Angiotensin-converting enzyme inhibitors in patients with coronary atherosclerosis

Activation of the renin-angiotensin-aldosterone system has been shown to be an independent risk factor for myocardial infarction (MI). The importance of this risk factor has been confirmed by the finding that patients with a DD genotype for the angiotensin-converting enzyme (ACE) gene, which is associated with increased serum ACE levels, have a higher incidence of MI than do patients without this genotype. ACE inhibitors have been shown to significantly reduce the incidence of recurrent MI in patients with left ventricular dysfunction. The mechanism by which activation of the renin-angiotensin-aldosterone system leads to MI has not been ascertained, but it may be related to the effect of angiotensin II or aldosterone on the development of atherosclerosis, endothelial dysfunction, plaque rupture, or thrombosis after plaque rupture. Experimental data suggest that each of these mechanisms may be of importance. Several prospective randomized studies are under way to determine the effect of ACE inhibitors on recurrent ischemic events and the progression of atherosclerosis in patients without left ventricular dysfunction. If these studies yield positive results, ACE inhibitors might assume an important role in the secondary and possibly primary prevention of ischemic heart disease.     

The beneficial effects of nafazatrom (BAYg6575) on experimental coronary thrombosis

An in vivo model of coronary artery thrombosis in the conscious dog was used to evaluate the potential antithrombotic effect of nafazatrom (BAYg6575). A silver wire electrode was implanted in the left circumflex coronary artery (LCX) and was used at a later time to deliver a 50 uA anodal current for 24 hours to the intimal surface of the vessel. The resulting injury to the endothelium was accompanied by the adhesion, aggregation, and subsequent formation of an occlusive thrombus in the LCX of vehicle-treated dogs. Nafazatrom was given as an intravenous dose of 1 mg/kg for 48 hours, before anodal stimulation of the coronary artery was initiated, and was repeated every 6 hours during anodal stimulation for a total treatment period of 72 hours. As compared to vehicle-treated control dogs, the dogs treated with nafazatrom had smaller thrombi, preservation of coronary blood flow, a lesser degree of ischemic injury in the myocardial region subserved by the LCX, and less frequent premature ventricular complexes during the final 12 hours of the study period. Concomitant ex vivo platelet aggregation studies revealed significant inhibition of platelet aggregation in response to collagen and adenosine diphosphate in drug-treated dogs. The results of these investigations provide evidence that nafazatrom prevents in vivo development of occlusive coronary artery thrombi in response to disruption of the endothelial surface of the vessel.     

A natural history study of the prognostic role of coronary arteriography

Coronary cinearteriograms, clinical records, and left ventriculograms of 304 patients studied for evaluation of chest pain were reviewed. Clinical and follow-up data on survival of the normal subjects and the nonoperative group with abnormal arteriograms are presented.Ninety-two per cent of patients with typical angina pectoris had serious coronary occlusive disease. Ninety-eight per cent of patients with relatively normal coronary arteriograms survived for one to 60 or more months (mean follow-up period 24 months).There was a high mortality rate when the left main coronary artery was involved (47 per cent) and when the left coronary anterior descending branch was seriously occluded (28 per cent when arteriographic scores were high and 14 per cent when total scores were low) and a low mortality rate (0 to 7 per cent) when the LAD was normal. Mean follow-up interval in these groups was 19 months.The mortality rate was nearly three times greater when patients had QRS changes on ECG of prior myocardial infarction and six times greater when left ventricular contraction was significantly impaired.     

Prevention of ventricular fibrillation by bretylium in a conscious canine model of sudden coronary death

In anesthetized dogs, a silver wire electrode was inserted into the lumen of the circumflex coronary artery (LCX) and myocardial infarction was produced by a temporary 90-minute occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion. Four days later while in the ambulatory state, a 150 μA current was applied to the intimal surface of the LCX of saline (n = 10) and bretylium (n = 10) treated animal. Intimal injury and coronary thrombosis produced ST segment changes at 138 ± 39 minutes (χ ± SEM), followed by premature ventricular beats (at 142 ± 37 minutes), ventricular tachycardia (at 156 ± 49 minutes), and ventricular fibrillation (at 163 ± 51 minutes) in 9 of 10 saline-treated animals. In bretylium-treated animals, ST segment changes appeared at 128 ± 35 minutes, with six animals surviving for 24 hours (p < 0.03 vs saline). LAD infarction was present in both saline (14.1 ± 2.3%) and bretylium (15.1 ± 2.1% of left ventricle) treated animals with only bretylium-treated animals developing LCX infarcts (16.1 ± 2.1%). Bretylium prevents ventricular fibrillation (VF) resulting from ischemia at a site distant to prior myocardial infarction in the conscious dog and deserves further attention as a potential antifibrillatory agent for prevention of sudden coronary death in man.     

Effect of exercise training on glucose tolerance, in vivo insulin sensitivity, lipid and lipoprotein concentrations in middle-aged men with mild hypertriglyceridemia

The effects of 9 weeks of aerobic exercise training with maintenance of stable body weight upon insulin sensitivity and upon glucose, lipid, and lipoprotein concentrations were studied in 10 middle-aged men with mild hypertriglyceridemia. Following training, mean maximum oxygen consumption improved from 33.5 +/- 1.9 to 39.3 +/- 1.9 mL/kg/min (means +/- SEM), (P less than 0.01). Glucose concentrations, both fasting and during oral glucose tolerance testing, remained stable but both fasting insulin concentrations and insulin responses to oral glucose decreased (P less than 0.1 and less than 0.01, respectively). In vivo insulin sensitivity improved 25 +/- 6.1% (P less than 0.01) following training. Exercise training resulted in decreases in fasting serum triglyceride concentrations from 203 +/- 12.6 to 126 +/- 9.0 mg/dL (P less than 0.01), primarily as a result of the reduction in VLDL-triglycerides (P less than 0.01). The magnitude in percentage decrease of VLDL-triglycerides was found to be significantly correlated (r = 0.71, P less than 0.05) with the magnitude in percent increase in max VO2. Serum cholesterol levels declined from 211 +/- 8.9 to 193 +/- 11.9 mg/dL (P less than 0.01), and the ratio of HDL-cholesterol to total cholesterol was improved. This study demonstrates that exercise training at a level of intensity feasible for many middle-aged men has beneficial effects on several factors that have been associated with an increased risk of cardiovascular disease.     

Hemolysis in patients with the cloth-covered aortic valve prosthesis. Changing severity of hemolysis and prediction of anemia

This paper is addressed to two questions: (1) Is there evidence for Increasing hemolysis in patients with a cloth-covered aortic valve prosthesis? (2) Is it possible to predict from the hematocrit, retriculocyte count, serum hemoglobin and serum lactic dehydrogenase (LDH) levels which patients are at risk of anemia? These screening studies were performed in patients attending the postoperative clinic from 1970 to 1973. Patients were classified into anemic and nonanemic groups. LDH values for the anemic group include all yearly values for that patient including preanemia levels. The median LDH levels showed a yearly increase in the anemic group and no change in the nonanemic group (P < 0.005). A subset of these patients had a mean 1 year increase of 3 LDH units for 15 nonanemic patients and 242 units in 17 anemic patients. The reticulocyte levels did not demonstrate any progressive increase in the anemic group. The LDH level was the most useful predictor of future anemia. A value of 250 units predicted anemia on the next yearly visit with 28 percent false positive and 4 percent false negative readings. The reticulocyte count of more than 2.5 percent also placed the patient at greater risk of anemia. A serum hemoglobin level in excess of $\text{40}\text{mg}\text{100}\text{ml}$ was common in the anemic patients and was present in only 3 of 17 nonanemic patients. It is suggested that the serum LDH level should be monitored in all patients with the aortic totally cloth-covered prosthesis. Values in excess of 250 units (four times the upper limit of normal by other LDH methods) or increasing levels, or both, suggest future anemia.     

Antidysrhythmic actions of meobentine sulfate

The antiarrhythmic efficacy of meobentine sulfate, a bethanidine derivative lacking inhibitory effects on adrenergic neuronal function, was assessed in three canine models. Intravenous meobentine sulfate, administered in dosages of 5.0, 10,0, and 20.0 mg/kg, produced a dose-related increase in the ventricular fibrillation threshold (VFT) under nonischemic conditions (7.6 +/- 1.8 mA vs 37.8 +/- 8.6 mA) (20 mg/kg; p less than 0.05) and during regional myocardial ischemia (5.6 +/- 1.5 mA vs 41.8 +/- 9.1 mA) (20 mg/kg; p less than 0.05). The VFT was also increased in the presence of chronic ischemic injury (6.4 +/- 1 mA to 31 +/- 10 mA) (20 mg/kg; p 0.05). In the conscious dog, 4 days after an anterior myocardial infarction, programmed electrical stimulation (PES) produced nonsustained ventricular tachycardia (VT) in five dogs. After meobentine sulfate administration, eight of nine animals had sustained VT and one animal developed ventricular fibrillation (VF). At a dose of 20 mg/kg, there was prolongation of the cycle length of the VT (169 +/- 11 msec to 237 +/- 20 msec), prolongation of the QRS duration (58 +/- 2.6 msec to 71 +/- 3.7 msec), and prolongation of the delay in epicardial activation. There was an enhanced potential after meobentine administration for programmed stimulation to produce ventricular arrhythmias with the introduction of fewer premature impulses. In the third canine model, conscious dogs with a previous anterior myocardial infarction developed VF in response to electrically induced left circumflex coronary artery injury. Meobentine (20 mg/kg) failed to prevent VF in eight of eight dogs. These results suggest that while meobentine sulfate significantly increases the electrical VFT, it does not protect the conscious canine from the induction of ventricular tachyarrhythmias in response to PES, and it does not prevent VF in a conscious canine model of sudden coronary death.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute idiopathic pericarditis and calcific aortic stenosis: unusual fatal disease combination

Acute idiopathic pericarditis with massive pericardial effusion complicated left ventricular enlargement due to calcific aortic stenosis and led to intractable congestive heart failure and death during aortic valve replacement in a 42-year-old white male. This unusual combination of acute and chronic diseases is lethal due to their combined deleterious effect upon myocardial function.