Louise Hartley

Impaired chronotropic response to exercise in patients with congestive heart failure. Role of postsynaptic beta-adrenergic desensitization.

The mechanism responsible for the attenuated heart rate (HR) response to exercise in patients with congestive heart failure (CHF) was investigated in 46 normal subjects and 59 patients with CHF stratified by peak exercise oxygen consumption (VO2). The peak exercise HR and the increment in HR from rest to peak exercise were decreased in CHF patients, and both correlated strongly with peak VO2 (r = 0.810, p less than 0.0001; r = 0.863, p less than 0.0001, respectively). Peak exercise norepinephrine level (NE) and the increment in NE from rest to peak exercise were not attenuated in CHF patients. Resting NE was elevated in CHF patients and correlated inversely with peak VO2 (r = -0.595, p less than 0.001). However, no significant correlation occurred between peak VO2 and either peak exercise NE or the exercise increment in NE. The ratio of the exercise increments in HR and NE, and indirect index of sinoatrial node sympathetic responsiveness, was markedly reduced in CHF patients and was inversely related to the severity of exercise impairment. Likewise, the HR response to a graded isoproterenol infusion was markedly reduced in CHF patients. Age-matching of normal subjects and CHF patients did not affect the foregoing observations. Infusion of CHF patients with the phosphodiesterase inhibitor milrinone caused a significant increase in the ratio of the exercise increments in HR and NE. These data strongly suggest that the attenuated HR response to exercise in CHF patients is due, at least in part, to postsynaptic desensitization of the beta-adrenergic receptor pathway.

Arterial Noradrenaline Concentration during Exercise in Relation to the Relative Work Levels

The noradrenaline (NA) levels in arterial blood plasma were followed at rest and during increasing muscular exercise in 5 healthy men. The levels were found to be significantly correlated to the oxygen consumption, measured at submaximal and calculated at supramaximal work. The NA levels increased slowly, up to about 75 % of the maximal oxygen consump tion, thereafter the NA levels increased rapidly. These increases are discussed with respect to increased sympathetic impulse flow, decreased inactivation of the circulating NA, and increased release from the nerve terminals per nerve impulse. At a work load requiring about 75 % or less of the maximal oxygen consumption the mean sympathetic impulse flow seems to be low. At the highest work loads (maximal to supramaximal) a markedly increased sympathetic impulse flow is of major importance for the rapidly increasing NA levels.

Efficacy and safety of perhexiline maleate in refractory angina. A double-blind placebo-controlled clinical trial of a novel antianginal agent.

Despite large gains in the medical and surgical treatment of angina pectoris in the past two decades, many patients are refractory to conventional medical therapy and are unsuitable for a first or, more commonly, repeat coronary revascularization procedure. We evaluated the efficacy of perhexiline maleate, a drug with an antianginal mechanism of action in humans that is as yet unknown, by using a randomized double-blind placebo-controlled crossover design in 17 patients with refractory angina who continued to receive maximal antianginal therapy, typically including nitrates, a beta-blocker, and a calcium channel antagonist. In view of perhexilines potential for hepatic and neurological toxicity, plasma drug levels were monitored and maintained in the 150-600 ng/ml range. Sixty-three percent of patients were judged perhexiline responders by objective exercise testing criteria, as compared with 18% of patients on placebo (p less than 0.05). By blinded review of subjective measures of anginal frequency and severity, 65% of patients noted an improvement while on perhexiline, whereas no patient identified the placebo phase with improvement. Side effects observed in 29% of patients were minor and related to transient elevations of blood levels of more than 600 ng/ml; no patient suffered hemodynamic or cardiac conduction abnormalities attributable to perhexiline. With attention to the pharmacokinetics of perhexilines elimination in individual patients, this novel antianginal agent seems to be safe and effective and deserves further evaluation in patients already receiving maximal antianginal therapy who are not candidates for revascularization procedures.

Physical Training in Sedentary Middle-aged and Older Men III. Cardiac Output and Gas Exchange at Submaximal and Maximal Exercise

Fifteen previously sedentary men (38–55 years old) participated in an endurance training program which consisted of running for 2–3 half-hours a week for 8–10 weeks. Maximal oxygen uptake increased in all subjects, mean increase from 2.68 to 3.06 l/min, i.e. 14 per cent. This increase was brought about by a 13 per cent increase in maximal cardiac output, from 18.7 to 21.1 l/min. Heart rate was 8–17 beats/min lower during submaximal exercise. The maximal heart rate decreased by 6 (from 182 to 176) beats/min. Thus stroke volume was increased 7–17 ml at submaximal and 17 ml (16 per cent) at maximal exercise. Heart volume determined from X-rays did not change. After the training, mean arterial blood pressure was on the average 5 mm Hg lower at a given submaximal oxygen uptake; no change was observed at maximal exercise.

Plasma cortisol and norepinephrine responses in anticipation of muscular exercise.

&NA; Strikingly consistent individual responses and significant mean elevations of plasma cortisol levels (5 to 9 &mgr; g%) and plasma norepinephrine levels (2.0 to 2.5 &mgr; g/1) were observed during a 20‐min interval prior to onset of the first exhausting exercise (70% max VO2) session in eight normal young men. No detectable plasma epinephrine response was observed. Such consistent anticipatory psychoendocrine responses were not found prior to subsequent exercise sessions involving milder degrees of muscular exercise. Psychoendocrine reactions to intravenous catheterization were also observed in some individual subjects, suggesting the need for precautions to minimize the possible effects of this variable in exercise experiments. Some implications of this study for psychoendocrine research are also discussed.

Long-term Sequential Changes in Exercise Capacity and Chronotropic Responsiveness After Cardiac Transplantation

BACKGROUND Peak exercise capacity improves early after orthotopic cardiac transplantation. However, the physiological response to exercise remains abnormal, with a reduced rate of heart rate (HR) rise and reductions in peak exercise HR and the increment in HR from rest to peak exercise. This chronotropic incompetence is due in large part to cardiac denervation. If reinnervation occurs after transplantation, it might result in an improvement in both chronotropic responsiveness and maximal exercise capacity. We therefore hypothesized that the chronotropic response to exercise and maximal exercise capacity would improve with time after transplantation. METHODS AND RESULTS Peak symptom-limited cardiopulmonary exercise tests performed in 57 clinically stable cardiac transplant recipients (mean age, 45 +/- 2 years) serially for up to 5 years after transplantation and in 33 control subjects without heart disease were analyzed retrospectively. Pretransplantation exercise tests were also performed in 41 patients an average of 4.7 +/- 0.6 months before transplantation. At 1 year after transplantation, peak oxygen consumption was 16.6 +/- 0.9 mL.kg-1.min-1, reflecting a 43% increase versus pretransplantation. Nevertheless, compared with control subjects, maximal exercise capacity and the HR response to exercise were subnormal in transplant recipients. There were no further increases in peak exercise capacity, peak exercise HR, or the peak increment in HR with exercise up to 5 years after transplantation. CONCLUSIONS One year after cardiac transplantation, peak exercise capacity and chronotropic responsiveness are subnormal. There is no further improvement in peak exercise capacity or chronotropic responsiveness as late as 5 years after transplantation. These data indicate that with regard to chronotropic responsiveness, functionally significant cardiac reinnervation does not occur between the first and fifth years after transplantation.

Physical training in sedentary middle-aged and older men. I. Medical evaluation.

In a group of 68 middle-aged sedentary men participating for 2 months in hard physical training, 5 were initially advised against participation for medical reasons; 54 subjects completed the training program. The frequency of orthopaedic complications was high. A slight decrease of the number of abnormal ECG findings at rest and at work (premature beats and ST-changes) was found after training. The blood pressure reaction during work in relation to the heart rate response was not changed. A significant reduction of the iron and cholesterol levels in the serum occurred.

Evidence for emotionally-induced coronary arterial spasm in patients with angina pectoris.

Twelve executives with typical angina pectoris, given a 12-minute quiz, designed to be psychologically stressful, responded with ST depressions of greater than or equal to 1.0 mm. Each of these patients was given an exercise tolerance test on an upright bicycle to induce an amount of ST depression equivalent to that observed during the quiz. A statistical analysis was made of the products of the heart rate and the systolic blood pressure (rate-pressure product), at the onset of equivalent ST depression on both tests. At the maximal ST depression during the quiz, the mean rate-pressure product was 181 +/- 64 (SD) X 10(2), and at an equivalent ST depression during exercise it was 225 +/- 54 X 10(2); the mean difference was 44 +/- 40 X 10(2). Inasmuch as the rate-pressure product is an index of myocardial oxygen consumption, the differences in rate-pressure product suggest that myocardial ischaemia occurred at a lower myocardial oxygen consumption during emotional stress than during exercise. If equivalent degrees of ST depression during exercise and the quiz are indicative of equivalent ischaemia, than a relative reduction in coronary blood flow during emotional stress, probably by coronary spasm, may be postulated as the most reasonable explanation for these observations.

Growth hormone and catecholamine response to exercise in relation to physical training

Exercise of moderate intensity results in an increase in growth hormone concentrations. During prolonged moderate work, growth hormone levels fall toward resting values, but training causes these levels to be maintained. Circulating norepinephrine increases with work, and the increment is less following physical training. The adjustments to endurance training may be mediated through the sympathetic nervous system.

Comparison of oxygen uptake during maximal work on the treadmill and the rowing ergometer.

ABSTRACTHarvard Medical Unit Thorndike Memorial Laboratory Boston City Hospital Boston, Massachusetts 02118. Maximal oxygen uptake has been reported to be greater if work is performed with both arms and legs rather than with the legs alone, Since rowing is exercise which requires the use of both arm