Eleven patients with severe left ventricular impairment (mean ejection fraction 24%) and moderate impairment of exercise tolerance underwent a double-blind, placebo-controlled, crossover trial of the orally administered /3-agonist prenalterol. Exercise hemodynamics and tolerance were measured during bicycle and treadmill exercise after 2 weeks of therapy with placebo or prenalterol. Cardiac index, ejection fraction, and stroke work index were not improved and exercise duration and peak oxygen consumption were not significantly different during the two treatments. During prenalterol treatment heart rate during exercise was consistently reduced. These results show that prolonged therapy with prenalterol does not improve hemodynamics or exercise tolerance and is associated with a diminished heart rate response to exercise. Circulation 69, No. 5, 955-962, 1984. SHORT-TERM administration of orally active l3-adrenergic agonists improves hemodynamics in patients with heart failure both at rest and during exercise.' -However, doubts exist as to the ability of the impaired ventricle, already exposed to increased sympathomimetic activity, to respond to additional longterm adrenergic stimulation.68 There have been no well-controlled trials of prolonged 8,3-agonist therapy in patients with heart failure. This study was designed to examine the effects of 2 weeks of oral therapy with the /3-agonist prenalterol on left ventricular function, exercise hemodynamics, and exercise tolerance in ambulant patients with moderately severe left ventricular impairment. (range 16% to 32%). All patients were New York Heart Association functional class II or I1l and on treadmill exercise testing had an estimated peak oxygen consumption equal to or less than 60% of that predicted for a healthy subject of similar age. 9 In all patients exercise was limited by dyspnea, fatigue, or both. No patient suffered chest pain or had evidence of exercise-induced myocardial ischemia and all were in sinus rhythm.Study protocol. All patients were studied as outpatients and gave written informed consent. After a 2 week stabilization period, patients entered a dose-ranging phase in which prenalterol10 was given in an initial dosage of 50 mg every 12 hr. After 4 days patients were reassessed and in the absence of adverse findings or side effects, the dosage was increased to 100 mg every 12 hr. The patients were again reassessed on day 8. Eight patients were able to tolerate the drug at the higher dosage. The remaining three patients tolerated only 50 mg bd due to sinus tachycardia (one patient), increasing frequency of ventricular ectopic beats (one patient), and unpleasant palpitations (one patient). A 1 week washout period then followed, after which patients were randomly assigned to receive either placebo or active drug at the appropriate dosage. After 2 weeks of oral therapy patients had a further 1 week washout period and then received the alternative treatment. Patients were studied on the last day of each treatment phase. Digoxin was stopp...

No abstract

SummaryThree patients with severe tetanus had episodes of profound arterial hypotension lasting from minutes to hours. The blood pressure was recorded continuously for 13, 19, and six days respectively by an intra-arterial catheter, and other measurements Included heart rate, central venous pressure, cardiac output, and blood gases.The hypotension was distinguished from that of "shock", for there was no clinical evidence of peripheral vasoconstriction and no tachycardia. It could not be attributed to disturbances of salt and water balance. During episodes of hypotension the blood pressure feil as low as 32/16 mm Hg, the heart rate fell from a mild tachycardia to normal values or a mild bradycardia, and the central venous pressure did not rise. The onset lnd the end of such episodes was often abrupt and the hypotension was often produced in response to a stimulus. In one patient extreme hypotension foilowed the aspiration of secretions from the trachea. These changes may represent another effect of tetanus on autonomic nervous activity, including impairment of baroreceptor reflexes.

In a placebo-controlled, randomized, cross-over, double-blind study of 12 patients with stable exertional angina, we measured at rest and during bicycle exercise the effects of 20 mg of nifedipine administered sublingually on hemodynamics and systemic and regional oxygen extraction and metabolism. Nifedipine decreased systemic vascular resistance by 38% at rest (p < .001) and by 28% during exercise (p < .001). Cardiac output increased from 4.6 ± 0.6 to 6.0 0.9 liters/min (p < .001) at rest after nifedipine and from 10.6 3.7 to 11.8 + 3.4 liters/min (p < .005) during exercise. After nifedipine, the arterial-mixed venous 02 content difference decreased from 4.7 ± 0.6 to 3.5 + 0.5 ml/100 ml (p < .001) at rest and from 10.5 ± 1.7 to 8.8 ± 1.6 ml/100 ml (p < .001) during exercise. After nifedipine the arterial-iliac venous 02 content difference also decreased at rest, from 5.9 + 1.5 to 4.8 ± 1.7 ml/100 ml (p = .06) but increased during exercise from 13.1 1.5 to 14.0 1.8 ml/100 ml (p < .05). Oxygen consumption was not significantly altered at rest or during exercise. Nifedipine decreased mixed venous carbon dioxide tension (PCo2) during exercise from 53 ± 3.5 to 50 + 4.0 mm Hg (p < .05) but increased iliac venous Pco2 slightly from 61 ± 4.6 to 63 ± 5.2 mm Hg (p < .01). Exercise pH was not significantly altered, but arterial lactate increased more after nifedipine (2.65 ± 1.95 mmol/liter placebo, 3.54 + 2.74 mmol/liter nifedipine; p < .05). Thus nifedipine produces similar changes in 02 extraction in mixed venous and iliac venous blood at rest but directionally opposite changes during exercise. The data support the hypothesis that nifedipine does not alter the distribution of cardiac output to the legs at rest, but during dynamic leg exercise reduces the redistribution of cardiac output to the legs. This probably results from the shunting of blood flow away from exercising muscles by the generalized vasodilatation of nifedipine. Circulation 71, No. 4, 787-796, 1985. NIFEDIPINE, a calcium blocker, is a potent arteriolar vasodilator that is effective in the treatment of exertionall' and vasospastic5 angina. Investigations of its potential use as an afterload-reducing agent in patients with cardiac failure have recently been reported.68 At rest it decreases systemic vascular resistance and arterial pressure and reflexly increases heart rate and cardiac output.9-12 Regional blood flow to the legs and splanchnic organs increases."3-15 However, the important effect of nifedipine on regional blood flow to working muscles during dynamic exercise has not been described.

No abstract