Roy H. Leiboff

A randomized, angiographically controlled trial of intracoronary streptokinase in acute myocardial infarction

Fifty-five patients with acute myocardial infarction evaluated within 4 hours of the onset of symptoms were entered into an angiographically controlled trial of intracoronary streptokinase (IC STK). Forty-three patients with total occlusion of their infarct artery were randomized to either IC STK or intracoronary nitroglycerin (IC NTG), and 12 patients with less-than-complete occlusion received only IC NTG. Reperfusion of a totally occluded vessel was achieved in 69% of STK patients and 17% of IC NTG patients. Time from onset of symptoms to peak CK activity was significantly shorter in reperfused patients and patients with subtotal occlusion on initial angiography than in patients with total occlusion who were not reperfused (p less than 0.0001). Comparison of radionuclide ejection fractions (EF) determined acutely and 10 to 14 days after infarction failed to show improvement in either the STK or IC NTG group (mean decrease of 2.8% and 0.4%, respectively). In contrast, patients with subtotal occlusion on baseline angiography demonstrated a significant (p = 0.05) spontaneous improvement in EF over 2 weeks (7.3% increase).

Spin trapping of oxygen and carbon-centered free radicals in ischemic canine myocardium.

Oxygen free radical injury has been postulated to occur during myocardial ischemia. We have used Electron Spin Resonance and Spin Trapping techniques to directly demonstrate the production of carbon-centered (R.) and oxygen-centered lipid radical (RO.) in ischemic canine heart. In addition, venous effluent from the ischemic region showed that conjugated dienes (lipid peroxidation products) increased with ischemic duration. Our results suggest that the formation of the oxygen-centered and carbon-centered lipid radical species during ischemia are a consequence of oxy-radical peroxidation of myocardial membrane lipids.

Myocarditis diagnosed by endpmyocardial biopsy in human immunodeficiency virus infection with cardiac dysfunction

Abstract Documentation of cardiac histopathology in patients with human immunodeficiency virus (HIV) infection has been limited to postmortem examination in patients with the acquired immunodeficiency syndrome (AIDS). Myocarditis is a common finding at autopsy in AIDS patients 1,2 and has been associated with clinical cardiac abnormalities including left ventricular dysfunction, ventricular tachycardia, pericardial effusion and fatal dilated cardiomyopathy 2,3 . We recently observed 2 patients with HIV infection and significant cardiac dysfunction in whom endomyocardial biopsy revealed lymphocytic myocarditis.

Potentiation of the hemodynamic effects of acutely administered nitroglycerin by methionine.

It is believed that nitroglycerin causes vasodilatation by interacting with sulfhydryl groups present in vascular smooth muscle. This study was performed to assess whether methionine, an amino acid capable of increasing sulfhydryl availability, would potentiate the hemodynamic effects of nitroglycerin. Nitroglycerin was initially infused in incremental doses from 1 to 50 micrograms/min in all patients to determine the dose required to reduce mean arterial pressure by 10% and pulmonary capillary wedge pressure by 30%. After a washout period, 10 patients received 5 g methionine i.v. and five patients received an equal volume of 5% dextrose in water (control). Nitroglycerin dose titration was then repeated. Methionine alone induced no hemodynamic effects, but after methionine infusion, there was a significant reduction in the nitroglycerin infusion rate required to reach each hemodynamic endpoint (p less than 0.01). In the control group, there was no significant change in responsiveness to nitroglycerin between infusions. Thus, methionine potentiates the hemodynamic effects of acutely administered intravenous nitroglycerin.

DETECTION AND MEASUREMENT OF FREE RADICAL GENERATION DURING CARDIOVASCULAR INJURY

It has been suggested thatduring myocardial ischemia short-lived free radicals such as superoxide (O 2 - ·), hydroxyl (·OH), or lipid peroxide (RO.) are produced. The evidence, however, of the participation of such radicals in cardiovascular injury has been, for the most part, based upon activation of lipid peroxidation and on myocardial protection provided by scavengers.1,2 Direct detection of such radicals, as might be possible by electron spin resonance spectroscopy (ESR) has not provided conclusive identification of radicals produced during these injuries. However, spin trapping and ESR offer an indirect technique that provides the evidence necessary to confirm the involvement of these labile intermediates. Spin trapping has been applied very successfully to studies of free radical mechanisms in a variety of chemical and photochemical reactions; however, it has only recently been applied to biological systems. The majority of the spin traps being used are molecules containing a nitroso or nitrone group which, upon addition of a labile free radical, form a stable nitroxide that is easily detected by ESR.