PubMed Health⌕ Search

Biomedical subjects

L H Hartley

Publications and source records attributed to L H Hartley.

At least 19 recordsLinked to original sources
PubMed1991

Prognostic significance of the Karnofsky Performance Status score in patients with acute myocardial infarction: comparison with the left ventricular ejection fraction and the exercise treadmill test performance. The MILIS Study Group.

The prognostic significance of functional status has not been previously studied in the setting of acute myocardial infarction. We assessed the Karnofsky Performance Status (KPS) score, a simple functional status scale that is commonly used to categorize physical ability, in 849 patients with acute myocardial infarction who were enrolled in the Multicenter Investigation of the Limitation of Infarct Size (MILIS) study. We then compared the KPS score with other predictors of prognosis in these patients. In patients who presented with acute myocardial infarction, a lower KPS score (less than 8 on a scale of 1 to 10) 3 weeks before the index infarction was associated with a higher incidence of congestive heart failure, in-hospital cardiac arrest, and mortality during hospitalization, as compared with patients with KPS scores greater than or equal to 8 (each p less than 0.001). Cumulative 1-year and 4-year mortality rates were significantly higher in patients with KPS scores less than 8, as compared with patients with KPS scores greater than or equal to 8 (42.5% vs. 12.6% at 1 year and 61.6% vs 25.1% at 4 years, respectively; both p less than 0.001). The left ventricular ejection fraction on admission was significantly lower in patients with KPS scores less than 8, as compared with those with KPS scores greater than or equal to 8 (p less than 0.019). The cumulative mortality rate was equally well predicted by low KPS score and by left ventricular ejection fraction (both p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Disability Evaluation↗
PubMed1990

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 perhexiline's 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 perhexiline's 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.

Aged↗
PubMed1990

Acute increase in exercise capacity with milrinone: lack of correlation with resting hemodynamic responses.

1. The acute administration of milrinone, a positive inotropic vasodilator agent, improves resting hemodynamic function and maximal and submaximal metabolic responses to exercise in patients with severe congestive heart failure. 2. To determine whether the improvement in exercise capacity induced by milrinone administration can be predicted by its acute positive inotropic and/or vasodilator effects at rest, milrinone was administered intravenously (progressive doses of 12.5 to 75 microns/kg) to 15 patients with heart failure (functional classes III and IV, New York Heart Association) at rest, and during maximal upright exercise testing on a cycle ergometer. Serum drug levels were matched for the resting and exercise tests. Drug administration for exercise tests was placebo-controlled and double-blind. 3. At rest, milrinone administration caused substantial decreases in right atrial pressure (-53%), left ventricular end-diastolic pressure (-30%), and systemic vascular resistance (-35%); and increases in cardiac index (+59%), peak positive dP/dt (+20%) and stroke work index (+51%). Administration of milrinone during exercise resulted in a 15% increase in peak oxygen uptake and a 16% increase in anaerobic threshold. However, none of the changes in resting hemodynamic function correlated significantly in magnitude with the changes in peak oxygen uptake and anaerobic threshold. 4. Thus, the acute improvement in exercise capacity that occurs with milrinone is not predicted by the positive inotropic or vasodilator effects of the drug at rest.

Anaerobic Threshold↗
PubMed1990

Hospital supervised vs home exercise in cardiac rehabilitation: effects on aerobic fitness, anxiety, and depression.

This study focused on the effects of hospital supervision and type of prescribed home exercise in cardiac rehabilitation programs on aerobic fitness, anxiety, and depression. Men who had a myocardial infarction were randomly assigned to four exercise programs: The first program consisted of purely hospital-based exercise. The second and third programs combined hospital and home exercise, including either bicycling or walking at home. In the fourth program, patients were encouraged to exercise at home, but were given no specific guidance. Fifty-two patients finished the eight-week exercise program and 35 completed the psychologic questionnaires. At the end of the eight weeks, there were significant differences in the programs' effects on aerobic fitness. Purely hospital-supervised exercise and the combination of hospital-supervised bicycling with home walking increased aerobic fitness more than completely unsupervised exercise. Furthermore, there were differences in the programs' effects on manifest anxiety. The combination of home and hospital bicycling was less beneficial than home walking and hospital bicycling or even completely unsupervised exercise at home. The results indicate that the degree of hospital supervision and the type of prescribed home exercise are important design features which may affect the success of cardiac rehabilitation exercise programs. No effects of the different exercise programs on patients' depression could be found. In general, a close relationship between aerobic fitness and anxiety or depression could not be demonstrated. Implications of these findings for the design of cardiac rehabilitation exercise programs are discussed.

Adult↗
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

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↗
PubMed1979

An exercise testing program for large populations.

A demonstration cardiovascular evaluation and exercise testing program was assessed for feasibility, cost, and accuracy. More than 1,800 people were examined in three years. The conditions of as many as 55 people per day were examined at a cost of $60 to $70 each. Abnormalities uncovered were similar to those observed in other studies. The program was considered successful in rendering services conveniently at low cost and with accuracy.

Adult↗