Yohimbine in neurally mediated syncope. Pathophysiological implications.

Mosqueda‐Garcia, Rogelio; Fernandez-Violante, Roxana; Tank, Jens; Snell, Marie; Cunningham, Gary; Furlan, Raffaello

doi:10.1172/jci3050

Cited by 49 publications

(31 citation statements)

References 27 publications

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“…Nitroprusside infusion led to an increase in heart rate and sympathetic traffic. 1,3,4 None of the subjects had any evidence for impaired autonomic function. Yet, baroreflex function and sensitivities to phenylephrine and nitroprusside were highly variable.…”

Section: Discussionmentioning

confidence: 98%

“…Application of a vasodilator is associated with a baroreflex-mediated increase in heart rate and sympathetic traffic to the vasculature. 1,3,4 In contrast, a vasoconstrictor elicits a decrease in heart rate and sympathetic nerve traffic. 1,3,4 Thus, the baroreflex buffers the effect of vasoactive medications.…”

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confidence: 99%

“…1,3,4 In contrast, a vasoconstrictor elicits a decrease in heart rate and sympathetic nerve traffic. 1,3,4 Thus, the baroreflex buffers the effect of vasoactive medications. In patients with damage to the afferent arc (baroreflex failure), the sensitivity to phenylephrine and nitroprusside is dramatically increased.…”

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confidence: 99%

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Baroreflex Buffering and Susceptibility to Vasoactive Drugs

et al. 2002

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Background-The overall effect of vasoactive drugs on blood pressure is determined by a combination of the direct effect on vascular tone and an indirect baroreflex-mediated effect, a baroreflex buffering of blood pressure. Differences in baroreflex function affect the responsiveness to vasoactive medications, particularly baroreflex buffering of blood pressure; however, the magnitude is not known. Methods and Results-We characterized baroreflex function and responses to vasoactive drugs in patients with idiopathic orthostatic intolerance, patients with essential hypertension, patients with monogenic hypertension and brachydactyly, patients with multiple system atrophy, and control subjects. We used phenylephrine sensitivity during ganglionic blockade as a measure of baroreflex buffering. Phenylephrine (25 g) increased systolic blood pressure 6Ϯ1.6 mm Hg in control subjects, 6Ϯ1.1 mm Hg in orthostatic intolerance patients, 18Ϯ3.9 mm Hg in patients with essential hypertension, 31Ϯ3.4 mm Hg in patients with monogenic hypertension, and 25Ϯ3.4 mm Hg in patients with multiple system atrophy. Similar differences in sensitivities between groups were observed with nitroprusside. The sensitivity to vasoactive drugs was highly correlated with baroreflex buffering function and to a lesser degree with baroreflex control of heart rate. In control subjects, sensitivities to nitroprusside and phenylephrine infusions were correlated with baroreflex heart rate control and sympathetic nerve traffic. Conclusions-Our findings are consistent with an important effect of baroreflex blood pressure buffering on the sensitivity to vasoactive drugs. They suggest that even moderate changes in baroreflex function may have a substantial effect on the sensitivity to vasoactive medications.

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Section: Discussionmentioning

confidence: 98%

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Baroreflex Buffering and Susceptibility to Vasoactive Drugs

et al. 2002

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“…BP reduction is followed by baroreflex-mediated increases in heart rate (HR) and sympathetic vasomotor tone. 1,3,4 An increase in BP attenuates HR and sympathetic vasomotor tone. 1,3,4 Thus, the baroreflex serves as a buffer to prevent excessive BP swings.…”

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confidence: 99%

α-2 Adrenergic Transmission and Human Baroreflex Regulation

et al. 2004

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Abstract-We observed earlier that central ␣-2 adrenoceptor stimulation in mice greatly augments parasympathetic tone.To test the effects in humans, we assessed autonomic vasomotor tone and baroreflex regulation in 9 normal young adults on 2 occasions, once with and once without clonidine. We determined heart rate (HR), beat-by-beat blood pressure (BP), and muscle sympathetic nerve activity. HR variability was analyzed in the time and frequency domain. Pharmacological baroreflex slopes were determined using incremental phenylephrine and nitroprusside infusions. Clonidine lowered resting BP (122Ϯ4/73Ϯ3 versus 100Ϯ7/55Ϯ3 mm Hg, PϽ0.01), muscle sympathetic nerve activity (18Ϯ3 versus 4Ϯ2 bursts/min, PϽ0.01), and HR (62Ϯ3 versus 56Ϯ3 bpm, PϽ0.05). The baroreflex heart rate curve was reset to much lower HR values and showed no saturation at low HR. HR variability profoundly increased during clonidine plus phenylephrine (total power: 3224Ϯ843 versus 8943Ϯ2329 ms 2 , PϽ0.05). High-frequency power was 1451Ϯ520 at baseline and 6720Ϯ2475 ms 2 during baroreceptor loading (PϽ0.05). The low-frequency/high-frequency ratio decreased (1.94Ϯ0.41 versus 0.69Ϯ0.10, PϽ0.05). In contrast, clonidine reduced resting sympathetic vasomotor tone and shifted the operating point of the sympathetic baroreflex to a flat part of the sympathetic baroreflex curve. The shift decreased the ability of the baroreflex to withdraw sympathetic vasomotor tone during baroreflex loading. These baroreflex changes were associated with a moderate increase in phenylephrine responsiveness. We conclude that ␣-2 adrenoceptor stimulation has a differential effect on baroreflex HR and vasomotor regulation. ␣-2 Adrenoceptor stimulation greatly augments baroreflex-mediated bradycardia, most likely by parasympathetic activation. Key Words: antihypertensive, agents Ⅲ blood pressure Ⅲ heart rate Ⅲ baroreflex Ⅲ sympathetic nervous system C hanges in arterial blood pressure (BP) are sensed by carotid, aortic, and perhaps coronary baroreceptors. 1,2 The signal is integrated in cardiovascular control centers in the brain stem and leads to compensatory adjustments in sympathetic and parasympathetic activity. BP reduction is followed by baroreflex-mediated increases in heart rate (HR) and sympathetic vasomotor tone. 1,3,4 An increase in BP attenuates HR and sympathetic vasomotor tone. 1,3,4 Thus, the baroreflex serves as a buffer to prevent excessive BP swings. 5,6 The buffering function is severely impaired in patients with bilateral damage to baroreceptors or baroreflex afferents (baroreflex failure). 7,8 These patients feature extreme volatility of BP. Neuronal degeneration of sympathetic and parasympathetic efferents is tantamount to autonomic failure. Patients with autonomic failure have severe orthostatic hypotension. 9,10 These rare diseases illustrate the pivotal role of baroreflexes in short-term cardiovascular regulation in humans. Even subtle changes in baroreflex function may elicit important cardiovascular effects. Adrenergic mechanisms in the brain have an impo...

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“…For many years, it has been thought that a combination of a left ventricular hypercontractile state with decreased cardiac filling precipitates neurocardiogenic syncope via "collapse firing" of cardiac or central venous baroreceptors (82,83). Recent studies have not supported aspects of this hypothesis because syncope usually is attended by a precipitous decrease in sympathetic nervous system outflow without clear preceding ventricular hypovolemia or hypercontractility (84,85).…”

Section: Dysautonomia and The Chronic Fatigue Syndromementioning

confidence: 99%

Dysautonomias: Clinical Disorders of the Autonomic Nervous System

Goldstein

Robertson²,

Esler³

et al. 2002

Ann Intern Med

182

111

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The term dysautonomia refers to a change in autonomic nervous system function that adversely affects health. The changes range from transient, occasional episodes of neurally mediated hypotension to progressive neurodegenerative diseases; from disorders in which altered autonomic function plays a primary pathophysiologic role to disorders in which it worsens an independent pathologic state; and from mechanistically straightforward to mysterious and controversial entities. In chronic autonomic failure (pure autonomic failure, multiple system atrophy, or autonomic failure in Parkinson disease), orthostatic hypotension reflects sympathetic neurocirculatory failure from sympathetic denervation or deranged reflexive regulation of sympathetic outflows. Chronic orthostatic intolerance associated with postural tachycardia can arise from cardiac sympathetic activation after "patchy" autonomic impairment or blood volume depletion or, as highlighted in this discussion, from a primary abnormality that augments delivery of the sympathetic neurotransmitter norepinephrine to its receptors in the heart. Increased sympathetic nerve traffic to the heart and kidneys seems to occur as essential hypertension develops. Acute panic can evoke coronary spasm that is associated with sympathoneural and adrenomedullary excitation. In congestive heart failure, compensatory cardiac sympathetic activation may chronically worsen myocardial function, which rationalizes treatment with ␤-adrenoceptor blockers. A high frequency of positive results on tilt-table testing has confirmed an association between the chronic fatigue syndrome and orthostatic intolerance; however, treatment with the salt-retaining steroid fludrocortisone, which is usually beneficial in primary chronic autonomic failure, does not seem to be beneficial in the chronic fatigue syndrome. Dysautonomias are an important subject in clinical neurocardiology. The notion that the sympathetic nervous system coordinates body functions probably originated with the second-century Greek physician Galen, who taught that nerves were hollow tubes distributing "animal spirits" in the body, thereby fostering concerted action, or "sympathy," of the organs. In 1552, Bartolomeo Eustachius first depicted the sympathetic nerves and the adrenal glands. Winslow reintroduced the sympathetic nervous system in 1732 to describe the chains of ganglia and nerves connected to the thoracic and lumbar spinal cord.The functions of these structures remained unknown until the 19th century, when Bernard and others first reported the effects of sympathetic nerve stimulation. In 1895, Oliver and Schäfer described the potent cardiovascular stimulatory effects of adrenal extracts. Soon afterward-almost exactly a century ago-Abel and Takamine identified epinephrine ("adrenaline" in British and European countries) as the active principle of the adrenal gland.Also in the late 19th century, Langley coined the term autonomic nervous system to denote the portion of the nervous system largely responsible for involuntary, unc...

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Yohimbine in neurally mediated syncope. Pathophysiological implications.

Cited by 49 publications

References 27 publications

Baroreflex Buffering and Susceptibility to Vasoactive Drugs

Baroreflex Buffering and Susceptibility to Vasoactive Drugs

α-2 Adrenergic Transmission and Human Baroreflex Regulation

Dysautonomias: Clinical Disorders of the Autonomic Nervous System

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