Decrease In Baroreflex Sensitivity Research Articles

The Duration of Impairment of Autonomic Control After Anticholinergic Drug Administration in Humans

Impaired parasympathetic control of heart rate is associated with increased incidence of cardiac dysrhythmias and ischemia.Anticholinergic drugs, commonly administered during reversal of neuromuscular blockade, suppress parasympathetic control in the early postoperative period. This could potentially be detrimental in patients at risk of cardiovascular complications. The duration of parasympathetic impairment by two anticholinergic drugs were compared in this double-blind randomized cross-over study. Fourteen healthy volunteers received a single intravenous injection of atropine 20 micro g/kg or glycopyrrolate 8 micro g/kg during two different study sessions. The methods of spontaneous baroreflex analysis and spectral analysis of heart rate variability generated indices of beat-by-beat parasympathetic modulation of heart rate. Both drugs resulted in a marked decrease in baroreflex sensitivity and high-frequency heart rate variability. The times to return to baseline values were approximately doubled after atropine compared to glycopyrrolate (177 +/- 22 vs 82 +/- 8 min for baroreflex sensitivity, 212 +/- 16 vs 111 +/- 14 min for high-frequency power, and 171 +/- 18 vs 95 +/- 18 min for high-frequency power normalized to total power; P < 0.01 for all variables). Atropine leads to more prolonged impairment of parasympathetic control than equipotent doses of glycopyrrolate, and its use may thus be less desirable in high-risk patients in the early postoperative period. (Anesth Analg 1997;84:155-9)

Baroreflex sensitivity in men with recent myocardial infarction; impact of age

We investigated the effect of age on baroreflex sensitivity (BRS) in 39 male patients, who had survived their first myocardial infarction (MI) and in 15 age-matched controls. BRS was inversely related to age in both MI patients (r = -0.632, P < 0.0001) and controls (r = -0.706, P < 0.0001). The relationship between BRS and age, however, was significantly different in MI patients as compared with healthy controls: BRS was markedly higher and the BRS-age regression slope was significantly steeper in controls than in MI patients. As a consequence, the decrease in BRS caused by MI (delta BRS = age-specific expected BRS--measured BRS) was related inversely to age (r = -0.66, P < 0.05) i.e. delta BRS was greatest among young MI patients. However, the relative BRS (BRS% = measured BRS divided by the age-specific expected BRS) did not correlate with age. The average BRS% of MI patients was 37% lower than that of controls. MI size and left ventricular (LV) systolic function did not correlate with BRS. BRS correlated with variables related to cardiac diastolic function (peak late LV filling rate r = -0.43, P < 0.05), exercise capacity (r = 0.31, P < 0.05) and the extent of ST-depression during exercise (r = -0.40, P < 0.05), but all these correlations lost their significance after the adjustment for age. In conclusion, age is a factor that should be taken into consideration when evaluating the mechanisms of BRS impairment associated with different diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Ethanol augments the baroreflex‐inhibitory effects of sciatic nerve stimulation in the anaesthetized dog

Electrical stimulation of somatic afferent fibres in the sciatic nerve has been used as a model of injury in the anaesthetized dog. Stimulation of the sciatic nerve (during reflexly induced periods of apnoea to obviate any respiratory effects of sciatic stimulation) led to a simultaneous increase in arterial blood pressure and heart rate and a decrease in baroreflex sensitivity. Infusion of ethanol sufficient to produce clinically relevant plasma ethanol levels (100-200 mg %) had no consistent effects on baroreflex sensitivity, but enhanced the pressor response and significantly augmented the inhibitory effects of sciatic stimulation on the baroreflex. Since ethanol is commonly associated with injury in man, such changes in the response to 'injury' may modify the patients' cardiovascular response to the injury and complicate diagnosis.

Protection by nicorandil against the dysfunction of the central vagal baroreflex system following transient global cerebral ischaemia in dogs

1. A possible cerebroprotective effect of nicorandil was investigated in a canine model of 5 min global cerebral ischaemia, and compared with protective effects of nitroglycerin and nicardipine. 2. Cerebral ischaemia was produced by occlusion of the left subclavian and the brachiocephalic arteries with preceding ligation of the intercostal arteries. The decrease in baroreflex sensitivity (BRS), measured by phenylephrine-induced reflex bradycardia, was used to assess the cerebroprotective effect. 3. Nicorandil (10 or 30 micrograms kg-1 min-1, i.v.), nitroglycerin (3 micrograms kg-1 min-1, i.v.) or nicardipine (0.3 micrograms kg-1 min-1, i.v.) were infused for 60 min just before ischaemia. Nitroglycerin and nicardipine decreased mean arterial blood pressure to an extent similar to that induced by the lower dose of nicorandil. Blood flow in the dorsal medulla oblongata was increased by nicorandil and nicardipine, but not by nitroglycerin. 4. Nicorandil at both doses and nitroglycerin prevented the post-ischaemic decrease in BRS. In these cases, bilateral vagotomy during the reperfusion period decreased BRS, indicating that the vagal component of BRS was protected from ischaemia. On the other hand, nicardipine failed to exert a cerebroprotective effect. 5. The present study suggests that nicorandil may possess a direct cerebroprotective effect and that its property as a nitrate might, at least in part, be important for the observed cerebral protection.

Effects of cocaine on baroreflex control of heart rate in conscious rats

Cocaine administration elicits a pressor response reportedly dependent upon central and peripheral actions. The present study was designed specifically to determine whether cocaine affects baroreflex sensitivity and whether this is mediated by an action in the CNS. Baroreflex control of heart rate was assessed by noting the change in the duration of the arterial pulse pressure or in the heart rate elicited by administration of pressor and depressor agents. The effects of intracerebroventricular and intravenous cocaine administration were compared. Cocaine (0.1-0.15 mg/kg/min, i.v.) produced a decrease in baroreflex sensitivity that was greater than that produced by an approximately equipressor infusion of phenylephrine (0.5-1.3 μg/kg/min, i.v.). Intracerebroventricular (i.c.v.) administration of cocaine (1.5–150 μg) or procaine (100 μg) had no effect on arterial pressure, heart rate or baroreflex control of heart rate. Furthermore, central administration of yohimbine (3 and 10 μg, i.c.v.) was capable of preventing the suppression of the heart rate responses induced by cocaine administration. Propranolol (15 μg, i.c.v.) was not able to attenuate the suppression of baroreflex sensitivity elicited by intravenous cocaine administration but higher doses (50–150 μg, i.c.v.) could mimic this effect. These data suggest that cocaine suppresses baroreflex control of heart rate by a central α 2-adrenergic mechanism. In contrast, the pressor response to intravenous cocaine is not likely to be dependent upon a forebrain periventricular site.

Selective contribution of two types of carotid sinus baroreceptors to the control of blood pressure.

This study was performed to determine if selective elimination of afferent input from two different types of previously described baroreceptors altered the ability of the dog to regulate blood pressure (BP), examining specifically if there was differential loss of baroreceptor control of tonic levels of baseline pressure versus dynamic changes in pressure. In the first series of experiments in this study, anodal block of the carotid sinus nerve was used to selectively block afferent input in a sequence from large-diameter A-fiber carotid baroreceptors (mostly type I) to smaller A-fiber and nonmyelinated C-fiber baroreceptors (mostly type II). In the second series of experiments, anesthetic block of the carotid sinus nerve with bupivacaine was used to selectively eliminate afferent input in reverse order from anodal block, first blocking input from baroreceptors with small afferent fibers and then additionally eliminating input from the larger-diameter A-fiber baroreceptors. The effects of selective elimination of each baroreceptor type were determined by monitoring baseline BP during constant carotid sinus pressure (CSP) perfusion of a vascularly isolated carotid sinus (tonic control) and obtaining baroreflex sensitivity (slope) during ramp pressure stimulations of the carotid sinus (dynamic control) under various blocking conditions. Low levels of anodal block significantly attenuated baroreflex sensitivity (-0.84 +/- 0.11 versus -0.63 +/- 0.10 mm Hg BP/mm Hg CSP) at levels of block that had no effect on tonic baseline BP (158.41 +/- 9.5 versus 160.7 +/- 9.5 mm Hg BP). In contrast, low levels of bupivacaine block produced significant increases in tonic BP (158.8 +/- 6.4 versus 169.0 +/- 6.5 mm Hg BP), whereas there was no effect on dynamic baroreflex sensitivity (-0.85 +/- 0.08 versus -0.73 +/- 0.08 mm Hg BP/mm Hg CSP). Thus, blocking large A-fiber baroreceptors resulted in significant decreases in baroreflex sensitivity without changes in baseline levels of BP, indicating primarily an attenuation in dynamic baroreflex regulation. Blocking of smaller A-fiber and unmyelinated C-fiber baroreceptors resulted in smaller decreases in baroreflex sensitivity and significant elevations in baseline BP, indicating a loss of tonic control of pressure. These results suggest that the two types of baroreceptors contribute differently to the regulation of blood pressure.

Contrasting Influences of Central and Peripheral Opioids on Cardiac Baroreflex Sensitivity in Rabbits

We studied the effects of naloxone [0.1 mg/kg intravenously (i.v.) or 7.5 micrograms/kg intracisternally (i.c.)], naloxone methyl iodide (NMI, 0.2 mg/kg, i.v. or 15 micrograms/kg i.c.) and morphine (2 mg/kg i.v.) on the cardiac baroreflex elicited in conscious rabbits especially bred for high and low baroreflex sensitivity (BRS) (group I, BRS > 5.5 beats/min/mm Hg and group II BRS < 4 beats/min/mm Hg, respectively). Full sigmoid barocurves were produced in 37 rabbits by i.v. injection of phenylephrine (1-15 micrograms/kg) and nitroglycerin (1-20 micrograms/kg) after pretreatment with saline or one of the above drugs. In group I, both naloxone i.v. and i.c. and NMI i.c. significantly reduced BRS and decreased the degree of bradycardia in response to a pressor stimulus; neither morphine nor NMI i.v. had any effect. In group II, naloxone i.v. and i.c. and NMI i.c. had no effect on BRS, but both morphine and NMI i.v. significantly increased BRS. An even greater increase was achieved by a combination of these drugs, which also increased specifically the degree of tachycardia in response to a decrease in blood pressure (BP). The results suggest that baroreceptor activation in group I released in the brainstem an opioid peptide that acts to increase BRS. In contrast, group II rabbits responded by peripheral opioid activation, which results in a decrease in BRS, possibly by inhibiting norepinephrine (NE) release from cardiac neurons. The predominance of peripheral or central opioid involvement in BRS modulation appears to be due to genetic factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Difference between Halothane and Barbiturate Anesthesia in the Influence of Cerebral Ischemia on the Vagal Baroreflex in Dogs.

In halothane-anesthetized dogs, a decrease in baroreflex sensitivity (BRS) of approximately 20% was observed during the reperfusion period following 5-min global cerebral ischemia. When compared with our previous study on animals under pentobarbital anesthesia, the extent of the decrease in BRS was smaller and apparently more severe ischemia was necessary to damage the vagal component of the baroreflex. Substitution of halothane with pentobarbital during the reperfusion period failed to affect either BRS or the ratio of the vagal component. In another group, pre- and post-ischemic measurements of BRS was performed under halothane anesthesia, but the ischemic insult was given under thiopental anesthesia. In these animals, the extent of decrease in BRS (about 50%) was greater than that in animals subjected to ischemia under halothane anesthesia. The present results suggest that the anesthetics used during the ischemic insult may affect the extent of post-ischemic dysfunction of the baroreflex. The vagal component of the baroreflex may be more resistant to ischemia under halothane anesthesia than under barbiturate anesthesia.

Difference between Halothane and Barbiturate Anesthesia in the Influence of Cerebral Ischemia on the Vagal Barorflex in Dogs

In halothane-anesthetized dogs, a decrease in baroreflex sensitivity (BRS) of approximately 20% was observed during the reperfusion period following 5-min global cerebral ischemia. When compared with our previous study on animals under pentobarbital anesthesia, the extent of the decrease in BRS was smaller and apparently more severe ischemia was necessary to damage the vagal component of the baroreflex. Substitution of halothane with pentobarbital during the reperfusion period failed to affect either BRS or the ratio of the vagal component. In another group, pre- and post-ischemic measurements of BRS was performed under halothane anesthesia, but the ischemic insult was given under thiopental anesthesia. In these animals, the extent of decrease in BRS (about 50%) was greater than that in animals subjected to ischemia under halothane anesthesia. The present results suggest that the anesthetics used during the ischemic insult may affect the extent of post-ischemic dysfunction of the baroreflex. The vagal component of the baroreflex may be more resistant to ischemia under halothane anesthesia than under barbiturate anesthesia.

Large dose of flunitrazepam attenuates baroreflex control of heart rate in man.

The effects of intravenous tranquilizers such as flunitrazepan, diazepam and droperidol on baroreflex control of heart rate were investigated using both pressor and depressor tests. The dose-dependency was also studied by the administration of the drugs at the usual or twofold dosage. The usual dosage caused no significant change in neuronal controlling mechanism of circulation. However, flunitrazepam at double the usual dosage produced a decrease in baroreflex sensitivity at depressor tests. The results suggest that flunitrazepam when given repeatedly might accelerate hemodynamic derangements induced by an acute decrease in blood pressure.

Hemodynamic and sympathetic effects of spinal administration of neuropeptide Y in rats

Intrathecal administration of 4 nmol/kg neuropeptide Y in Dial-urethane-anesthetized rats elicited decreases in arterial pressure, renal sympathetic nerve activity, and a slight decrease in heart rate. The depressor response was associated with a sustained hindquarters and mesenteric vasodilation resulting in a decrease in total peripheral resistance. Intrathecal NPY also resulted in a decrease in renal sympathetic nerve activity. There was a positive correlation between the percent changes in arterial pressure and renal sympathetic nerve activity. With the use of renal nerve activity and heart rate as indexes, NPY resulted in a decrease in baroreflex sensitivity. The depressor effect of intrathecal NPY did not appear to be due to spinal vasoconstriction and ischemia, since spinal microvascular resistance was decreased slightly. We conclude that the intrathecal administration of NPY produces an inhibition of sympathetic nerve activity, resulting in a decrease in total peripheral resistance and arterial pressure.

Selective dysfunction of the vagal component of the baroreflex following cerebral Ischemia: protection by ifenprodil and flunarizine

Baroreflex sensitivity assessed from the phenylephrine-induced reflex bradycardia was significantly decreased following 5 min global incomplete cerebral ischemia in pentobarbitalized dogs. Although bilateral vagotomy in the cervical region decreased baroreflex sensitivity by about 50% in sham-operated animals, it hardly affected the baroreflex in animals subjected to ischemia. The extent of the decrease in she influence of vagotomy on the baroreflex was dependent on the severity of ischemia in the dorsal medulla oblongata. In animals vagotomized before ischemia, no significant decrease in baroreflex sensitivity was observed following ischemia. Pretreatment with ifenprodil or flunarizine, 1 mg/kg i.V., 5 min prior to ischemia prevented the post-ischemic decrease in baroreflex sensitivity. Vagotomy decreased baroreflex sensitivity during the reperfusion period in these treated animals. These results suggest that the post-ischemic attenuation of reflex bradycardia may be due to a selective dysfunction of the vagal component of baroreflex, which can be prevented by the cerebroprotective agents.

Effect of flunarizine on the attenuation of baroreflex by transient cerebral ischemia

Baroreflex sensitivity assessed by phenylephrine-induced reflex bradycardia was markedly decreased by 5- an 10-min global cerebral ischemia in anesthetized dogs. Flunarizine, 0.1 and 1 mg/kg i.v., administered 5 min prior to 5-min ischemia, completely inhibited the decrease in baroreflex sensitivity while such a protective effect of the latter dose was incomplete against 10-min ischemia. In contrast, papaverine, 0.5 mg/kg per min i.v., infused for 5 min prior to 5-min ischemia, failed to protect the decrease in baroreflex sensitivity. Flunarizine may possess a certain direct cerebroprotective effect in addition to its cerebrocirculatory effect.

Deterioration of Baroreflex by Transient Global Cerebral Ischemia: Its Correlation with the Degree of Ischemia or Post-lschemic Hypoperfusion in the Medulla Oblongata

AbstractIn a canine model of transient global cerebral ischemia, the correlation between the decrease in baroreflex sensitivity (BRS) following 5-min ischemia and the degree of ischemia or post-ischemic hypoperfusion was investigated. Although the medulla oblongata and the cerebral cortex suffered a similar degree of ischemia, the extent of post-ischemic decrease in BRS was inversely correlated with the residual blood flow during ischemia in the medulla, but not with that in the cerebral cortex. A similar degree of post-ischemic hypoperfusion occurred in the medulla and the cerebral cortex. However, the extent of decrease in BRS was not correlated with the degree of hypoperfusion, and the cortical EEG was not significantly affected. These results suggest that the decrease in BRS may be due to the functional damage in the medulla and that the selective decrease in BRS without concomitant impairment of the EEG cannot be ascribed to the regional difference in the degree of ischemia or post-ischemic hypoperfusion

Deterioration of baroreflex by transient global cerebral ischemia: its correlation with the degree of ischemia or post-ischemic hypoperfusion in the medulla oblongata.

In a canine model of transient global cerebral ischemia, the correlation between the decrease in baroreflex sensitivity (BRS) following 5-min ischemia and the degree of ischemia or post-ischemic hypoperfusion was investigated. Although the medulla oblongata and the cerebral cortex suffered a similar degree of ischemia, the extent of post-ischemic decrease in BRS was inversely correlated with the residual blood flow during ischemia in the medulla, but not with that in the cerebral cortex. A similar degree of post-ischemic hypoperfusion occurred in the medulla and the cerebral cortex. However, the extent of decrease in BRS was not correlated with the degree of hypoperfusion, and the cortical EEG was not significantly affected. These results suggest that the decrease in BRS may be due to the functional damage in the medulla and that the selective decrease in BRS without concomitant impairment of the EEG cannot be ascribed to the regional difference in the degree of ischemia or post-ischemic hypoperfusion.

Acute effects of ethanol on baroreceptor reflex control of heart rate and on pressor and depressor responsiveness in rats.

In rats anesthetized with alpha-chloralose, doses of 0.1, 0.5, and 1 g/kg of ethanol produced an upward shift of baroreflex curves constructed by plotting the heart rate response against mean arterial pressure following evoked rises in mean arterial pressures by phenylephrine or angiotensin II. Whereas the upward shift of baroreceptor curves may be related, at least in part, to a higher base-line heart rate after ethanol, the data showed that the 1 g/kg dose of ethanol significantly depressed baroreflex sensitivity, suggesting that higher doses of ethanol impair baroreflex-mediated bradycardia. The phenylephrine, but not the angiotensin II or the nitroprusside, dose-response curves were shifted to the right after ethanol, indicating a decreased pressor responsiveness and suggesting that ethanol may have alpha-adrenergic blocking activity. This effect was also obtained in conscious rats. That this effect was not influenced by changes in baroreflex sensitivity was supported by the finding that a similar shift of the phenylephrine pressor-response curve was obtained in bilaterally vagotomized and hexamethonium-treated rats. Whether this effect of ethanol on baroreflex control of heart rate was influenced by anesthesia was investigated in conscious rats; the 1 g/kg dose of ethanol that produced the most significant decrease in baroreflex sensitivity was used in these experiments. Ethanol was still able to significantly inhibit baroreflex sensitivity in conscious rats, but the upward shift of the baroreflex curve and the elevated base-line heart rate no longer occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Metoclopramide decreases baroreflex sensitivity in patients with essential hypertension

The effect of metoclopramide (10 mg, iv.) or physiological saline on the exercise-induced (standardized bicycle ergometry) increase in blood pressure and heart rate of patients with essential hypertension was investigated in a double blind, randomized, self controlled study. Metoclopramide had no effect on the exercise -induced increase in blood pressure but significantly enhanced the tachycardia due to ergometry after 4–6 min exercise. The mean slope of linear regression lines calculated from the systolic blood pressure and the corresponding heart rate measured before and during (at 1,2,3,4,5 min) exercise after metoclopramide was significantly steeper than after physiological saline (1.1±0.12 vs 0.79±0.09; mean±SEM), indicating the decrease in baroreflex sensitivity after metoclopramide. On the basis of results the possible role of endogeneous dopaminergic mechanisms in suppressing some components of pressor effect of physical exercise can be hypothesized.

The cardiovascular effects of oxytocin in conscious male rats

In conscious, chronically instrumented normotensive male Wistar rats intravenous (i.v.) administration of oxytocin (OXT) (⩾ 100 ng) induced a dose-related biphasic change in mean arterial pressure (MAP). This consisted of an initial pressor effect accompanied by bradycardia and a decrease in cardiac output (CO), followed by a more prolonged fall in MAP which reached a maximum 30 min after injection and was accompanied by an increase in CO. The more specific (Thr4, Gly7]OXT analogue (0.01–10 μg i.v.) caused a dose-related fall in MAP and a rise in CO which reached a maximum after 15–30 min. Similarly in spontaneously hypertensive rats of the stroke prone strain (SHRSP) an initial pressor effect and delayed fall in MAP were apparent after OXT (0.1 and 10 μg i.v.) only the decrease in MAP being evident with the [Thr4, Gly7]OXT analogue. These responses were significantly larger than those observed in Wistar Kyoto controls. The pressor effects are therefore interpreted to be due to vasopressin receptor activation while the depressor effects appear to be oxytocin specific. In sinoaortic denervated rats, OXT (0.1 and 10 μg i.v.) induced an enhanced initial pressor effect with a much reduced reflex bradycardia and fall in CO. A larger and more prolonged delayed fall in MAP was apparent with both OXT and [Thr4, Gly7]OXT accompanied by a decrease in CO when compared to sham-operated controls. Intracisternally (i.c.) administered OXT (0.05–10 ng) had no effect on MAP or heart rate. However OXT and [Thr4, Gly7]OXT (10 ng i.c.) caused a decrease in baroreflex sensitivity in response to both a rise and a fall in MAP induced by phenylephrine (1 μg) and sodium nitroprusside (13 μg) respectively. It is concluded that OXT is involved in cardiovascular regulation, inducing a decrease in baroreflex sensitivity upon central administration and a fall in MAP when injected i.v.

Baroreflex sensitivity during operant blood pressure conditioning.

Baroreflex sensitivity was measured in baboons operantly conditioned to increase their diastolic blood pressure in daily, 12-hr sessions, by using the extent of increases in interpulse interval per unit of increase in systolic pressure after intravenous phenylephrine injection as an index of baroreflex sensitivity. Following training, baroreflex sensitivity increases averaging 32% were observed before and after the 12-hr conditioning sessions. During the conditioning sessions, however, consistent diastolic blood pressure elevations averaging 17% (14 mmHg) were accompanied by significant decreases in baroreflex sensitivity averaging 44% relative to the increased "before" and "after" sensitivity levels. The results suggest that changes in baroreflex sensitivity participate in operantly conditioned blood pressure changes.

Decrease in baroreflex sensitivity with increasing arterial pressure and with increasing age.

Decrease in baroreflex sensitivity with increasing arterial pressure and with increasing age.