G. David Beiser

Control of Heart Rate by the Autonomic Nervous System STUDIES IN MAN ON THE INTERRELATION BETWEEN BARORECEPTOR MECHANISMS AND EXERCISE

The control of heart rate by the autonomic nervous system was investigated in conscious human subjects by observing the effects of β-adrenergic blockade with propranolol, of parasympathetic blockade with atropine, and of combined sympathetic and parasympathetic blockade. The increase in heart rate with mild exercise in supine men was mediated predominantly by a decrease in parasympathetic activity; at higher levels of work, however, sympathetic stimulation also contributed to cardiac acceleration. When the response to 80° head-up tilt was compared with the response to exercise in the same subject supine, it appeared that the attainment of an equivalent heart rate was associated with a significantly greater degree of sympathetic activity during tilting than during exercise. Although heart rate was always higher at any given pressure during exercise than it had been at rest, the changes in heart rate that followed alterations in arterial pressure were found to be of similar magnitudes at rest and during exercise; it was therefore concluded that the sensitivity of the baroreceptor system was not altered during exercise. Investigation of the efferent pathways concerned in mediating the baroreceptor-induced changes in heart rate suggested that the relative roles of the sympathetic and parasympathetic systems were nearly equal in the resting state. During exercise, on the other hand, changes in sympathetic activity appeared to be the predominant mechanism by which speeding and slowing of the heart was achieved. It thus appears that baroreceptor-induced alterations in heart rate may be mediated by increased or decreased activity of either efferent system; the ultimate balance, however, is critically dependent on the preexisting level of background autonomic activity.

Blood Fibrinolytic Activity in Man Diurnal Variation and the Response to Varying Intensities of Exercise

This investigation was undertaken in normal subjects to define the relationship between the intensity of exercise and magnitude of fibrinolytic response and to examine the effect of diurnal variations on the exercise response. Fibrinolytic activity was measured on fibrin plates and expressed as mm2. Diurnal variations occurred with lowest activity at 8:00 AM (mean, 66 mm2), and peak activity between 5:00 and 8:00 PM (mean, 266 mm2, P<0.001). Five minutes of maximal treadmill exercise caused a marked increase in mean activity from 90 to 658 mm2 (P<0.001). Five minutes of 70% maximal exercise produced no significant increase, but 30 minutes increased activity to 626 mm2 (P<0.005). In contrast, 30 minutes of 40% maximal exercise produced a small elevation from 80 to 173 mm2 (P<0.005). Maximal and 40% maximal exercise evoked greater responses at 4:00 PM than 8:00 AM. Exercise produces increases in fibrinolytic activity which are related to the relative intensity of exercise, its duration, and the time of day it is performed. Short bursts of intense exercise cause marked increases, but more prolonged bouts of moderate exercise are required to produce similar increases. The increases with prolonged mild exercise are small and comparable to those observed during resting diurnal variations.

Role of the Capacitance and Resistance Vessels in Vasovagal Syncope

Withdrawal of sympathetic tone to the veins resulting in peripheral pooling of blood has been suggested as an important factor contributing to the decrease in cardiac output and hence arterial pressure that occurs during vasovagal syncope. However, no measurements of venous tone during syncope have been reported. In the course of other studies on the circulatory effects of negative pressure below the iliac crests, and 80° head-up tilt, vasovagal reactions occurred in 10 subjects. Heart rate, central venous pressure, arterial pressure, forearm blood flow, forearm vascular resistance, and forearm or hand venous tone were measured. The typical vasovagal reaction could be divided into two phases. A gradual fall in arterial pressure signified the onset of phase I, during which forearm vascular resistance did not change significantly. The duration of phase I was highly variable. The onset of phase II was denoted by an abrupt fall in arterial pressure and heart rate and a decrease of 62% in forearm vascular resistance, from 36 to 14 mm Hg/ml/100 g/min. However, venoconstriction rather than venodilatation occurred in the forearm or hand veins. Since central venous pressure did not change prior to or during the onset of the reaction, it is unlikely that venodilatation occurred in other vascular beds. It is concluded that two of the major mechanisms responsible for the hypotension of vasovagal syncope initiated by orthostasis or lower body negative pressure are bradycardia and dilatation of the resistance vessels. In contrast, it appears that the venous bed, by constricting, tends to maintain filling pressure and thereby cardiac output, and thus works in an opposite direction.

Clinical and Circulatory Effects of Isosorbide Dinitrate Comparison with Nitroglycerin

In order to resolve current controversies on isosorbide dinitrate (ISDN), we employed a particularly sensitive testing protocol to evaluate effects of sublingual ISDN and nitroglycerin on the exercise capacity of patients with angina. Ten minutes after ISDN 21 of 23 patients exercised longer (average 2.7 minutes, P < 0.001) than after placebo. Benefit was evident in only a minority of patients tested one hour and in none tested two hours after either ISDN or nitroglycerin. A given amount of exercise resulted in lower mean blood pressure (average 13 mm Hg, P < 0.001), higher heart rate (average 10 beats/min, P < 0.001), and shorter ejection time (average 0.04 second, P < 0.001) after ISDN. Similar changes were seen after nitroglycerin. The product of blood pressure, heart rate, and ejection time, an index of myocardial O2 consumption, was unchanged at angina after ISDN or nitroglycerin despite the increased exercise capacity, suggesting that clinical improvement after these drugs may be due to circulatory changes causing decreased myocardial O2 demand. We conclude that sublingual ISDN closely resembles nitroglycerin in its alteration of circulatory responses to exercise and in the duration of the resultant improvement in exercise capacity.

Effects of Chronic Right Ventricular Volume and Pressure Loading on Left Ventricular Performance

The effects of chronic right ventricular (RV) distension on left ventricular (LV) function were assessed in dogs 3 weeks after pressure and volume loading of the RV had been produced by the emplacement of a constricting band around the pulmonary artery and the creation of tricuspid insufficiency. This resulted in ascites, RV hypertrophy and dilatation, an increase in RV end-diastolic pressure (EDP), and a reduction of RV and LV norepinephrine concentrations. Peak LV pressure, wall stress, and dp/dt were measured during isovolumic beats at LVEDPs of 1 to 20 mm Hg, and comparisons at matched EDPs were made among the normal, sham-operated, and RV stressed dogs. Under these circumstances, LV function appeared to be depressed appreciably. The effects of RV volume loading on the pressure-volume curve of the LV in the potassium-arrested heart were assessed in a separate group of dogs. The pressure-volume curve of the LV was shifted so that any given LV volume was associated with a higher LV pressure. Thus, when peak pressure and wall stress were related to LV end-diastolic volume rather than to LVEDP, the relationship did not appear to differ from normal; peak dp/dt and peak VCE, however, remained depressed. This depression may represent a decrease in LV contractility consequent to the chronic RV stress or may reflect alterations in LV geometry. Thus, when the RV is subjected to a chronic flow and pressure load, assessment of LV function may be unreliable when indices of contractility are employed that require measurements of LVEDP.

Characterization of the Circulatory Response to Maximal Upright Exercise in Normal Subjects and Patients with Heart Disease

The circulatory responses to mild and maximal upright exercise were studied in six normal subjects and 21 patients with various types of cardiac disease. It was found that the usual hemodynamic indices employed to evaluate cardiac performance during exertion were unreliable in separating patients from normal persons. In contrast, the cardiac index achieved at a pulmonary arterial (PA) O2 saturation of 30% was found to be highly reliable and sensitive for distinguishing the normal from the abnormal response to exercise. At a level of exercise that lowers PA O2 saturation to 30%, all normal subjects achieved a cardiac index greater than 7.0 L/minm2 while no patient exceeded 4.8 L/min/m.2 In addition, the maximal capacity to extract O2 was greater in patients than in normal subjects; thus, during maximal exercise it was not unusual for patients to achieve PA O2 saturations of 15% or less, while the lowest value achieved in normal subjects was 23%.

Impairment of cardiac function in patients with pectus excavatum, with improvement after operative correction.

Abstract Although pectus excavatum is thought to impair cardiac performance, no consistent hemodynamic abnormalities have been identified. We hypothesized that cardiac function might be impaired during upright exercise when the heart descends into the pectus deformity. Catheterization of the right side of the heart in six patients with pectus excavatum gave normal results, and the hemodynamic response to supine exercise was normal. In contrast, cardiac output (CO) during intense upright exercise was low in two patients, at the lower limits of normal in one, and low normal in two. The CO and stroke-volume responses to mild upright exercise also differed from normal. After operative repair in three patients, CO during intense upright exercise increased an average of 38 per cent, and hemodynamic responses to mild upright exercise also changed toward normal. No alterations occurred in the response to supine exercise. Thus, pectus excavatum can reduce the pumping capacity of the heart during upright exercise, ...

Angina Pectoris: Pathophysiology, Evaluation, and Treatment

Abstract Accurate assessment of the effects and mechanisms of action of any intervention altering exercise performance of patients with angina pectoris caused by coronary artery disease requires us...

The role of skin and muscle resistance vessels in reflexes mediated by the baroreceptor system

The role of skin and muscle vascular beds in baroreceptor-mediated alterations of peripheral vascular resistance was evaluated in six normal subjects in whom the skin circulation in one forearm was temporarily suppressed by epinephrine iontophoresis. Baroreceptor activity was enhanced by application of negative pressure to the neck (neck suction) and inhibited by application of lower body negative pressure. Forearm blood flow was measured simultaneously in both arms with strain gauge plethysmographs. Since blood flow in the treated arm consisted entirely of muscle flow, skin flow was calculated from the difference between total forearm flow in the intact arm and muscle flow in the treated arm. Vascular resistances were calculated as the ratio of mean arterial pressure to the blood flow of each vascular bed. During neck suction, mean arterial pressure decreased from an average of 89 to 75 mm of Hg (P < 0.005), heart rate decreased from an average of 60 to 55 beats/min (P < 0.005), and total skin and muscle flows remained essentially unchanged. Cutaneous vascular resistance decreased from an average of 75 to 49 mm of Hg/ml per 100 g per min (P < 0.05), muscle vascular resistance from 68 to 51 (P < 0.005), and total forearm vascular resistance from 36 to 24 (P < 0.025). During lower body negative pressure, heart rate increased from an average of 59 to 69 beats/min (P < 0.005), mean arterial pressure did not change significantly, and significant decreases occurred in forearm blood flow from 5.4 to 2.7 ml/100 g per min, in skin blood flow from 3.1 to 1.4, and in muscle blood flow from 2.3 to 1.3. Cutaneous vascular resistance increased from an average of 47 to 110 mm of Hg/ml per 100 g per min (P < 0.05), muscle vascular resistance from 43 to 72 (P < 0.005), and total forearm vascular resistance from 20 to 38 (P < 0.001). These results demonstrate that both the skin and muscle resistance vessels participate in reflex changes initiated by alterations in baroreceptor activity.

Effects of a Reduction in Environmental Temperature on the Circulatory Response to Exercise in Man: Implications Concerning Angina Pectoris

Abstract The physiologic basis for the frequent complaint of worsening of symptoms in a cold environment was investigated in six patients with and five without coronary-artery disease, at rest and during identical levels of mild upright exercise at 25 and 15°C, with similar results. Significantly higher at the lower temperature were mean systemic arterial pressure (105 vs 92 mm of mercury at rest and 110 vs 92 during exercise; p less than 0.001), total peripheral resistance (1821 vs 1609 dynes-sec-cm-5 at rest, 1213 vs 993 during exercise; p less than 0.02) and left ventricular minute work (6.5 vs 5.7 kg-m at rest, 10.9 vs 9.0 during exercise; p less than 0.001). Exposure to cold did not change heart rate, cardiac output or stroke volume at rest or during exercise. These results indicate that a cold environment increases peripheral resistance at rest and during exercise. The consequent rise in arterial pressure, by augmenting myocardial oxygen requirements, would thus more readily provoke an attack of angina.