Monotherapy with felodipine, a new calcium antagonist, in mild and moderate hypertension.

The role of felodipine, a new calcium antagonist, in monotherapy for mild and moderate hypertension was investigated in a placebo-controlled double-blind study of 109 patients from 13 centres. The patients were randomised in a double-blind fashion to receive felodipine, 2.5 mg b.i.d. (32 patients), 5 mg b.i.d. (30 patients), 10 mg b.i.d. (24 patients), or placebo (23 patients). Two hours after the first tablet was administered, there was a reduction in systolic and diastolic blood pressure, both supine (p less than 0.05) and standing (p less than 0.001), that was significantly correlated with dose. Three and 8 weeks later, 2 h after dosage, this correlation was still apparent in both supine and standing blood pressure (p less than 0.001). One week after randomisation, at 12 hours after administration there was a significant correlation with dose in the standing systolic (p less than 0.05) and diastolic (p less than 0.01) blood pressure. After 8 weeks therapy, a significant correlation with dose occurred in both supine and standing systolic (p less than 0.05) and diastolic (p less than 0.01) blood pressure 12 h after therapy. The proportion of patients completing the study who achieved a supine diastolic blood pressure of 90 mm Hg or less after 8 weeks therapy at 2 h after dosage was 9% on placebo, 67% on felodipine 2.5 mg b.i.d., 57% on felodipine 5 mg b.i.d., and 92% on felodipine 10 mg b.i.d. Felodipine was generally well tolerated although 10 patients on the highest dose withdrew due to adverse experiences. Plasma felodipine levels were significantly correlated with dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Haemodynamic effects of hydralazine at rest and during exercise in patients with chronic heart failure.

The administration of vasodilator drugs has been shown to have beneficial effects at rest in patients with acute or chronic heart failure. To determine the efficacy of hydralazine during exercise, 10 severely symptomatic patients with chronic left ventricular failure from diffuse coronary disease or cardiomyopathy were studied at rest and during upright exercise on a bicycle ergometer. All patients were already receiving optimal treatment with digitalis and diuretics. At rest treatment with hydralazine resulted in a fall in both mean arterial and pulmonary wedge pressure. There was a 50 per cent reduction in systemic vascular resistance compared with pretreatment measurements and there was an equally impressive increase in stroke volume index. During exertion the changes noted at rest were sustained though occurred to a lesser degree; thus there was a 20 per cent fall in arterial resistance and a 20 per cent rise in stroke volume index compared with control. These findings show that hydralazine administration not only results in a beneficial effect on cardiac function at rest but that this effect is maintained during upright exercise in patients with impaired left ventricular function, thus providing further support for its use in the long-term management of such patients.

Value of pacing in cardiac failure associated with chronic atrioventricular block.

The effect of permanent pacing on chronic complete atrioventricular block complicated by cardiac failure was studied in 6 patients by measurement of indirect left atrial pressure 15 minutes after institution of pacing and again 3 to 12 months later. In addition, 21 patients with complete heart block and clinical plus radiological evidence of cardiac failure at the time of pacing 3 to 6 years earlier were also reviewed. Only 1 of 6 patients studied haemodynamically improved and 1 died in cardiac failure. Of 21 patients assessed clinically, 10 had improved and 8 had died after a mean follow-up of 53 months. In the absence of syncope, pacing was of little symptomatic benefit but still may be justified to prolong survival. Both studies indicated a particularly poor prognosis for patients known to have coronary artery disease. No reliable means were found of determining the prognosis in the individual patient with cardiac failure before pacing.

Long-term prognosis after acute anterior infarction with atrioventricular block.

The purpose of this study was to evaluate the need for permanent pacing in patients who have survived the effects of anterior myocardial infarction with complete heart block and have returned to sinus rhythm but who are left with impairment of intraventricular conduction. We have reviewed 52 patients with complete heart block complicating recent anterior myocardial infarction. Temporary pacing was instituted in all patients. There were 25 hospital survivors who were followed for an average of 49 months. Long-term pacing was established in 4 patients. Of the 21 patients in sinus rhythm, 14 had partial bilateral bundle-branch block with either right bundle-branch block and left anterior hemiblock or right bundle-branch block and left posterior hemiblock; at the end of the follow-up period, 10 of these 14 were alive and well. Furthermore, permanent pacing failed to prevent sudden death in 2 patients. At the present time, therefore, we conclude that long-term pacing is not justified in patients, otherwise asymptomatic, with partial bilateral bundle-branch block persisting after transient complete heart block in anterior myocardial infarction.

Coronary artery reperfusion. I. Early effects on local myocardial function and the extent of myocardial necrosis.

The effects of coronary artery reperfusion 3 hr after coronary occlusion on contractile function and the development of myocardial damage at 24 hr was studied experimentally. In 14 control and 6 reperfused dogs, relationships between epicardial ST segment elevation 15 min after coronary occlusion and myocardial creatine phosphokinase activity (CPK) and histologic appearance 24 hr later were examined. The electrocardiograms were recorded from 10 to 15 sites on the left ventricular epicardium and transmural samples for CPK and histology were obtained from the same sites where epicardial electrocardiograms had been recorded. An inverse relation existed between ST segment elevation (mv) 15 min after occlusion and log CPK activity (IU/ mg of protein) 24 hr later, log CPK = - 0.06ST + 1.26. In dogs subjected to coronary artery reperfusion, there was significantly less CPK depression (log CPK = - 0.01ST + 1.31, [P < 0.01]) than that expected from the control group. In the control group 97% of specimens showing ST segment elevations over 2 mv at 15 min showed abnormal histology 24 hr later. In contrast, in the reperfused group 43% of sites exhibiting elevated ST segment at 15 min showed abnormal histology 24 hr later. In six additional dogs it was shown that the paradoxical movement of the left ventricular wall could be reversed within 1 hr of perfusion. Therefore, by enzymatic and histologic criteria, as well as by functional assessment, coronary artery reperfusion 3 hr after occlusion resulted in salvage of myocardial tissue.

Coronary artery reperfusion. II. Reduction of myocardial infarct size at 1 week after the coronary occlusion.

The question of whether or not the size of an area of myocardial infarction, measured at 1 wk after coronary occlusion, can be influenced by coronary artery reperfusion was examined in dogs. In seven control experiments the anterior descending coronary artery was ligated, while in seven other studies the occlusion was released after 3 hr. In all animals calibrated photographs were used to assess the zone of hypoperfusion and the acutely injured area of epicardial ST segment elevation, as well as the extent of damage at postmortem 1 wk later. In control dogs, the gross infarct size at postmortem averaged 63.8+/-7.3% of that predicted from the acutely injured zone. However, in reperfused hearts the average gross infarct size at 1 wk was only 10.2+/-4.4% of that predicted. Transmural specimens were obtained at autopsy for histology and measurement of myocardial creatine phosphokinase (CPK) activity from sites initially used for epicardial electrocardiography. In control animals, there was a direct relationship between the degree of ST segment elevation and the degree of cell necrosis in transmural histologic sections. ST segment elevation also predicted myocardial CPK (international units per milligram protein): log CPK = - 0.0613 ST + 1.17 (r = 0.66, n = 56 sites). In the reperfused animals, log CPK = - 0.166 ST + 1.36 (r = 0.69, n = 46 sites) showing almost complete preservation of CPK activity at 1 wk, sparing being most prominent in the epicardial zone. Similarly, there was a good correlation between myocardial CPK activity and the histological assessment of cell destruction, the degree of cell damage = - 0.152 CPK + 3.86 (r = 0.86; n = 102 sites). Thus, control dogs showed severe myocardial CPK depletion and histologic evidence of extensive cell destruction, whereas animals subjected to coronary artery reperfusion had little CPK depletion and much less evidence of myocardial cell necrosis 1 wk later.