Hydralazine in the long-term treatment of chronic heart failure: lack of difference from placebo.

Although hydralazine improves cardiac performance in patients with chronic left ventricular failure, its long-term clinical efficacy has not been established in controlled trials. We carried out a double-blind randomized trial of hydralazine (200 mg daily in 16 patients) versus placebo (16 patients) in patients with class III and IV symptoms while they were taking digitalis and diuretics. Maximal treadmill exercise time was determined prior to and at 4, 10, 18, and 26 weeks of hydralazine or placebo treatment; average follow-up was 20 weeks. We found no change in body weight, clinical class, resting heart rate and blood pressure, or heart size (by chest x-ray examination and echocardiogram) during treatment in either group. The total number of complicating clinical events was insignificantly fewer in the hydralazine treated group (8 vs 13). Control exercise duration in the hydralazine group averaged 259 +/- 21 seconds (SEM), and increased to 347 +/- 35 seconds at 4 weeks (p less than 0.01) and 421 +/- 38 seconds at 26 weeks (p less than 0.001). Exercise duration also increased significantly in the placebo group, from 271 +/- 30 seconds at control to 340 +/- 44 seconds at 4 weeks (p less than 0.02) and 339 +/- 46 seconds at 26 weeks (p less than 0.02). No differences between groups were significant. Left ventricular ejection fraction remained depressed and unchanged in both groups. Thus long-term vasodilator treatment with hydralazine alone is not significantly more effective than placebo in chronic heart failure.

A comparative study of subcutaneously administered terbutaline and epinephrine in the treatment of acute bronchial asthma.

Terbutaline, a new bronchodilator drug reported to have selective affinity for beta 2-adrenergic receptors, was compared with epinephrine in the treatment of 49 adult subjects with acute bronchial asthma. Under double-blind conditions, 24 subjects received 1.0 mg of terbutaline sulfate, and 25 subjects received 0.5 mg of epinephrine hydrochloride subcutaneously. Spirometric measurements, heart rate, and blood pressure, as well as subjective responses, were recorded prior to, and then at 5, 15, 30, 60, and 120 minutes after administration of the drug. The results indicate that terbutaline is an effective bronchodilator drug in subjects with acute asthma; however, the heart rate rose significantly after administration of terbutaline, with a maximal increase of 25 percent above control. Review of the literature reveals that tachycardia is a consistent finding when subcutaneous doses of terbutaline in excess of 0.25 mg are administered. Stimulation of beta 1-adrenergic receptors in the heart appears to be the most important factor involved in this response. A lesser cardioaccelerator effect was observed after administering epinephrine in a dose producing an equivalent degree of bronchodilatation.

Abnormal regional metabolism and mechanical function in patients with ischemic heart diseases: improvement after successful regional revascularization by aortocoronary bypass.

Left ventricular anterior wall metabolism was investigated concurrently with global myocardail metabolism by simultaneous preoperation sampling of anterior interventricular venous (AIV) and coronary sinus (CS) as well as arterial bloods in seven patients with severe obstructive lesions of the major coronary arteries, including left anterior descending. Postoperative study was performed two weeks to six months following successful aortocoronary artery bypass surgery. All grafts including the aorto-left anterior descending artery grafts were patent. Preoperatively in three of the seven patients, anterior wall lactate extraction (R%L) was negative at rest. The average R%L at rest (7 +/- 14%) was abnormal and was negative (-49 +/- 26%) at a maximum supraventricular pacing rate (MPR) of 137 +/- 4.6 beats/min. Postoperatively, not only was resting R%L (39 +/- 4;4%) normal but also it remained normal during atrial pacing (32 +/- 8.5%) even though the postoperative MPR (164 +/- 4.4 beats/min) was much higher than the preoperative MPR; Postoperatively AIV pO2 both at rest (21 +/- 1.1 mm Hg) and at MPR (22 +/- 1.3 mm Hg) and directly determined O2 saturations (resting: 34 +/- 3.0%; MPR:35 +/- 2.1%) tended to be higher than the preoperative values (AIV pO2, resting: 18 +/- 1.7; MPR: 19 +/- 1.7 mm Hg; AIV O2 saturation resting: 30 +/- 2.7; MPR: 33 +/- 3.3%), although only differences in pO2 were statistically significant. In five of the seven patients in whom the pre and postoperative left ventricular angiograms could be compared, systolic wall motion of the left ventricular anterior wall improved markedly postoperatively. Average global myocardial lactate extraction (G%L) preoperatively was normal (19 +/- 4.8%) at rest but was negative (-22 +/- 12%) at MPR. Postoperatively however, G%L both at rest (44 +/- 5.5%) and at MPR (34 +/- 7.9%) were normal. Coronary sinus pO2 and O2 saturation were also higher postoperatively compared to the preoperative values. Over-all left ventricular performance indicated by increase in ejection fraction also improved postoperatively. This improvement was not caused by increased coronary blood flow. Postoperative coronary sinus blood flow both at rest (114 +/- 19 ml/min) and at MPR (199 +/- 27 ml/min) however were less than the preoperative values (resting 136 +/- 24, MPR 261 +/- 40 ml/min), There was also no increase in global O2 delivery and O2 consumption despite higher heart rate and rate-pressure product achieved during postoperative pacing stress and the patients did not develop angina. These findings suggest that improved regional and global metabolism and mechanical functions observed postoperatively in these patients may be due to redistribution of blood flow to the ischemic and nonischemic myocardium following successful aortocoronary artery bypass surgery.