Cardiovascular and endocrine responses during the cold pressor test in subjects with cervical spinal cord injuries

OBJECTIVE: To investigate cardiovascular regulation and endocrine responses during the cold pressor test in patients with chronic spinal cord injury (SCI). DESIGN: Experimental and control study. SETTING: University laboratory, department of rehabilitation medicine, in Japan. PARTICIPANTS: Eight quadriplegic subjects with complete spinal cord transection at the C6 to C8 level and 6 age-matched healthy subjects. INTERVENTIONS: Cardiovascular and endocrine responses were examined during 2 minutes of control, 3 minutes of ice-water immersion of the foot, followed by a 3-minute recovery. MAIN OUTCOME MEASURES: Blood pressure, heart rate, the Borg 15-point Rating of Perceived Pain Scale, and blood samples for measurement of plasma norepinephrine, epinephrine, plasma renin activity, plasma aldosterone, and arginine vasopressin. RESULTS: The rise in the mean arterial blood pressure during the cold pressor test in patients with SCI (baseline, 81.6+/-3.7mmHg; increased by 30%+/-6.1%) was significantly (P<.05) higher than that in healthy subjects (baseline, 101.2+/-4.5mmHg; increased by 20%+/-4.5%). The SCI subjects had no change in heart rate throughout the test, in contrast to the tachycardia noted in normal subjects. Baseline plasma norepinephrine in SCI subjects (63.0+/-18.3pg/mL) was significantly lower than in normal subjects (162.3+/-19.6pg/mL) and plasma norepinephrine increased significantly during the cold pressor test in both groups. CONCLUSIONS: In the SCI subjects, a reflex sympathetic discharge through the isolated spinal cord results in a more profound rise in mean blood pressure during ice-water immersion. This response was free of inhibitory impulses from supraspinal center and baroreceptor reflexes, either of which might restrain the increase in blood pressure.     

Influence of sibutramine treatment on sympathetic vasomotor tone in obese subjects

BACKGROUND: Sibutramine, a serotonin and norepinephrine transporter blocker, is used as adjunctive obesity treatment. Studies in healthy subjects suggested that sibutramine might have opposing effects on peripheral and central sympathetic activity; an increase in blood pressure has been claimed. Direct measurements of muscle sympathetic nerve activity (MSNA) in sibutramine-treated patients have not been conducted. METHODS AND RESULTS: Twenty nondiabetic obese men and women completed the study (mean body mass index, 35 +/- 3 kg/m2; mean age, 42 +/- 8 years). They were treated for 5 days with 15 mg sibutramine per day or matching placebo in a randomized, double-blind, crossover fashion. At the end of each intervention, heart rate, blood pressure, and MSNA were recorded. Patients underwent cold pressor testing and phenylephrine and nitroprusside infusions. RESULTS: The mean blood pressure (systolic/diastolic) was 118 +/- 13 mm Hg/70 +/- 9 mm Hg with placebo and 120 +/- 13 mm Hg/69 +/- 8 mm Hg with sibutramine (P = .29). The mean resting MSNA was 28 +/- 14 bursts/min with placebo and 12 +/- 10 bursts/min with sibutramine (P < .0001). Sibutramine attenuated the rise in blood pressure (25 +/- 9 mm Hg/9 +/- 9 mm Hg versus 31 +/- 12 mm Hg/14 +/- 9 mm Hg, P < .01) and MSNA (0.3 +/- 0.5 arbitrary units/min versus 1.0 +/- 1.1 arbitrary units/min, P = .01) in response to cold pressor testing. Baroreflex heart rate control was similar with sibutramine and with placebo. The sympathetic baroreflex was shifted such that at a given blood pressure, MSNA was substantially decreased (top, 44 +/- 1.23 bursts/min versus 58 +/- 2.99 bursts/min [P < .001]; center point, 65 +/- 0.32 mm Hg versus 67 +/- 0.81 mm Hg [P < .05]). CONCLUSIONS: Sibutramine treatment profoundly and selectively reduces sympathetic nerve traffic at rest and attenuates the responsiveness to sympathetic stimuli. Our data support the idea that sibutramine's peripheral sympathomimetic effect is counteracted by a central sympatholytic mechanism.     

Cardiovascular responses and postexercise hypotension after arm cycling exercise in subjects with spinal cord injury

OBJECTIVE: To examine postexercise hypotension and contributing factors in subjects with spinal cord injury (SCI). DESIGN: Prospective clinical research study. SETTING: Rehabilitation center. PARTICIPANTS: Subjects with chronic cervical-level (n=19) and thoracic-level (n=8) SCI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Subjects underwent graded arm-cycling with electrocardiogram and oxygen uptake monitoring to exhaustion. Heart rates and blood pressures were measured before and after exercising. Injury to motor and sensory pathways was determined by American Spinal Injury Association grade, and to autonomic pathways by sympathetic skin responses (SSRs) (n=16). RESULTS: Resting blood pressures and heart rates were lower in cervical than thoracic SCI (mean arterial pressure [MAP]: cervical, 76.6+/-2 mmHg; thoracic, 93.5+/-3 mmHg; P<.001). Following exercise, heart rate responses were greater in thoracic than cervical SCI; MAP increased in thoracic SCI (8.4+/-5 mmHg) and markedly decreased in cervical SCI (-9.3+/-2 mmHg) (P<.001). No subject had significant electrocardiographic abnormalities at rest or during exercise. There were correlations between SSR and heart rate and blood pressure responses to exercise; the correlation between the SSR and blood pressure response was due to an interaction between the heart rate and blood pressure responses. CONCLUSIONS: Abnormal cardiovascular responses to exercise and transient postexercise hypotension were common in cervical, but not thoracic SCI. This may be partly related to loss of descending sympathetic nervous control of the heart and vasculature following high SCI.     

Left ventricular performance during prolonged exercise: absence of systolic dysfunction

We assessed left ventricular systolic and diastolic performance during and after prolonged exercise under controlled conditions in a group of healthy, trained men. Previous studies have examined the effects of prolonged effort on left ventricular function, yet it remains unclear whether or not left ventricular dysfunction (e.g. cardiac fatigue) can be produced under such conditions. We studied 15 healthy men, aged 27+/-1 years (mean+/-S.E.M.). Subjects exercised on bicycles at a constant work rate (60% of maximum oxygen uptake per min) for 150 min. Measurements of gas exchange, blood pressure and haematocrit were obtained, concurrent with the assessment of left ventricular function using equilibrium radionuclide angiography, at rest, during exercise (every 30 min) and after 30 min of recovery. Fluid replacement was provided and monitored during the exercise period. The baseline resting and exercise ejection fractions were 66+/-2% and 78+/-2% respectively. During exercise, subjects consumed 1816+/-136 ml of fluid, and the haematocrit had increased at 120 min of exercise (from 47.2%+/-0.6 to 49.9+/-0.8%; P<0.05). There was no change in either systolic or diastolic blood pressure throughout the exercise period, but heart rate drifted upwards from 141+/-2 beats/min after 30 min to 154+/-3 beats/min after 150 min (P<0.05). There was a small decline (8%; P<0.05) in end-diastolic volume at 150 min. No changes were observed in left ventricular ejection fraction, the pressure/volume ratio or end-systolic volume. After 30 min of sitting in recovery, heart rate was still higher than the pre-exercise value (84+/-3 compared with 69+/-2 beats/min; P<0.05), as were measures of peak filling rate and time to peak filling (P<0.05). The ejection fraction in the post-exercise recovery period was similar to the pre-exercise value. The results indicate that prolonged exercise of moderate duration may not induce abnormal left ventricular systolic function or cardiac fatigue during exercise.     

Effects of graduated compression stockings on cardiovascular and metabolic responses to exercise and exercise recovery in persons with spinal cord injury

OBJECTIVE: To investigate whether reporting blood redistribution by means of graduated elastic stockings affects exercise and postexercise responses in people with spinal cord injury (SCI). DESIGN: Crossover trial. SETTING: Physical medicine and rehabilitation department in France. PARTICIPANTS: Fourteen men with traumatic SCI, grouped according to their level of injury. INTERVENTIONS: Subjects performed 2 maximal wheelchair exercise tests 1 week apart, in random order and under a counter-balanced design. One test was done with and the other without graduated elastic stockings (21 mmHg). MAIN OUTCOME MEASURES: Blood lactate, blood pressure, heart rate, maximal power output, and oxygen consumption (Vo2). RESULTS: Postexercise venous lactate concentration was reduced in SCI subjects with lesion levels below T6 while wearing graduated elastic stockings during both exercise and recovery (10.9+/-3.9 mmol/L vs 12.5+/-4.6 mmol/L, P<.05). There were no significant differences in submaximal and maximal values (heart rate, Vo2, power output) between subjects tested with and without graduated elastic stockings. CONCLUSIONS: Wearing elastic stockings affects postexercise responses by decreasing lactate concentration in well-trained, low-level paraplegic patients after a maximal exercise. The relatively low pressure generated by the stockings may not, however, influence the venous system enough to produce improved performance and cardiovascular responses.     

Cardiac vagal response to water ingestion in normal human subjects

In healthy young subjects there is direct evidence for sympathetic vasoconstrictor activation after drinking water, but this is not accompanied by an increase in arterial blood pressure. A marked pressor response to water ingestion has, however, been observed in elderly subjects and in patients with autonomic failure. We examined the effect of water ingestion on haemodynamic variables and heart rate variability (HRV) markers of cardiac vagal control in ten healthy young subjects and four cardiac transplant recipients with confirmed persistent cardiac vagal denervation. In a random order crossover protocol, changes in heart rate, blood pressure and measures of high frequency (HF) HRV were compared over time following the ingestion of 500 ml and 20 ml (control) of tap water. In healthy subjects, after drinking 500 ml of water the heart rate fell from 67.6+/-2.0 (mean+/-S.E.M.) to 60.7+/-2.4 beats/min (P<0.01), and the bradycardic response peaked between 20 and 25 min. There were no significant changes in arterial blood pressure. Over the same time course, water ingestion caused increases in measurements of HF HRV: root-mean-square of successive RR interval differences (RMSSD) increased by 13+/-2.7 ms after 500 ml versus 2+/-3.1 ms after 20 ml (P<0.05); HF power increased by 686+/-400 versus -63+/-322 (P<0.01). In transplant recipients water ingestion was followed by a pressor response (range 13 to 29 mmHg). These results provide evidence that water ingestion in normal subjects is followed by an increase in cardiac vagal control that may counteract the pressor effects of sympathetic activation. We suggest that in the elderly, in transplant recipients and in autonomic failure, loss of this buffering mechanism explains the pressor response to drinking water.     

Role of aortic baroreceptors in ethanol-induced impairment of baroreflex control of heart rate in conscious rats.

This study investigated the relative contribution of aortic baroreceptors to the depressant effect of ethanol on arterial baroreceptor function. The acute hemodynamic effects of ethanol were studied in conscious freely moving aortic baroreceptor denervated (ABD) and sham-operated (SO) rats. ABD but not the sham operation caused immediate and significant (P less than .05) increases in mean arterial pressure and heart rate (HR) and an impairment of the baroreflex-mediated control of HR (baroreflex sensitivity, BRS). Two to three days after ABD, these parameters, except the BRS, subsided to near-control levels. Both operations (ABD and sham) significantly reduced the daily water intake but the reduction was significantly greater in ABD rats. Intravenous administration of ethanol (0.1, 0.5 or 1.0 g/kg) to either SO or ABD rats produced short-lived dose-related pressor and bradycardiac responses which correlated well with blood ethanol concentration. In SO rats, ethanol caused dose-related decreases in the slopes of the curves relating increments in mean arterial pressure induced by phenylephrine to corresponding bradycardiac responses; the higher dose significantly (P less than .05) reduced the slope from -2.03 +/- 0.14 to -1.28 +/- 0.18 beats/min/mm Hg, indicating an impairment of BRS. Conversely, in ABD rats, ethanol failed to influence the BRS; the slopes before and after ethanol (1 g/kg) were similar (-1.1 +/- 0.07 vs. -1.0 +/- 0.23 beats/min/mm Hg). The lack of ethanol effect in ABD rats cannot be accounted for by the assumption that aortic barodenervation depressed the baroreceptor reflex to its nadir or by a difference in concentration of blood ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Abnormal cardiovascular response to exercise in patients with peripheral arterial disease: Implications for management

Exercise is beneficial in improving claudication and functional capacity in patients with peripheral arterial disease (PAD). However, the physiologic response during and after exercise testing in this patient population has not been fully described. This study examined the cardiovascular response to exercise and explored the potential contribution of vascular noncompliance to exercise-induced hypertension in 124 patients with PAD and claudication and 31 comparison (C) patients with PAD with no walking limitations. Maximal walking distance was determined by an exercise treadmill test. Heart rate and blood pressure were monitored before, during, and immediately after an exercise test. Vascular compliance of the small and large vessels was measured using pulse waveform analysis. Individuals with low supine resting heart rate had longer pain-free walking distance (r = -0.195, P = .019) and maximal walking versus the C group (62 beats/min, standard deviation [SD] = 10, P = .02). Systolic blood pressure during supine rest was significantly lower for the PAD group (mean = 141 mm Hg, +/- SD = 22) versus the C group (mean = 153 mm Hg, +/- SD = 20, P = .003). Vascular compliance of large vessels was higher in the C group (mean = 4.13 +/- 4.13 mL/mm Hg x 100) compared with the PAD group (mean = 2.95 +/- 1.6 mL/mm Hg x 100). This study describes the exaggerated exercise cardiovascular response and impaired vascular compliance in patients with PAD. These results provide further evidence supporting the importance of a monitored treadmill exercise test before initiation of an exercise program to ensure safe and accurate exercise recommendations, and to identify individuals that require more intensive pharmacotherapy to prevent exercise-induced hypertension and tachycardia.     

The Efficacy of Esmolol versus Lidocaine to Attenuate the Hemodynamic Response to Intubation in Isolated Head Trauma Patients

OBJECTIVE: To assess the effect of esmolol vs lidocaine to attenuate the detrimental rise in heart rate and blood pressure during intubation of patients with isolated head trauma. METHODS: This was a prospective, double-blind, randomized study, performed at an urban, county teaching emergency department. Participants were 30 patients with isolated head trauma. Each underwent a standardized intubation protocol including esmolol or lidocaine, both at 2 mg/kg. RESULTS: Esmolol was used in 16 patients and lidocaine in 14. Mechanisms of injury included 12 assaults, 6 motor vehicle collisions, 6 falls, 4 auto-vs-pedestrian crashes, and 2 bicycle incidents. Mean ethanol level was 0.116+/-0.133 SD (range 0-0.482). Mean Glasgow Coma Scale (GCS) score was 7.9+/-4.0 SD. Cranial computed tomography (CT) hemorrhagic findings included 9 subdural/epidural hematomas, 6 cortex hemorrhages, and 2 multi-hemorrhages. Eleven patients received surgical intervention: 9 patients received a craniotomy, and 2 a ventricular catheter. The 2-minute time interval around intubation was used to assess each drug's efficacy. The mean difference change between groups for heart rate was 4.0 beats/min (95% CI = -17.7 to 9.7 beats/min), for systolic blood pressure was 1.3 mm Hg (95% CI = -27.8 to 30.4 mm Hg), and for diastolic blood pressure was 2.6 mm Hg (95% CI = -27.1 to 21.9 mm Hg). The power of this study was 90% to detect a 20-beat/min difference in heart rate, a 35-mm Hg difference in systolic blood pressure, and a 20-mm Hg difference in diastolic blood pressure. CONCLUSIONS: Esmolol and lidocaine have similar efficacies to attenuate moderate hemodynamic response to intubation of patients with isolated head trauma.     

The central hypotensive effect of clonidine. Studies in tetraplegic subjects.

A single oral dose of 300 microng of clonidine lowered systolic blood pressure by 20 +/- 4 mm Hg and diastolic blood pressure by 13 +/- 4 mm Hg in five healthy normotensive subjects (controls). Heart rate fell from 56 +/- 2 to 52 +/- 2 beats/min. In six tetraplegic subjects with physiologically complete chronic cervical spinal cord transection above the level of the sympathetic outflow, the same dose of clonidine did not significantly lower either systolic or diastolic blood pressure. Heart rate fell from 67 +/- 4 to 53 +/- 2 beats/min. Peak plasma concentrations of clonidine, measured by mass fragmentography, and elimination of the drug from plasma were similar in tetraplegic and control subjects and there was no difference in the incidence of the principal side effects of clonidine--sedation and dry mouth. Although the number of subjects studied is small, the absence of a fall in blood pressure after clonidine in the tetraplegic subjects suggests that the hypotensive action of clonidine in man is dependent on intact descending bulbospinal pathways and is mediated by withdrawal of sympathetic tone and provides direct evidence that some antihypertensive drugs may lower blood pressure in man by a direct action on the brain.     

Muscle sympathetic nerve activity during isometric exercise in patients with cerebrovascular accidents

OBJECTIVES: To define isometric exercise-induced pressor responses in patients with cerebrovascular accidents (CVAs) and to assess potential cardiovascular and sympathetic nervous system abnormalities during isometric exercise in CVA. DESIGN: Nonrandomized study. SETTING: University laboratory setting. PARTICIPANTS: Eight men with CVA who had documented damage of subcortical structures and 8 sex-matched controls. INTERVENTIONS: A 2-minute sustained contraction of elbow flexor muscles in the unaffected side at 35% of maximal voluntary contraction (MVC; isometric exercise). MAIN OUTCOME MEASURES: Heart rate, arterial blood pressure, and muscle sympathetic nerve activity (MSNA), recorded from the peroneal nerve on the affected side. RESULTS: The percent changes in total MSNA, heart rate, and mean blood pressure in patients with CVA increased during isometric exercise but were attenuated compared with the controls. Total MSNA (mean burst amplitude per minute times burst rate) increased significantly in CVA and control subjects during isometric exercise by 18.7%+/-6.3% and 95.8%+/-25.2%, respectively. CONCLUSIONS: The attenuated pressor responses during isometric exercise in subjects with CVA relative to the controls indicated damage to subcortical structures; such damage lowered sympathetic nervous response to isometric exercise. Our findings suggest that isometric exercise at 35% of MVC does not put patients with CVA at risk for serious tachycardia or hypertension.     

Myocardial ischemia and weaning failure in patients with coronary artery disease: an update.

OBJECTIVE: To determine the frequency and effects of weaning-related myocardial ischemia on weaning outcomes in patients with coronary artery disease. DESIGN: Prospective cohort study. SETTING: Medical and cardiac intensive care units of a 300-bed teaching community hospital. MEASUREMENTS AND MAIN RESULTS: Three-lead ST segments, heart rate-systolic blood pressure products, and respiratory rate/tidal volume ratios were obtained for patients with coronary artery disease just before and during their initial trials of weaning from mechanical ventilation. ST segments were interpreted by a blinded cardiologist. Eighty-three patients with a mean age of 72.4 +/- 1.1 years (mean +/- SEM), a mean Acute Physiology and Chronic Health Evaluation II score of 16.4 +/- 0.8, and a mean duration of mechanical ventilation of 4.6 +/- 0.9 days were studied. Eight patients showed electrocardiographic evidence of ischemia during weaning, and seven of these patients failed to be liberated on their first day of weaning. The presence of ischemia significantly increased the risk of weaning failure (risk ratio, 2.1; 95% confidence interval, 1.4-3.1). The rate-pressure product for the group as a whole increased significantly during weaning, from 11.9 +/- 0.4 to 13.5 +/- 0.5 mm Hg x beats/min x 10(3) (p < .01). The increase in rate-pressure product tended to be greater in patients who became ischemic (12.8 +/- 0.9 to 17.3 +/- 2.0 mm Hg x beats/min x 10(3)) than in patients who were not ischemic during weaning (11.8 +/- 0.4 to 13.0 +/- 0.5 mm Hg x beats/min x 10(3); p = .05). The rate/volume ratio did not change significantly during weaning, but the rate/volume ratios after both 1 min (65.6 +/- 4.6 vs. 98.0 +/- 9.4 breaths/min/L; p < .05) and 30 mins (68.6 +/- 4.3 vs. 91.1 +/- 8.9 breaths/min/L; p < .05) of unassisted breathing were lower in successful than in unsuccessful patients. CONCLUSION: Electrocardiographic evidence of myocardial ischemia occurs frequently and is associated with significantly increased risk of first-day weaning failure in patients with coronary artery disease.     

Alterations in the Baroreceptor Reflex in Conscious Dogs with Heart Failure

The effectiveness of the baroreceptor reflex in conscious dogs with experimental cardiac hypertrophy and heart failure was compared with that in a group of normal conscious dogs. Cardiac hypertrophy and heart failure were produced by tricuspid avulsion and progressive pulmonary stenosis. The sensitivity of the baroreceptor reflex to transient hypertension was assessed by determining the slope of the regression line relating the prolongation of the R-R interval to the rise in systolic arterial pressure during the transient elevation of arterial pressure induced by an intravenous injection of 1-phenylephrine. The mean slope averaged 22.4+/-2.3 msec/nm Hg in 16 normal animals. 23.1 +/-1.5 in five sham-operated animals, and was significantly reduced to 8.3 +/-0.8 in 10 dogs with hypertrophy alone (P < 0.001), and to 3.3+/-0.5 in nine dogs with heart failure (P < 0.001). The response to baroreceptor hypotension was compared during bilateral carotid artery occlusion (BCO) in six normal and six heart failure dogs previously instrumented with Doppler flow transducers on the superior mesenteric and renal arteries. During BCO, in normal dogs arterial pressure increased 52+/-4 mm Hg, heart rate 33+/-2 beats/min, mesenteric resistance 0.17+/-0.03 mm Hg/ml per min, and renal resistance 0.37+/-0.10 mm Hg/ml per min. In the heart failure group all of these variables increased significantly less (P < 0.01); arterial pressure rose 25 +/-3 mm Hg, heart rate 13 +/-4 beats/min, mesenteric resistance 0.04+/-0.007 mm Hg/ml per min, and renal resistance 0.18+/-0.09 mm Hg/ml per min.Thus, in heart failure, all measured systemic and regional circulatory adjustments consequent to baroreceptor hypo- and hypertension are markedly attenuated. This study demonstrates a profound derangement of a major cardiovascular control mechanism in experimental heart failure.     

Comparison of propofol and thiopental for the induction of anesthesia

We compared the safety, efficacy, and side effects of induction of anesthesia with propofol (2.5 mg/kg), a new intravenous agent, and thiopental (4.0 mg/kg) in 62 patients in American Society of Anesthesiologists class I or II. There was no significant difference between induction times for the propofol (40.0 +/- 2.0 sec) and thiopental (44.0 +/- 4.0 sec) groups. Propofol administration produced a significant fall (P less than .05) in systolic blood pressure (SBP), from 134.1 +/- 2.6 mm Hg before injection to 128.3 +/- 2.4, 118.2 +/- 2.7, and 114.4 +/- 2.8 mm Hg one, two, and three minutes after injection, respectively. Diastolic blood pressure (DBP) fell significantly (P less than .05) during the three postinjection periods. Heart rate (HR) rose significantly (P less than .05), from 78.6 +/- 3.1 beats per minute before injection to 89.4 +/- 3.4 beats per minute one minute after injection. In patients given thiopental, SBP fell significantly (P less than .05), from 131.7 +/- 2.7 mm Hg before induction to 126.4 +/- 3.4 and 126.9 +/- 4.0 mm Hg two and three minutes after injection, respectively. The DBP did not change significantly in the thiopental group, but the HR rose significantly (P less than .05), from 73.3 +/- 2.8 beats per minute before injection to 83.9 +/- 3.0, 90.1 +/- 2.3, and 84.2 +/- 2.4 beats per minute one, two, and three minutes after injection, respectively. In 94% of patients given propofol, there were apneic periods of more than 60 seconds, compared to 50% in the thiopental group (P less than .05). There was a significant difference (P less than .05) between groups for the incidence of pain on injection; 31% of the patients receiving propofol had pain, compared to 3% of those receiving thiopental.     

Wavelet analysis of skin blood oscillations in persons with spinal cord injury and able-bodied subjects

OBJECTIVE: To assess the blood oscillations in the skin over the ischial tuberosity (high-risk area for pressure ulcer) using spectral analysis of laser Doppler flowmetry signals based on wavelet transform. DESIGN: Wavelet analysis of skin blood oscillations in persons with spinal cord injury (SCI) and able-bodied subjects. SETTING: Seating and body support interface laboratory. PARTICIPANTS: Ten men were recruited for this study, of whom 5 were able-bodied subjects (age, 31.2+/-3.3 y) and 5 were persons with SCI (age, 37.2+/-7.3 y). INTERVENTIONS: External pressure of 16.0 kPa (120 mmHg) was applied to the ischial tuberosity via 1 specifically designed pneumatic indentor. The loading duration was 30 minutes. MAIN OUTCOME MEASURES: Skin blood flow was monitored for 10 minutes prior to loading and 20 minutes after the prescribed loading period. With spectral analysis based on wavelet transform, 5 frequency intervals were identified (.01-.02, .02-.06, .06-.15, .15-.40, .40-2.0 Hz) corresponding to endothelial related metabolic, neurogenic, myogenic, respiratory, and cardiac activities, respectively. RESULTS: The relative amplitude of the metabolic component for persons with SCI was significantly lower (F=5.26, P=.032) during the resting conditions as compared with able-bodied subjects. During the postloading period, the response of oscillatory activities was evidently lower in the skin over the ischial tuberosity for persons with SCI when compared with able-bodied subjects. In addition, the relative amplitude of the neurogenic component (.02-.06 Hz) during postloading was significantly lower for persons with SCI (F=5.44, P=.029). CONCLUSIONS: These findings suggest that the contributions of endothelial related metabolic and neurogenic activities to the blood perfusion regulation become relatively less for persons with SCI during the resting and postloading periods, respectively.     

Comparative study of spirapril (quadropril) and amlodipine efficacy. Results of randomized trial in patients with mild to moderate arterial hypertension

AIM: To compare in the non-blind randomised parallel study the efficiency of quadropril and amlodipine in the treatment of mild to moderate arterial hypertension. MATERIAL AND METHODS: A total of 80 patients (57.6 +/- 1.0 years) were included in this study. The patients were randomised in two groups, 40 patients each. Patients of group 1 received monotherapy with quadropril, while those of group 2 were treated with amlodipine. The treatment duration was 8 weeks in both groups. Quadropril was given in a fixed dose of 6 mg once daily. The initial dose of amlodipine was 5 mg/day. In case of insufficient effect the dose was elevated to 10 mg/day. The efficacy was evaluated by changes in blood pressure (BP) measured at rest. Moreover, in 50 randomly chosen patients 24-h monitoring of BP was performed at the start and end of the treatment. RESULTS: In the quadropril group baseline systolic BP reached 158.6 +/- 2.1 mm Hg, diastolic BP--101.8 +/- 0.8 mm Hg, heart rate was 74.3 +/- 1.6 beats/min. In the amlodipine group baseline systolic BP was 159.9 +/- 2.4 mm Hg, diastolic BP--101.8 +/- 1.0 mm Hg, heart rate was 71.3 +/- 1.0 beats/min. Systolic BP decreased at the end of quadropril therapy to 138.5 +/- 2.2 mm Hg, diastolic BP to 88.1 +/- 1.4 mm Hg. No significant change of the heart rate was observed. Under 5 mg of amlodipine systolic BP decreased to 137.9 +/- 2.5 mm Hg and diastolic BP to 87.1 +/- 1.6 mm Hg. Heart rate increased to 73.3 +/- 2.2 beats/min. Under therapy with 10 mg amlodipine systolic BP decreased to 145.9 +/- 3.8 mm Hg, diastolic BP to 89.7 +/- 3.4 mm Hg. Heart rate increased to 77.3 +/- 4.0 beats/min (p < 0.01). The hypotensive effect of quadropril remained stable while the effect of amlodipine decreased by the 8th week of therapy (p < 0.01). Side effects were observed significantly more often in the amlodipine group, then in the quadropril group. The main quadropril side effect was cough. Side effects observed in the amlodipine group were edemas, tachycardia, weakness. CONCLUSION: Both quadropril and amlodipine demonstrated a comparable antihypertensive effect although in 11 of 40 patients in the amlodipine group a dose increase was necessary and tolerability of quadropril was better.     

Importance of central nervous system serotonin-1A receptors for mediating the hypotensive effect of urapidil

Urapidil is thought to lower blood pressure by both a peripheral and a central mechanism. The former effect is caused by blockade of alpha-1 adrenoceptors whereas the latter effect has been shown to occur in the medulla, specifically at the intermediate area on the ventral surface of the medulla. The receptor mediating the central effect is not the alpha-1 adrenoceptor, but has been postulated to be the serotonin (5-HT)1A receptor. To determine whether urapidil lowers blood pressure by stimulating 5-HT1A receptors at the intermediate area, we applied urapidil bilaterally (50 micrograms/side) to the intermediate area of chloralose-anesthetized cats while monitoring arterial blood pressure and heart rate. Application of urapidil caused decreases in mean blood pressure and heart rate of 66 +/- 8 mm Hg and 31 +/- 7 beats/min, respectively. Pretreatment with the 5-HT1A and 5-HT2 receptor antagonist, spiperone (30 micrograms/side), counteracted the effects of urapidil. Pretreatment with the 5-HT2 receptor antagonist, ketanserin, did not alter the hypotensive effect of urapidil. Urapidil given i.v. in a dose of 2 mg/kg decreased mean blood pressure and heart rate by 53 +/- 6 mm Hg and 10 +/- 2 beats/min, respectively. At the peak of the i.v. response, spiperone (30 micrograms/side) was applied to the intermediate area and increased mean blood pressure and heart rate by 52 +/- 6 mm Hg and 20 +/- 4 beats/min, respectively, thus effectively reversing the effects of i.v. urapidil.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of the angiotensin II receptor antagonist Losartan (DuP 753/MK 954) on arterial blood pressure, heart rate, plasma concentrations of angiotensin II and renin and the pressor response to infused angiotensin II in the salt-deplete dog.

1. The blood pressure, heart rate, hormonal and pressor responses to constant rate infusion of various doses of the angiotensin (type 1) receptor antagonist Losartan (DuP 753/MK 954) were studied in the conscious salt-deplete dog. 2. Doses in the range 0.1-3 micrograms min-1 kg-1 caused no change in blood pressure, heart rate or pressor response to angiotensin II (54 ng min-1 kg-1), and a dose of 10 micrograms min-1 kg-1 had no effect on blood pressure, but caused a small fall in the pressor response to angiotensin II. Infusion of Losartan at 30 micrograms min-1 kg-1 for 3 h caused a fall in mean blood arterial pressure from baseline (110.9 +/- 11.2 to 95.0 +/- 12.8 mmHg) and a rise in heart rate (from 84.6 +/- 15.1 to 103 +/- 15.2 beats/min). Baseline plasma angiotensin II (42.5 +/- 11.8 pg/ml) and renin (64.5 +/- 92.7 mu-units/ml) concentrations were already elevated in response to salt depletion and rose significantly after Losartan infusion to reach a plateau by 70 min. The rise in mean arterial blood pressure after a test infusion of angiotensin II (35.3 +/- 11.6 mmHg) was reduced at 15 min (11.8 +/- 6.8 mmHg) by Losartan and fell progressively with continued infusion (3 h, 4.3 +/- 3.3 mmHg). The peak plasma angiotensin II concentration during infusion of angiotensin II was unaffected by Losartan, but the rise in plasma angiotensin II concentration during infusion was reduced because of the elevated background concentration. Noradrenaline infusion caused a dose-related rise in mean blood arterial pressure (1000 ng min-1 kg-1, +19.9 +/- 8 mmHg; 2000 ng min-1 kg-1, +52.8 +/- 13.9 mmHg) with a fall in heart rate (1000 ng min-1 kg-1, -27.9 +/- 11.5 beats/min; 2000 ng min-1 kg-1, -31.2 +/- 17.3 beats/min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Altered pressor responses in long-term nitrendipine treatment

The effect of long-term treatment with nitrendipine on systemic pressor responses to norepinephrine (NE) and angiotensin II (AII) was evaluated in 11 subjects with mild, uncomplicated hypertension. Pressor responses to NE and AII were measured at the end of a 4-wk placebo period and after 5 wk treatment with nitrendipine (final dose 16 mg twice daily; range 5 to 20 mg/day) or placebo. In subjects who received nitrendipine, clinic supine blood pressure was reduced from 152 +/- 12/96 +/- 4 mm Hg to 134 +/- 11/84 +/- 5 mm Hg and pressor responses to NE but not to AII were attenuated. Endogenous plasma levels of NE and renin activity were not changed by nitrendipine. Data suggest that noradrenergic blood pressure control mechanisms depend more on cellular calcium transport than do AII-mediated ones and may help explain the greater effectiveness of calcium entry blockers in the treatment of low-renin hypertension.     

Blood pressure response to isometric exercise in patients with peripheral atherosclerotic disease

BACKGROUND: The purpose of this study was to compare the circulatory responses to isometric exercise in patients with peripheral atherosclerotic disease (PAD) with healthy controls. METHODS: Eleven patients with diagnosed PAD, a control group of eleven healthy young adults, and a control group of eleven healthy age-matched adults participated. Blood pressure, heart rate, stroke volume, cardiac output, blood velocity in the brachial artery, acral skin perfusion was continuously recorded and total peripheral resistance calculated before, during and after 2 min of 40% maximum voluntary contraction of the forearm. RESULTS: At rest we found a consistently higher level of mean arterial pressure (MAP) and systolic pressure (SP) in the elderly, both PAD patients and elderly controls, compared with the young controls. We found no significant difference in diastolic blood pressure. Two minutes isometric handgrip exercise induced a similar increase in MAP in all three groups (patients 32.6 (17.9) mm Hg [mean (SD)], young control group 25.3 (8.9) mm Hg, age-matched control group 36.1 (10.6) mm Hg). No significant differences were found in the other measured cardiovascular variables during isometric handgrip. Increased TPR is the main factor contributing to the increase in blood pressure in all three groups. CONCLUSION: Our study indicates that the pressor response continues to be well regulated with age, also when the cardiovascular system is altered by marked atherosclerosis. The consequence is that both PAD patients and elderly controls reach higher SP values during isometric exercise due to higher SP baseline values.