Reduced Cardiopulmonary Baroreflex Sensitivity in Patients With Hypertrophic Cardiomyopathy

Objectives. We sought to assess baroreflex function in patients with hypertrophic cardiomyopathy (HCM).Background. We have previously demonstrated a specific abnormality in the afferent limb of the cardiopulmonary baroreflex in patients with vasovagal syncope. Patients with HCM exhibit abnormal control of their vasculature during exercise and upright tilt; we therefore hypothesize a similar abnormality in the afferent limb of the cardiopulmonary baroreflex arc.Methods. We investigated 29 patients with HCM and 32 control subjects. Integrated baroreceptor sensitivity was assessed after administration of phenylephrine. Cardiopulmonary baroreceptor sensitivity was assessed by measuring forearm vascular resistance (FVR) during lower body negative pressure (LBNP). Carotid artery baroreflex sensitivity was assessed by measuring the in RR interval during manipulation of carotid artery transmural pressure. The integrity of the efferent limb of the reflex arc was determined by studying responses to both handgrip and peripheral alpha-receptor sensitivity.Results. During LBNP, FVR increased by only 2.36 ± 9 U in patients, compared with an increase of 12.3 ± 8.76 U in control subjects (p = 0.001). FVR paradoxically fell in eight patients, but in none of the control subjects. Furthermore, FVR fell by 4.9 ± 5.6 U in patients with a history of syncope, compared with an increase of 4.7 ± 7.2 U in those without syncope (p = 0.014). Integrated and carotid artery baroreflex sensitivities were similar in patients and control subjects (14 ± 7 vs. 14 ± 6 ms/mm Hg, p = NS and −3 ± 2 vs. −4 ± 2 ms/mm Hg, p = NS, respectively). Similarly, handgrip responses and the dose/response ratio to phenylephrine were not significantly different.Conclusions. This study suggests that patients with HCM have a defect in the afferent limb of the cardiopulmonary reflex arc.     

Neurohumoral and hemodynamic effects of lower body negative pressure in patients with congestive heart failure

Baroreflex modulation of forearm vascular resistance (FVR) has been reported to be abnormal in patients with congestive heart failure (CHF). However, the neurohumoral mechanisms for this impairment are not defined. We assessed the responses of arterial pressure, FVR, plasma norepinephrine, and plasma renin activity to lower body negative pressure in 29 patients with compensated CHF (New York Heart Association class III and IV) and in 11 normal age-matched control subjects. Baseline mean arterial pressure (83 +/- 2 vs 84 +/- 2 mm Hg) and mean arterial pressure during LBNP (-10, -20, and -40 mm Hg) were not significantly different in the two groups. Basal FVR (43.7 +/- 4 vs 27 +/- 2 units), plasma norepinephrine (605 +/- 81 vs 155 +/- 8 pg/ml), and plasma renin activity (8.3 +/- 1.7 vs 1.2 +/- 0.2 ng/ml/hr) were significantly (p less than 0.01) higher in patients with CHF. The relative increases in FVR responses during LBNP of -10, -20, and -40 mm Hg (10 +/- 4% vs 70 +/- 12%, 17 +/- 6% vs 106 +/- 21%, and 24 +/- 9% vs 152 +/- 28%) were markedly attenuated in patients with CHF compared to control subjects. Plasma norepinephrine and plasma renin activity responses during LBNP were also attenuated in patients with heart failure. Our results suggest that baroreflex control of FVR and plasma norepinephrine and plasma renin activity is impaired in CHF because of the inability of the cardiopulmonary baroreceptors to alter sympathetic outflow.     

Atrial natriuretic peptide attenuates the reflex sympathetic responses to lower body negative pressure

The authors studied the effect of intravenous infusion of atrial natriuretic peptide (ANP) on the plasma catecholamine and forearm vasoconstrictor responses to cardiopulmonary baroreflex deactivation in six normal, male volunteers in order to determine whether ANP influences reflex forearm vasoconstriction in humans. Unloading of low-pressure cardiopulmonary baroreceptors (CPBR) was accomplished by application of low levels (-10 and -20 mm Hg) of lower body negative pressure (LBNP). The authors measured the plasma norepinephrine (NE) and epinephrine, the mean arterial pressure (MAP), and the forearm vascular resistance (FVR) responses to reflex sympathetic activation by LBNP. ANP infusion (0.1 microgram.kg-1.min-1) decreased (p less than 0.01) basal MAP, as well as plasma renin activity and plasma aldosterone levels (p less than 0.05). ANP infusion also reduced (p less than 0.01) plasma NE responses to both levels of LBNP and tended to decrease both epinephrine and FVR during ANP infusion at -20 mm Hg LBNP (p = 0.8). These data suggest that exogenous ANP inhibits the reflex sympathetic responses that occur with CPBR unloading. The blunted plasma NE responses to CPBR unloading parallel the attenuation of FVR response to LBNP during ANP infusion, despite significant LBNP-induced hypotension.     

Limited maximal vasodilator capacity of forearm resistance vessels in patients with hypertrophic cardiomyopathy

Summary It is not known whether hypertrophic cardiomyopathy (HCM) is accompanied by an abnormality in vascular smooth muscles. In this study, we examined the maximal vasodilator capacity of forearm resistance vessels by measuring minimal forearm vascular resistance (min. FVR) during peak reactive hyperemia after 10 min of arterial occlusion in patients with HCM (n=15, 41±4 years old) and age-matched control subjects (n=12, 42±3 years old). Forearm blood flow (FBF) was measured by a mercury-in-silastic strain gauge plethysmograph and FVR was calculated by dividing mean blood pressure by FBF. Resting FBF was lower (P<0.05) and resting FVR was higher (P<0.01) in patients with HCM than in control subjects. Min. FVR was significantly greater in patients with HCM than in control subjects (2.7±0.2 vs 1.5±0.2 units,P<0.005). We also examined vasoconstrictive responses to intra-arterially infused angiotensin II (20 and 40 ng/min); responses were greater in patients with HCM than in control subjects (P<0.05). These results indicate that forearm circulation is altered in patients with HCM. The result that the maximal vasodilator capacity of forearm resistance vessels is limited in patients with HCM as compared with that in age-matched control subjects suggests that there may be abnormalities in forearm resistance vessels in patients with HCM, which might involve increased wall thickness or intrinsic abnormalities in vascular smooth muscle.     

Attenuation of reflex forearm vasoconstriction by alpha-human atrial natriuretic peptide in men

This study examined whether atrial natriuretic peptide (ANP) modulates reflex forearm vasoconstriction in humans. Synthetic alpha-human ANP (alpha-hANP) was infused at a rate of 0.03 microgram/kg/min in 8 healthy men (mean age 23 +/- 0.7 years, mean +/- SEM). The alpha-hANP decreased systolic blood pressure and central venous pressure (CVP) but did not significantly alter resting heart rate and forearm vascular resistance (FVR). The magnitudes of reflex increases in FVR during lower body negative pressure (LBNP) at -110, -20, and -40 mm Hg were less during infusion of alpha-ANP than those magnitudes during infusion of saline solution. The slope of the regression line relating changes in CVP and those in FVR was less during infusion of alpha-hANP than the slope during infusion of saline solution. Forearm vascular responses to intra-arterial infusion of norepinephrine at doses of 100, 200, and 500 ng/min did not significantly differ during infusion of alpha-hANP and saline solution. These results suggest that alpha-hANP attenuates cardiopulmonary baroreflex control of FVR in normal men.     

Exercise training augments cardiopulmonary baroreflex control of forearm vascular resistance in middle-aged subjects

Nine subjects (average age 56 +/- 7 years old) underwent sitting cycle ergometer exercise for four months. Exercise capacity and maximal VO2 increased after exercise training in these subjects. Forearm vascular responses to lower body negative pressure (LBNP) at -10 and -40 mmHg were compared before and after exercise training. The magnitude of reflex forearm vasoconstriction in response to LBNP at -10 mmHg was greater after exercise training than before. The decreases in central venous pressure during LBNP at -10 mmHg were similar before and after exercise training. The pressor and forearm vasoconstrictive responses to the cold pressor test also did not differ before and after exercise training. These results suggest that mild exercise training in middle-aged subjects augments the tonic inhibitory influence of the cardiopulmonary receptors on forearm vascular resistance.     

Effects of paroxetine hydrochloride, a selective serotonin reuptake inhibitor, on refractory vasovagal syncope: a randomized, double-blind, placebo-controlled study

OBJECTIVES: The purpose of the study was to determine whether the well tolerated serotonin reuptake inhibitor paroxetine hydrochloride could prevent vasovagal syncope in patients resistant to or intolerant of previous traditional therapies. BACKGROUND: Serotonergic mechanisms play a major role in the processes leading to neurocardiogenic vasovagal syncope, and serotonin reuptake inhibitors have been reported to be effective in preventing refractory syncope. METHODS: Sixty-eight consecutive patients (26 men and 42 women, mean age 44.7+/-16.5 years) with recurrent syncope and positive head-up tilt test and in whom standard therapies with beta-adrenergic blocking agents, vagolytic, negative inotropic or mineral corticoid agents were ineffectual or poorly tolerated were referred for study. Patients randomly received either paroxetine at 20 mg once a day or a placebo. A head-up tilt test was then reperformed after one month of treatment, and the clinical effect was noted over a mean follow-up of 25.4+/-7.9 months. RESULTS: The response rates (negative tilt test) after one month of treatment were 61.8% versus 38.2% (p < 0.001) in the paroxetine and placebo groups, respectively. During follow-up spontaneous syncope was reported in six patients (17.6%) in the paroxetine group as compared to 18 patients (52.9%) in the placebo group (p < 0.0001). Only one patient (2.9%) asked to be discontinued from the drug for severe side effects. CONCLUSIONS: Paroxetine was found to significantly improve the symptoms of patients with vasovagal syncope unresponsive to or intolerant of traditional medications and was well tolerated by patients.     

Effects of nifedipine on baroreflex modulation of vascular resistance in man

Studies in animals have demonstrated that, in addition to their vascular effects, calcium channel blockers have important effects on baroreceptor function. We performed a series of experiments to determine if nifedipine, in doses employed clinically, alters baroreflex control of vascular resistance in normal humans. Forearm vasoconstrictor responses of 14 normal subjects to unloading of baroreceptors with lower body negative pressure (LBNP), to a cold pressor test and during intra-arterial infusions of norepinephrine were studied in the control state and following administration of nifedipine. Nifedipine had no effect on baseline mean arterial pressure or central venous pressure. Heart rate and forearm blood flow (FBF) increased significantly following nifedipine: heart rate = 59.7 +/- 2.4 bpm before and 72.6 +/- 4.4 bpm after nifedipine (mean +/- SE, p less than 0.001, n = 14); FBF = 4.6 +/- 0.4 ml X min-1 X 100 ml-1 before and 6.7 +/- 1.0 ml X min1 X 100 ml-1 after nifedipine (p less than 0.02, n = 14). Forearm vascular resistance (FVR) tended to decrease following nifedipine but the difference was not significant: FVR = 21.1 +/- 1.4 units before and 17.8 +/- 2.3 units after nifedipine (p = 0.07, n = 14). Nifedipine attenuated forearm vasoconstrictor responses to cold pressor stimulus: delta FVR during cold pressor test = +10.3 +/- 2.4 units before and +4.7 +/- 1.4 units after nifedipine (p less than 0.02, n = 14). Likewise, nifedipine depressed vasoconstrictor responses to intra-arterial infusion of norepinephrine: delta FVR during norepinephrine = +15.5 +/- 3.4 units before and +10.2 +/- 2.9 units after nifedipine (p less than 0.05, n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic significance of heart rate in neurally mediated syncope

BACKGROUND: Vasovagal and vasodepressor syncope are used interchangeably in the literature to describe the common faint syndrome, now collectively named neurally mediated syncope. The significance of heart rate (HR) in these reflex-induced reactions remains unclear. Hypothesis: The study was undertaken to investigate the hemodynamic significance of HR in tilt-induced neurally mediated syncope. METHODS: In all, 113 patients with syncope of unknown etiology were studied by head-up tilt test with invasive hemodynamic monitoring. Thirty-five patients (15 women, 20 men, age range 21 to 72 years) developed syncope and were enrolled for analysis. The hemodynamic data were compared between patients who developed bradycardia (vasovagal group, n = 15) and those without bradycardia (vasodepressor group, n = 20). RESULTS: The baseline hemodynamic data (mean +/- standard deviation) and the hemodynamic responses after 10-min headup tilt were similar between patients in the vasovagal and vasodepressor groups. During syncope, patients with vasovagal reaction developed hypotension and paradoxical bradycardia (HR = 52.4 +/- 5.9 beats/min), while patients with vasodepressor reaction developed a precipitous drop in arterial blood pressure with inappropriate HR (105 +/- 21 beats/min) compensation. Patients with vasovagal syncope manifested a significantly lower cardiac index and a significantly higher systemic vascular resistance index than patients with vasodepressor syncope (1.47 +/- 0.29 vs. 1.97 +/- 0.41 1/min/m2, p < 0.001 and 2098 +/- 615 vs. 1573 +/- 353 dynes x s x cm(-5) x m2, p < 0.003, respectively). A positive correlation existed between HR and cardiac index (r = 0.44, p = 0.008) during syncope in the patients studied. CONCLUSIONS: These findings suggest that the hemodynamic characteristics of vasovagal and vasodepressor reactions are different, and that HR plays a significant role in neurally mediated syncope.     

Effects of mild exercise on insulin sensitivity in hypertensive subjects

Physical exercise increases insulin sensitivity in conditions associated with insulin resistance, such as obesity and diabetes, but little is known in this regard in hypertension. Whether postexercise changes in hemodynamics and/or changes in insulin-induced vasodilatation could contribute to a postexercise increase in insulin sensitivity in hypertensive subjects is unknown. We investigated the effects of acute physical exercise on insulin sensitivity in 10 hypertensive and 10 normotensive subjects during a control evaluation (CTRL), during lower body negative pressure (LBNP), after 30 minutes of mild bicycle exercise (POSTEX), and during LBNP after exercise (POSTEX+LBNP). Insulin-induced vasodilatation was assessed from peak forearm blood flow during the intravenous glucose tolerance test. Cardiac output (4.9+/-0.3 versus 5.3+/-0.4 L/min, mean+/-SEM) and insulin sensitivity (the glucose disappearance rate over insulin area under the curve: 0.91+/-0.07 versus 1.38+/-0.25 min(-1)/[pmol. L(-1)]. minute) were lower (both P<0.05) in hypertensive than in normotensive subjects, respectively. Cardiac output decreased during LBNP, increased during POSTEX, and was similar to control during POSTEX+LBNP in both groups. Insulin sensitivity was unchanged during LBNP, increased during POSTEX, and remained elevated during POSTEX+LBNP in hypertensive subjects, whereas it remained unchanged in normotensives. Peak forearm blood flow was significantly lower in hypertensive than in normotensive subjects, despite higher insulin levels in hypertensives, and was not modified by LBNP or exercise. In conclusion, insulin sensitivity increases after exercise in hypertensive subjects, and the increase in cardiac output does not contribute to this effect. Endogenous insulin-induced vasodilatation is reduced in hypertensive subjects, and this insulin action is not affected by physical exercise.     

Impaired responsiveness of the ventricular sensory receptor in hypertensive patients with left ventricular hypertrophy

We studied the control of forearm vascular resistance (FVR) by cardiopulmonary receptors in seven patients with hypertension and left ventricular hypertrophy (LVH) and in seven normotensive control subjects. Increasing levels of lower body negative pressure (LBNP) (-10 and -40 mm Hg) induced a progressive decrease in central venous pressure (CVP) and an increase in FVR. The changes in these two variables were correlated both in normal subjects and patients with hypertension (slope for normal subjects = -29.9, for patients with hypertension = -40.3, NS). After propranolol, there was a significant reduction in the increase in FVR induced by -40 mm Hg LBNP in normal subjects (+107 +/- 5 vs +129 +/- 15 mm Hg/ml/sec, p less than .05) but not in patients with hypertension. Consequently, the slope of the delta CVP/delta FVR regression was reduced in normal subjects (-20.6, p less than .01) but not in patients with hypertension. In another seven normal subjects and seven patients with hypertension and LVH we assessed the effects of -10 and -40 mm Hg LBNP on left ventricular filling pressure (LVFP). LBNP induced similar changes in CVP, LVFP, and total peripheral resistance both in normal subjects and in patients with hypertension. Propranolol failed to modify the effects of LBNP on CVP and LVFP in both groups and reduced the response of total peripheral resistance to -40 mm Hg LBNP only in normal subjects. Propranolol did not reduce the response of FVR to the cold pressor test and sustained handgrip or the arterial baroreflex response to the injection of phenylephrine and increased neck tissue pressure. Thus, hypertension-induced LVH seems to be associated with a selective impairment of the left ventricular sensory receptors.     

Effectiveness of paroxetine in the treatment of refractory vasovagal syncope in young patients

OBJECTIVES: The aim of the study was to assess whether the well-tolerated serotonin re-uptake inhibitor paroxetine hydrochloride could prevent vasovagal syncope in young patients resistant to or intolerant of previous traditional therapies. BACKGROUND: Serotonergic mechanisms may play a major role in the pathophysiology of neurocardiogenic syncope, and serotonin re-uptake inhibitors have been recently reported to be effective in preventing episodes. METHODS: Forty-one consecutive young patients (13 male and 28 female), aged less than thirty years with recurrent syncope and positive head-up tilt test, and in whom standard therapies with beta-blocking, vagolytic, negative inotropic or mineral corticoid agents were ineffectual, poorly tolerated or contraindicated, randomly received either paroxetine at 20 mg once a day or a placebo. A head-up tilt test was then re-performed after one month of treatment, and the clinical effect was noted over a mean follow-up of 27.1 +/- 6.6 months. RESULTS: The response rates (negative tilt test) after one month of treatment were 57.1 versus 33.3% (p < 0.001) in the paroxetine and placebo groups, respectively. During follow-up, spontaneous syncope was observed in 4 patients (19%) in the paroxetine group and in 12 patients (60%) in the placebo group (p < 0.001). Only one patient (4.8%) asked to be discontinued from the drug for severe recurrent headache. CONCLUSIONS: Paroxetine significantly improved symptoms of young patients with recurrent vasovagal syncope unresponsive to or intolerant of traditional medications and was well tolerated by patients.     

Reduced susceptibility to syncope during postural tilt in old age. Is beta-blockade protective?

Clinical studies of syncope suggest a decreased prevalence of vasovagal syncope in old age. To examine this possibility and its pathophysiologic implications, we report the results of two studies. The first evaluated responses to head-up tilt in young and old subjects. Presyncopal vasovagal symptoms occurred in 4 of 9 young subjects and only 1 of 22 old subjects. The second study asked whether decreased beta-adrenergic responsiveness protected the old during tilt via unopposed alpha-adrenergic-mediated vasoconstriction. Blood pressure, heart rate, and forearm vascular resistance responses to tilt in 11 healthy young subjects randomized to receive intravenous propranolol hydrochloride or saline were compared with those of 10 healthy elderly. Propranolol attenuated heart rate and forearm vascular resistance responses. Vasovagal symptoms occurred in 4 young and no old subjects; 2 were symptomatic during propranolol administration. Thus, presyncopal vasovagal symptoms are less common during tilt in old age. Propranolol did not prevent the vasovagal reaction or enhance forearm vasoconstriction. Propranolol's attenuation of vasoconstriction may be due to decreased activation of cardiopulmonary baroreceptors during beta-blockade.     

Usefulness of physical maneuvers for prevention of vasovagal syncope.

BACKGROUND: It is known that approximately two-thirds of patients with vasovagal syncope have prodromal symptoms and when these start, physical maneuvers that can increase venous return may abort the syncopal attack. The aims of this study were to evaluate the effects of 3 physical maneuvers, squatting, leg-crossing with muscle tensing, and handgrip, on improving hemodynamic status, and to compare the effect of each on aborting or preventing vasovagal syncope. METHODS AND RESULTS: Of 50 patients who underwent the head-up tilt test (HUT) to evaluate syncope, 27 patients with positive HUT were classified as group I (14 men, 13 women; mean age 44.5+/-15.3 years), 23 patients with negative HUT were classified as group II (13 men, 10 women; mean age 41.2 +/-16.7 years), and 21 normal subjects were classified as group III (10 men, 11 women; mean age 28.6+/-6.3 years). The effects of the physical maneuvers were evaluated in 21 patients from group I who underwent a repeat HUT 1 week after the initial test. Leg-crossing significantly increased systolic blood pressure (SBP) in all 3 groups (8.0+/-5.8 mmHg in group I, 7.0+/-8.5 mmHg in group II, 8.7+/-5.7 mmHg in group III; p < 0.05), but not diastolic blood pressure (DBP). Squatting significantly increased SBP and DBP in all 3 groups (7.1 +/-5.1, 4.6+/-5.8 mmHg in group I, 7.8+/-5.9, 4.3+/-4.7 mmHg in group II, 6.5+/-5.0, 3.7+/-3.9 mmHg in group III; p < 0.05). However, handgrip did not exert any significant influence on the hemodynamics in any group nor did heart rate change significantly during the physical maneuvers in any group. During the repeat HUT, prodromal symptoms with hypotension developed in 13 of the 21 patients and of these 5 fainted immediately after and were not able to do the physical maneuvers. Squatting and leg-crossing aborted syncope in 7 of 8 patients, but handgrip aborted syncope in only 1 patient. CONCLUSION: Squatting and leg-crossing with muscle tensing improved the hemodynamics of normal subjects as well as those of patients with vasovagal syncope. Squatting and leg-crossing can be used as a simple and effective preventive maneuver in patients with vasovagal syncope.     

Augmented cardiopulmonary baroreflex control of forearm vascular resistance in young athletes

The aim of this study was to examine the effect of exercise training on reflex control of vascular resistance in human males. Forearm vascular responses to lower body negative pressure (LBNP) at -10 and -40 mm Hg were compared between highly trained young athletes (21.5 +/- 0.5 years old, n = 14) and age-matched nonathletes (20.7 +/- 0.5 years old, n = 16). Resting heart rate was lower in athletes than in nonathletes. Resting blood pressure, central venous pressure, forearm blood flow, and forearm vascular resistance were not different between the two groups. The magnitude of reflex forearm vasoconstriction in response to LBNP at -10 mm Hg, which decreased central venous pressure but did not alter blood pressure or heart rate, was greater in athletes than in nonathletes. The slope of the regression line relating changes in central venous pressure and forearm vascular resistance was steeper in athletes than in nonathletes. Vasoconstrictive responses to intraarterially administered norepinephrine and angiotensin II did not differ between athletes and nonathletes. These results suggest that the tonic inhibitory influence of the cardiopulmonary receptors is augmented in athletes. This augmentation may contribute to some of cardiovascular and endocrine adaptations that occur with exercise training.     

Distinct hemodynamic profiles in patients with vasovagal syncope: a heterogeneous population

OBJECTIVE: The objective was to investigate mechanisms of vasovagal syncope by identifying laboratory techniques that characterize cardiovascular profiles in patients with vasovagal syncope. BACKGROUND: The triggering mechanisms of vasovagal syncope are complex. The patient population is likely heterogeneous. We hypothesized that distinct hemodynamic profiles are definable with provocative maneuvers. METHODS: Three groups of subjects were matched for age and gender: 16 patients with a history of syncope and an inducible vasovagal response during passive tilt table testing (70 degrees, 45 min, group I), 16 with a history of syncope, negative passive tilt table testing but positive isoproterenol tilt table testing (0.05 microg/kg per min, 70 degrees, 10 min, group II), and 16 control subjects. Beat-to-beat hemodynamic functions were determined noninvasively by photo-plethysmography and impedance cardiography. RESULTS: At baseline, hemodynamic functions were not different among the three groups (supine). In response to tilt before any symptoms developed, total peripheral resistance decreased 9% +/- 14% in group I from baseline supine to tilt position but increased 27% +/- 18% in group II and 28% +/- 17% in controls (p < 0.001). Responses to isoproterenol were not significantly different between group II and controls in supine position. In response to tilt during isoproterenol infusion before any symptoms developed, total peripheral resistance decreased 24% +/- 20% in group II and increased 20% +/- 48% in controls (p = 0.002). CONCLUSIONS: Group I patients may have impaired ability to increase vascular resistance during orthostatic stress. The inability to overcome isoproterenol-induced vasodilatation during tilt is important in triggering a vasovagal response in group II patients. These data suggest that the population with vasovagal response is heterogeneous. Distinct hemodynamic profiles in response to various provocative maneuvers are definable with noninvasive, continuous monitoring techniques.     

Systolic dysfunction and blood pressure responses to supine exercise in patients with hypertrophic cardiomyopathy

Left ventricular function and blood pressure responses were evaluated in 56 patients with non-obstructive hypertrophic cardiomyopathy (HCM) and 12 control subjects by using a radionuclide ventricular function monitor during supine ergometer exercise. Patients with HCM were divided into 2 groups: (i) group A had no decrease in ejection fraction (EF) during exercise; and (ii) group B had a decrease in EF during exercise. During exercise, the change in end-diastolic volume did not differ between the 3 groups. In contrast, the change in end-systolic volume differed between the 3 groups (p<0.0001). The change in systolic blood pressure (SBP) also differed significantly between the 3 groups. The change in SBP in group B was smaller than that in the control group and group A, and changes in the EF and changes in the SBP between rest and peak exercise showed a significant correlation (p<0.005). These results suggest that exercise-induced systolic dysfunction in patients with non-obstructive HCM may contribute to abnormal blood pressure response in those patients.     

Cardiovascular and catecholamine changes induced by supine exercise and upright posture in vasovagal syncope: Comparisons with normal subjects and subjects with sympathetic denervation

The haemodynamic and catecholamine responses to supine leg exercisewere studied in vasovagal syncope (n=10), pure autonomic failure(n=10) and in control (n=10) subjects. With exercise, blood pressure increased in controls; with asmaller rise in vasovagal syncope, and a substantial fall inpure autonomic failure. Heart rate increased similarly in controlsand vasovagal syncope, but less in pure autonomic failure. Theincrease in cardiac index was less in controls and pure autonomicfailure than vasovagal syncope; the fall in systemic vascularresistance was greatest in pure autonomic failure, but alsofell more in vasovagal syncope than controls. Plasma noradrenalinelevels increased in controls; with a smaller rise in vasovagalsyncope and no increase in pure autonomic failure. Plasma adrenalinelevels increased in vasovagal syncope only. The blood pressureresponses to standing before and after exercise were similarin controls and vasovagal syncope, with no postural blood pressurefall; in pure autonomic failure there was a greater posturalblood pressure fall post exercise. In conclusion, with supine exercise, blood pressure rose incontrols and vasovagal syncope, and fell in pure autonomic failure.Systemic vascular resistance fell more in vasovagal syncopeand pure autonomic failure, than controls. Noradrenaline responsesdiffered and adrenaline rose in vasovagal syncope only. Standingpost exercise did not induce syncope in vasovagal syncope, butincreased postural hypotension in pure autonomic failure. Thereare clear differences in response to exercise in vasovagal syncopeand pure autonomic failure. The differences between vasovagalsyncope and control subjects suggest an underlying abnormalitywhich may predispose to vasodepression in subjects with vasovagalsyncope.     

Isometric arm counter-pressure maneuvers to abort impending vasovagal syncope

OBJECTIVES: We hypothesized that isometric arm exercises were able to increase blood pressure (BP) during the phase of impending vasovagal syncope and allow the patient to avoid losing consciousness. BACKGROUND: Hypotension is always present during the prodromal phase of vasovagal syncope. METHODS: We evaluated the effect of handgrip (HG) and arm-tensing in 19 patients affected by tilt-induced vasovagal syncope. The study consisted of an acute single-blind, placebo-controlled, randomized, cross-over tilt-table efficacy study and a clinical follow-up feasibility study. RESULTS: In the acute tilt study, HG was administered for 2 min, starting at the time of onset of symptoms of impending syncope. In the active arm, HG caused an increase in systolic blood pressure (SBP) from 92 +/- 10 mm Hg to 105 +/- 38 mm Hg, whereas in the placebo arm SBP decreased from 91 +/- 11 mm Hg to 73 +/- 21 mm Hg (p = 0.008). Heart rate behavior was similar in the two arms. In the active arm, 63% of patients became asymptomatic, versus 11% in the control arm (p = 0.02); conversely, only 5% of patients developed syncope, versus 47% in the control arm (p = 0.01). The patients were trained to self-administer arm-tensing treatment as soon as symptoms of impending syncope occurred. During 9 +/- 3 months of follow-up, the treatment was actually performed in 95/97 episodes of impending syncope (98%) and was successful in 94/95 (99%). No patients suffered injury or other adverse morbidity related to the relapses. CONCLUSIONS: Isometric arm contraction is able to abort impending vasovagal syncope by increasing systemic BP. Arm counter-pressure maneuvers can be proposed as a new, feasible, safe, and well accepted first-line treatment for vasovagal syncope.     

Effects of α1-Blockade on the Forearm Vascular Resistance Responses to Lower Body Negative Pressure in Young Borderline Hypertensives

To determine whether α₁-blockade affects the forearm vascular resistance responses to lower body negative pressure (LBNP) in borderline hypertensives, six hypertensives (HTN; mean arterial pressure [MAP] = 109.9 ± 1.7 mm Hg, mean ± SE) and seven normotensives (NTN; MAP = 81.5 ± 1.4 mm Hg) underwent exposures of LBNP at pressures of −10, −20, and −40 mm Hg during systemic α₁-receptor blockade (BLK) and during placebo (PLA). Resting forearm vascular resistance (FVR) was greater in HTN than in NTN during PLA (34.8 ± 5.4 v 17.5 ± 3.1 units; P < .05), but not during BLK (28.1 ± 5.2 v 25.3 ± 9.9 units). When expressed as a percentage of resting FVR, LBNP evoked an increased FVR (P < .001) that did not differ significantly between BLK and PLA in either group. FVR was higher (P < .001) in HTN than in NTN throughout both trials; at −40 mm Hg of LBNP during BLK, the increase in FVR was greater (P < .05) in HTN than in NTN (131 ± 42 v 48 ± 15%). MAP (relative to resting) was maintained throughout LBNP during PLA but, at −40 mm Hg, was lower (P < .01) during BLK for both groups. HR was elevated in BLK and was increased at −40 mm Hg (P < .01) for each group in each trial. This increase was greater during BLK (P < .05). These data suggest that borderline hypertensives have a greater vasoconstrictor response to LBNP than do normotensives and α₁-blockade does not appear to attenuate this response.