Allopurinol therapy of ischemic heart disease with infarct extension.

OBJECTIVE: Free radicals produced by the hypoxanthine-xanthine oxidase reaction in ischemia/reperfusion experiments have been proposed as contributing to myocardial cell necrosis in acute myocardial infarction. In this study, the hypothesis was tested that a commonly observed late phase of necrosis, infarct extension, could be prevented by allopurinol, an inhibitor of xanthine oxidase. STUDY DESIGN: Allopurinol, a xanthine oxidase inhibitor, was used with placebo in a double-blind randomized therapy study in 140 patients with ischemic heart disease admitted to the authors' hospital. Eighty-four had acute myocardial infarction and the remaining 56 had unstable angina. Of the 84 patients with infarction, 39 received allopurinol treatment. If xanthine oxidase production of cytotoxic free radical plays a major role in the pathogenesis of infarct extension, blockade of the reaction with allopurinol should decrease the occurrence of extension. RESULTS: Nineteen infarct extensions were observed; five (11%) in the placebo group and 14 (36%) in the allopurinol. CONCLUSIONS: The increased incidence of extension (P less than 0.007) in the treatment group does not support the hypothesis that xanthine oxidase contributes to infarct extension, which is consistent with recent reports that xanthine oxidase is not a significant component of the human myocardium. These findings indicate that allopurinol may actually be contraindicated in patients with ischemic heart disease.

The clinical spectrum of cardiac fibroma with diagnostic and surgical considerations: noninvasive imaging enhances management.

A cardiac fibroma was successfully resected from the interventricular septum of a 25-year-old woman. The clinical data were correlated with a review of the data on 144 other patients, thereby providing a clinical profile and management strategy for this type of tumor. Initial manifestations of a fibroma were determined to be congestive heart failure (21%), tachyarrhythmias (13%), and chest pain (3.5%). A majority of patients were asymptomatic (36%) with abnormal physical findings or an abnormal chest roentgenogram. Finding the tumor at autopsy incidentally or on sudden death (23%) indicated the lethal potential. A few (3.5%) of the reports on patients with cardiac fibroma were without clinical data. Noninvasive imaging by echocardiography, computed tomography, and nuclear magnetic resonance improved the diagnosis. Surgical treatment was successful in 53 of the 84 patients for whom it was attempted.

Infarct size limitation by the xanthine oxidase inhibitor, allopurinol, in closed-chest dogs with small infarcts.

The present study was designed to evaluate the ability of allopurinol to limit infarct size following permanent coronary occlusion in the greyhound. Coronary occlusion was produced by injecting 2.5 mm plastic beads into the coronary artery of the closed chest dog. Non-perfused myocardium, the area at risk, was visualised by autoradiography of 141Cerium labelled microspheres which were infused immediately following coronary embolization. The treated dogs (n = 12) received 400 mg of allopurinol orally one day before surgery. A 25 mg . kg-1 bolus was administered (iv) immediately before occlusion, and repeated every 8 h. 11 dogs served as controls. After 24 h, the dogs were killed and the hearts were sliced into 5.0 mm transverse sections. The infarcted myocardium was visualised by triphenyl tetrazolium chloride staining. The percentage of the risk zone which evolved to infarct was calculated. This percentage was 18.1 +/- 3.95% in the allopurinol group vs 58.4 +/- 2.81% in the control group (p less than 0.001). We conclude that allopurinol is a potent drug for the limitation of infarct size in the dog with permanent coronary occlusion.

Xanthine oxidase as a source of free radical damage in myocardial ischemia.

Experiments were performed to determine if xanthine oxidase is a source of free radicals during myocardial ischemia. Open chest dogs were subjected to 1 h of total occlusion of the left anterior descending coronary artery followed by 4 h of reperfusion. Directly after coronary artery occlusion, Ce141 microspheres were injected into the left atrium to mark the ischemic bed. At the end of reperfusion, the hearts were removed and sectioned. Autoradiography determined the ischemic myocardium at risk, and the necrotic zone was determined by triphenyl-tetrazolium staining. Animals were divided into three groups: control, allopurinol (24-h oral pretreatment 400 mg, then 50 mg/kg IV bolus on occlusion); and superoxide dismutase starting with occlusion (15 000 U/kg). The size of the infarct as a percentage of the tissue at risk was: 23.1 +/- 4.1 for the control; 8.7 +/- 1.2 for the allopurinol group; and 5.4 +/- 1.2 for the superoxide dismutase group. The infarcts in the allopurinol and superoxide dismutase groups were significantly smaller than those in the control groups. In a second series of experiments we determined the xanthine oxidase/xanthine dehydrogenase content of dog myocardium. The left anterior descending branch was ligated for 30 min and then biopsies were removed from both the normal and the ischemic regions. Total enzyme content did not differ between the two regions averaging 0.259 U/g protein for the ischemic tissue and 0.225 U/g protein for the normal region. Only 9.8% of the enzyme was in the oxidase form in the normal region while 32.8% was in the oxidase form in the ischemic zone.(ABSTRACT TRUNCATED AT 250 WORDS)

Left main coronary artery disease in a 19-year-old woman. Treatment by saphenous vein grafting.

Syncope, palpitations, ventricular tachycardia, and electrocardiographic changes of acute myocardial ischemia in a 19-year-old woman resulted from significant narrowing of the left main coronary artery and its ostium, producing high-grade obstruction to flow as documented by selective coronary arteriography. Because of these findings and markedly positive results of cardiovascular stress testing, surgical treatment by aortocoronary artery saphenous vein bypass grafting to the left anterior descending artery was carried out. Four years postoperatively, the patient was asymptomatic, and there are no abnormal findings on cardiovascular stress testing.

Determination of left-ventricular volume from first-pass kinetics of labeled red cells.

A mathematical model is presented for the dynamics of a bolus of technetium-99m-labeled red blood cells through the left ventricle. It is used to correct for attenuation the count rate observed over the left ventricle during a conventional gated blood-pool study. The left-ventricular volumes are calculated from the corrected count rates and expressed as a percentage of total blood volume, or in absolute terms if a blood sample is obtained. The procedure is applied to a number of patients with nonvalvular cardiac disease. Cardiac volumes determined by the method are found to correlate well (r = 0.98) with those determined by contrast left ventriculography. The method is simple, requires no special equipment, and can be applied with existing computer software.

The effect of lorazepam on hypertension-associated anxiety: a double-blind study.

Sixty-two adults with a current diagnosis of significant hypertension and accompanying moderate to severe anxiety were medicated with lorazepam or with placebo for a period of 4 weeks. The patients were assessed by 7 cardiologists under double-blind conditions and the results pooled. Symptoms of anxiety were quantified using a Global Physician Rating, the Hamilton Anxiety Scale and a Patient Self-Rating Scale. The symptoms of anxiety associated with hypertension were significantly relieved by lorazepam in comparison to placebo. Most lorazepam patients were controlled with 3 mg/day; except for 1 patient, side effects were mild and transient.

Accumulation of technetium-99m stannous pyrophosphate in contused myocardium.

The uptake of technetium-99m stannous pyrophosphate in contused myocardium was measured as a function of time from the insult. The free wall of the dog's left ventricle was surgically exposed and struck with a spring-loaded paddle. Pyrophosphate was injected intravenously from 1 1/2 to 47 1/2 hr after the injury. After 1/2 hr of incubation the hearts were removed and the Tc-99m content of contused and noncontused myocardium was measured. Pyrophosphate was concentrated in contused myocardium at all of the time periods tested. Contused-to-normal ratios for pyrophosphate uptake ranged from 8.1 (8 hr) to 41.9 (48 hr).