Aging and arteriosclerosis. I. Development of myointimal hyperplasia after endothelial injury.

Old Fischer 344 rats are more susceptible to vascular lesions after arterial endothelial injury than are young animals. Thus, 20-26-mo-old Fischer 344 rats developed greater and more persistent intimal proliferative lesions than did 2-5-mo-old rats after aortic endothelial denudation. 3 d after deendothelialization, intimal thickness was increased two-fold in both old and young animals. However, 14 d after endothelial injury, intimal thickness had increased nearly five times in old animals, but had regressed to normal in young animals. Intimal thickness of young aortic grafts transplanted into young recipients did not differ significantly from adjacent host aorta or autotransplanted aortic segments 6 wk after surgery. In contrast, intimal thickness of old grafts transplanted into young recipients was eight times greater than adjacent young host aorta 6 wk after surgery. The density of cell nuclei in the intima of old grafts was also much greater than that in young grafts. Thus, in two experimental models of vascular injury, old rats have consistently had greater myointimal hyperplasia than young rats. The increased proliferative response of aortic smooth muscle cells after vascular injury of old animals may contribute to the increased prevalence of vascular disease with age.

Early infarct expansion: structural or functional?

With the onset of ischemia, the length of myocardial segments increases rapidly, distorting ventricular geometry. Permanent stretching and thinning of infarcted zones have been termed infarct expansion. Although these changes are noted within minutes in vivo, infarct expansion may not be seen for days in postmortem preparations. The apparent postmortem reversal of early infarct expansion suggests that early expansion may be a functional phenomenon, reversible in the early hours of infarction. Alternatively, reversal of expansion may be a postmortem artifact, concealing the importance of underlying structural abnormalities. Myocardial infarction was produced in five dogs by occluding the left anterior descending coronary artery. Ultrasound sonomicrometers were used to measure myocardial segment end-diastolic length in the infarct and normal zones. After 3 hours of ischemia, the heart was arrested in diastole and biopsy specimens were taken from the normal and infarct zones. Sarcomere length was measured from electron photomicrographs, and myofiber width was measured from light photomicrographs. After 3 hours of ischemia, infarct zone segment length had increased significantly more than normal zone length (116 +/- 11 [SD] versus 103 +/- 4% of control length, p less than 0.05), whereas 2 minutes after cardiac arrest, both the infarct and normal zones returned to preischemic segment length, demonstrating apparent reversibility of early infarct expansion. However, histologic study revealed that the infarct zone myofibers were significantly thinner than normal zone myofibers (7.9 +/- 0.3 versus 9.4 +/- 0.3 micron, p less than 0.001) and sarcomere length in the infarct zone was significantly longer than that in the normal zone (1.9 +/- 0.2 versus 1.5 +/- 0.2 micron, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Cost-effectiveness of echocardiography and electrocardiography for detection of left ventricular hypertrophy in patients with systemic hypertension.

Although echocardiography is more accurate than electrocardiography for detection of left ventricular hypertrophy, it is also more expensive, making it uncertain whether echocardiography is cost-effective for detection of this abnormality in hypertensive patients. Accordingly, the sensitivity of M-mode echocardiographic and electrocardiographic criteria for left ventricular hypertrophy was determined in necropsied patients with anatomic hypertrophy of mild (n = 26), moderate (n = 21) or severe (n = 46) degree, and the prevalence of each degree of hypertrophy was determined in 561 hypertensive adults drawn from clinical and employed population samples. The sensitivity of echocardiographic left ventricular mass index criteria was 57% in necropsied patients with mild hypertrophy and 98% in patients with moderate or severe hypertrophy. All electrocardiographic criteria exhibited lower sensitivity: 15 to 42% for mild, 10 to 38% for moderate, and 30 to 57% for severe hypertrophy. Cost estimates from three sources were $160 for M-mode echocardiography and $48 to $64 for 12-lead electrocardiography. In populations with a 12 to 40% prevalence of hypertrophy, echocardiography was calculated to cost less than electrocardiography per instance of hypertrophy detected ($390-$1013 vs $800-$1829), yielded better separation in predicted incidence of morbid events between hypertensive patients with or without hypertrophy (3.4-4.7 vs 1.5-2.1 per 100 patient-years as opposed to 3.0-4.4 vs 1.9-2.9 per 100 patient-years), and required smaller case and control samples for hypothetical research studies (n = 254-309 vs 397-3478).(ABSTRACT TRUNCATED AT 250 WORDS)

Ischemia and infarction in the isolated rabbit heart: a model for the evaluation of myocardial imaging agents.

An isolated-heart preparation has been adapted to permit rapid evaluation of, and imaging by, myocardial tracers. The rabbit heart provided a mass large enough for imaging and serial biopsies. Coronary arteries could be selectively ligated and provided landmarks for epicardial ST segment mapping. Uptake ratios between a tissue sample and normal myocardium (T/N), obtained using Tc-99m glucoheptonate as an infarct-seeker, increased with duration of the ischemic period, which was followed by reflow. After 25 min of occlusion the T/N was 4.5; after 40 min T/N = 6; after 60 min T/N = 8; and after 120 min T/N = 19. This well-controlled adjunct to in vivo studies allows evaluation of myocardial imaging agents without interfering with systemic effects or blood and tissue background. Functional and structural changes can be sequentially measured and correlated with the localization of various radiopharmaceuticals.

Early diagnosis of myocardial infarction in the dog with 99mTc-glucoheptonate.

Early gamma imaging of acute experimental myocardial infarcts was evaluated in mongrel dogs with 99mTc-glucoheptonate. From 15 to 20 mCi were injected between 1 and 27 hr after coronary artery occlusion. Nine dogs imaged 3 hr after injection (4 hr after occlusion) showed unequivocal uptake in the region of the infarct. Fifteen dogs imaged 5-7 hr after injection (6-8 hr after occlusion) showed sufficiently well-defined regions of abnormal uptake so that planimetry could be performed reliably. Five animals imaged serially showed improvement of the image only up to about 5-7 hr after injection. Infarct-to-normal myocardium and infarct-to-blood ratios were slightly higher in dogs injected 15-27 hr after infarction than in those injected 1 hr after infarction, implying that equally good results can be obtained with injection and imaging of 99mTc-glucoheptonate at any time within the first day. No other infarct-labeling radiopharmaceutical shares this capability for the early detection a delineation of acute infarcts.

Multiple aortic aneurysms in relapsing polychondritis.

A patient with relapsing polychondritis and thoracic and abdominal aortic aneurysms is described. The aortic changes were due to aortitis, which primarily involved the media, with increased vascularization, perviascular infiltration of mononuclear cells, increased amounts of collagen and decreased amounts of elastic tissue and sulfated acid mucopolysaccharides. Aortic aneurysms frequently occur in relapsing polychondritis; they are usually in the ascending aorta but may be multiple and involve the abdominal aorta; involvement of the ascending aorta results in aortic regurgitation and left ventricular failure, and involvement of the abdominal aorta may be clinically silent and result in fatal rupture.

Performance of primary and derived M-mode echocardiographic measurements for detection of left ventricular hypertrophy in necropsied subjects and in patients with systemic hypertension, mitral regurgitation and dilated cardiomyopathy.

To determine which M-mode echocardiographic (echo) measurement best detects left ventricular (LV) hypertrophy, the sensitivity and specificity of upper normal limits of echo LV anatomic measurements (previously shown to have 97% specificity in living normal subjects) were tested in 60 necropsied patients with anatomic hypertrophy and in 28 necropsied patients with normal left ventricles. The prevalence of hypertrophy by each echo criterion was determined in 165 living patients with systemic hypertension, mitral regurgitation or dilated cardiomyopathy. The best separation between patients with normal vs increased necropsy LV mass was obtained using sex-specific echo LV mass index criteria (overall accuracy = 73 of 88 patients, 83%). Lower overall accuracies for separation of patients with and without hypertrophy were observed for echo cross-sectional area (59 of 88 patients, 67%; p less than 0.05 vs LV mass index) and indexes of LV wall thickness (39 to 51%, p less than 0.001). Among 113 living patients with moderate or severe hypertension, mitral regurgitation or dilated cardiomyopathy, LV mass index was increased in 73%, cross-sectional area index in 58% (p less than 0.02 vs LV mass index), and posterior wall thickness, septal thickness and relative wall thickness in only 11 to 32% (all p less than 0.001 vs LV mass index). Thus, an M-mode echo LV mass index of more than 134 g/m2 in men and more than 110 g/m2 in women detects concentric and eccentric LV hypertrophy accurately by comparison with necropsy and clinical reference standards; cross-sectional area is slightly less useful; and other M-mode echo criteria of LV hypertrophy perform too poorly to be clinically applicable.

Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings.

To determine the accuracy of echocardiographic left ventricular (LV) dimension and mass measurements for detection and quantification of LV hypertrophy, results of blindly read antemortem echocardiograms were compared with LV mass measurements made at necropsy in 55 patients. LV mass was calculated using M-mode LV measurements by Penn and American Society of Echocardiography (ASE) conventions and cube function and volume correction formulas in 52 patients. Penn-cube LV mass correlated closely with necropsy LV mass (r = 0.92, p less than 0.001) and overestimated it by only 6%; sensitivity in 18 patients with LV hypertrophy (necropsy LV mass more than 215 g) was 100% (18 of 18 patients) and specificity was 86% (29 of 34 patients). ASE-cube LV mass correlated similarly to necropsy LV mass (r = 0.90, p less than 0.001), but systematically overestimated it (by a mean of 25%); the overestimation could be corrected by the equation: LV mass = 0.80 (ASE-cube LV mass) + 0.6 g. Use of ASE measurements in the volume correction formula systematically underestimated necropsy LV mass (by a mean of 30%). In a subset of 9 patients, 3 of whom had technically inadequate M-mode echocardiograms, 2-dimensional echocardiographic (echo) LV mass by 2 methods was also significantly related to necropsy LV mass (r = 0.68, p less than 0.05 and r = 0.82, p less than 0.01). Among other indexes of LV anatomy, only measurement of myocardial cross-sectional area was acceptably accurate for quantitation of LV mass (r = 0.80, p less than 0.001) or diagnosis of LV hypertrophy (sensitivity = 72%, specificity = 94%).(ABSTRACT TRUNCATED AT 250 WORDS)

Early quantification of experimental myocardial infarction with technetium-99m glucoheptonate: scintigraphic and anatomic studies.

Recent advances in understanding of the pathophysiology of myocardial necrosis indicate the need for a noninvasive method that will allow detection and quantification of infarcts in the first few hours after the onset of infarction. Myocardial infarct scintigraphy using technetium-99m glucoheptonate is capable of detecting infarction in dogs and man within 4 to 6 hours of onset. Studies were performed in 45 dogs with acute myocardial infarction: 28 with with an anterior infarct, 5 with an inferior infarct, 6 with an anterior infarct studied after infusion of mannitol and 6 with ligation of the left anterior descending coronary coronary artery and reperfusion of the ischemic area. The dogs were given 20 m Ci of technetium-99m glucoheptonate 1 hour after coronary occlusion, subjected to imaging 5 to 9 hours later and then killed. The experiments revealed that (1) scintigraphic infarct size correlated with infarct weight for anterior (r = 0.85) and inferior (r = 0.88) infarcts; (2) technetium-99m glucoheptonate also concentrated in a rim of myocardium around the infarct that probably represented the ischemic zone; and (3) technetium-99m glucoheptonate uptake by infarcted myocardium could be greatly increased with mannitol and reperfusion.

Pathogenesis of an unexpected sudden death: role of early cycle ventricular premature contractions.

A 61 year old man who had been studied extensively died unexpectedly ("instantaneously") outside the hospital while wearing an electrocardiographic recorder. Death was caused by ventricular fibrillation, which was initiated by an early cycle ventricular premature contraction occurring in the vulnerable period of repolarization. Such early cycle ventricular premature contraction had been noted in recordings 4 years previously but had never been observed to encroach on the T wave until 5 minutes before death. In the intervening period, the patient had shown increasing evidence of myocardial ischemia and hypertrophy and congestive heart failure, which had been partly obscured by his concealment or denial of symptoms and refusal to change his pattern of activities. Autopsy revealed two old myocardial infarcts and pronounced left ventricular hypertrophy. There was advanced occlusive arteriosclerosis of the major coronary vessels with a recent thrombus in the right coronary artery.

Anterior S-T segment depression in acute inferior myocardial infarction: indicator of posterolateral infarction.

Although patients with acute inferior myocardial infarction often manifest S-T segment depression in precordial electrocardiographic leads, the pathophysiologic abnormalities associated with this finding are poorly understood. To examine this problem, electrocardiographic findings on admission were compared with results of radionuclide cineangiography performed within 38 hours of the onset of symptoms in 25 patients with inferior infarction. Summation of S-T depression in leads V1 through V4 permitted the separation of patients into two groups: Group A (11 patients with 0.20 mV or less of S-T depression) and Group B (14 patients with 0.45 vM or more of S-T depression). The radionuclide cineangiogram revealed inferior wall dysfunction in all patients. Additional posterolateral dysfunction was seen in 13 patients, all in Group B. Patients in Group B had a relatively larger infarction (peak creatine kinase Units - 756 +2- 358 in Group A versus 1,566 +/- 983 units in Group B, p less than 0.01) and greater functional impairment (ejection fraction - 45 +/- 12 in Group A versus 33 +/- 12 in Group B, p less than 0.01). The relation between precordial S-T segment depression and posterolateral dysfunction appears to be largely independent of electrocardiographic evidence of "true posterior infarction." Thus moderate or severe anterior precordial S-T depression in patients with acute inferior infarction is a sensitive and specific indicator of relatively extensive myocardial damage, primarily involving the posterolateral region.

Role of delayed intraaortic balloon pumping in treatment of experimental myocardial infarction.

Intraaortic balloon pumping improves coronary blood flow characteristics while simultaneously reducing myocardial oxygen demands by reducing aortic systolic pressure. Clinical application of intraaortic balloon pumping has largely been in the "high risk" patient (cardiogenic shock, postinfarction angina, left main coronary artery disease and unstable angina) for support during diagnostic studies or cardiac surgery, or both. In addition, there is some evidence that balloon pumping immediately after coronary occlusion reduces the size of experimentally induced myocardial infarcts. In this study, myocardial infarcts were produced by ligation of the left anterior descending coronary artery in 12 dogs, 6 of which were treated with balloon counterpulsation beginning 3 hours after coronary occlusion. All dogs were killed 8 hours after coronary ligation. Intraaortic balloon pumping resulted in the expected hemodynamic changes (decreased aortic systolic pressure, left ventricular end-diastolic pressure and heart rate and increased aortic peak diastolic pressure). In addition, there was a significant reduction in infarct size in the group with balloon pumping as determined with epicardial S-T segment mapping, myocardial imaging with technetium-99m-glucoheptonate and histochemical staining with nitroblue tetrazolium. These results suggest that even when instituted as long as 3 hours after coronary occlusion, intraaortic balloon pumping results in significant reduction in infarct size and, it might be speculated, the mortality and morbidity associated with acute myocardial infarction may also be decreased.

Evaluation of a QRS scoring system for estimating myocardial infarct size. IV. Correlation with quantitative anatomic findings for posterolateral infarcts.

This study correlated the location and size of posterolateral myocardial infarcts (MIs) measured anatomically with that estimated by quantitative criteria derived from the standard 12-lead ECG. Twenty patients were studied who had autopsy-proved, single, posterolateral MIs and no confounding factors of ventricular hypertrophy or bundle branch block in their ECG. Left ventricular anatomic MI size ranged from 1 to 46%. No patient had a greater than or equal to 0.04-second Q wave in any electrocardiographic lead and only 55% had a 0.03-second Q wave. A 29-point, simplified QRS scoring system consisting of 37 weighted criteria was applied to the ECG. Points were scored by the ECG in 85% of the patients (range 1 to 8 points). MI was indicated by a wide variety of QRS criteria; 19 of the 37 criteria from 8 different electrocardiographic leads were met. The correlation coefficient between MI size measured anatomically and that estimated by the QRS score was 0.72. Each point represented approximately 4% MI of the left ventricular wall.

Evaluation of a QRS scoring system for estimating myocardial infarct size. III. Correlation with quantitative anatomic findings for inferior infarcts.

This study evaluated by quantitative autopsy correlation a previously developed scoring system for estimating the size of myocardial infarcts based on the QRS complex of the electrocardiogram. This system was tested using electrocardiograms from patients with infarcts shown by autopsy to predominate in the inferior third of the left ventricle. The study was limited to patients whose electrocardiogram did not indicate left or right ventricular hypertrophy, left or right bundle branch block, or left anterior or posterior fascicular block. Thirty-one patients from 6 medical centers met these criteria. In the electrocardiogram of 28 of the 31 patients (90%), lead a VF exhibited a Q wave of at least 30 ms. The correlation coefficient between the total QRS score and the percent infarction of the left ventricle was 0.74. In patients without confounding factors in the electrocardiogram and with single infarcts, the electrocardiogram provides a marker for infarcts in the inferior third of the left ventricle and a quantitative QRS scoring system provides an estimate of infarct size.

Evaluation of a QRS scoring system for estimating myocardial infarct size. II. Correlation with quantitative anatomic findings for anterior infarcts.

The ability of an independently developed QRS point score to estimate the size of infarcts predominantly within the anterior third of the left ventricular was evaluated by quantitative pathologic-electrocardiographic correlation. The study was limited to 21 patients with a single infarct documented by postmortem examination, for whom an appropriately timed standard 12 lead electrocardiogram was available that did not exhibit signs of left or right ventricular hypertrophy, left or right bundle branch block or anterior or posterior fascicular block. At necropsy the heart was cut into five to seven slices. The location and size of the infarct was quantitated by computer-assisted planimetry of the slices. The electrocardiogram of 19 (90 percent) of the patients exhibited either a Q wave or an R wave of no more than 20 ms in lead V2. The infarct in the two patients without this electrocardiographic finding was small, occupying 2 and 3 percent of the left ventricle, respectively. The percent infarction of the left ventricle correlated with the QRS point score (r=0.80). Thus in patients without complicating factors in the electrocardiogram and with a single infarct, the electrocardiogram provides a marker for infarction in the anterior third of the left ventricle and permits estimation of infarct size.

Electrocardiographic poor R-wave progression. Correlation with postmortem findings.

Electrocardiographic criteria have been derived from vectorcardiographic and angiographic correlation which allow division of patients with electrocardiographic "poor R-wave progression" or "reversed R-wave progression" into the following four etiologic groups: (1) anterior myocardial infarction; (2) left ventricular hypertrophy; (3) type-C right ventricular hypertrophy; and (4) the normal variant. The sensitivity, specificity, and predictive value of this approach to the electrocardiogram with poor or reversed R-wave progression were studied in a series of 33 patients examined at autopsy. Using the scheme and criteria outlined, 85 percent (11/13) of the pathologic anterior myocardial infarctions were correctly diagnosed. The electrocardiographic criteria correctly identified 75 percent (15) of 20 patients with poor or reversed R-wave progression without postmortem evidence of myocardial infarction, with only 12 percent (2/17) predictive error. The relative risk of autopsy-documented anterior myocardial infarction in patients meeting the specified electrocardiographic criteria was six times that of other patients with poor or reversed R-wave progression.

Advantages of hypothermic potassium cardioplegia and superiority of continuous versus intermittent aortic cross-clamping.

The relative effectivenss of hypothermic potassium (K) cardioplegia in conjunction with either continuous or intermittent aortic cross-clamping was evaluated in 20 mongrel dogs. Isovolumetric left ventricular (LV) contractions and myocardial biopsies were obtained before and after a total of 90 minutes of aortic cross-clamping. The dogs were randomly divided into four groups of five dogs each as follows: Group I, continuous 90 minute cross-clamping and multidose K at 4 degrees C (40 mEq/L); Group II, intermittent cross-clamping consisting of six 15 minute periods of cross-clamping separated by 5 minute reperfusion periods and K cardioplegia at 4 degrees C given at the start of each cross-clamping period; Group III, continuous 90 minute cross-clamping and multidose buffered saline at 4 degrees C; Group IV, intermittent cross-clamping, consisting of six 15 minute periods of cross-clamping separated by 5 minute reperfusion periods and buffered saline at 4 degrees C given at the initiation of each cross-clamp period. Group I dogs had the best myocardial performance, with no difference between control values of peak LV pressure and dP/dtmax and those recordings obtained 60 minutes after release of the aortic cross-clamp. Significant depression of LV function was noted in all other groups. Examination of force-velocity and length-tension relationships confirmed better myocardial performance in Groups I and II (multidose K at 4 degrees C) than in Groups III and IV (buffered saline at 4 degrees C). Groups I and III (continuous cross-clamping) had no de-rease in diastolic LV compliance after cross-clamping, whereas compliance was decreased in both Groups II and IV (intermittent cross-clamping) at higher preloads (p less than 0.05 and p less than 0.025, respectively). The wet weight/dry weight myocardial ratios were lower in Groups I and III (continuous cross-clamping) than in Groups II and IV (intermittent cross-clamping). Although creatine phosphate (CP) concentrations were rapidly restored by reperfusion in all groups, adenosine triphosphate (ATP) and glycogen myocardial stores were better preserved at the end of cross-clamping in Groups I and II (multidose K at 4 degrees C). Although LV diastolic compliance was decreased and myocardial water content was increased in Groups II and IV (intermittent cross-clamping), no differences in the minimal extent of subendocardial hemorrhage, edema, and contraction-band necrosis were observed among any of the groups examined electron microscopically. The present study identifies continuous aortic cross-clamping with multidose K at 4 degrees C as a superior method of myocardial protection.

Transcatheter embolization with Gelfoam and Avitene: the effect of Sotradecol on the duration of arterial occlusion.

Selective catheterization and embolization of both profunda femoris arteries were performed on eight mongrel dogs. In four dogs, Gelfoam alone (one side), and Gelfoam soaked in Sotradecol (contralateral side) was the embolic agent. In the other four dogs, Avitene in saline (one side), and Avitene suspended in Sotradecol (contralateral side) was the embolic agent. Ateriography followed by sacrifice and histologic examination were performed at two weeks (two dogs in each group) and two months (two dogs in each group) following embolization. In all dogs, histology confirmed the arteriographic appearance. In Gelfoam-embolized dogs, arteries embolized with Gelfoam alone were recanalized by two weeks; arteries embolized with Gelfoam/Sotradecol remained occluded at two months. In Avitene-embolized dogs, arteries embolized with Avitene in saline were moderately recanalized by two weeks and totally recanalized by two months; arteries embolized with Avitene/Sotradecol remained occluded at two months. Inflammatory changes were present in the walls of arteries embolized with Sotradecol. Sotradecol greatly increases the duration of arterial occlusion in Gelfoam and Avitene-embolized arteries.

Functional endothelial damage by high-potassium cardioplegic solutions to saphenous vein bypass grafts.

High-potassium cardioplegic solutions (CSs) may induce endothelial cell damage in vascular grafts, promoting graft thrombosis after coronary bypass operations. We studied prostacyclin (PGI2) production by saphenous veins as a marker of endothelial cell function in a model mimicking actual operative conditions. Fresh saphenous vein segments from patients who had undergone coronary bypass were cut in half; each part was perfused and incubated sequentially with CS (with 20, 40, or 80 mEq potassium/L) or a control buffer (5 mEq potassium/L) at 4 degrees C for 30 minutes (perfusion I), buffer at 37 degrees C for 15 minutes (perfusion II), and buffer plus 25 microM sodium arachidonate at 37 degrees C for 15 minutes (perfusion III). This permitted evaluation of changes in PGI2 production during or after exposure to CS, in basal and stimulated conditions. CS with 20 mEq potassium/L did not alter PGI2 production as compared with control buffer. CS with 40 mEq potassium/L decreased PGI2 production during perfusions I and II. CS with 80 mEq potassium/L also decreased sodium arachidonate-stimulated PGI2 production. Endothelial coverage (immunoperoxidase staining for factor VIII antigen) was intact at all potassium concentrations tested. Thus potassium in CSs can depress endothelial PGI2 production without causing immediate endothelial detachment. This effect may favor thrombosis in bypass grafts.

Physiologic observations of the heart six months after ischemic normothermic cardioplegia.

The late effects of normothermic ischemic cardioplegia were studied in four experimental groups of dogs subjected to intervals of aortic cross-clamping during cardiopulmonary bypass. Groups which had zero, 20, 30, or 40 minutes of aortic cross-clamping, respectively, were studied 6 months later for cardiac performance and morphology. The immediate operative mortality rate of animals subjected to 40 minutes of ischemia was 65 percent, compared to 22 percent in controls. There were no late deaths in any group Compliance, histology, biochemical determination of deoxyribonucleic acid: ribonucleic acid, and Vmax determinations after cross-clamping revealed no differences between the experimental groups. Open chest isovolumetric contraction curves showed decreased experimental groups. Open chest isovolumetric contraction curves showed decreased function in the 40 minute ischemia group at the extreme levels of cardiac stress. These results suggest that under the conditions of this study normothermic cardiac ischemia of greater than 30 minutes in duration results in a high initial mortality rate (65 percent) and leads to compromise of cardiac function under stress in the late postoperative period.