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Biomedical subjects

L H Hartley

Publications and source records attributed to L H Hartley.

At least 37 records · Page 2Linked to original sources
PubMed1989

Mechanism of the attenuated peak heart rate response to exercise after orthotopic cardiac transplantation.

The mechanism responsible for attenuation of the peak heart rate response to exercise in patients after cardiac transplantation was studied. Because the donor heart is believed to be surgically denervated, the peak heart rate response to exercise is dependent primarily on 1) an increase in the circulating levels of the catecholamines norepinephrine and epinephrine at peak exercise, and 2) the end-organ responsiveness of the sinoatrial (SA) node to beta-adrenergic stimulation. To assess the former mechanism, the levels of plasma nonepinephrine and epinephrine were measured at rest and at peak exercise on a cycle ergometer in 23 transplant recipients an average of 7 +/- 1 months after transplantation and in 23 normal subjects matched for age. To assess the latter mechanism, the heart rate response to a graded infusion of isoproterenol was determined in six normal subjects with and without atropine pretreatment and in eight transplant recipients. In transplant recipients, both the absolute plasma levels of nonepinephrine and epinephrine at peak exercise and the increments from baseline to peak exercise were comparable with or greater than those in normal subjects. In transplant recipients, the isoproterenol dose that increased heart rate by 25 beats/min over baseline was not different from that in atropine-treated normal subjects (normal subjects 9 +/- 2 ng/kg per min; transplant recipients 11 +/- 1 ng/kg per min; p = NS). These data show that after cardiac transplantation, there is a normal or slight elevation of circulating catecholamines at peak exercise, and that the responsiveness of the SA node to beta-adrenergic stimulation is normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Effects of aerobic conditioning in lupus fatigue: a pilot study.

Fatigue, a complex symptom, significantly affects the quality of life in many patients with systemic lupus erythematosus (SLE). To understand this phenomenon, 23 patients with SLE and fatigue were studied. Standardized tests of depression (NIMH), fatigue, exercise tolerance (ETT) on a bicycle ergometer, and SLE activity were obtained. At baseline, SLE patients had significantly lower maximum oxygen consumption (VO2 max) than normals (p less than 0.005). Adjusted for age and sex, SLE patients perform at 54% of their expected maximum VO2, which is similar to published data from patients with rheumatoid arthritis. Depression by NIMH was not correlated with VO2 max or length of time on ETT. Fatigue measured by Profile of Mood States (POMS) was correlated with ETT time (r = 0.476, p less than 0.025) and with VO2 max (r = -0.402, p less than 0.07). After an 8-week aerobic conditioning programme the experimental group increased their aerobic capacity by 19% in contrast to 8% in controls. This change correlated with decreased fatigue as measured by visual analogue scales. Exercise did not exacerbate disease, and only two of 16 experimental subjects experienced transient joint symptoms during exercise.

Adult↗
PubMed1989

Modulation of cardiac autonomic activity during and immediately after exercise.

Fluctuations in heart rate above 0.03 Hz reflect autonomic modulation of sinoatrial node activity. To assess the dynamics of autonomic nervous activity during and immediately after exercise, we determined the power spectrum of heart rate and respiratory fluctuations in 43 normal subjects without known cardiac disease, 8 patients with severe congestive heart failure, and 6 patients status-post cardiac transplantation before, during, and after graded-work load exercise on a cycle ergometer. Before exercise, heart rate fluctuations (spectral power) at both high (0.15-0.80 Hz) and low (0.03-0.15 Hz) frequencies were significantly higher in normal subjects than in either heart failure or transplant patients but were not different between the two groups with heart disease. During exercise, heart rate power at all frequencies rapidly and progressively decreased in normal subjects, until at peak exercise it was not different from the other two groups. During recovery, heart rate power increased in normal subjects but remained significantly below base line. The findings demonstrate a marked reduction of autonomic modulation of heart rate in patients with heart failure and after cardiac transplant and support a progressive withdrawal of vagal activity during exercise with a gradual increase during recovery in normal subjects.

Adolescent↗
PubMed1989

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.

Adult↗
PubMed1989

Effects of renin inhibition in the conscious primate Macaca fascicularis.

Pro-His-Pro-Phe-His-Statine-Ile-Phe-NH2 (R-Pep-27), a potent renin inhibitory peptide, was infused into the conscious, sodium-depleted Macaca fascicularis at doses of 0, 0.1, 1, 4, 16, and 32 micrograms/kg/min for 10 minutes. At all doses greater than 0.1 microgram/kg/min, there was a parallel decrease in mean arterial pressure (MAP), plasma renin activity, and plasma angiotensin II (Ang II) concentration. On the other hand, assays with monoclonal antibodies specific for total renin and active renin demonstrated that the peptide's inhibition of circulating active renin stimulated the release of both. The maximal effective R-Pep-27 dose was approximately 16 micrograms/kg/min, which reduced MAP by an average of 15.8 +/- 1.4 mm Hg (n = 14) and plasma renin activity and plasma Ang II concentration to 3% (n = 9) and 15% (n = 5), respectively, of the pretreatment values. At 0.1 microgram/kg/min, there was no significant decrease in MAP; however, measurement of plasma renin activity showed an average decrease in activity of 42% (n = 3). No significant change in the heart rate was observed at all the doses studied. For comparison, intravenous captopril (400 micrograms/kg bolus) was administered after the MAP of the monkeys had recovered from the peptide experiments, and it reduced MAP by 25.1 +/- 2.4 mm Hg (n = 10) without significantly changing plasma renin activity. As anticipated, injection of angiotensin I (80-160 ng/kg bolus) into sodium-depleted monkeys during peptide infusion caused a transient rise in MAP of 14.8 +/- 5.4 mm Hg (n = 4) above the mean pretreatment value.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗
PubMed1989

Characterization of inheritance patterns of blood pressure in Macaca fascicularis.

A breeding colony of Macaca fascicularis was established at the New England Regional Primate Center in 1977 and continued through 1984. Characterization of the offspring of this colony at 18 and 30 months of age suggested that higher blood pressure levels are hereditary in M. fascicularis, but evidence to date cannot determine if this condition is harmful to the animals.

Animals↗
PubMed1987

Hypotensive effects of the renin inhibitor (RI-78) and the converting enzyme inhibitor (teprotide) in conscious monkeys.

Effects of the pentapeptide renin inhibitor (RI-78; Phe(4Cl)-Phe-Val-Tyr-Lys-NH2) and the angiotensin converting enzyme (ACE) inhibitor (teprotide) on mean arterial pressure (MAP) were examined in conscious monkeys (M. fascicularis). In salt depleted normotensive monkeys with a MAP of 95 +/- 4 mmHg and plasma renin activity (PRA) of 15.9 +/- 2.7 ngAI/ml/h, a bolus injection of a dose of 375 micrograms/kg of RI-78 caused a prompt hypotensive effect. Maximal hypotensive action was seen within 1 min, and MAP returned to the basal level within 15 min. With this dose, MAP was reduced by 20 +/- 6 mmHg. Teprotide (1 mg/kg) decreased MAP and reached a nadir after 13 min. There was no significant difference between maximal hypotensive responses seen with RI-78 (375 micrograms/kg) and with teprotide (1 mg/kg). Hypotensive effects of RI-78 and teprotide were also examined in acute renal hypertensive monkeys with a MAP of 125 +/- 5 mmHg and a PRA of 27.1 +/- 5.7 ngAI/ml/h. Again, similar hypotensive effects were observed. We conclude that antihypertensive effect of RI-78 is comparable to that seen with teprotide.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

Exercise responses before and after long-term treatment with oral milrinone in patients with severe heart failure.

Administration of the positive inotropic vasodilator milrinone results in immediate improvement in the maximal and submaximal metabolic responses to exercise. To determine whether these effects persist during long-term therapy, nine patients with severe congestive heart failure were evaluated by upright maximal exercise testing before therapy (baseline), after 10 +/- 1 weeks of oral therapy, and during double-blind, placebo-controlled readministration of intravenous milrinone after withdrawal of oral drug for 24 hours. During long-term oral therapy, maximal oxygen uptake was unchanged (baseline 792 +/- 72 ml per minute, oral therapy 820 +/- 83 ml per minute), whereas the anaerobic threshold was increased significantly from 570 +/- 53 ml per minute to 681 +/- 61 ml per minute. After withdrawal of milrinone, maximal oxygen uptake and anaerobic threshold decreased significantly; subsequent intravenous administration caused significant increases in maximal oxygen uptake and anaerobic threshold, back to the values measured during oral therapy. After oral milrinone withdrawal, maximal oxygen uptake decreased below baseline values, suggesting progression of the underlying disease. The anaerobic threshold expressed as a percent of maximal oxygen uptake was significantly increased during oral therapy (baseline 73 +/- 2 percent, oral therapy 84 +/- 2 percent) and remained significantly increased after drug withdrawal, suggesting a peripheral circulatory effect. These results indicate that in selected patients with severe congestive heart failure, milrinone exerts persistent effects on the metabolic responses to both maximal and submaximal exercise. Because of progressive deterioration in exercise capacity during long-term oral therapy, the effects of milrinone may not be apparent unless it is withdrawn. The relation of milrinone therapy to disease progression is not known.

Administration, Oral↗
PubMed1986

Autonomic nervous system activity in Macaca fascicularis.

This study was performed to determine the contributions of the sympathetic and parasympathetic nervous systems to cardiovascular control. Hexamethonium was administered to block the autonomic ganglia, propranolol to block beta adrenergic receptors of the sympathetic nervous system, and methylatropine to block the parasympathetic nervous system. The results of this study indicate high sympathetic tone and low parasympathetic tone in resting Macaca fascicularis. These findings are different from those in man but are similar to other nonhuman primates.

Animals↗
PubMed1985

Immediate effects of milrinone on metabolic and sympathetic responses to exercise in severe congestive heart failure.

A randomized, double-blind, placebo-controlled protocol was used to determine whether milrinone exerts an immediate effect on exercise performance in patients with severe congestive heart failure. In each of 14 patients with New York Heart Association class III or IV congestive heart failure, intravenous milrinone (mean 57 +/- 5 micrograms/kg) and placebo were randomly administered just before maximal progressive upright cycle ergometry. The duration of exercise was significantly longer with milrinone than with placebo treatment (placebo 11.0 +/- 0.6 minutes, milrinone 12.5 +/- 0.9 minutes, p = 0.01). Compared with placebo, milrinone caused a higher peak oxygen uptake (placebo 10.8 +/- 0.6 ml/kg/min, milrinone 12.4 +/- 0.7 ml/kg/min, p = 0.001) and oxygen uptake at the anaerobic threshold (placebo 7.8 +/- 0.4 ml/kg/min, milrinone 9.2 +/- 0.4 ml/kg/min, p = 0.001). At peak exercise intensity, systolic blood pressure (placebo 119 +/- 5 mm Hg, milrinone 131 +/- 5 mm Hg, p = 0.001) and heart rate (placebo 114 +/- 5 beats/min, milrinone 126 +/- 6 beats/min, p = 0.001) were both increased with milrinone. Likewise, at matched submaximal exercise intensities, heart rate (placebo 111 +/- 19 beats/min, milrinone 117 +/- 20 beats/min, p less than 0.05) and systolic blood pressure (placebo 116 +/- 19 mm Hg, milrinone 121 +/- 19 mm Hg, p = 0.04) were higher with milrinone; plasma norepinephrine (placebo 1,692 +/- 208 ng/liter, milrinone 1,320 +/- 216 ng/liter, p = 0.05) and blood lactate concentrations (placebo 2.2 +/- 0.2 mM, milrinone 1.9 +/- 0.2 mM, p less than 0.05) were lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1985

The role of exercise in the primary and secondary prevention of atherosclerotic coronary artery disease.

Although exact definitions of exercise requirements for primary and secondary prevention of coronary disease cannot be stated with certainty on the basis of currently available information, we can make some general conclusions. The characteristics associated with lowered risk from coronary disease in apparently normal populations are: 8 MET-hours of activity during leisure time or job: walking briskly during leisure time (1 hour = 1 MET-hour) walking at job (same as above) jogging during leisure time (30 minutes of activity = 1 MET-hour) walking to and from work (same as walking above) performing very heavy work in occupational pursuits (few jobs today have those energy requirements) regularly climbing 5 flights or more of stairs (10 steps per flight) regularly walking 5 city blocks per day (12 blocks per mile) regularly engaging in strenuous sports (basketball, running, mountaineering, skiing, swimming, or tennis) accumulating activities that use 2000 or more kcal per week Conclusions concerning the prevention of reinfarction in patients who are recovering from a first heart attack include: Exercise is helpful in hastening the recovery process after myocardial infarction and should be started early in the recovery period. Exercise helps to reduce mortality when used in conjunction with a multifactorial program.

Clinical Trials as Topic↗
PubMed1984

Effect of beta blockade on plasma catecholamine levels during psychological and exercise stress.

The effect of a single oral dose of 50 mg of metoprolol on plasma catecholamine levels was examined in 11 healthy young men. Subjects were studied during baseline at rest, postural challenge, psychological stressors and graded maximal exercise testing. Metoprolol induced significant increases in plasma norepinephrine (NE) levels across most experimental conditions. Metoprolol did not have a consistent effect on plasma epinephrine levels. Because of wide interindividual variation in drug levels, the NE levels in subjects with high drug levels were compared with the NE levels in subjects who had negligible drug levels. NE levels were higher in subjects with higher drug levels.

Adult↗
PubMed1984

Postexercise peril. Plasma catecholamines and exercise.

Postexercise cardiac morbidity is noted both in the exercise testing laboratory and in the field, but the physiology of this phenomenon has been unclear. Plasma catecholamine levels were studied in ten healthy men at each work load during exercise testing and during the recovery period after exercise. Both norepinephrine and epinephrine levels increased in response to exercise, although the response was much more noteworthy for norepinephrine. In the recovery period after exercise, both catecholamine levels continued to increase, with the norepinephrine level increasing tenfold over baseline. Such increases may have profound effects, particularly for subjects with preexisting coronary disease.

Adult↗
PubMed1984

The effectiveness of a low lipid diet and exercise in the management of coronary artery disease.

To evaluate the effects of a high complex carbohydrate, low lipid diet on the management of coronary artery disease, we reviewed data on 32 patients, who had participated in a diet and exercise program, and compared the results with 40 patients who had been managed only with exercise. After a follow-up period of 10 to 16 weeks the patients on the diet-exercise program showed significant reduction in body weight (-6 +/- 2 kg mean +/- standard deviation), serum cholesterol (-43 +/- 41 mg/dl), and triglycerides (-51 +/- 70 mg/dl), while patients who were managed only with exercise had no significant changes in weight or serum lipids. Both the diet-exercise and the exercise groups showed significant improvement in working capacity and reduction in resting systolic blood pressure. Patients on the diet-exercise program had significantly less angina (21.9%) occurring on the exercise test after the program compared to before, even though the same double product was reached. Multiple logistic regression analysis of the data for patients with angina on the exercise test demonstrated that the only significant (p = 0.004) contributor for reduction in angina was the dietary intervention. Beta-blocking drugs did not affect the results. Although randomized controlled trials must be run in order to ascertain the significance of this finding, this study strongly suggests that a low lipid, high carbohydrate diet is a useful addition to exercise in the management of patients with coronary disease.

Adult↗