Hemodynamics and leg muscle metabolism at rest and during exercise in young healthy men after prenalterol.

In eight young healthy men the effects of short-term treatment with prenalterol, a new beta-adrenergic agonist, on peripheral hemodynamics and leg muscle metabolism were studied at rest and during exercise at a moderate and a heavy workload. At rest prenalterol treatment significantly increased pulmonary oxygen uptake, heart rate, rate pressure product, and leg blood flow and decreased leg arteriovenous oxygen content difference. During exercise fewer hemodynamic effects of prenalterol were observed. At the moderate workload there was a slight increase in heart rate, but at the heavy workload heart rate fell. Prenalterol raised the arterial concentrations of free fatty acids and glycerol at rest by 70% and 40%, but during exercise these alterations were not present. The plasma levels of epinephrine and dopamine in subjects at rest decreased significantly during influence of prenalterol, but these differences were also abolished during exercise. The leg exchange of metabolites and the concentrations of endogenous muscle metabolites were not influenced by prenalterol, although the lactate concentrations in muscle tended to be lower at rest and during exercise. The results at rest demonstrate that prenalterol in this situation acts predominantly as a stimulator of beta 1-adrenoceptors. During heavy exercise, however, when the endogenous sympathetic tone is high, the beta-stimulating effects are no longer overt and instead reduced heart rate indicates a blocking effect on beta-adrenoceptors. The hemodynamic and metabolic results are concordant with the hypothesis that prenalterol acts as a partial beta-receptor agonist.

Experience with pindolol, a betareceptor blocker, in the treatment of hypertension.

Ten patients, mean age 48 years, with essential hypertension of stage I and II according to the WHO classification, were studied at rest and during work before and after an average of two and 16 months of oral treatment with the beta-adrenergic blocking agent, pindolol. The pindolol treatment caused a significant decrease in the systemic systolic and diastolic blood pressure, both at rest and during work. Three mechanisms seem to be involved in the antihypertensive effect of pindolol: (1) a negative chronotropic effect on the heart, (2) a decrease in peripheral vascular resistance, and (3) an increase in venous capacitance affecting the venous return. However, the significance of these mechanisms seems to differ when the situations after two months of treatment are compared with those after 16 months of treatment. In the beginning, a decrease in cardiac output seems to be the main cause of the lowering of the blood pressure; later, a decrease in systemic vascular resistance might be of greater importance.

Effect of digoxin on the electrocardiogram at rest and during exercise in healthy subjects.

The effect of digoxin on the electrocardiogram at rest and during and after exercise was studied in 11 healthy subjects. Exercise was performed on a heart rate-controlled bicycle ergometer with stepwise increased loads up to a heart rate of 170 beats/min. The subjects were studied after peroral intake of digoxin at 2 dose levels and after withdrawal of digoxin. Administration of digoxin induced significant ST-T depression at rest and during exercise even at the small dose (2.4 +/- 0.8 microgram/kg body weight, mean +/- standard deviation). The ST-T changes were numerically small and dose-dependent. The most pronounced ST and T depression occurred at a heart rate of 110 to 130 beats/min. At higher heart rates the ST depression was less pronounced but still statistically significant. During the first minutes after exercise no significant digitalis-induced ST-T depression was seen. This reaction is not of the type usually seen in myocardial ischemia. Fourteen days after withdrawal of the drug there were no significant digitalis-induced ST-T changes at rest or during or after exercise.

Prevalence of primary T-wave changes in young men and their relationship to psychological and anthropometric data.

The T wave in leads II, V4, and V6 in the electrocardiograms of 1,401 consecutively entering 18-year-old male conscripts at a military processing center in 1975 were classified, and the relationship between the frequency of the T-wave changes relative to the psychosocial and medical data of the subjects was examined. One percent of the conscripts had a negative T in one or more of these leads, and twelve percent showed some deviation from the "normal T," usually a T wave of less than ten percent of the R-wave amplitude. A common finding was the presence of a "notch" in the T wave of lad V4 (a negative deflection in the middle of a positive T wave). Those with T-wave changes showed the same incidence of signs and history of heart disease as those with a normal T. However, those with an abnormal T showed higher heart rate and systolic blood pressure at rest. Further, they had more nervous symptoms and a higher consumption of alcohol and tranquilizers. These findings were as common in the larger group of flat T waves as in the smaller group with T-wave changes of the type normally attributed to organic heart disease (i.e., having notched, or more or less inverted T waves without ST depression). The maximal work capacity and vital capacity were slightly lower in subjects with abnormal T waves. However, this was fully explained by lesser height. It is suggested that in the majority of these cases, T-wave changes in young adults are due to increased sympathetic tone rather than to organic heart disease.

[The hemodynamic effect of verapamil by intravenous administration in middle-aged, subjectively healthy subjects at rest and during exercise]. / Effetto emodinamico del veraa,il per via endovenosa su soggetti di mezza età soggettivamente in buona salute, a riposo e sotto sforzo

After an intravenous injection of 0.1 mg Verapamil per kg body weight and during an infusion of 0.007 mg Verapamil per kg body weight and minute the heart rate increased, P,Q,-time increased, pulmonary vascular pressures increased. Aortic pressures decreased. No change in maximum dp/dt of the aortic pressure. The word maximum is still missing. Pre-ejection period decreased. During an exercise on a load of 650 kpm/min on average heart rate after Verapamil was increased, aortic pressures decreased, stroke work decreased and there were no signs of any negative inotropic effect.

Significance of primary T wave aberrations in the electrocardiogram of asymptomatic young men. Part 1. Electrocardiographic data.

The electrocardiogram (ECG) at rest and during orthostasis and exercise in 51 healthy men 18-19 years of age without history or symptoms of heart disease, but with T wave aberrations in the ECG (group T) were compared to the normal ECGs of 112 controls of the same age. These aberrations (which literature suggests to be due to organic heart disease) consisted of either a notch in the T wave, especially in the midprecordial leads, that sometimes became inverted, or a low T wave without concomitant ST depression. The T wave aberrations at rest in group T were similar to what 25% of the controls evidenced during orthostasis (group B). Both group T and group B had signs of increased sympathetic tone at rest with a higher heart rate and systolic blood pressure than did the subjects with normal ECG both at rest and during orthostasis. These T wave aberrations disappeared for the majority during exercise. Both group T and group B had prolonged QTc intervals. Group T had increased R wave amplitudes which did not correlate to the severity of the T wave aberration or to systolic blood pressure. Our opinion is that primary T wave aberrations in the majority of these young men were because of increased sympathetic tone.

Significance of primary T wave aberrations in the electrocardiogram of asymptomatic young men. Part II. Working capacity and anthropometric data.

Fifty-one healthy men, 18 - 19 years of age, with "organic" T wave aberrations (group T) were compared to 112 controls of the same age with normal electrocardiograms (Group A + B). Group T had increased heart rate and higher systolic and diastolic blood pressures. Their lower physical work capacity could be "explained" in multivariate analysis by their shorter height, smaller heart volume and lower total hemoglobin (the latter not constituting a significant difference between the groups). Multiple regression analysis indicated that differences in heart rate, systolic blood pressure and blood volumes explained differences between subjects with and without primary T wave aberrations. These variables are all influenced by changes in sympathetic discharge, whereas no variable representing performance or body dimensions contributed to the explanation.

A 5-year follow-up of young men with primary T wave aberrations in their electrocardiograms.

Forty-eight subjects (group T) with primary T wave aberrations in their electrocardiograms (e.g. notches, flattening or inversion in leads II, CR4 and CR7 but without a concomitant ST depression) and 38 controls (group C), examined previously at the age of 18-19 years, were re-examined after 5.4 and 7.5 years respectively. The incidence of heart disease between the two examinations was lower in group T than in the controls. The T wave aberration had decreased in severity in 22 subjects in group T, but 66% of them still showed T wave aberrations at rest. Only one subject was free from T wave aberrations during orthostasis. Beta-adrenergic blockade in 27 subjects in group T suggested that 3 possibly had organic genesis to the aberrations. The earlier reported signs of high sympathetic tone in group T had decreased, but a somewhat higher heart rate and diastolic blood pressure than in the controls still remained. The systolic time intervals suggested larger stroke volumes in group T than in the controls and did not indicate decreased myocardial performance in group T. The attenuated differences between groups T and C in T wave abnormality, heart rate and blood pressure over the follow-up period suggest that T wave abnormality as an isolated finding in young men is a benign finding.

Significance of primary T wave aberrations in the electrocardiogram of asymptomatic young men, III. Systolic time intervals and autonomic tone.

Fifteen healthy male subjects, aged 18-19 years, with primary T wave aberrations consisting mainly of notches in the T wave without concomitant ST depression (group T) were compared to twenty-six controls of the same age with normal electrocardiograms. The T wave aberrations were eliminated by beta-adrenergic blockade in thirteen subjects in group T. Physical exercise decreased all the T wave aberrations. Group T was on average shorter and had signs of higher sympathetic tone, as shown by a higher heart rate and systolic blood pressure, than the controls and the parasympathetic tone was lower, as indicated by a higher heart rate during beta-adrenergic blockade. No significant differences in physical work capacity and heart volumes were found. Measurement of systolic time intervals suggested increased sympathetic influence on the heart and no signs of cardiac impairment. Thus the majority of subjects with aberrant T waves had changes in the autonomic tone and no signs of functional impairment of the heart.

Haemodynamic effects of intravenous verapamil at rest and during exercise in subjectively healthy middle-aged men.

Verapamil, 0.1 mg/kg body wt, was injected i.v. over 2 minutes in 8 subjectively healthy middle-aged men, followed by a continuous infusion of 0.007 mg/kg body wt per minute. Prior to the injection several of the subjects had raised pulmonary or systemic arterial pressures. At rest, the central pressures increased slightly, which was taken as a sign of a moderate negative inotropic effect, but there was no change in pre-ejection period or maximal dp/dt of the aortic pressure. The heart rate increased and there was a small decrease in systemic arterial pressure, probably due to a fall of systemic vascular resistance. The PQ time was prolonged. During exercise, with its positive inotropic stimulation, the moderate negative inotropic effect of verapamil disappeared, whereas the increase in heart rate and decrease in aortic pressures persisted. Some variables that reflected the oxygen demand of the heart decreased. The slight negative inotropic effect does not appear to be a particular contraindication to the use of verapamil, but it should be employed cautiously in conditions with a compensatory rise in systemic vascular resistance, or if atrioventricular conduction is impaired.

P-R interval in relation to heart rate during exercise and the influence of posture and autonomic tone.

P-R interval (PR) in relation to heart rate (HR) during exercise was studied in healthy men. When subjects were in a recumbent position, mean PR between HR 90-140 beats/min (bpm) decreased linearly from 167 +/- 8 ms to 136 +/- 5 ms. (Regression line: PR = 0.287 HR + 182.9, r = 0.40). PR did not decrease further at HR up to 180 bpm. When subjects were in a sitting position, a further decrease occurred after HR 150-160 bpm. The shortest PR observed during exercise was 100 ms. The decrease of PR between HR 90-140 bpm was affected by atropine but not by propranolol. Higher HR was not achieved after propranolol, and after atropine there was no difference in PR in either exercise position compared to the two exercises without any drug. Thus, exercise induces a decrease in PR which is for the most part completed at HR 140-150 bpm and is mainly achieved by a withdrawal of the parasympathetic tone. PR at HR 90 bpm was correlated to body surface area, indicating that the PR duration is related to the body and heart dimensions.

Exercise testing: a prospective study of complication rates.

Twenty departments of clinical physiology in Sweden, doing annually 30,000 exercise stress tests, mainly of patients, completed a questionnaire regarding how they carried out exercise testing. Bicycle ergometry was predominantely used. The criteria for inclusion of patients for exercise testing and for interruption of the test were generally wide, allowing the patient to work until symptoms limited the test. In a second part of the investigation, the departments continuously reported all complications that occurred during an 18-month period which included 50,000 exercise tests. The complication rate was 18.4, the morbidity rate was 5.2, and the mortality rate was 0.4 per 10,000 tests. The number of complications leading to permanent damage was low and it could not be proved that the exercise test had induced a higher complication rate than otherwise would have occurred during the observation period. Patients with aortic stenosis had a high risk for complications. With adequate safety measures and a well-trained staff, exercise stress testing can be regarded as a safe method to be used in the evaluation of even very ill patients.

Exercise testing in Sweden: a survey of procedures.

This report surveys the techniques of exercise testing of patients in twenty out of twenty-four (83%) Clinical Physiological Departments in Sweden. The study shows that bicycle ergometry is the predominant technique used. In the vast majority of hospitals, the standards of practice employed are high and adequate safety precautions are observed. However, criteria for exclusion from and interruption of exercise testing differ from one hospital to another. Limit values for heart rate, breathing frequency and blood pressure are by no means standardized. The criteria for distinguishing between normal and pathological electrocardiographic response vary. We conclude that in order to reduce complication rates and prevent accidents there is a need for further evaluations of the optimal use of exercise stress testing.

Effect of nifedipine on exercise tolerance in patients with angina pectoris.

To test if nifedipine, 10 mg sublingually, could increase exercise tolerance, ten patients with angina pectoris each performed two types of bicycle exercise test, one with a stepwise increase in load and the other with a continuously increasing load. The drug was given in a double-blind cross-over trial. Nifedipine raised the heart rate and diminished the systemic blood pressure at rest, on standing and during exercise at comparable loads. Work time was prolonged and higher work loads were achieved. The total work performed rose by 50 per cent in one of the tests and by 23 per cent in the other, about 50 minutes after taking the drug. The mechanism of the greater work capacity in angina pectoris after nifedipine was assumed to be diminished heart work due to a fall in systemic vascular resistance.

Effects of prazosin on hemodynamics and sympatho-adrenal activity in hypertensive patients.

We studied peripheral and central hemodynamics and plasma catecholamine levels in 12 previously untreated patients with essential hypertension before and during treatment with the alpha 1-adrenoceptor antagonist prazosin (9.8 +/- 1.1 mg/day for 3-6 weeks following dose titration) as a single drug. Prazosin did not alter intra-arterially recorded blood pressures in the group as a whole, in spite of adequate plasma levels (12.6 +/- 1.2 ng/ml). There were no changes in cardiac output, blood volume, systemic or forearm vascular resistance, or forearm venous tone at rest during treatment. The blood pressure response to prazosin was correlated to pretreatment systemic and forearm vascular resistances. Arterial adrenaline levels were unchanged, but noradrenaline levels increased from 1.30 +/- 0.10 to 1.85 +/- 0.20 nM (p less than 0.05). Both noradrenaline and blood pressure responses to isometric hand-grip exercise were delayed and reduced during treatment. The hemodynamic and plasma catecholamine responses to a cold pressor test and tilting (50% head-up during 10 min) were similar before and during treatment. Our results may be related to development of tolerance to the alpha-adrenoceptor blocking effect of prazosin during long-term treatment. The elevation of arterial noradrenaline levels suggests that increased sympathetic activity also may have opposed the hypotensive response to prazosin.

Prevalence of ECG findings in 18-19 year old Swedish men.

2268 consecutive men, 18-19 years of age, were examined at an enlistment centre regarding their health, some anthropometric variables and electrocardiogram. ECG items according to the modified Minnesota code [1] were found in 230 subjects (10%). Most common ECG findings were T wave abnormalities (2.2%). Heart rate was higher in the groups with QRS axis deviation, T wave items, sinus tachycardia and supraventricular ectopic beats. Systolic and/or diastolic blood pressure was increased in the groups with T wave items, sinus tachycardia and ventricular ectopic beats. A dysfunction of the autonomic tone can often be suspected as a cause of the abnormality, especially in the groups with tachycardia, T wave changes, AV block grade I and AV junctional rhythm. An ECG recording during orthostasis was considered to be of value to clarify the nature of the ECG abnormality.

Increased sympathetic activity and blood pressure in young asymptomatic men with 'organic' T-wave aberrations in the electrocardiogram.

1. Twelve asymptomatic young men with 'primary' T-wave aberrations in the electrocardiogram (group T) and 13 matched controls were subjected to a mental stress test, isometric exercise and a cold pressor test. 2. Plasma catecholamines and haemodynamics were studied. 3. Group T had signs of increased sympathetic activity at rest and enhanced sympatho-adrenal reactivity during stress. 4. Systolic blood pressure was consistently elevated in group T. 5. The T-wave aberrations may be explained by the increased sympathetic activity. 6. Several similarities exist between group T and borderline hypertensive subjects.