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Biomedical subjects

M F Wilson

Publications and source records attributed to M F Wilson.

At least 73 records · Page 4Linked to original sources
PubMed1989

Changes in myocardial contractile protein ATPases in chronically adrenalectomized rats with and without glucocorticoid replacement.

Studies were conducted to examine the effects of chronic adrenalectomy (Adx) and adrenalectomy plus glucocorticoid replacement therapy on rat cardiac contractile protein ATPase activities. The Ca2+-dependent Mg-ATPase activity of myofibrils isolated from rat ventricles 3 weeks postadrenalectomy (Adx) was significantly decreased at all pCa2+ concentrations (P less than 0.01), compared to sham-operated (SO) rats. Similarly, Ca2+-, K+-EDTA, and actin-activated myosin ATPase activities of Adx rat hearts were markedly decreased below that of SO rats (P less than 0.01). Dexamethasone administration to Adx rats prevented the decrease of Ca2+- and K+-ATPase activities of myosin, but not of myofibrillar Ca2+-dependent Mg-ATPase or actin-activated myosin Mg-ATPase activities. These studies suggest that glucocorticoid insufficiency induced by adrenalectomy results in altered myocardial contractile protein ATPase activity which may underlie impaired cardiac performance.

Adenosine Triphosphatases↗
PubMed1989

Caffeine may potentiate adrenocortical stress responses in hypertension-prone men.

The effect of caffeine on blood cortisol levels and blood pressures was examined during rest and in response to a challenging psychomotor task in men with a low versus high risk of essential hypertension. Thirty-four healthy men ages 21-35 years were selected such that 17 were at high risk for hypertension (positive parental history and screening blood pressures of 135/85-155/95 mm Hg) and 17 were at low risk (negative parental history and no pressures above 132/84 mm Hg). Testing consisted of quiet rest (20 minutes); oral placebo (grapefruit juice) or caffeine administration (3.3 mg/kg in grapefruit juice); rest during a postdrug absorption period (40 minutes); work on an unsignalled simple reaction time task (15 minutes); and quiet rest (20 minutes). Blood pressures were recorded at 2-minute intervals, and blood samples were withdrawn via an indwelling catheter at the end of the baseline, drug absorption, task, and recovery periods. The combination of task plus caffeine produced the highest blood pressures in men at risk for hypertension. Cortisol levels were found to be sustained during rest in members of the high risk group after they had consumed caffeine, whereas members of the low risk group showed a modest decline. The high risk subjects also showed a significant rise in cortisol during (+3.7 micrograms/dl) and after (+4.0 micrograms/dl) work on the reaction time task after caffeine consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1989

Spin trapping of free radicals produced in vivo in heart and liver during endotoxemia.

Studies using free radical scavengers and measurements of lipid peroxidation have suggested that free radicals are generated during endotoxemia. Conclusions from these studies have implied that free radicals may participate in the sequence of pathologic events following endotoxin challenge in the experimental animal. Current inferences of free radical generation and involvement have been derived from indirect evidence and are therefore inconclusive. To quantitate the generation of free radicals in vivo during endotoxemia this study employed the use of electron paramagnetic resonance spectroscopy (EPR) combined with spin trapping techniques. Five minutes before intraperitoneal endotoxin administration, trimethoxy-a-phenyl-t-butyl-nitrone [(MeO)3 PBN] was administered intraperitoneally. Experimental animals were always matched with control animals receiving no endotoxin. At either five minutes or twenty-five minutes following endotoxin administration animals were decapitated and hearts and livers were rapidly taken for lipid extraction and EPR evaluation. Analysis of the EPR spectra revealed hyperfine splitting constants that indicated the presence of carbon-centered radical spin adducts in both organ tissues from animals exposed to endotoxin for twenty-five minutes. No signals were present in hearts and livers taken five minutes after endotoxin administration. EPR evaluation did not indicate spin adduct formation in control tissue. These data directly demonstrate that activation of processes in vivo involving free radical generation occur early during endotoxemia, but are not detectable immediately after the endotoxin challenge.

Animals↗
PubMed1989

Cardiovascular changes in chronically adrenalectomized conscious rats.

Mean arterial blood pressure (MABP), heart rate (HR), stroke volume index (SVI), cardiac index (CI), systemic vascular resistance index (SVRI), and central venous pressure (CVP) were measured in conscious, freely moving, sham-operated (SO) and chronically adrenalectomized (ADX) rats. After 3 weeks of ADX, the rats exhibited hypotension, tachycardia, and diminished SVI and CI. From 3 to 6 weeks after surgery, the HR decreased and SVRI increased. These changes were obscured when the same measurements were obtained in the same rats under enflurane anesthesia. Cardiovascular responses to an epinephrine (0.4 microgram/kg/min) infusion were measured in conscious SO and ADX rats. The magnitude of change from baseline to peak was similar in all groups, indicating that ADX did not alter the responsiveness of the cardiovascular system to epinephrine. The peak MABP response to epinephrine in ADX rats was significantly below that of SO control rats, suggesting that ADX impaired the ability of the cardiovascular system to maintain normal arterial blood pressure. No differences were found in plasma concentrations of Na+, K+, Cl-, PO4 =, or hematocrit that would help to explain the effect of long-term adrenalectomy. The data underscore the cardio-depressant effect of enflurane anesthesia, demonstrate the importance of a conscious rat model in studying the effects of ADX on the cardiovascular system, and emphasize that the full effects of ADX occur over a period of several weeks.

Adrenal Insufficiency↗
PubMed1989

Effect on airway resistance of ketamine by aerosol in guinea pigs.

The effect of aerosolized ketamine hydrochloride was investigated by measuring airway resistance with a two-compartment plethysmograph in guinea pigs challenged with histamine. In the first phase of the study, treatment with ketamine prior to histamine challenge did not protect against elevation of airway resistance. In the second phase of the study, ketamine inhalation after histamine challenge did not significantly diminish airway resistance. Aerosolized ketamine is not recommended for use in human subjects with asthma.

Aerosols↗
PubMed1988

Evaluation of left ventricular contractility indexes for the detection of symptomatic and silent myocardial ischemia.

This study evaluated the role of left ventricular (LV) ejection fraction and systolic blood pressure (BP) to end-systolic volume ratio to detect symptomatic and silent myocardial ischemia. The sensitivity and diagnostic accuracy of these contractility indexes were compared with angina and ST depression during exercise. Thirty consecutive patients referred for chest pain performed symptom-limited bicycle exercise and had coronary angiography within 3 months. Twenty-two had angiographically significant coronary artery disease and 8 had normal coronary anatomy. Systolic BP was measured by sphygmomanometry; LV ejection fraction and end-systolic volume were obtained by nuclear ventriculography. Normal values for contractility indexes were defined as LV ejection fraction greater than 52% at rest and increment of greater than or equal to 5% during exercise, and systolic BP to end-systolic volume ratio greater than 2.2 mm Hg/ml at rest and greater than 3.0 mm Hg/ml during exercise. The sensitivity of systolic BP to end-systolic volume ratio to identify patients with coronary artery disease at rest was 71 vs 33% for LV ejection fraction. During exercise, each contractility index had a sensitivity of 95% and there was a combined sensitivity of 100%. This compares with 71% for ST depression and 48% for exercise-induced angina. Thus, 52% had no angina and 36% of them were also silent by electrocardiography. Among the patients with symptomatic ischemia, 20% had no ST-segment depression. Measurement of contractility indexes enhanced the detection of silent myocardial ischemia and provided information on LV function vital to prognosis and management of patients with coronary artery disease.

Adult↗
PubMed1988

Effect of behavior state on caffeine's ability to alter blood pressure.

Caffeine use during exposure to mental stress is an extremely common occurrence. Because both have been shown to alter blood pressure (BP) and its underlying hemodynamic mechanisms, the potential exists for additive or even synergistic effects. Changes in heart rate, BP and noninvasive thoracic impedance measures of left ventricular function were examined in young men (ages 20 to 36) at rest and during a demanding behavioral task performed 40 minutes after predosing with caffeine (3.3 mg/kg, equivalent to 2 to 3 cups of coffee) or placebo in a double-blind crossover design. All subjects were healthy young men without history of cardiovascular disease, regular use of nicotine, recreational or prescription drugs or caffeine intolerance. Caffeine abstinence was required for 12 hours before each test session. Systolic and diastolic BP were elevated by both caffeine and the behavioral task alone (p less than 0.01 for each); when combined, caffeine's pressor effects were additive to those of the behavioral task. However, caffeine's pressor effect was produced by different mechanisms depending on the behavioral state. Caffeine increased systemic vascular resistance (p less than 0.01) under resting conditions, but it enhanced cardiac output (p less than 0.01) during behavioral arousal associated with the task. The combined influence of caffeine and the task increased the number of men in whom peak systolic BP reached hypertensive levels, and also synergistically increased cardiac minute work (p less than 0.01) and the rate-pressure product estimate of myocardial oxygen demand (p less than 0.05). Implications of these findings are discussed for long standing theoretical disputes regarding caffeine, its health consequences, and for methodologic issues in behavioral and clinical studies.

Adult↗
PubMed1988

Effects of 1-epinephrine on hemodynamics and cardiac function in coronary disease: dose-response studies.

To assess the effects of elevated epinephrine levels on cardiovascular performance in patients with coronary artery disease (CAD), epinephrine was infused intravenously into eight patients with normal coronary anatomy and 22 patients with CAD at dose rates of 0.06, 0.12, 0.18, and 0.24 micrograms/kg/min. Hemodynamic responses to epinephrine were not significantly different between the two groups. However, contractility increased significantly more (P less than 0.05) and end-systolic volume decreased significantly more (P less than 0.025) in normal subjects than in those with CAD. Plasma norepinephrine concentrations increased significantly (P less than 0.05) at 0.24 micrograms/kg/min epinephrine, indicating activation of sympathetic nervous system. Epinephrine ischemic thresholds ranged from 652 to 3362 pg/ml. Patients with CAD compared with normal subjects had more frequent ventricular arrhythmias (55% vs. 25%), chest pain (50% vs. 13%), and ischemic ECG changes (73% vs. 13%). These results indicate that although epinephrine induced myocardial ischemia in CAD, hemodynamics and ventricular pump function were maintained.

Adult↗
PubMed1988

Improved techniques for cardiovascular monitoring in rats as applied during endotoxemia.

We describe a new combination of techniques for measurements of systemic blood pressure, central venous pressure, pulmonary arterial (PA) pressure, PA wedge pressure, and cardiac output in the rat. Application of the method to the conscious rat in a septic shock (Escherichia coli endotoxin iv injection) model demonstrated a response pattern of decreased cardiac output and stroke volume, increased total peripheral vascular resistance and heart rate, and transiently decreased systemic arterial pressure. In the pulmonary circulation, a very brief hypertension and a sustained increase in pulmonary vascular resistance were observed, but changes in PA wedge pressure were small. The soft PA catheter (0.3 mm ID, 0.6 mm OD) had no undue effects on cardiovascular function. We suggest that this combined technique could be useful for many cardiovascular studies in the rat, not only as related to shock research.

Animals↗
PubMed1987

Digitizing and signal averaging of left ventricular pressure signals using a dedicated radionuclide imaging system.

A method for obtaining left ventricular (LV) volume curves, synchronized with average LV pressure (LVP) curves for calculation of LV contractility, is described. Multiple gated blood pool imaging was performed to calculate average LV volume curves. Simultaneously with this acquisition, LVPs and aortic pressures were measured by indwelling catheters and recorded on an FM tape recorder. These signals were fed to the computer as image information and averaged and processed by the software developed for this purpose. Pressure resolution of the calibrated images was 4 mmHg/pixel when provision was made for a maximum pressure of 200 mmHg. A good correlation (r = 0.99) was obtained between the calculated peak LVPs and mean peak LVPs read from the chart recorder. The regression equation was: digitized peak LVP = 1.04 x chart recording--5.11 mmHg and the standard error of the estimate was 2.9 mmHg. Similar results were obtained with the aortic pressure (AP) measurements (digitized AP = 0.94 x chart recording + 6.37 mmHg, the standard error of the estimate was 3.8 mmHg). The digitized data also allowed the construction of pressure-volume loops for interpretation of ventricular contractility.

Animals↗
PubMed1987

Caffeine enhances the physiological response to occupational stress in medical students.

Caffeine (3.3 mg/kg) was tested against a placebo in 20 male medical students during periods of low (no exams) versus high (final exams) work stress. On each of 8 test days, heart rate and blood pressure were measured at baseline and over a 40-min postdrug interval; immediately afterward, blood was drawn to test plasma cortisol and serum lipid concentrations. Exams increased heart rate (p less than .005) and systolic blood pressure (p less than .02). Caffeine decreased heart rate (p less than .0001) and increased systolic blood pressure (p less than .005), diastolic blood pressure (p less than .0001), plasma cortisol levels (p less than .01), and serum cholesterol levels (p less than .02). Caffeine effects were additive with those of exams, and together they increased the number of men showing systolic blood pressures in the borderline hypertensive range. Thus, caffeine use during periods of increased occupational stress may enhance the cumulative stress response.

Adult↗
PubMed1987

Dose-related effects of isoflurane on superior mesenteric vasoconstriction induced by endotoxemia in the rat.

To investigate the interplay between endotoxin-induced circulatory shock and the cardiovascular effects of different doses of isoflurane, mean aortic pressure (MAP), central venous pressure (CVP), mean pulmonary arterial pressure (MPAP), heart rate (HR), cardiac output and superior mesenteric artery flow (SMAF), were monitored in rats anesthetized with either 1.4% or 2.0% isoflurane in oxygen. Cardiac index (Cl), total peripheral vascular resistance (TPR) and superior mesenteric vascular resistance (SMVR) were derived. During continuous administration of isoflurane, endotoxin (LD90, 40 mg X kg-1 iv) was given after a 30-min baseline period, and data were collected for an additional 2-h period. Sham-challenged (saline) animals served as controls. The response to endotoxin in the systemic circulation showed a decrease in Cl and MAP, while HR and TPR increased. MPAP and CVP were essentially unchanged. There were no significant differences in the systemic circulation variables between endotoxin groups, apart from a more pronounced HR increase during 1.4% isoflurane. Regionally, however, SMAF was lower and SMVR was higher in the 2.0% versus the 1.4% isoflurane group following endotoxin. To conclude, the degree of mesenteric vasoconstriction during endotoxemia was dependent on the dose of isoflurane. This dose-related effect seems to be mediated through interaction with intrinsic vascular control, a higher dose allowing a more pronounced local blood flow reduction.

Animals↗
PubMed1987

Choice of anesthetic alters the circulatory shock pattern as gauged by conscious rat endotoxemia.

A standardized rat endotoxin shock model was used to assess the differential effects of four commonly used anesthetics upon hemodynamics before and during endotoxin shock. Forty-nine male Sprague-Dawley rats weighing 307 +/- 4 g were divided into five groups:freely-moving conscious, enflurane (2%), isoflurane (1.4%), pentobarbital (6 mg.kg-1.h-1 i.v.), and ketamine (45 mg.kg-1.h-1 i.v.). Anesthetic doses were chosen as 1.0 MAC equivalent. Anesthetized rats were intubated and ventilated with oxygen. The right carotid artery was cannulated with a thermocouple-catheter for aortic blood pressure, heart rate, and thermodilution cardiac output measurements. The right jugular vein was cannulated for measurement of central venous pressure and for i.v. injections. Data were collected over a 30-min baseline period and for 4 h after an i.v. bolus of endotoxin (40 mg.kg-1, LD100 within 24 h). Gross small intestinal pathology was rated on a 0-4 scale. Anesthetic effects were judged in terms of significant deviations from the awake data on each parameter. Despite differing patterns, total deviations were similar for enflurane, ketamine, and pentobarbital, although the latter drug was the least preferable due to particularly high systemic vascular resistance. Significantly less hemorrhagic small intestinal pathology occurred with enflurane. Ketamine offered no advantage over the inhalation anesthetics. Among the four anesthetics tested, results were closest to the awake pattern with isoflurane anesthesia, thus making it the logical choice for hemodynamic studies in experimental shock research.

Anesthetics↗
PubMed1986

Comparison of guanfacine versus clonidine for efficacy, safety and occurrence of withdrawal syndrome in step-2 treatment of mild to moderate essential hypertension.

Guanfacine, an alpha 2-adrenoceptor agonist, was compared with clonidine as step-2 therapy of mild to moderate essential hypertension in a 24-week, double-blind, randomized, parallel evaluation to determine efficacy, safety and occurrence of withdrawal syndrome. During a 5-week period, patients were weaned from current antihypertensives, if any, and stabilized on step-1 therapy with 25 mg of chlorthalidone once a day. Those with a diastolic blood pressure (BP) from 95 to 114 mm Hg while taking chlorthalidone were randomized to treatment. The 2 agents had equal efficacy; 149 of 270 patients treated with guanfacine (55%) and 164 of 276 treated with clonidine (59%) achieved goal diastolic BP of less than or equal to 90 mm Hg. Terminations because of adverse effects were relatively low. Dry mouth (30% of guanfacine and 37% of clonidine groups) and somnolence (21% of guanfacine and 35% of clonidine groups, p less than 0.05) were reported most frequently. Nonsyncopal dizziness was reported in 11% of guanfacine-treated and 8% of clonidine-treated patients. This difference was not statistically significant. To evaluate the occurrence of a withdrawal syndrome in 316 outpatients and 156 inpatients, vital signs were monitored at least twice a day for up to 7 days after the end of therapy. Segmented 24-hour urine studies were performed on inpatients. Abrupt withdrawal of clonidine produced a rapid increase in diastolic and, especially, systolic BP, whereas guanfacine withdrawal produced more gradual increases. The differences were significant over the first 3 withdrawal days. It is concluded that guanfacine is a safe, effective, second-generation alpha 2-adrenoceptor agonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗