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Biomedical subjects

P Hanson

Publications and source records attributed to P Hanson.

At least 73 records · Page 4Linked to original sources

Cyclosporine-induced sympathetic activation and hypertension after heart transplantation.

BACKGROUND: Hypertension is a frequent complication of cyclosporine-induced immunosuppression, but the underlying mechanism is unknown. In anesthetized animals, the administration of cyclosporine increases sympathetic-nerve discharge, which may contribute to hypertension. METHODS: To determine whether cyclosporine-induced hypertension is accompanied by sustained sympathetic neural activation in patients, we recorded sympathetic action potentials using intraneural microelectrodes (in the peroneal nerve) in heart-transplant recipients receiving azathioprine and prednisone alone (n = 5) or in combination with cyclosporine (n = 14). We performed the same studies in eight patients with myasthenia gravis who were receiving cyclosporine and eight who were not, in five patients with essential hypertension, and in nine normal controls. RESULTS: Heart-transplant recipients receiving cyclosporine had higher mean arterial blood pressure (+/- SE) than those not receiving cyclosporine (112 +/- 3 vs. 96 +/- 4 mm Hg; P less than 0.05) and a 2.7-fold higher rate of sympathetic-nerve firing (80 +/- 3 vs. 30 +/- 4 bursts per minute; P less than 0.05). For patients with myasthenia gravis, similar doses of cyclosporine were associated with smaller elevations in mean arterial blood pressure (100 +/- 2 mm Hg, as compared with 91 +/- 4 mm Hg in those not receiving cyclosporine; P less than 0.05) and in the rate of sympathetic-nerve firing (46 +/- 3 bursts per minute, as compared with 25 +/- 4 bursts per minute; P less than 0.05). Sympathetic activity in patients with heart transplants or myasthenia gravis who were not being treated with cyclosporine was no different from that in patients with essential hypertension or in normal controls. CONCLUSIONS: Cyclosporine-induced hypertension is associated with sympathetic neural activation, which may be accentuated by the cardiac denervation that results from heart transplantation.

Action Potentials↗

Attenuation of exercise-induced ST depression during combined isometric and dynamic exercise in coronary artery disease.

ST-segment depression was measured during submaximal dynamic (treadmill) and combined isometric-dynamic (isodynamic) exercise at comparable rate-pressure products in 11 patients (mean age 63 years) with stable coronary artery disease who were participating in an exercise training program. Each patient completed 3 separate trials. Trial 1 (baseline) was a submaximal treadmill exercise test to determine the threshold heart rate-systolic blood pressure (rate-pressure product) for ST-segment depression (greater than or equal to 1.0 mm). During trials 2 and 3, patients performed (in random order) dynamic treadmill exercise and isodynamic exercise (treadmill walking 1.5 to 2.0 mph carrying 15 to 25 kg) until threshold rate-pressure product was achieved. During trial 1, each patient showed significant ST depression (mean 1.7 mm) at target rate-pressure product (mean 18,200). Subsequent dynamic exercise trials 2 and 3 showed similar mean ST depression (1.5 mm) and rate-pressure product (18,000). During isodynamic exercise trials 2 and 3, subjects showed only minimal ST depression (mean 0.4 mm) at a rate-pressure product similar to dynamic exercise (mean 18,590). Heart rates were significantly lower (-10/min) and systolic (+20 mm Hg) and diastolic (+25 mm Hg) pressure was higher during isodynamic exercise (p less than 0.05). The rate-pressure product is not a valid index of ST response during isodynamic exercise in stable exercise-trained cardiac patients. Attenuation of ST depression during isodynamic exercise may be attributed to a combination of increased diastolic perfusion pressure, decreased heart rate and possibly to reductions in venous return and ventricular diastolic wall tension due to increased intrathoracic and abdominal pressure.

Aged↗

Dehydroepiandrosterone and a beta-agonist, energy transducers, alter antioxidant enzyme systems: influence of chronic training and acute exercise in rats.

We examined the influence of dehydroepiandrosterone (DHEA), a beta-agonist, and exercise training on enzymes that detoxify toxic oxygen species. Feeding 0.4% DHEA decreased hepatic cytosolic (c) selenium-dependent glutathione peroxidase (GPX), (-26%, P less than 0.0001) and increased hepatic mitochondrial (m) Mn superoxide dismutase (SOD), (+38%, P less than 0.001). DHEA decreased myocardial c-GPX (-21%, P less than 0.05) when compared to a beta-agonist (beta A; L644969 Merck and Co.) fed at 5 ppm but neither differed from the Control (C). In contrast, the beta A increased hepatic m-GPX (+25%, P less than 0.05). In skeletal muscle, DHEA and beta A decreased muscle c-GPX by 20 and 12%, respectively (P less than 0.0009). DHEA increased both muscle (+20%, P less than 0.01) and myocardial (+20%, P less than 0.05) c-glutathione S-transferase (GST) over beta A (+20%, P less than 0.01) but neither was significantly different from C. Similar to DHEA, chronic training (Tr) (1 h/day, 5 days/week at 27 m/min, 15% grade on treadmill) decreased hepatic c-GPX (-16%, P less than 0.003). Tr elevates muscle c-GPX (+36%, P less than 0.05) in C. Tr increased myocardial c-GPX by 28% in the beta A-treated rats, whereas Tr decreased myocardial c-GPX by 22% in the C (P less than 0.05, interaction). One hour of acute exercise (Ex) (70% VO2 max relative work load) decreased hepatic homogenate catalase (-12%, P less than 0.02) and increased hepatic m-Mn SOD (+28%, P less than 0.03). Ex decreased myocardial c-GST (P less than 0.05) only in the DHEA-treated rats. DHEA and Tr may improve efficiency of oxygen utilization at the tissue level with lower antioxidant enzyme activity in liver and locally protective up-regulation in muscle. beta A stresses oxygen utilization systems and liver responds by up-regulation of antioxidant enzymes. The increase in myocardial c-GPX activity in the beta A-treated group may be a protective effect against indirect catecholamine-induced myocardial necrosis which results from free radical generation.

Adrenergic beta-Agonists↗

Impairment of left ventricular function during maximal isometric dead lifting.

High-intensity short-duration lifting is frequently performed by athletes and laborers. Little is known about the magnitude and pattern of blood pressure response and resultant effects on left ventricular (LV) function during this form of intense isometric exercise. We monitored brachial intra-arterial pressure and LV ejection fraction (LVEF) during upright isometric dead lifting performed on a force platform. Fourteen healthy male subjects (age 27 yr) maintained maximal sustained isometric dead lift (140 +/- 34 kg) for 32 s. LVEF was measured by 99mTc first-pass radionuclide ventriculography. Mean arterial pressure increased from 107 +/- 15 mmHg at rest to a peak of 174 +/- 28 mmHg and fell precipitously to 88 +/- 13 mmHg within 10 s after release of the dead lift. LVEF decreased from 63 +/- 8 to 51 +/- 14% (P less than 0.02) in seven subjects with technically acceptable ventriculograms. We conclude that maximal upright isometric dead-lift exercise produces a marked increase in arterial pressure and corresponding LV afterload that is associated with a transient reduction in LVEF in normal men.

Adult↗

Ventricular ectopy in cardiac rehabilitation patients on exercise training and nonexercising days.

We evaluated the effect of routine exercise training sessions on the frequency of ventricular ectopic activity (VEA) in 18 coronary artery disease patients (mean age = 60 years) who were active participants in a cardiac rehabilitation program. Nine patients were classified as high risk and nine patients were low risk according to clinical status and cardiac catheterization criteria. Five patients in each group were on beta blockade, but none were on antiarrhythmic agents. Serial 24-h ECG monitoring was obtained on a routine supervised exercise day and nonexercise control day. VEA were compared during three time periods: (1) exercise training and recovery (4 h) and the corresponding 4 h during control, (2) activities of daily living (12 h), and (3) sleep (8 h). Both groups showed a moderate increase in total VEA during the three activity periods from control day to exercise day. However, this increase was only significant (p less than 0.05) in the high-risk group during the 12-h activity of daily living period postexercise. VEA was significantly greater (p less than 0.05) in the high-risk group during all activity intervals except the sleep period on the exercise day. We conclude that VEA occurs with similar frequency during exercise training or corresponding control periods. High-risk patients have significantly greater VEA on exercise and control days and show additional increased in VEA during activities of daily living (eating and driving) on exercise days.

Activities of Daily Living↗

Impact of lemongrass oil, an essential oil, on serum cholesterol.

To test the hypothesis that non-sterol mevalonate pathway end products lower serum cholesterol levels, we asked 22 hypercholesterolemic subjects (315 +/- 9 mg cholesterol/dl) to take a daily capsule containing 140 mg of lemongrass oil, an essential oil rich in geraniol and citral. The paired difference in serum cholesterol levels of subjects completing the 90-day study approached significance (P less than 0.06, 2-tailed t-test). The subjects segregated into two groups, one consisting of 14 subjects resistant to the protocol and the other consisting of 8 subjects who responded. Paired differences in cholesterol level at 30, 60 and 90 d for resistant subjects were +2 +/- 6, +2 +/- 7 and -1 +/- 6 mg/dl; paired differences for the responding subjects were -25 +/- 10 (p less than 0.05), -33 +/- 8 (p less than 0.01) and -38 +/- 10 (p less than 0.025), respectively. The paired difference (+8 +/- 4) in the cholesterol levels of six responders 90 days after the discontinuation of lemongrass oil was not significant.

Cholesterol↗

Normal and malignant human urothelium: in vitro response to blockade of polyamine synthesis and interconversion.

To assess the effect of polyamine blockade on urinary epithelium, growth of normal human urothelial cell cultures and human transitional cell carcinoma (TCC) cell lines in the presence of various inhibitors of polyamine synthesis was evaluated. All four human TCC cell lines tested were quite sensitive to the specific inhibitor of ornithine decarboxylase, alpha-difluoromethylornithine (DFMO), requiring less than or equal to 1.0 mM DFMO to double generation time. Alternatively, all three human urothelial cultures tested required 5-20-fold higher DFMO concentrations to achieve similar growth inhibition. The inhibitory effect of DFMO on TCC was found to act synergistically with that of the inhibitor of S-adenosylmethionine decarboxylase, methylglyoxal bis(guanylhydrazone), and additively with that of recombinant beta-serine interferon. Addition of individual polyamines entirely prevented the inhibitory effects of DFMO and/or methylglyoxal bis(guanylhydrazone) but not that of beta-serine interferon. It appears that inhibition of polyamine synthesis and/or interconversion holds promise in the management of TCC and that the in vitro model described will be of value in investigating such clinical applications.

Carcinoma, Transitional Cell↗

Arm exercise testing for coronary artery disease in patients with peripheral vascular disease.

We evaluated 74 peripheral vascular disease (PVD) patients (54 men, age 61 +/- 7 years and 17 women, age 63 +/- 7 years) for potential coronary heart disease (CAD) using an arm exercise test (AET) protocol. All patients performed upright two-arm cranking using discontinuous stages of 2 minutes of exercise separated by 2 minutes of rest. Exercise intensity was increased by +100 or 200 kpm (kilopond meters) with each stage. ECG was monitored continuously and blood pressure and 12-lead ECG tracings were obtained at the end of each exercise stage. All patients reached an endpoint of subjective exhaustion. Men achieved 91 +/- 14% of age-predicted heart rate at 597 +/- 167 kpm, while women achieved 86 +/- 14% of age-predicted heart rate at 335 +/- 117 kpm. Ischemic ECG responses (+AET) defined as new or additional ST depression greater than 1.0 mm X 80 ms, occurred in 35 men (65%) and 7 women (42%). Coronary angiography was performed in a subset of 22 patients (15 males and 7 females). CAD (greater than 70% stenosis) was found in 11 of 12 men and 4 of 5 women who showed positive or strongly positive AET responses (overall predictive value for AET = 88%). We conclude that arm exercise stress testing is safely performed in PVD patients who cannot complete treadmill exercise. In this limited series of PVD patients, the predictive value of a +AET response for diagnosis of CAD is similar to established values for treadmill exercise.

Adrenergic beta-Antagonists↗

Time to fatigue during isometric exercise using different muscle masses.

The purpose of this study was to test the hypothesis that differences in the pressor response to static exercise using varying muscle masses are due to differences in endurance time. i.e., time to fatigue. Ten healthy, male subjects (mean age 24 +/- 3 years) participated in the study. With no knowledge of the purpose of the study, the subjects were instructed to maintain static contractions for as long as possible during 30% maximal voluntary contraction (MVC) in handgrip (HG), two-leg extension (LE), and dead lifting (DL). Inability to sustain a contraction within 10% of the designated force (30% MVC) marked the endurance time end point. During sustained contractions, heart rate, blood pressure, and time to fatigue were measured. Times to fatigue were 3.39 +/- 0.92, 3.61 +/- 1.67, and 3.68 +/- 1.34 min for HG, LE, and DL, respectively. These differences were not significant (p greater than 0.05). Heart rate and blood pressure increased progressively with sustained contractions, DL greater than LE greater than HG. LE and DL responses were consistently and significantly (P less than 0.05) higher than HG responses reflecting the magnitude of absolute force of contractions. The magnitude of the pressor response to the three sustained static contraction maneuvers was not related to the time to fatigue. The data affirm the view that the pressor response is a function of muscle mass activated and the absolute force developed during static exercise.

Adult↗

Left ventricular and hemodynamic responses during upright isometric exercise in normal young and elderly men.

Cardiovascular responses were studied echocardiographically in 10 young (23 +/- 3 years) and 10 elderly (67 +/- 4 years) men, during upright isometric handgrip and deadlift. During handgrip and deadlift both groups showed significant increases in systolic and diastolic blood pressure. Those responses were significantly greater in both groups during deadlift. Heart rate was significantly higher in both groups during deadlift than resting and handgrip values. Oxygen uptake increased progressively and significantly across conditions, and was significantly higher for the younger subjects. Ejection fraction remained unchanged during handgrip in both groups. During deadlift it remained unchanged in the elderly while it increased significantly in the younger. Both groups increased significantly heart volumes from rest to handgrip. During deadlift end systolic volume was significantly lower from resting and handgrip values only in the young group. These data indicate a similar cardiovascular response to acute pressure overload in both groups.

Adult↗