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Biomedical subjects

M F Wilson

Publications and source records attributed to M F Wilson.

At least 55 records · Page 3Linked to original sources

Cardiac adaptation to increased systemic blood pressure in borderline hypertensive men.

The present study examined cardiac characteristics of borderline hypertensive men with a positive parental history of hypertension. Hemodynamics in relation to left ventricular function and structure were evaluated in 15 borderline hypertensive men with a parental history of hypertension and in 20 normotensive control subjects with a negative parental history. Groups were matched in age, height, weight and percent body fat. Left ventricular mass and dimensions were measured by M-mode echocardiography, and left ventricular function was assessed by radionuclide ventriculography. Both groups had similar left ventricular mass, dimensions and wall thicknesses. In relation to control subjects, borderline hypertensive men had a significantly higher heart rate and blood pressure (BP) (p < 0.001), but a similar cardiac index. Borderline hypertensive men had a higher peripheral resistance index (p < 0.02), longer time to peak filling rate, and reduced cardiac efficiency, whereas they had higher contractility, minute and stroke work indexes than did control subjects (all p < 0.05); they also had higher diastolic BP (p < 0.03) during exercise, and sustained higher BP during recovery than did controls. Although this group of borderline hypertensive men did not have an altered cardiac anatomy, they had an increased vascular resistance, an altered diastolic function and a reduced cardiac efficiency while undergoing a greater work load. These cardiodynamic profiles are consistent with functional vascular changes and a parallel compensation by the heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

Impedance cardiography used to assess patterns of cardiovascular response to behavioral stressors.

This paper presents two examples of how impedance cardiography may be used to interpret the hemodynamic influences on blood pressures measured during behavioral stress. In Study 1, blood pressure changes which were similar during two tasks were shown to have important differences in their cardiac output and vascular resistance components. During work on a reaction time task having aversive incentives compared with a neutral task, the blood pressure changes were seen to be associated with lowered vascular resistance and raised cardiac activity, a "fight-flight" pattern. In Study 2, blood pressure response differences between two subject groups working on an identical task were found to have blood pressure changes differing in their underlying cardiac and vascular components as measured by impedance. Such uses impedance cardiography have widespread potential application in psychophysiological research with humans.

Adult↗

Consistency of cardiovascular response pattern to caffeine across multiple studies using impedance and nuclear cardiography.

This paper illustrates the use of impedance cardiography in an applied research setting to examine some of the pharmacological effects of caffeine on cardiovascular function. A primary advantage of the technique was in providing a noninvasive approach for studying cardiac versus vascular mechanisms underlying blood pressure responses to acute caffeine challenge. Impedance cardiography allowed the quantification of stroke volumes and cardiac output, and the change in these variables over time in a within-subjects design. Systemic vascular resistances were then calculated when impedance data were combined with simultaneously measured blood pressures. Results from four studies are summarized in which caffeine significantly elevated systolic and diastolic blood pressures. Impedance-derived measures indicate that caffeine's pressor response can be attributed to increased systemic vascular resistance rather than to elevated cardiac output. Our findings were consistent across all four studies, and across all protocols within those studies. Furthermore, these response patterns were confirmed by obtaining similar results using nuclear ventriculography. Thus, with respect to the outcome of testing an applied question, impedance-derived findings were found to be reliable and valid when compared with another technique used more commonly in clinical settings.

Administration, Oral↗

Hemodynamic characteristics of young men at risk for hypertension at rest and during laboratory stressors.

Examined hemodynamic activity--at rest, during mental arithmetic, and during hand cold pressor--in young men varying in risk for hypertension. Classification into low-risk (n = 72), moderate-risk (n = 20), and high-risk (n = 13) groups was based on resting systolic blood pressure (SBP) and parental history of essential hypertension (PH). Dependent variables were SBP, diastolic BP (DBP), heart rate, and rate-pressure product (RPP). Progressively greater hemodynamic activity was seen across risk groups at rest and during the tasks. Risk groups differed significantly in SBP, DBP, and RPP at baseline (ps less than .003) and in size of response to mental arithmetic (ps less than .05) but not to cold pressor. These relationships were either absent or weaker when using either risk factor alone to form risk groups. These findings suggest that hemodynamic reactivity to mental stress is predicted better by a combination of resting SBP and PH than by either risk factor alone and that physiological reactivity may be an important accompaniment of increased risk for hypertension.

Adult↗

Cardiovascular responses to occupational stress in male medical students: a paradigm for ambulatory monitoring studies.

Hemodynamic responses to systematic variations in occupational stress were examined using ambulatory blood pressure monitors (ABPMs). The goals of this study were (a) to illustrate the effectiveness of employing naturally occurring, controlled variations in psychological stress levels in studies incorporating ABPMs and (b) to document the patterns of cardiovascular responses to acute examination stress in medical students. Heart rate, systolic blood pressure, diastolic blood pressure, rate-pressure product, and mood states were measured before, during, and after low-stress (lecture) and high-stress (examination) work in 44 healthy male medical students. The lecture day was characterized by stable patterns of cardiovascular activity across all three periods. Hemodynamic activity and reports of activation and distress were greater on the examination day than on the lecture day. Cardiovascular activity during the preexamination period was as high as that seen during the examination period itself, indicating an anticipatory stress effect. Pressor activity decreased after the examination, although some residual chronotropic activity was seen. Systematic changes in physiological responses to controlled variations in the level of this naturalistic stressor support the use of this paradigm for other ABPM studies. The elevations in preexamination responses seen here suggest the need to consider prestressor experiences in such studies.

Achievement↗

Antihypertensive efficacy of guanfacine and methyldopa in patients with mild to moderate essential hypertension.

Guanfacine, an alpha-2 adrenoceptor agonist, was compared with methyldopa as step-2 therapy for patients with mild-to-moderate essential hypertension in a 12-week, double-blind, randomized, parallel evaluation of efficacy and safety. The study consisted of a 2-week screening/weaning period (phase I), a 3-week treatment period with a diuretic (phase II), and a 12-week treatment period with a diuretic plus methyldopa or guanfacine (phase III). Patients were weaned from prior anti-hypertensive medication during the screening/weaning period and began receiving chlorthalidone 25 mg every morning. Patients received only 25 mg of chlorthalidone each morning during the phase II period. Those who had an average seated diastolic blood pressure (BP) of 95-114 mm Hg at the end of the phase II period were eligible to enter the phase III period and were randomly assigned to chlorthalidone plus guanfacine, 1 mg every night, or methyldopa, 250 mg tid. Seated and standing systolic and diastolic BP and pulses were measured biweekly for 12 weeks after randomization. Of the 112 patients who were randomly assigned to guanfacine or methyldopa, 87% completed the entire study. The mean seated systolic and diastolic BP were reduced 13/13 mm Hg by guanfacine administration and 15/13 mm Hg by methyldopa administration. No significant changes in seated pulse were seen in either group. Similar changes occurred in the standing position. Very few adverse effects were reported during the study, the most prevalent side effect was xerostomia (13% guanfacine, 9% methyldopa). No significant differences were observed between treatment groups for the incidence of cardiac arrhythmias after methyldopa or guanfacine administration was stopped.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of caffeine on pressor regulation during rest and exercise in men at risk for hypertension.

Caffeine-induced blood pressure elevations are well documented in habitual consumers, occurring through both vasoconstrictive and cardiostimulatory actions. Whether caffeine hinders pressor regulation during exercise has been uncertain, particularly in those at risk for hypertension. Thus effects of caffeine versus placebo were studied during supine bicycle exercise in healthy men (ages 20 to 35). Hypertension risk was defined during screening: high risk (HRISK) = 135 to 154/85 to 94 mm Hg plus parental hypertension (n = 20); low risk (LRISK) = less than or equal to 132/84 mm Hg and no parental hypertension (n = 14). Exaggerated pressor responses (greater than or equal to 230/100 mm Hg) seen during exercise after placebo identified a subgroup of seven HRISKs indistinguishable at rest from the remaining HRISK men. This subgroup showed a larger resting diastolic response to caffeine (p less than 0.05) than LRISKs and other HRISKs. Compared with placebo, caffeine increased the number of LRISK (0% to 36%) and HRISK (35% to 50%) men reaching abnormal exercise blood pressures, and blunted normal increments in cardiac index at higher workloads among HRISK men (p = 0.05). Thus restriction of caffeine before exercise might benefit persons with either risk for hypertension or unusual sensitivity to caffeine.

Adult↗

Hypertension risk and caffeine's effect on cardiovascular activity during mental stress in young men.

Examined the cardiovascular effects of caffeine plus behavioral stress in men low versus high in risk of essential hypertension. Caffeine (3.3 mg/kg, equivalent to 2 to 3 cups of coffee) or placebo was given on alternate days to 19 low-risk men (negative for parental hypertension and low-normal resting blood pressure, BP) and 20 high-risk men (positive history, high-normal BP). Forty minutes later, each worked for 15 min on a demanding psychomotor task during which BP, cardiac output, and vascular resistance were determined. During rest, caffeine raised vascular resistance in both groups. During the task, it supra-additively increased the systolic BP response by enhancing the rise in cardiac output, producing equivalent BP rises in both groups. Due to the higher resting pressures of the high-risk men, caffeine plus the task resulted in 50% of these having transient BP of 140/90 mg Hg or greater. Caffeine in combination with mental stress may produce undesirable BP in those at risk for hypertension.

Adult↗

Heart rate reactivity, behavior pattern, and parental hypertension as predictors of cardiovascular activity during cognitive challenge.

Hemodynamic responses were studied during work on serial subtraction and digits backwards tasks in 99 healthy male undergraduates jointly classified as high or low heart rate reactors, Type A or Type B behavior pattern, and as having positive or negative parental history of hypertension. Heart rate, systolic blood pressure, and diastolic blood pressure were recorded, and rate pressure product was calculated at rest and during the tasks. High heart rate reactors to a cold pressor task responded with relatively higher heart rate and rate pressure product during both cognitive tasks than low heart rate reactors. Type A subjects defined by Jenkins Activity Survey did not differ from Type Bs on any of these physiological variables, although behavioral evidence demonstrated greater effort and superior performance by the Type As. Subjects with a positive parental history of hypertension manifested greater systolic and diastolic pressures and rate pressure product responses to the cognitive challenge than those lacking such parental history. These results indicate that the individual difference variables of heart rate reactivity and parental history of hypertension predicted different hemodynamic response patterns to behavioral challenge.

Adult↗

Dimethyl sulfoxide antagonizes hypotensive, metabolic, and pathologic responses induced by endotoxin.

There is evidence that free radical activity may be important in the development of endotoxemia. Dimethyl sulfoxide is a hydroxyl radical scavenger that readily penetrates cell membranes. Using the conscious, instrumented rat this study tests the ability of dimethyl sulfoxide to modify the course of endotoxemia by evaluating cardiovascular, metabolic, and tissue injury parameters for 4 hr after the toxic insult. Treatment with dimethyl sulfoxide (6.5 g/kg; i.p.) evoked significant decreases in cardiac output, stroke volume, and central venous pressure and increases in heart rate, systemic vascular resistance, mean aortic pressure, respiration rate, and concentrations of blood glucose and plasma lactate. Following endotoxin (40 mg/kg, i.v. LD90- 24 hr), dimethyl sulfoxide pretreatment blocked the early hypotensive episode but all other cardiovascular and respiratory responses to endotoxin were essentially unaltered. The pH, PO2, PCO2, and hematocrit were the same for both treated and untreated groups; however, dimethyl sulfoxide prevented the endotoxin-induced hypoglycemia and significantly attenuated the hyperlacticemia at 4 hr. The severe hemorrhagic intestinal pathology characteristic of this model of endotoxemia was not present in the dimethyl-sulfoxide-treated group. From these results we conclude that dimethyl sulfoxide caused significant cardiovascular alterations conducive to impaired systemic blood flow. However, when administered prior to endotoxin, dimethyl sulfoxide induced significant beneficial modifications in the course of endotoxemia despite few improvements in cardiovascular function. The data indicate that the hydroxyl radical may be a mediator of tissue injury in this model of endotoxemia.

Animals↗

Exaggerated pressure response to exercise in men at risk for systemic hypertension.

Normotensive persons at high risk of developing systemic hypertension have greater cardiovascular reactivity to mental and physical stressors. This study compared cardiovascular responses to exercise in normotensive men (aged 28 +/- 0.8 years [mean +/- standard error of the mean]) at high risk (positive parental history and high normal resting blood pressure [BP], n = 20) and at low risk (negative history, low normal BP, n = 15) of hypertension. All men had normal body weight and exercise tolerance. During graded supine bicycle exercise, 35% (7 of 20) of high-risk men had exaggerated BP responses (greater than or equal to 230/100 mm Hg) versus 0% of low-risk men, thus forming 3 groups (low risk, high-risk normal BP response, high-risk exaggerated response). Cardiac function was measured by nuclear cardiography. Cardiac index, peripheral resistance index, left ventricular ejection fraction and contractility index were measured at rest and during each exercise work load. High-risk exaggerated responders could not be distinguished from their high-risk normal-responding counterparts using resting BP or other cardiovascular variables. During exercise all 3 groups had equivalent increases in cardiac output. However, the high-risk exaggerated responders had blunting in peripheral resistance decline, resulting in excessive BP increases. This finding suggests an impaired capacity for exercise-induced vasodilation, indicating that the exaggerated response group may be at highest risk for future hypertension in these 3 groups.

Adult↗

Evaluation of thyrotropin releasing hormone as a therapeutic intervention for endotoxemia.

Thyrotropin releasing hormone (TRH) has been reported to reduce endotoxin-induced hypotension and mortality rate in conscious rats. Limited data are available to explain these effects. We evaluated hemodynamic parameters, metabolic function, tissue injury, and survival rate in three groups of instrumented conscious rats following intravenous endotoxin (20 mg/kg, LD/90-24 h) challenge. Pretreatment with TRH (2.0 mg/kg, i.v.) was administered 10 min before endotoxin (n = 10) and control (n = 10) animals were given an equivalent volume of saline. The post-treated group (n = 7) was given TRH at the nadir of the hypotensive response following endotoxin to duplicate published protocols. 5 min after endotoxin blood pressure and cardiac output were significantly higher in the post and pre-treatment groups, respectively, compared to the untreated group. There were no differences at other times. Systemic vascular resistance was not affected by either treatment mode at any time. TRH treatment following endotoxin resulted in transient increases in heart and respiration rates and decreased central venous pressure during the first 30 min. Metabolic function indicated by measurements of glucose, lactate, hematocrit, pH, PO2, and PCO2 at 60 and 240 min after endotoxin was not modified by TRH. The hemorrhagic small intestine characteristic of this model was not improved by either treatment mode. Mortality rates at 4 h after endotoxin were 20% for the untreated, 40% for the pre-treated, and 43% for the post-treated. These results suggest TRH exerts early transient effects on cardiovascular responses evoked by endotoxin in the conscious rat but no lasting beneficial effects were found to support the use of TRH as a mono-therapy for endotoxemia.

Animals↗

Effects of caffeine on blood pressure response during exercise in normotensive healthy young men.

The possible combined effects of caffeine and exercise on blood pressure (BP) regulation were examined in 34 healthy, normotensive (BP less than 135/85 mm Hg) young men (mean age 27 +/- 3 years) in a placebo-controlled, double-blind crossover design. Each subject performed submaximal and symptom-limited maximal supine bicycle exercise 1 hour apart after ingestion of placebo or caffeine (3.3 mg/kg). Heart rate, BP, cardiac output and peripheral vascular resistance were compared for placebo and caffeine days. Postdrug baseline showed that caffeine increased systolic and diastolic BP and peripheral vascular resistance (p less than 0.001 for each) and decreased heart rate (p less than 0.01) but did not change stroke volume or cardiac output. BP and vascular resistance effects of caffeine remained during submaximal exercise resulting in an additive increase in BP while negative chronotropic effects of caffeine disappeared. At maximal exercise substantially more subjects (15 on caffeine vs 7 on placebo, p less than 0.02) had systolic BP greater than or equal to 230 mm Hg and/or greater than or equal to 100 mm Hg for diastolic BP. Plasma norepinephrine levels were not significantly different across days, but epinephrine was higher at maximal exercise and cortisol was increased post-drug and throughout maximal exercise on caffeine days. Data indicate that caffeine increases BP additively during submaximal exercise and may cause excessive BP responses at maximal exercise for some individuals. The pressor effects of caffeine appear to be due to increasing vascular resistance rather than cardiac output.

Adult↗

An assessment of plasma histamine concentrations during documented endotoxic shock.

Recent reviews of the literature involving histamine release during sepsis and endotoxemia have reported that the majority of the studies are inconclusive due to inadequate assays or experimental protocols. In a controlled experimental setting we have employed a specific and sensitive radioenzymatic assay to determine plasma histamine concentrations temporally during documented endotoxin-induced shock in the conscious rat. Cardiovascular and metabolic measurements for the control group (n = 7) were normal during the study period. Endotoxin (n = 8, LD/90-24 hrs.) induced an early transient hypotensive episode and increase in systemic vascular resistance and a sustained decrease in cardiac index and central venous pressure and increase in heart and respiratory rates. Hypoglycemia and hyperlacticemia were present at the end of the four-hour study period. The small intestine was severely hemorrhaged in all animals given endotoxin. Histamine concentrations for the control group were unchanged throughout the study period. Contrary to previous reports, this model of endotoxemia revealed unchanging histamine concentrations during the first 30 minutes which were temporally coincident with the characteristic early hypotensive episode evoked by endotoxin. The histamine concentrations at 60 and 240 minutes following endotoxin were increased two and three-fold, respectively, compared to the control group. Three of the 8 rats given endotoxin died before four hours; histamine concentrations in plasma taken when death appeared certain were 42, 91, and 174, compared to the control value of approximately 8 ng/ml. There was no clear association of the increases in plasma histamine with any of the parameters measured in this study: however, established histamine effects may have been masked by the pre-existing effects of other mediators known to be active during endotoxemia. In separate groups of animals endotoxin (n = 5) elicited early increases in plasma concentrations of norepinephrine (5-fold) and epinephrine (8-fold) that remained elevated for the 4-hour study period while the control group (n = 4) remained stable. This study establishes that a) plasma histamine concentrations are increased during endotoxemia, b) plasma histamine is not elevated during the initial hypotension episode following endotoxin, c) plasma histamine increases during the progression of endotoxic shock, and d) plasma histamine concentrations are extremely high prior to death.

Animals↗

Impact of encephalopathy on mortality in the sepsis syndrome. The Veterans Administration Systemic Sepsis Cooperative Study Group.

Sepsis, an important cause of hospital mortality, continues to be a diagnostic and therapeutic challenge. To define more clearly the impact of encephalopathy on the course of sepsis, the various clinical signs of sepsis, blood culture results, and mortality rates were examined in relation to mental status in septic patients. Patients were classified as having an acutely altered mental status due to sepsis (AAMS), preexisting altered mental status (PAMS), or normal mental status (NMS). Twenty-three (307/1333) percent of the study patients had an acutely altered sensorium secondary to sepsis. Patients with AAMS had a higher mortality (49%) than patients with PAMS (41%) or patients with NMS (26%) (p less than .000001). Multivariate analysis disclosed that altered mental status, hypothermia, hypotension, thrombocytopenia, and the absence of shaking chills were independent predictors of increased mortality in the sepsis syndrome. Patients with Gram-negative bacteremia (28%) were as likely to have AAMS as patients with Gram-positive bacteremia (25%) or patients with negative blood cultures (23%). In summary, alterations in mental status are common in septic patients, and are associated with significantly higher mortality.

Bacterial Infections↗

Simultaneous measurement of stroke volume by impedance cardiography and nuclear ventriculography: comparisons at rest and exercise.

UNLABELLED: We have conducted four major impedance cardiography (ZCG) studies to provide data on validity, reproducibility, and sensitivity of response to interventions. The reference technique was quantitative nuclear ventriculography (NVG). Subjects were healthy young men in situations where minimally invasive and unobtrusive techniques were preferred. Interventions used included caffeine ingestion and exercise. Validity of ZCG estimates of stroke volume index (SVI, ml/m2) was tested in 35 men at rest. SVI was 49 +/- 9 by ZCG and 46 +/- 7 by NVG (r = 0.82). Measurements of SVI during bicycle exercise showed no overall difference by the two methods (F = 0.26, P = NS). Vascular resistance index (mean BP/CI) increased comparably by both techniques (+9.6% by ZCG and +9.7% by NVG) following caffeine (3.3 mg/kg). The reproducibility of ZCG was demonstrated in the day-to-day consistency of caffeine's effect on vascular resistance in 3 other studies (+11.9%, 12%, and 8.9%). Reliability across and within days was shown by repeated tests in the same subjects (SVI, r's = .96, .92). CONCLUSION: Impedance cardiography was shown to be a useful noninvasive technique for evaluation of cardiodynamics in biomedical research since it was highly reproducible and yielded equivalent results of relative changes produced by pharmacological and physical challenge. In addition, there was good agreement with NVG in absolute values for grouped data.

Cardiography, Impedance↗

Respiratory and cardiovascular effects of thyrotropin-releasing hormone as modified by isoflurane, enflurane, pentobarbital and ketamine.

Thyrotropin-releasing hormone (TRH) possesses significant arousing and cardio-respiratory stimulant actions. The effects of a 2 mg/kg i.v. bolus dose of TRH on respiration and systemic hemodynamics were compared in conscious, freely-moving rats and during anesthesia with 4 different anesthetics. Fifty-four male Sprague-Dawley rats weighing 285 +/- 4 g (mean +/- S.E.M.) were divided into 5 groups: conscious, enflurane (2%), isoflurane (1.4%), pentobarbital (8 mg/kg/h i.v.), and ketamine (60 mg/kg/h i.v.). Anesthetized rats were intubated and breathed oxygen or anesthetic/oxygen spontaneously. Aortic blood pressure, heart rate, cardiac output, respiratory rate, arterial blood pH, blood gases, lactate and glucose were measured, and data were collected over a 20 min baseline period and for 130 min post-TRH. TRH increased respiratory rate in all groups; concomitant changes in arterial PCO2 indicated increased minute ventilation in the inhalation agent groups but not in the i.v. anesthetic groups or in the awake group. Significant respiratory depression in the enflurane group was rapidly reversed by TRH. The respiratory stimulant and arousing effects of TRH were smallest with ketamine anesthesia. The hemodynamic responses to TRH were consistent with a pattern of sympathoadrenalmedullary activation and were relatively uniform across groups despite anesthetic-induced alterations in baseline values. TRH or its analogues may prove useful as an analeptic in clinical anesthesia.

Animals↗