Faculty Bibliography

Acute myocardial infarct expansion is associated with a poor prognosis. This study was performed to assess potential beneficial effects of beta-blockers on inhibiting expansion. A pilot study showed that atenolol (10 mg/kg) achieved sustained beta-blockade in rats. In the main study, following left coronary ligation, 36 rats received atenolol and 18 rats received placebo daily for 7 days. Infarct size was similar in treated and control rats (25 +/- 13% versus 28 +/- 11%). Expansion grades and a quantitative index of expansion were similar for both groups. Infarct size and expansion index were significantly related, but linear regression lines were similar for treated and control rats. We conclude that atenolol has no significant effect on infarct expansion in this nonreperfused rat model

Although it is often stated that proximal atherosclerotic coronary artery disease occurs more frequently than distal disease, several autopsy studies have disputed this. To examine the prevalence of proximal vs mid and distal disease and its relationship with cardiac risk factors, we studied more than 14,000 sections from 102 hearts with coronary artery disease at autopsy. After postmortem angiography, the coronary arteries were removed, divided into proximal, mid, and distal thirds, sectioned at 2.5 mm intervals, and graded for percentage reduction in cross-sectional area by atherosclerosis. Of 252 vessels in 84 patients with greater than or equal to 75% stenosis, 166 (66%) has proximal disease vs 107 (42%) with mid disease and 40 (16%) with distal disease (p less than 0.001). No patient had a mid or distal stenosis greater than 75% without proximal disease. When atherosclerosis of any severity was assessed, proximal atherosclerotic lesions were long and diffuse, whereas distal lesions were more often short and discrete. Proximal circumflex lesions were shorter in length than those in the right or left anterior descending coronary arteries. The prevalence of proximal, mid, and distal stenoses in 25 diabetic patients was similar to that in nondiabetic persons (53%, 47%, and 17%, p greater than 0.3). Similarly, hypertension, smoking, and obesity were not associated with an increase in prevalence of distal disease. Patients with distal stenoses were younger than patients without (mean age, 64 +/- 13 vs 73 +/- 10 years, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Very early reperfusion after coronary occlusion can reduce infarct size and preserve left ventricular function. Whether later reperfusion is of benefit is unclear. We studied the effect of very early reperfusion with myocardial salvage and 'late' reperfusion without myocardial salvage on infarct expansion and aneurysm formation. Sixty-eight rats underwent left coronary artery ligation and were randomized to 30 min reperfusion, 2 hr reperfusion, or permanent coronary artery ligation. The animals were killed and the hearts examined at 2 weeks. Thirty minute reperfusion reduced infarct size, extent of transmurality, and infarct expansion. Two hour reperfusion reduced neither infarct size nor transmurality but inhibited infarct expansion. The results of this study in the rat preparation suggest a beneficial effect of 'late' reperfusion on infarct expansion independent of myocardial salvage. If these results are confirmed in human beings, the period after myocardial infarction during which a patient can be considered for thrombolytic therapy or reperfusion by percutaneous transluminal coronary angioplasty could be greatly prolonged

Infarct expansion, the time-related thinning and dilation of an acute transmural infarct, leads to aneurysm formation and cardiac rupture in humans. In this study, the effect of exercise on acute infarct expansion early after myocardial infarction was examined in 129 rats. Ninety rats were exercised on a treadmill for 1.5 hours daily for 1 week beginning on the day of coronary artery ligation; the remaining 39 rats remained in their cages. There was no effect on the prevalence or extent of expansion; specifically, infarct wall thickness, left ventricular diameter and expansion grade (0 to 4+) were similar in the exercise and control rats. There was no difference in infarct size or the number of animals with aneurysmal shape changes in the exercise and control groups. There was no significant difference between the two groups in the histologic finding of intramural hemorrhage, a feature that has been associated with cardiac rupture, and no complete rupture was seen. However, there was a nonsignificant trend toward higher mortality in the exercised group. Thus, the findings of this study suggest that moderate exercise early after myocardial infarction produces no significant detrimental effect on infarct size or left ventricular topography in the rat model

To correlate morphologic subgroups of left ventricular aneurysms with the major clinical manifestations (ventricular arrhythmias, congestive heart failure, and systemic emboli), we studied 73 patients with such aneurysms--34 at autopsy and 45 after surgical excision. Sixty-three patients had a history of congestive heart failure, 5 had systemic emboli, and 28 had recurrent ventricular tachycardia. Two types of endocardial abnormalities were noted: thick endocardial plaque composed of fibrous elastic tissue that contained little or no thrombus (type I, 30 patients); and aneurysms with little or no endocardial fibroelastosis (type II, 43 patients), some with layers of thrombus obliterating the aneurysmal cavity. Emboli only occurred in 5 patients with type II aneurysms who had mural thrombi. Recurrent ventricular tachycardia occurred in 20 patients with type I aneurysms but only in 8 with type II (p less than 0.001), showing a relation between endocardial fibroelastosis and ventricular tachycardia. Structural differences in ventricular aneurysms thus appear to have pathophysiologic significance. Our findings have implications for the mechanisms of ventricular tachycardia in postinfarction patients and for its prevention by endocardial resection

Serum estradiol and serum estrone levels were assessed in 29 men in 14 men in whom myocardial infarction was ruled out; in 12 men without apparent coronary heart disease but hospitalized in an intensive care unit; and in 28 men who were not hospitalized and who acted as control subjects. (The 12 men who were hospitalized but who did not have coronary heart disease were included to control for physical and emotional stress of a severe medical illness.) Ages ranged from 21 to 56 years. Age, height, and weight did not differ significantly among groups. Blood samples were obtained in the patient groups on each of the first three days of hospitalization. The serum estrone level was significantly elevated in all four patient groups when compared with that in the control group. Estrone level, then, did not differentiate patients with and without coronary heart disease. Serum estradiol levels were significantly elevated in the groups with myocardial infarction, unstable angina, and in the group in whom myocardial infarction was ruled out. However, estradiol levels were not significantly elevated in the group in the intensive care unit without coronary heart disease when compared to the level in the normal control group. Serum estradiol levels, then, were elevated in men with confirmed or suspected coronary heart disease but were not elevated in men without coronary heart disease even under the stressful conditions found in an intensive care unit. Serum estradiol levels were significantly and positively correlated (p less than 0.03) with serum total creatine phosphokinase levels in the patients with myocardial infarction. The five patients with myocardial infarction who died within 10 days of admission had markedly elevated serum estradiol levels. The potential significance of these serum estradiol elevations is discussed in terms of estradiol's ability to enhance adrenergic neural activity and the resultant increase in myocardial oxygen demand

Left ventricular aneurysms, convex protrusions at sites of transmural scar, are clinically recognized late after myocardial infarction because of their hemodynamic or arrhythmic complications. Whether aneurysms develop from dilation of freshly infarcted myocardium early after myocardial infarction or from late dilation of scar is not known. To investigate this question, the time course of changes in shape of the left ventricle early and late after myocardial infarction was studied. One hundred forty-one myocardial infarcts were produced in rats by coronary ligation, and the animals were killed at time periods of up to 6 weeks. True aneurysms developed as early as 2 weeks and only in rats with a transmural infarct. The percent of rats that manifested 'aneurysmal shape changes' (defined as a protrusion of the full thickness of the left ventricular wall) increased from day 1 to day 5, but did not change significantly thereafter. The extent of left ventricular dilation in hearts with early aneurysmal shape changes did not progress significantly up to day 42. Accordingly, in the rat, regional aneurysmal shape alterations are due not to late dilation of scare tissue, but rather to 'expansion' of freshly necrotic myocardium within the first 5 days of infarction. Thus, early changes in shape appear to determine late aneurysm formation

Expansion (regional dilatation and thinning) of acutely infarcted myocardium in man has been shown to correlate with overall cardiac dilatation and rupture. We studied gross and histopathologic features and the time course of expansion in rats. Infarcts were produced in 84 rats by ligation of the left coronary artery and studied at 1, 2, 3, 4, 5 and 7 days. All hearts were prepared by potassium diastolic arrest, gel distention and fixation. Expansion was graded 0 to 4+ : 1+, mild thinning of infarcted wall; 2+, mild thinning and dilatation; 3+, moderate thinning and dilatation; and 4+, marked thinning and dilatation. There were 80 transmural infarcts, and 66% showed expansion; 36 of 80 (45%) were graded 1-2+ and 17 of 80 (21%) 3-4+. None of the four exclusively nontransmural infarcts showed expansion. Expansion was present in 61% of transmural infarcts at 1-2 days, in 65% at 3-4 days and in 80% at 5-7 days. The percentage of rats with severe (3-4+) expansion increased markedly over this period, from 0% at 1-2 days to 23% at 3-4 days to 65% at 5-7 days. Histopathologic infarct evolution was roughly twice as rapid as that of humans; 5-7 day-old infarcts showed well-developed granulation tissue. Thus, expansion can be produced in an animal model. A critical infarct size of 17% appeared necessary for significant (greater than 1+) expansion, and the degree of expansion correlated with infarct size. Although this phenomenon begins early after infarction, its extent progresses over days, making interventions to interrupt its development feasible