 42 16

5/12 6/38

*Denominators indicate number of patients where enzymes were determined.

Table IV. Valve replacement and valvular surgery

performed in 74 patients who also had SVBG surgery. The 9 other operations included 5 p a t i e n t s who had mitral commissurotomy and 4 who had mitral annuloplasty

[ No. Aortic valve r e p l a c e m e n t M i t r a l valve r e p l a c e m e n t Mitral a n d aortic valve r e p l a c e m e n t O t h e r valve o p e r a t i o n s

50 11 4 9

Table Y. Number a n d incidence (%) of ECG

abnormalities, SGOT values over 90 units and LDH values over 900 units in 40 patients who had "valve replacement surgery and SVBG surgery"

ECG a b n o r Abnormal realities lenzyies] SGOT LDH No. % > 90 % > 900 Acute infarction Ischemic injury Neither of above

15 28 31

20 38 42

12/14" 24/28 9/28

86 86 32

10/13 20/23 7/22

% 77 87 32

*Denominators indicate number of patients where enzymes were determined.

tive coronary arteriography. In all patients symptoms were primarily related to valvular heart disease. The operations performed are summarized in Table IV. Forty-three patients had single vein bypass grafts, 27 had double grafts, and four had a triple graft. Mean bypass time was 142 minutes (range 51 to 270 minutes). Mean aortic cross clamp time in 64 patients was 47 minutes (range 0 to 90 minutes). 149

Hultgren et al.

Table Yl. Incidence of SGOT levels exceeding 90 units and L D H units exceeding 900 units in patients with ECG evidence of acute infarction, ischemic injury or neither of these ECG abnormalities. The analysis includes all patients with abnormal elevations of SGOT or L D H

SGOT 1 LDH elevated (%) elevated(%)

ECG changes A c u t e infarction Ischemic i n j u r y N e i t h e r of above

79 56 16

68 44 10

Table VII. Incidence of acute myocardial infarc-

tion (AMI), acute ischemic injury {AID, abnormal SGOT elevations and abnormal L D H elevations in the four groups of operations evaluated

IAMII AIISGOT~LDH' Vineberg SVBG-Stable AP SVBG-Unstable

40 112 60

27.5 14.3 20,8

30.0 22.3 17.6

29 31 41

37 26 36

AP VR + SVBG VR only*

74 126

20.0 7.0

38.0 30.0

64 32

64 37

*Data from valve replacement operations also was obtained from a previous study'"

The operative technique employed in the valve replacement operation has been previously described? Results. ECG evidence of acute intraoperative myocardial infarction was found in 15 of 74 patients (20 per cent) and evidence of acute ischemic injury was noted in 28 patients (38 per cent). Serum enzyme data are shown in Table V. SGOT levels exceeded 90 units in 45 patients (64 per cent) and L D H exceeded 900 units in 37 patients (64 per cent). In 53 patients who had an abnormal elevation of either SGOT or L D H there were 43 patients (81 per c e n t ) w h o had ECG signs of acute infarction or ischemic injury. Nine operative deaths (in 30 days) occurred for a mortality rate of 12.2 per cent. Four deaths occurred in association with ECG and serum enzyme evidence of acute intraoperative myocardial infarction.

150

Discussion

Most previous reports of intraoperative myocardial infarction during coronary surgery have only identified patients who had the appearance of ECG abnormalities compatible with acute transmural myocardial infarction. In this study and in previous studies from this hospital an additional group of patients have been identified who have had ECG evidence of acute ischemic myocardial injury. 1 Electrocardiographic abnormalities in this group have consisted of changes in the T waves and ST segments compatible w i t h severe ischemia or injury and, in some patients, recurring episodes of ventricular tachycardia or AV block. Such changes occurring in the presence of abnormal elevations of serum enzymes strongly suggest that subendocardial, intramural, or focal infarction is probably present. Table VI illustrates the incidence of abnormal serum enzymes in all patients with ECG changes of acute transmural infarction, ischemic injury patterns, and neither of these ECG changes in the immediate postoperative period. I n patients without such ECG changes, abnormal rises of either SGOT or L D H were observed in only 16 per cent and 10 per cent, respectively. In patients with ischemic injury patterns abnormal rises of SGOT or L D H occurred in 56 per cent and 44 per cent, respectively. These data should be compared with patients with typical ECG signs of transmural infarction where the incidence of abnormal SGOT and L D H levels were 79 per cent and 68 per cent, respectively. These data support the validity of identifying acute ischemic injury as a complication of coronary surgery and indicate that in approximately 50 per cent of such episodes acute myocardial infarction is probably present, based on the presence of associated elevations in serum enzymes and ECG abnormalities. It would appear, therefore, that the true incidence of acute myocardial infarction associated with coronary surgery is probably higher than is generally reported. Support for this view can be obtained by inspection of Table VII and Fig. 1. In each operation the incidence of abnormal enzyme elevations is greater than the incidence of acute myocardial infarction and in three operations {vein bypass grafts for stable angina, for unstable angina, and vein bypass grafts and valve replacemer/t surgery) the incidence of abnormal enzyme

August, 1977, Vol. 94, No. 2

I n f a r c t i o n in c o r o n a r y artery surgery

100-

80-

7 _

60-

'~

i

MI iMI GOT LDHI MI IMI GOT LDHI MI IMI GOT LDH M! IMI GOT LDH Vineberg

n - 40 Mortality

10%

Angina

SVBG

I

SVBG UoAo

SVBG V.R.

n - 112

n -40

n - 44

3%

3%

11%

Fig. 1. Comparativeincidence of myocardialinfarction (MI), ischemic myocardialinjury (IMI), and abnormal elevations of SGOT (GOT) and L D H in four operations for coronary artery disease. S V B G = saphenous vein bypass graft; UA = unstable angina; VR = valve replacement. Operative mortality indicated at the bottom of panels. elevations is almost equal to the sum of the acute infarcts and acute ischemic injury episodes. Serum enzyme data in the present study have several limitations. Isoenzymes (myocardial components) for CPK and LDH were not determined. Total CPK values are unreliable and do not correlate well with ECG changes, probably due to the effect of skeletal muscle CPK. LDH values may be high due to hemolysis in addition to myocardial infarction. SGOT values are probably most reliable since very few patients with right ventricular failure and hepatic congestion or necrosis were subjected to surgery. Such patients were confined to the group of patients having combined valve replacement surgery and vein bypass grafts. Only 4 out of 74 of these patients had right ventricular failure prior to surgery and preoperative serum enzymes were normal in these patients. It is evident from Fig. 1 t h a t the highest incidence of acute infarction was observed in patients who had internal m a m m a r y implants. Several reasons may account for the high incidence of these complications observed with internal mammary implants. The patients represent the early, initial experience with the opera-

American Heart Journal

tion, hence, the surgical technique may not be optimum. Internal m a m m a r y implantation does not provide the immediate revascularization t h a t can be accomplished with vein bypass graft surgery. The internal m a m m a r y implant operation causes considerably more epicardial and myocardial damage in the creation of the myocardial tunnel than does the vein bypass graft technique. The high incidence of enzyme elevations in the group of patients having combined valve replacement surgery and vein bypass grafts is prob'ably due in part to the longer aortic cross clamp time required for the combined procedure?' It has been previously shown t h a t valve replacement sHrgery alone, even in the absence of significant coronary artery disease, may be accompanied by acute infarction, ischemic injury, or abnormal rises in serum enzymes. '~' These complications tended to occur more frequently in patients with double valve replacement operations and with prolonged cross clamp times. These data are summarized in Table VIII. The incidence of perioperative infarcts and acute ischemic injury is not significantly higher than in operations for stable and unstable angina. This may be due to the difficulty

151

H u l t g r e n et al.

Table VIII. Cardiopulmonary bypass time and

aortic cross clamp time in patients with valve replacement and SVBG survery (VR & SVBG), valve replacement alone (VR), SVBG for stable angina and SVBG for unstable angina Bypass time (minutes)

Cross clamp time (minutes)

142 88 103 132

47 43 17 30

V R & SVBG V R alone SVBG-Stable angina S V B G - U n s t a b l e angina*

*This group had more graftw per patient than the group with stable angina; i.e., 2.2 grafts per patient compared to 1.9 grafts.

IX. Mean of highest enzyme values observed in four operations in patients with ECG signs of acute infarction or acute ischemic injury

Table

ZDH

SGOT Operation Vineberg SVBG-Unstable AP SVBG-Stable AP SVBG + VR

Acute infarcts

Ischemic injury

167 217

153 120

1305 1054

1219 894

194

94

1434

810

384

185

18o6

1270

Acute I Ischemic infarcts injury

in the ECG diagnosis of infarction in this group of patients, most of whom had abnormal preoperative ECGs including left ventricular hypertrophy and bundle branch block patterns. In the group of patients having valve replacement surgery and bypass grafts, 30 patients who had acute infarction or ischemic injury with abnormal enzymes had a mean bypass time of 158 minutes and a mean cross clamp time of 50 minutes, compared to 118 minutes and 42 minutes, respectively, in 20 patients without these complications. A more detailed analysis revealed that all patients (combined aortic valve replacement and vein bypass graft) with cross clamp times exceeding 70 minutes and 88 per cent of patients with anoxia plus fibrillation times exceeding two hours developed myocardial infarcts. +' Most of the data presented in this study relate to the incidence of intraoperative infarction and

152

acute ischemic injury in the four types of operations. The a m o u n t of myocardial necrosis occurring with such episodes can be roughly related to the magnitude of the enzyme elevation associated with the ECG changes. These data are indicated in Table IX. It is evident t h a t the highest mean levels of enzymes were observed in patients who had combined vein bypass grafts and valvular surgery. This difference is at a significant level (P = < .012). The highest incidence of serum enzyme abnormalities in this operation probably indicates a greater a m o u n t of myocardial necrosis. Patients with left ventricular hypertrophy are especially susceptible to myocardial injury with prolonged ischemic arrest and cross clamp times? Acute intraoperative myocardial infarction is not only an important non-fatal complication of coronary surgery, but is also an important cause of death, since 10 of the 17 deaths occurring in the combined series of 294 patients were associated with clear evidence of recent myocardial infarction. Similar observations have been reported by Assad-Morell and co-workersY' In 500 consecutive patients undergoing saphenous vein bypass surgery, perioperative infarction occurred in 67 (13 per cent) and 10 of the 16 deaths were due to infarction. +'

Summary The incidence of myocardial infarction, acute ischemic injury, and associated serum enzyme abnormalities has been evaluated in four operations involving the coronary circulation. The highest incidence of infarction was associated with internal m a m m a r y implantation (Vineberg procedure). There was no significant difference in the incidence of infarction, ischemic injury, or abnormal enzyme levels between patients with stable angina and those with unstable angina who had vein bypass surgery. In operations involving combined vein bypass grafting and valve replacement surgery, the incidence of abnormal serum enzyme elevations was higher than in any other procedure. The incidence of infarction and acute ischemic injury i n combined operations was similar to that in other procedures but this may have been due to the difficulty in the ECG diagnosis of infarction in this group of patients, most of whom had abnormal preoperative ECGs.

August, 1977, Vol. 94, No. 2

Infarction in coronary artery surgery

REFERENCES

1, Hultgren, H., Miyagawa, M., Buck, W., and Angell, W.: Ischemic myocardial injury during coronary artery surgery, AM. HEART J. 82:624, 1971. 2. Dixon, S., Jr., Limbird, L., Roe, C., Wagner, G., Oldham, H., Jr., and Sabiston, D., Jr: Recognition of postoperative acute myocardial infarction, Circulation 48(Supp III):137, 1972. 3. Brewer, D., Bilbro, R., and Bartel, A.: Myocardial infarction as a complication of coronary bypass surgery, Circulation, 47:58, 1973. 4. Reitman, S., and Frankel, S.: A colorimetric method for the determination of serum glutamic pyruvic transaminases, Am. J. Clin. Pathol. 28:56, 1957. 5. Cobaud, P., and Wroblewski, F.: Colorimetric measurement of lactic dehydrogenase activity of body fluids, Am. J. Clin. Pathol. 30:234, 1958. 6. Rosalki, S.: An improved procedure for serum creatine phosphokinase determination, J. Lab. Clin. Med. 69:696, 1967.

American Heart Journal

7. Hultgren, H., and Hurley, E.: Surgery in obstructive coronary artery disease. Advances in Internal Medicine, XIV, Snapper, I., and Stollerman, G., eds., Chicago, 1968, Year Book Medical Publishers, Inc., pp. 107-150. 8. Oury, J., Quint, R., Angell, W., and Wuerflein, R.: Coronary artery vein bypass grafts in patients requiring valve replacement, Surgery 72:1037, 1972. 9. Rossiter, S., Hultgren, H., Kosek, J., Wuerflein, R., and Angell, W.: Ischemic myocardial injury with aortic valve replacement and coronary bypass, Arch. Surg. 109:652, 1974. 10. Hult~en, H., Miyagawa, M., Buck, W., and Angell, W.: Ischemic myocardial injury during cardiopulmonary bypass surgery, AM. HEART J. 85:167, 1973. 11. Assad-Morell, J., Frye, R., Connolly, D., et al.: Aortacoronary artery saphenous vein bypass surgery, clinical and angiographic results, Mayo Clin. Proc. 50:379, 1975.

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Acute myocardial infarction and ischemic injury during surgery for coronary artery disease.

Acute myocardial infarction and ischemic injury during surgery for coronary artery disease Herbert N. Hultgren, M.D. Udipi R. Shettigar, M.D. James F...
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