Search

Left ventricular (LV) function and survival can be improved with captopril when initiated later than 24 hours after acute myocardial infarction. Animal studies suggest additional benefits may be obtained with earlier initiation of angiotensin-converting enzyme (ACE) inhibitors. The effects on LV function of captopril and enalapril initiated within 24 hours of myocardial infarction were studied. Two hundred twenty-five patients with acute myocardial infarction were enrolled within 24 hours of the onset of chest pain. They were randomized to receive either captopril 25 mg three times daily, enalapril 5 mg three times daily, or placebo. LV ejection fraction (EF) and volumes were measured by radionuclide ventriculography at baseline during treatment and at 3 months after a 3-day withdrawal from therapy. The ACE inhibitor group had a significant increase in EF (45 [+ or -] 1 to 47 [+ or -] 1%; p = 0.005) and significantly attenuated LV dilatation compared with results in the placebo group (175 [+ or -] 6 to 189 [+ or -] 7 ml in the placebo group vs 168 [+ or -] 4 to 172 [+ or -] 4 ml in the ACE inhibitor group; p = 0.051 for LV end-diastolic volume; and 99 [+ or -] 6 to 108 [+ or -] 7 ml in the placebo group vs 94 [+ or -] 3 to 94 [+ or -] 4 ml; p = 0.026 for LV end-systolic volume). The beneficial effects of ACE inhibitor therapy on LV function were observed irrespective of the degree of initial LV dysfunction and were comparable in bath the captopril and enalapril groups. Survival at 90 days and 12 months was significantly improved in the enalapril group (7 placebo, 9 captopril, 1 enalapril [p = 0.038] and 12 placebo, 10 captopril, 2 enalapril [p = 0.022]; deaths at 90 days and 12 months, respectively). Immediate administration of captopril and enalapril improved LV function and prevented LV dilatation after acute myocardial infarction. The benefit was similar with both ACE inhibitors and was in excess of the benefits of optimal conventional therapy. (Am J Cardiol 1994;73:1180-1186)

In response to early reports indicating a beneficial adrenoceptor effect of [beta] blockade, 2 small trials were conducted to investigate the hemodynamic effects of acute and chronic [beta]-adrenocoptot blockade in patients with congestive cardiomyopathy. Acute [beta]-blocker therapy with intravenous acabetolol, 25 mg, resulted in a significant decline in cardiac performance, whereas chronic therapy with acebatolol, 200 mg twice daily, resulted in no beneficial effects on exercise tolerance, as reported by the original Swedish investigators. Further, [beta]-adrenoceptor blockade has been associated with a number of clinical problem: [beta] blockers tend to interfere with the compensatory mechanisms that support circulation during early or mild heart failure and therefore have little value as routine therapy at that stage of the disorder. Although excessive [beta]-adrenoceptor blockade may worsen ventricular function by decreasing myocardial contractility, [beta]-blockers appear to have a useful role in patients with moderate heart failure accompanied by tachycardla. Carefully titrated doses of p blockers in conjunction with afterlead-reducing agents may also provide a benefit in patients with rapid heart rates and grossly elevated levels of circulating catecholamines. (Am J Cardiol 1993;71:54C-60C)

The effects of acute reduction of left ventricular (LV) loading in valvular aortic stenosis (AS) were examined. Thirty-five consecutive patients with AS (peak-to-peak aortic valve gradient 66 [+ or -] 26 mm Hg, aortic valve area 0.65 [+ or -] 0.22 [cm.sup.2]) were given intravenous sodium nitroprusside (1 to 3 [mu]g/kg/min) to reduce systolic aortic pressures by >10 mm Hg (mean aortic pressure 99 [+ or -] 15 to 80 [+ or -] 15 mm Hg; p Overall, nitroprusside infusion resulted in little change in cardiac index (2.72 [+ or -] 0.61 to 2.67 [+ or -] 0.58 liters/min/[m.sup.2]; p = not significant). Individual patients had a range of responses. Fourteen patients (group 1) had an increase in cardiac index (2.42 [+ or -] 0.59 to 2.74 [+ or -] 0.67 liters/min/[m.sup.2]; p It is concluded that there is a disparate response to acute vasodilatation in AS. Potentially beneficial effects are seen in a subgroup of patients, especially those with increased filling presures and impaired LV function. It is postulated that the hemodynamic effects of sodium nitroprusside in patients with AS can be explained by the balance of effects on preload and afterload.

A pilot study was Performed to assess the shortterm effects of intravenous captopril on anginal threshold and systemic and coronary hemodynamics in patients with stable angina pectoris. Twelve patients with documented coronary artery disease, stable angina pectoris and normal left ventricular function were studied by an incremental atrial pacing stress test before and after intravenous captopril (n = 8) or placebo (n = 4). There were no significant differences in the extent of coronary dis. ease Or left ventricular function between the 2 groups and resting plasma-renin levels were normal. Captopril increased the time to angina (14 [plus or minus] 4 to 19 [plus or minus] 5 minutes, p [less than] 0.05), increased heart rate at development of angina (126 [plus or minus] 7 to 142 [plus or minus] 7 beats/min, p [less than] 0.05) and tended to increase coronary blood flow (229 [plus or minus] 154 to 296 [plus or minus] 259 ml/min, p = 0.11) and decrease coronary vascular resistance (53 [plus or minus] 10 to 47 [plus or minus] 3 dynes s [cm.sup.-5]/1,000, p= 0.11) at peak stress without alteration in systemic hemodynamics. No significant changes were seen after placebo administration. Therefore, intravenous captopril appears to cause a short-term increase of coronary vascular reserve, and anginal threshold in patients with chronic stable angina. This effect appears to be independent of inhibition of the systemic renin-anglotensin system or systemic hemodynamic changes. (Am J Cardiol 1990;66:164-167), Angina pectoris is chest pain resulting from an imbalance between the demand for and supply of oxygen to the heart. Angiotensin-converting enzyme inhibitors, such as captopril, may improve the imbalance between oxygen demand and supply by dilating blood vessels, inhibiting the adrenergic nervous system, and decreasing heart rate. The effects of captopril on the development of angina and on blood flow within the coronary arteries, the major blood vessels supplying the heart, were assessed in 12 patients with coronary artery disease. Eight of the patients received captopril, and four were given a placebo, a substance with no known therapeutic effect. Under maximal stress conditions, captopril delayed the development of angina, increased the heart rate during the development of angina, and increased blood flow within the coronary arteries. In addition, captopril decreased coronary vascular resistance (the force against which blood flows inside the coronary arteries), but did not alter circulation in the peripheral vessels. No changes were observed in the circulatory characteristics of patients given a placebo. These findings demonstrate that captopril improves the coronary circulation and delays the development of angina without influencing peripheral circulation. (Consumer Summary produced by Reliance Medical Information, Inc.)

The clinical effect of a low-dose rapid-infusion intravenous regimen was assessed using human recombinant tissue-type plasminogen activator (rt-PA) in unstable angina. Fifty patients with unstable angina pectoris were randomly assigned to blinded treatment with either placebo (24 patients) or low-dose (20 mg bolus, 30 mg infusion over 1 hour) intravenous rt-PA (26 patients). Before randomization, all patients were treated with aspirin, twice-daily subcutaneous heparin, and maximally tolerated antianginal therapy. Of the 50 patients assigned, 26 received rt-PA and the outcome was successful in 15 (58%) (angina settled, no myocardial infarction or urgent intervention) compared with 9 (38%) successful outcomes in the 24 who received placebo (0.5 >p >0.1). Angina remained refractory in 8 (31%) of the rt-PA group and in 13 (54%) of the placebo group (0.1 >p >0.05). Urgent interventions were required in 6 patients (23%) who received rt-PA and in 11 patients (46%) who received placebo. Three patients in each group sustained a myocardial infarction within 72 hours of entering the trail and there wer 3 deaths (1 in the active treatment group, 2 in placebo group) within 2 weeks of the trial (p = not significant). Administration of intravenous rt-PA was not associated with any complications. Low-dose rt-PA administration in patients with unstable angina was associated with a tendency to stabilization of anginal symptoms and a reduction in the needs for urgent intervention. However, these trends did not achieve statistical significance.

Atrial natriuretic factor (ANF) is a hormone secreted by the atrial tissue of the heart in response to a rise in blood pressure. This hormone regulates blood pressure, blood volume, and cardiac output (the volume of blood pumped by the heart), and increases the excretion of sodium in the urine. These actions of ANF help to reduce the workload of the heart. Studies have shown that ANF increases sodium excretion, dilates blood vessels, and improves ventricular function and cardiac output in patients with congestive heart failure (the inability of the heart to pump blood leading to lung congestion). The effectiveness of ANF was compared with the drug furosemide in treating four patients with congestive heart failure. Furosemide is a diuretic (an agent that increases the excretion of water), and has been commonly used to treat congestive heart failure and high blood pressure. The results show that the administration of up to 1,000 micrograms of ANF intravenously per day was ineffective in controlling congestive heart failure in patients who responded to treatment with furosemide. Other studies show that continuous intravenous administration of ANF has beneficial effects in treating CHF. The lack of effectiveness of ANF may be due to the inability to maintain adequate levels of the drug in the body. It is suggested that the use of ANF derivatives that are not as susceptible to degradation, or the use of inhibitors of ANF degradation, may supplement the treatment of congestive heart failure. (Consumer Summary produced by Reliance Medical Information, Inc.)