Previous studies have suggested that (1) nitroglycerin causes vasodilatation by interacting with sulfhydryl groups in vascular smooth muscle, thereby activating guanylate cyclase and increasing the intracellular concentration of cyclic GMP, and (2) N-acetylcysteine, a source of sulfhydryl groups, potentiates the peripheral vasodilatory effect of nitroglycerin. This study was performed to explore the influence of N-acetylcysteine on nitroglycerin-induced coronary dilatation. In 18 patients (13 men and five women, 30 to 76 years old), coronary sinus blood flow (by thermodilution) was measured before and during intracoronary administration of nitroglycerin, 25 ,g, both before and 5 min after a 15 min intravenous infusion of (1) 5% dextrose in water (n = 8, control) or (2) 100 mg/kg N-acetylcysteine (n = 10). Nitroglycerin caused no change in heart rate or systemic arterial pressure. In the control patients, coronary sinus blood flow behaved similarly during the two injections: it was 134 36 ml/min (mean ± SD) before and 183 + 50 ml/min during injection No. 1 (average increase, 49 25 ml/min; average percent increase, 38 + 21%); and it was 131 ± 34 ml/min before and 178 + 45 ml/min during injection No. 2 (average increase, 47 + 23 ml/min; average percent increase, 37 + 20%) (NS compared with injection 1). In the patients who received N-acetylcysteine, coronary sinus blood flow was 149 + 48 ml/min before and 191 + 54 ml/min during injection 1 (average increase, 42 + 15 ml/min; average percent increase, 30 + 12%) (NS compared with eight control values). After Nacetylcysteine, coronary sinus blood flow was similar before nitroglycerin (145 ± 44 ml/min), but it rose markedly with nitroglycerin (218 + 68 ml/min) (average increase, 73 + 35 ml/min; average percent increase, 50 20%) (p < .01 compared with the values obtained in the same patients during injection 1). Thus, N-acetylcysteine, a source of sulfhydryl groups, potentiates the coronary vasodilative effect of nitroglycerin.
In this study, we tested the hypothesis that myocardial ischemia induced by exercise in patients is associated with diminished metabolism and/or delayed clearance of an intravenously injected fatty acid, iodine 123-labeled phenylpentadecanoic acid (IPPA). Fifteen normal volunteers and 18 patients with significant coronary heart disease (CHD) received IPPA during exercise. In the patients with CHD, radionuclide ventriculograms were also obtained during exercise. The normal volunteers had relatively uniform initial left ventricular segmental IPPA activity after exercise and uniform IPPA clearance in the interval from 4 to 20 min immediately after exercise. In contrast, the patients with CHD had increased initial left ventricular segmental IPPA activity (63%, p < .001) and delayed IPPA clearance (44%, p < .01) in segments supplied by significantly narrowed coronary arteries. Based on analysis with the mean values + 1 SD for initial IPPA activity, clearance, or both in normal volunteers, the sensitivity and specificity of exercise IPPA scintigraphy for detecting CHD were 89% and 67%, respectively; when + 2 SD differences from the mean values in the normal volunteers were considered, the sensitivity and specificity were 72% and 100%, respectively. Among the total of 27 noninfarcted left ventricular segments supplied by significantly narrowed coronary arteries in the study patients, 26 (96%) had an abnormality (mean + 1 SD) of either initial IPPA activity or clearance compared with corresponding segments in the normal volunteers and/or with other left ventricular segments in the same image that were not supplied by significantly narrowed coronary arteries. Thus, these data suggest that IPPA scintigraphy may be used in the identification of myocardial ischemia in patients with CHD by demonstrating abnormal initial left ventricular segmental IPPA activity and/or delayed clearance after exercise. Circulation 74, No. 5, 1007No. 5, -1015No. 5, , 1986 UNDER AEROBIC and fasting conditions, free fatty acids are the preferred substrate of normal myocardium, providing up to 90% of resting energy requirements." 2 Therefore, radiolabeled fatty acids have attracted great interest for cardiac imaging and as potential probes of myocardial metabolism. Studies by Sobel, Schelbert, and Weiss and their colleagues and others using "C-palmitate with positron tomography have shown great promise for this technique in defin-
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