Verapamil in stable effort angina: Effects on left ventricular function evaluated with exercise radionuclide ventriculography

A double blind placebo-controlled study was performed in 12 patients with stable angina pectoris to evaluate the effects of oral verapamil (320 mg/day) on left ventricular function, as measured at rest and during exercise with gated equilibrium radionuclide ventriculography. On verapamil, patients had a lower heart rate-blood pressure product at each work load than with placebo. Anginal threshold increased by 28 ± 19 watts (p < 3.005), and maximal exercise capacity increased by 20 ± 14 watts (p < 0.001) with verapamil, but the rate-pressure product at the onset of angina and at maximal exercise was unchanged. Left ventricular ejection fraction at rest during verapamil therapy was the same as with placebo therapy. On exercise during placebo therapy, the ejection fraction decreased from 40 ± 9 to 35 ± 11 percent (p < 0.025) because end-systolic volume increased disproportionately compared with end-diastolic volume. On exercise during verapamil therapy, the ejection fraction did not decrease (44 ± 8 versus 45 ± 12 percent) and was significantly higher at identical work loads than on placebo because of a smaller increase in end-systolic volume. Oral verapamil is effective treatment for effort angina and may prevent the decrease in left ventricular ejection fraction due to exercise-induced ischemia.     

The effect of high-dose intravenous nitroglycerin on cardiovascular hemodynamic features and left ventricular function at rest and during exercise in patients with exertional angina

Intravascular pressures, cardiac output and left ventricular function were measured at rest and during exercise in 14 patients with stable angina pectoris before and during an intravenous nitroglycerin infusion. Nitroglycerin was infused at a rate sufficient to reduce mean arterial pressure at rest by 15 to 25 mm Hg.At rest, the end-diastolic volume index decreased from 57 ± 13 to 39 ± 3 ml/m², stroke volume index from 32 ± 6 to 24 ± 5 ml/m² and mean arterial pressure from 112 ± 16 to 91 ± 14 mm Hg. The cardiac output was maintained by an increase in heart rate from 73 ± 9 to 92 ± 37 beats/min. The left ventricular ejection fraction increased from 57 ± 7 to 62 ± 9% because the stroke volume decreased less than the end-diastolic volume.All 14 patients were limited by angina in the prenitroglycerin exercise study, and the mean ST-segment depression at maximal work load was 2.2 ± 1.2 mm. At identical work loads in the nitroglycerin study, only 4 patients had angina, and the mean ST-segment depression was 0.3 ± 0.5 mm. Ten of the 14 patients improved their exercise performance by at least 30 W.Comparing the 2 exercise studies at the maximal work load achieved in the prenitroglycerin study, the mean pulmonary artery wedge pressure was decreased from 23 ± 6 to 6 ± 4 mm Hg, the end-diastolic volume index from 38 ± 15 to 27 ± 12 ml/m², and the mean arterial pressure from 132 ± 8 to 114 ±13 mm Hg. The stroke volume index and the heart rate were not significantly altered and the ejection fraction increased from 56 ± 8% to 66 ± 8%.Thus, in the high dose administered, nitroglycerin decreased left ventricular filling pressure, heart size, and stroke volume at rest and increased the ejection fraction. During exercise, nitroglycerin decreased myocardial ischemia and improved exercise tolerance. An increase in exercise ejection fraction was associated with an increase in the ratio of systolic pressure to end-systolic volume, suggesting that there was an improvement in contractile performance.     

The QRS scoring system for estimating myocardial infarct size: clinical, angiographic and prognostic correlations

The relation between a QRS score derived from the routine electrocardiogram and left ventricular function was investigated in 181 patients after myocardial infarction. Patients with left ventricular hypertrophy and conduction defects were excluded. The QRS score correlated closely with the severity of wall motion abnormalities and left ventricular ejection fraction. The more severe the dyssynergy, the higher the QRS score (hypokinesia = 3.0; akinesia = 5.4; dyskinesia = 9.1). The left ventricular ejection fraction (percent) = 66 - (3.3 x QRS score) (correlation coefficient [r] = -0.81, probability [p] less than 0.001). With use of this regression equation, the QRS score predicted angiographic left ventricular ejection fraction to within 12% of the angiographic ejection fraction in 29 of 30 additional patients studied prospectively. The QRS score was also related to clinical functional class. The worse the clinical manifestation of left ventricular dysfunction, the higher the QRS score (Killip class I = 3.5; class II = 6.5; class III = 7.1). A QRS score greater than or equal to 7 had a specificity of 97% and a sensitivity of 59% for predicting an ejection fraction of less than 45%. Patients with a QRS score of 7 or greater had severe wall motion abnormalities, higher peak serum creatine kinase levels, higher prevalence of multivessel coronary disease, poor clinical functional class and an unfavorable outcome. The QRS score provides an inexpensive, clinically useful estimate of left ventricular function after myocardial infarction and can identify patients at high risk.     

Long-term follow-up of verapamil and nitrate treatment for coronary artery spasm

Thirty-seven patients with coronary artery spasm and minor coronary atherosclerosis (34) or normal coronary arteries (3) were followed up long-term. All had angina at rest, 32 had nocturnal angina, and 13 had a positive exercise test with S-T elevation. Three had a previous subendocardial infarction; 10 had had serious arrhythmias, which caused syncope in 7. At last review, 21 months (range 1 to 61) after starting therapy, 27 patients continued on verapamil, 314 (120 to 600) mg/day; 4 who did not respond to verapamil were taking nifedipine, 58 (30 to 80) mg/day; and 16 were also taking isosorbide dinitrate, 41 (20 to 80) mg/day. Of the 31 patients on therapy, 21 were asymptomatic, 9 were improved (1 to 4 attacks/month), and 1 had an average of 8 anginal attacks/month; the remaining 6 had stopped therapy and 5 were asymptomatic a mean of 10 (3 to 18) months after stopping. The exercise test became negative in all 12 patients tested on therapy, although 3 required nitrates in addition to verapamil or nifedipine.In 26 supervised treatment withdrawals in the hospital, a mean of 15 (1 to 55) months on therapy, 10 developed angina in less than 48 hours. Angina recurred in all 6 unsupervised, patient-initiated withdrawals. Failure to stop smoking was positively associated with recurrence of angina on treatment withdrawal (p < 0.02).Long-term treatment of coronary artery spasm with verapamil or nifedipine together with isosorbide dinitrate was well tolerated and effectively relieved angina. No documented serious arrhythmias, syncopal episodes, myocardial infarction, or death occurred during follow-up.     

Clinical studies of patients with coronary spasm

Coronary artery spasm may cause myocardial ischemia in patients without severe coronary atherosclerotic obstruction. Spontaneous rest angina, particularly at night, is the predominant symptom; most patients are smokers. Ergonovine tests have high sensitivity and specificity for the diagnosis of coronary spasm, but should be used when vasospasm is suspected but no electrocardiogram was recorded during spontaneous angina. Arterial constriction measured during ergonovine testing suggests that the arterial hypersensitivity to vasoconstrictors at sites of atherosclerotic lesions is independent of the severity of the lesion. Coronary vasospasm may also be provoked by exercise, possibly through an alpha-adrenergic mechanism. Both spontaneous and exercise-induced attacks of vasospasm are prevented by calcium-antagonist drugs that remain effective during longer-term treatment. The cyclic nature of the condition is demonstrated when successful therapy is discontinued without recurrence of symptoms and may be due to alteration of arterial hypersensitivity.     

Calcium channel blocking drugs for chronic, stable angina. Verapamil

Verapamil is effective primary therapy for angina pectoris at a dosage of about 120 mg three times a day. In equal doses it has the same antianginal effect as propranolol although the mechanism of action is different. Long-term therapy is effective and well tolerated. Side effects are few and if required, verapamil may be given with nitrates or beta-blockers.     

Changes in rat liver prolactin binding sites in diabetes are sex dependent

The effect of streptozotocin-induced diabetes (100 mg/kg) on lactogenic binding sites, measured by iodinated ovine prolactin (PRL) binding, has been studied in liver microsomal membranes from males and female rats. In females, specific binding was reduced in diabetes from 13% to 4.5% of total tracer, while in males specific binding increased from 0.5% to 2.5%. Similar results were obtained using iodinated human growth hormone as tracer, through overall binding was higher. Scatchard plots of binding curves in females showed that changes in binding were due to changes in receptor concentration, while affinity remained unchanged at 2 X 10(9) M-1. In diabetes, serum PRL and estradiol levels fell by 60% in males but showed no significant change in females, and could therefore not account for receptor changes. In contrast, mean testosterone levels fell in diabetic males from 9.0 to 3.9 nM, and rose in diabetic females from 2.1 to 5.8 nM. Estrogen treatment of male rats caused a marked induction of binding in nondiabetic animals, and a change from the male to the female response to diabetes. Testosterone treatment of nondiabetic females suppressed binding, although not to the male levels, and diabetes caused further suppression. These results are consistent with a role for testosterone in regulating PRL receptors in experimental diabetes, but suggest that other hormonal influences are also involved.