Reflex Increase In Heart Rate Research Articles

The exercise pressor reflex: An update.

The exercise pressor reflex is a feedback mechanism engaged upon stimulation of mechano- and metabosensitive skeletal muscle afferents. Activation of these afferents elicits a reflex increase in heart rate, blood pressure, and ventilation in an intensity-dependent manner. Consequently, the exercise pressor reflex has been postulated to be one of the principal mediators of the cardiorespiratory responses to exercise. In this updated review, we will discuss classical and recent advancements in our understating of the exercise pressor reflex function in both human and animal models. Particular attention will be paid to the afferent mechanisms and pathways involved during its activation, its effects on different target organs, its potential role in the abnormal cardiovascular response to exercise in diseased states, and the impact of age and biological sex on these responses. Finally, we will highlight some unanswered questions in the literature that may inspire future investigations in the field.

English

BACKGROUND Stress response to intubation produces marked hemodynamic changes during direct laryngoscopy using muscle relaxants. Since attenuation of hemodynamic response to laryngoscopy and tracheal intubation leads to better outcomes, a method for providing good intubating conditions rapidly without using muscle relaxants is being sought. The objective of the present study was to compare the hemodynamic changes occurring while intubating with 2 different doses of propofol. METHODS We compared heart rate, systolic blood pressure, diastolic pressure and mean arterial pressure changes during tracheal intubation with 2 different propofol doses without using muscle relaxants. Intravenous fentanyl inhibits the sympathetic nervous response to direct laryngoscopy and tracheal intubation in both groups of patients and acts as pre-emptive analgesia. RESULTS Comparison of the hemodynamic parameters revealed no statistically significant differences between the low dose propofol (PL) and high dose propofol (PH) groups with regard to heart rate or blood pressure changes at similar intervals postintubation. Both patient groups showed blood pressure fall along with a reflex increase in heart rate at 1 minute to 5 minutes post-intubation, returning to nearbaseline values 10 minutes post-intubation. None of these changes was either clinically detrimental or produced incidents of desaturation or arrhythmias in any study patient. CONCLUSIONS Low dose propofol may be useful in elderly or mildly hypovolemic patients, intolerant to a higher drug dosage whereas, the higher propofol dose may be particularly useful in the adult with a higher muscle mass in situations where muscle relaxant is to be restricted or avoided. KEY WORDS Tracheal Intubation, Hemodynamic Changes, Different Doses Propofol.

Pharmacological characterization of MT-1207, a novel multitarget antihypertensive agent.

Hypertension is a serious public health problem worldwide. MT-1207, chemically named 3-(4-(4-(1H-benzotriazole-1-yl)butyl)piperazine-1-yl) benzisothiazole hydrochloride, is a new chemical entity that has entered into clinical trial as antihypertensive agent in China. In this paper we report the pharmacological profile of MT-1207 regarding its acute, subacute, and long-term effects on hypertensive animal models, and its actions on isolated organs in vitro as well as its molecular targets. Blood pressure (BP) was measured in conscious animals; amlodipine was taken as a positive control drug. We showed that both single dose of MT-1207 (1.25-20 mg/kg, ig) in spontaneously hypertensive rats (SHR) and MT-1207 (0.25-6 mg/kg, ig) in two-kidney one-clip (2K1C) dogs dose-dependently decreased BP. MT-1207 quickly decreased BP within 5 min after administration; the hypotensive effect lasted for 8 and 12 h, respectively, in SHR and 2K1C dogs without reflex increase in heart rate. Multiple doses of MT-1207 (5 mg · kg-1 · d-1 in SHR; 2 mg · kg-1 · d-1 in 2K1C dogs, for 7 days) significantly decreased BP, slightly reduced heart rate, and both of them recovered after withdrawal. Long-term administration of MT-1207 (10 mg · kg-1 · d-1 for 4 months or more time) produced a stable BP reduction, improved baroreflex sensitivity, reduced renal and cardiovascular damage in SHR, and delayed stroke occurrence and death in stroke-prone SHR. In isolated rat aortic rings precontracted by adrenaline, KCl, noradrenaline or 5-hydroxytryptamine (5-HT), MT-1207 (10-9-10-4 M) caused concentration-dependent relaxation. In a panel of enzyme activity or radioligand binding assays of 87 molecular targets, MT-1207 potently inhibited adrenergic α1A, α1B, α1D, and 5-HT2A receptors with Ki < 1 nM. The antagonism of MT-1207 against these receptors was confirmed in isolated rabbit arteries. We conclude that MT-1207 is a novel and promising single-molecule multitarget agent for hypertension treatment to reduce hypertensive organ damage and stroke mortality.

Implantation of Combined Telemetric ECG and Blood Pressure Transmitters to Determine Spontaneous Baroreflex Sensitivity in Conscious Mice.

Blood pressure (BP) and heart rate (HR) are both controlled by the autonomic nervous system (ANS) and are closely intertwined due to reflex mechanisms. The baroreflex is a key homeostatic mechanism to counteract acute, short-term changes in arterial BP and to maintain BP in a relatively narrow physiological range. BP is sensed by baroreceptors located in the aortic arch and carotid sinus. When BP changes, signals are transmitted to the central nervous system and are then communicated to the parasympathetic and sympathetic branches of the autonomic nervous system to adjust HR. A rise in BP causes a reflex decrease in HR, a drop in BP causes a reflex increase in HR. Baroreflex sensitivity (BRS) is the quantitative relationship between changes in arterial BP and corresponding changes in HR. Cardiovascular diseases are often associated with impaired baroreflex function. In various studies reduced BRS has been reported in e.g., heart failure, myocardial infarction, or coronary artery disease. Determination of BRS requires information from both BP and HR, which can be recorded simultaneously using telemetric devices. The surgical procedure is described beginning with the insertion of the pressure sensor into the left carotid artery and positioning of its tip in the aortic arch to monitor arterial pressure followed by the subcutaneous placement of the transmitter and ECG electrodes. We also describe postoperative intensive care and analgesic management. After a two-week period of post-surgery recovery long-term ECG and BP recordings are performed in conscious and unrestrained mice. Finally, we include examples of high-quality recordings and the analysis of spontaneous baroreceptor sensitivity using the sequence method.

Differential sympathetic vasomotor control by spinal AT1 and V1a receptors in the acute phase of hemorrhagic shock

The role of the renin-angiotensin-aldosterone system and arginine vasopressin (AVP) as humoral components in maintaining blood pressure (BP) during hemorrhagic shock (HS) is well established. However, little is known about the role of angiotensin II (Ang II) and AVP in the control of preganglionic sympathetic neuron activity. We studied the effects evoked by spinal Ang II type I (AT1) and V1a receptors antagonism on cardiovascular and sympathetic responses during HS. A catheter (PE-10) was inserted into the subarachnoid space and advanced to the T10-11 vertebral level in urethane-anesthetized rats. The effects of HS on BP, heart rate (HR), and renal and splanchnic sympathetic nerve activity (rSNA and sSNA, respectively) were analyzed in the presence or absence (HS rats) of intrathecally injected losartan (HS-Los rats) or V1a antagonist (HS–V1a rats). The right femoral artery was catheterized for bleeding. Using a 5 ml syringe, hemorrhage was maintained continuously until a BP reduction of ~50 mmHg was achieved. We found that bleeding caused a reflex increase in HR, rSNA and sSNA in the HS rats. However, such responses were attenuated in the HS-Los rats. HS-V1a rats showed a reflex increase in HR, rSNA and sSNA in terms of frequency (spikes/s) but not in amplitude. Nevertheless, the BP recovery of the groups was similar. Our data showed that spinal AT1 receptors are essential for sympathoexcitation during the acute phase of HS. Moreover, spinal AVP seems to be a neuromodulator that controls the recruitment of spinal sympathetic vasomotor neurons during the acute phase of HS.

A STUDY OF HAEMODYNAMIC RESPONSE TO LARYNGOSCOPY AND ENDOTRACHEAL INTUBATION WHEN USING FENTANYL:

Direct laryngoscopy is used to facilitate tracheal intubation under vision.Direct laryngoscopy and passage of a tracheal tube are noxious stimuli that can provoke adverse responses in the cardiovascular system. They cause intense reflex increase in heart rate,blood pressure and serum concentration of catecholamines.This study makes an effort to find the haemodynamic response to laryngoscope and endotracheal intubation using Fentanyl.

Comparative analysis of efficacy of lignocaine 1.5 mg/kg and two different doses of dexmedetomidine (0.5 μg/kg and 1 μg/kg) in attenuating the hemodynamic pressure response to laryngoscopy and intubation.

Context:Laryngoscopy and intubation cause an intense reflex increase in heart rate, blood pressure, due to an increased sympathoadrenal pressor response. Lignoocaine has shown blunting of pressor response to intubation. Dexmedetomidine has sympatholytic effects.Aims:To the best of our knowledge there is no study comparing the efficacy of lignocaine with two different doses of dexmedetomidine for attenuating the pressor response. With this idea, we planned to conduct the present study.Materials and Methods:After approval by the Hospital Ethics committee, 90 consenting adults aged 18-65 years of age of either sex of non-hypertensive ASA Grade I or II were randomly allocated into three groups. Group D1- IV Dexmedetomidine 0.5μg/kg over 10 minutes Group D2- IV Dexmedetomidine 1μg/kg over 10 minutes Group X- IV Lignocaine 1.5mg/kg in 10 ml normal salineStatistical Analysis Used:ANOVA and Student's t test used for analysis.Results:Dexmedetomidine 1µg/kg was more effective than 0.5µg/kg and lignocaine 1.5mg/kg in attenuating the pressor response.Conclusions:We conclude that dexmedetomidine 1μg/kg adequately attenuates the hemodynamic response to laryngoscopy and endotracheal intubation when compared with dexmedetomidine 0.5μg/kg and lignocaine 1.5mg/kg.

Distension of central great vein decreases sympathetic outflow in humans

Classic canine studies suggest that central great vein distension evokes an autonomic reflex tachycardia (Bainbridge reflex). It is unclear whether central venous distension in humans is a necessary and sufficient stimulus to evoke a reflex increase in heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA). Prior work from our laboratory suggests that limb venous distension evokes a reflex increase in BP and MSNA in humans. We hypothesized that in humans, compared with the limb venous distension, inferior vena cava (IVC) distension would evoke a less prominent increase in HR and MSNA. IVC distension (monitored with ultrasonography) was induced by two methods: 1) head-down tilt (HDT, N = 13); and 2) lower-body positive pressure (LBPP, N = 10). Two minutes of HDT induced IVC distension (Δ2.6 ± 0.2 mm, P < 0.001, ~27% in cross-sectional area), slightly increased mean BP (Δ2.3 ± 0.7 mmHg, P = 0.005), decreased MSNA (Δ5.2 ± 0.8 bursts/min, P < 0.001, N = 10), and did not alter HR (P = 0.37). LBPP induced similar IVC distension, increased BP (Δ2.0 ± 0.7 mmHg, P < 0.01), and did not alter HR (P = 0.34). Thus central venous distension leads to a rapid increase in BP and a subsequent fall in MSNA. Central venous distension does not evoke either bradycardia or tachycardia in humans. The absence of a baroreflex-mediated bradycardia suggests that the Bainbridge reflex is engaged. Clearly, this reflex differs from the powerful sympathoexcitation peripheral venous distension reflex described in humans.

Comparison of the effects of amlodipine and cilnidipine on blood pressure, heart rate, proteinuria and lipid profile in hypertensive patients

Background: Hypertension is a widespread public health problem and a major risk factor. Amlodipine, a calcium channel blocker is frequently used in the treatment of hypertension. Since Amlodipine primarily L-type calcium channel blocker (CCB) and thus reduces blood pressure, it stimulates sympathetic nerve activity leading to reflex increase in heart rate. Cilnidipine, a new type of CCB which can inhibit L- type calcium channels but also N-type calcium channels. We compare the clinical effectiveness of Amlodipine and Cilnidipine on blood pressure, heart rate, proteinuria and lipid profile in hypertensive patients. Methods: The study was a prospective, randomized, open label comparison, total ninety five patients were recruited for study in which 45 patients received 5-10mg Amlodipine and other 55 patients of same age groups received 10-20mg Cilnidipine. 15 patients in Amlodipine group and 18 patients in Cilnidipine group were diabetic, whereas 12 and 14 patients were proteinuric in Amlodipine and Cilnidipine group respectively. Results: Both the groups were well matched in term of age, weight, clinical findings and laboratory values. Both the drug significantly reduced both systolic (SBP) and diastolic blood pressure (DSP). In the Amlodipine group the pulse rate (PR) after treatment tended to be higher than those before treatment. In the Cilnidipine group there was decrease in PR after treatment. Unlike Amlodipine, Cilnidipine decreased urinary protein excretion and in diabetic patients reduced serum triglyceride. Conclusions: The study indicates that unlike Amlodipine, Cilnidipine which inhibits L-and N-type calcium channels will be useful for patients with hypertension and cardiovascular disease, diabetes mellitus or renal disease and proves to be a better alternative to existing calcium channel blockers.

Clevidipine: a review of its use in the management of acute hypertension.

Clevidipine: a review of its use in the management of acute hypertension.

Combined simvastatin–manidipine protect against ischemia–reperfusion injury in isolated hearts from normocholesterolemic rats

This study investigated whether oral simvastatin and manidipine interact in protecting the perfused rat heart from ischemia–reperfusion damage. Simvastatin (0.3 to 3 mg/kg) and manidipine (1 to 10 mg/kg) were given orally singly or together to normocholesterolemic rats once a day for seven consecutive days. At the end of treatment, systolic blood pressure and heart rate were measured in conscious rats, and the lipid profile and other biochemical markers, such as thromboxane B 2, nitrite/nitrates and 6-keto-prostaglandin F 1α (6-keto-PGF 1α) were determined in the plasma. Hearts were then isolated, perfused with Krebs–Henseleit, and subjected to low flow ischemia–reperfusion injury. Post-ischemic recovery of left ventricular function was measured as left ventricular developed pressure and left ventricular end-diastolic pressure. Creatine kinase, lactate dehydrogenase, tumor necrosis factor-alpha and 6-keto-PGF 1α were measured in the heart effluents. In conscious animals, simvastatin alone increased plasma 6-keto-PGF 1α release while manidipine alone reduced systolic blood pressure with a slight sympathetic reflex increase in heart rate, and increased plasma nitrite/nitrates. The combined treatment produced the same effects, but significantly more marked, and accompanied by a significant reduction of thromboxane B 2. Combined treatment was also significantly more effective than the single drugs in protecting the hearts from ischemia–reperfusion injury, with inhibition of creatine kinase, lactate dehydrogenase and tumor necrosis factor-alpha, and enhancement of 6-keto-PGF 1α during reperfusion. These data show that simvastatin and manidipine interact positively in protecting the rat heart from ischemia–reperfusion injury, possibly through increased prostaglandin and nitric oxide formation by the vascular endothelial cells.

Cardiovascular effects of a novel potent and highly selective azaindole‐based inhibitor of Rho‐kinase

Rho-kinase (ROCK) has been implicated in the pathophysiology of altered vasoregulation leading to hypertension. Here we describe the pharmacological characterization of a potent, highly selective and orally active ROCK inhibitor, the derivative of a class of azaindoles, azaindole 1 (6-chloro-N4-{3,5-difluoro-4-[(3-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]-phenyl}pyrimidine-2,4-diamine). Pharmacological characterization of azaindole 1 was performed with human recombinant ROCK in vitro. Vasodilator activity was determined using isolated vessels in vitro and different animal models in vivo. This compound inhibited the ROCK-1 and ROCK-2 isoenzymes with IC50 s of 0.6 and 1.1 nM in an ATP-competitive manner. Although ATP-competitive, azaindole 1 was inactive against 89 kinases (IC50>10 microM) and showed only weak activity against an additional 21 different kinases (IC50=1-10 microM). Only the kinases TRK und FLT3 were inhibited by azaindole 1 in the sub-micromolar range, albeit with IC50 values of 252 and 303 nM, respectively. In vivo, azaindole 1 lowered blood pressure dose-dependently after i.v. administration in anaesthetized normotensive rats. In conscious normotensive and spontaneously hypertensive rats azaindole 1 induced a dose-dependent decrease in blood pressure after oral administration without inducing a significant reflex increase in heart rate. In anaesthetized dogs, azaindole 1 induced vasodilatation with a moderately elevated heart rate. Azaindole 1 is representative of a new class of selective and potent ROCK inhibitors and is a valuable tool for the elucidation of the role of ROCK in the cardiovascular system.

Cardiovascular safety of sildenafil citrate (Viagra ®): An updated perspective

Sildenafil citrate (Viagra ®; Pfizer Inc, New York, NY) relaxes vascular smooth muscle, resulting in modest reductions in blood pressure that are insufficient to stimulate a reflex increase in heart rate. These blood pressure reductions are similar for healthy men and men with coronary artery disease (CAD) or who use antihypertensive drugs. Sildenafil does not affect the force of cardiac contraction, and cardiac performance is unaffected. Sildenafil is mildly vasodilating in the coronary circulation and does not increase the risk of ventricular arrhythmia. During exercise and recovery, sildenafil does not cause clinically significant alterations in hemodynamic parameters in men with CAD, and it has no negative effects on coronary oxygen consumption, ischemia, or exercise capacity. Clinical trial data from >13,000 patients, 7 years of international postmarketing data, and observational studies of >28,000 men in the United Kingdom and 3813 men in the European Union reveal that (1) there are no special cardiovascular concerns when sildenafil is used in accordance with product labeling and (2) the risk for serious events such as myocardial infarction or death is not increased. However, because safety has not been established in patients with recent serious cardiovascular events, hypotension or uncontrolled hypertension, or retinitis pigmentosa, physicians should consult their current local prescribing information before prescribing sildenafil for these patients. Among men with erectile dysfunction treated with sildenafil, the adverse event profile is similar overall to that in men with comorbid cardiovascular disease (CVD), it is similar between those with and without CAD, and it is similar between those who take and those who do not take antihypertensive drugs (regardless of the number or class). In a controlled interaction study of sildenafil and amlodipine, the mean additional reduction in supine blood pressure was 8 mm Hg systolic and 7 mm Hg diastolic. Sildenafil should be used with caution in patients who take α-blockers because coadministration may lead to symptomatic hypotension in some individuals. When sildenafil is coadministered with an α-blocker, patients should be stable on α-blocker therapy before initiating sildenafil treatment and sildenafil should be initiated at the lowest dose. Also, in the absence of information specific to mixed α/β blockers, such as carvedilol and labetalol, similar care should be taken as for α-blockers. Sildenafil potentiates the hypotensive effects of nitrates, and its administration to patients who are using organic nitrates in any form, either regularly or intermittently, is contraindicated. Before prescribing sildenafil, physicians should carefully consider whether their patients with underlying CVD could be affected adversely by resuming sexual activity. Management recommendations based on cardiovascular risk, from the Second Princeton Consensus Conference, are presented.

The Articulo-Cardiac Sympathetic Reflex in Spinalized, Anesthetized Rats

Somatic afferent regulation of heart rate by noxious knee joint stimulation has been proven in anesthetized cats to be a reflex response whose reflex center is in the brain and whose efferent arc is a cardiac sympathetic nerve. In the present study we examined whether articular stimulation could influence heart rate by this efferent sympathetic pathway in spinalized rats. In central nervous system (CNS)-intact rats, noxious articular movement of either the knee or elbow joint resulted in an increase in cardiac sympathetic nerve activity and heart rate. However, although in acutely spinalized rats a noxious movement of the elbow joint resulted in a significant increase in cardiac sympathetic nerve activity and heart rate, a noxious movement of the knee joint had no such effect and resulted in only a marginal increase in heart rate. Because this marginal increase was abolished by adrenalectomy suggests that it was due to the release of adrenal catecholamines. In conclusion, the spinal cord appears to be capable of mediating, by way of cardiac sympathetic nerves, the propriospinally induced reflex increase in heart rate that follows noxious stimulation of the elbow joint, but not the knee joint.

In vivo interaction of endotoxin and recombinant bactericidal/permeability-increasing protein (rBPI23): Hemodynamic effects in a human endotoxemia model

The cardiovascular derangement that results from the administration of endotoxin in healthy subjects is qualitatively similar to what is observed in patients in septic shock. The biological response to endotoxin is attributed in part to cytokine release. In experimental endotoxemia, recombinant bactericidal/permeability increasing protein (rBPI23) has shown a protective effect by binding endotoxin with the subsequent inhibition of the endotoxin-induced cytokine release and of neutrophil activation. In a controlled, blinded crossover study the early cardiovascular effects of rBPI23 were investigated in an experimental endotoxemia model in humans. The beat-to-beat changes in arterial pressure and cardiac output following infusion of endotoxin (40 EU/kg body weight) and rBPI23 (1 mg/kg) or placebo (human serum albumin, 0.2 mg/kg) were studied for 2 hours in 8 healthy male adults. Endotoxin or rBPI23 alone did not induce significant cardiovascular changes. Endotoxin following rBPI23 infusion elicited a fall in total peripheral resistance with its nadir after 4 minutes to 40% (range 16-53; P <.001) of control level. Mean arterial pressure showed little change, and the fall in total peripheral resistance was associated with a reflex increase in heart rate and cardiac output (32%; range 43-106). Changes in cardiovascular variables in the subsequent 2 hours were not significant. In vitro activation of the contact system by, respectively, rBPI23, LPS, and LPS-rBPI23 complexes was assessed. Following incubation with rBPI23, LPS, and LPS-rBPI23 complexes, complex levels were generated at levels comparable to those observed in the buffer control. The rapid vasodilatation by endotoxin administered concomitantly with rBPI23 is not mediated by complement or contact system activation. The early vasodilatation is compensated by an increase in cardiac output, which therefore does not result in arterial hypotension. The monitoring of continuous cardiac output allows for the detection of rapid effects on systemic flow and conductance that go unnoticed in a recording of arterial pressure. (J Lab Clin Med 2002;140:228-35)

Anesthesia for electroconvulsive therapy.

Anesthesia for electroconvulsive therapy.

Experimental study of the effect of pentaerythritol tetranitrate in acute myocardial infarct

Pentaerithrityltetranitrate (PETN) is an organic nitrate ester with high selectivity to venous vessels and little development of tolerance. Here we report experimental results concerning the hemodynamic and antiischemic effects of intravenously administered PETN. The experiments were performed with anesthetized, open-chest minipigs (25 to 35 kg body weight [bw]). PETN (0.125, 0.25, 0.5 mg/kg bw, i.v.) dose-dependently decreased left ventricular systolic pressure without change in peripheral vascular resistance. A reflex increase in heart rate returned to normal within 20 minutes (0.125 and 0.25 mg/kg). PETN (0.5 mg/kg) also transiently (10 minutes) decreased left ventricular contractility. In additional experiments, myocardial infarction was induced by LAD occlusion (1 hour), followed by reperfusion (3 hours). PETN (0.6 mg/h, i.v.) was administered starting 20 minutes before ischemia until the end of reperfusion. While PETN did not cause hemodynamic changes, infarct size was significantly decreased compared with vehicle (56 +/- 6% vs 83 +/- 3% of area at risk, p < 0.05). Regional contractile function (ultrasound crystals) was completely abolished during ischemia and did not recover during 3 hours reperfusion in control hearts. However, PETN-treated pigs showed partial functional recovery (19 +/- 5%, p < 0.05 vs vehicle) during the first hour of reperfusion. Histologic evaluation revealed a decreased number of granulocytes accumulated in the ischemic myocardium of PETN-treated animals. Accordingly, in-vitro experiments showed a reduction by PETN of the adherence of HL-60 cells differentiated to granulocytes to vascular smooth muscle cells. Therefore, PETN reduced infarct size and improved myocardial function after LAD occlusion and reperfusion. It is concluded that the intravenous administration of PETN might be of advantage in the treatment of acute myocardial ischemia.

Baroreceptor control of heart rate in the awake toad: peripheral autonomic effectors and arterial baroreceptor areas

Systemic injection of sodium nitroprusside (30 μg/kg, i.v.) in the awake Bufo paracnemis toad induced a fall in arterial blood pressure and tachycardia. This tachycardia, but not the hypotension, was significantly reduced in toads with bilateral electrolytic lesion of the caudal and commissural regions of the solitary tract nucleus and in animals with transection of the spinal cord, 2 mm below the obex. This indicates that the tachycardia is reflex, depends on the integrity of the solitary tract nucleus and is due to descending spinal autonomic activation. Pretreatment with propranolol (4 mg/kg, i.v.) significantly reduced the tachycardia but did not block it completely, showing the importance of beta-adrenoceptors in its genesis. The reflex increase in heart rate induced by nitroprusside was not statistically significant in animals with bilateral section of the laryngeal nerve, whose baroreceptor fibers originate from the pulmocutaneous artery or in animals in which the bilateral section of the laryngeal nerve was performed together with section of the glossopharyngeal nerves, which incorporate fibers originating from the carotid labyrinth. The reduction of the reflex tachycardia was significant in toads with aortic arch denervation alone or combined with section of the laryngeal nerves or in animals with complete denervation of the three baroreceptors areas. These results suggest that the region of the aortic arch, when submitted to unloading, is the most important baroreceptor zone for cardiac compensation in toads.

Coronary and systemic hemodynamic effects of clevidipine, an ultra-short-acting calcium antagonist, for treatment of hypertension after coronary artery surgery.

The aim was to evaluate the use of clevidipine, a new vascular selective, ultra-short-acting calcium antagonist for blood pressure control after coronary artery bypass grafting (CABG). The effects of clevidipine on central hemodynamics, myocardial blood flow and metabolism were studied at two different phases after CABG. In phase 1 (n=13), the hypertensive phase, the effects of clevidipine were compared to those of sodium nitroprusside (SNP) when used to control postoperative hypertension. In phase 2 (n=9), the normotensive phase, a clevidipine dose-response relationship was established. At a target mean arterial pressure (MAP) of 75 mmHg, systemic vascular resistance (SVR) and heart rate (HR) were lower, preload, stroke volume (SV) and pulmonary vascular resistance (PVR) were higher, while there were no differences in myocardial lactate metabolism or oxygen extraction with clevidipine compared to SNP. In the normotensive phase, clevidipine induced a dose-dependent decrease in MAP (-19%), SVR (-27%) and PVR (-15%), accompanied by an increase in SV (10%), but no reflex increase in HR or changes in cardiac preload. Clevidipine caused a direct coronary vasodilation, as indicated by a decrease in myocardial oxygen extraction from 54% to 45%. Myocardial lactate metabolism was unaffected by clevidipine. The blood clearance of clevidipine was 0.05 l x min(-1) x kg(-1), the volume of distribution at steady state was 0.08 l x kg(-1) and the initial and terminal half-lives were <1 min and 4 min, respectively. Clevidipine rapidly reduced MAP and induced a systemic, pulmonary and coronary vasodilation with no effect on venous capacitance vessels or HR. Clevidipine caused no adverse effects on myocardial lactate metabolism. Clevidipine thus appears suitable to control blood pressure after CABG.

The effects of morphine on supraspinal and propriospinal somatocardiac reflexes in anesthetized rats

In anesthetized rats, the effects of i.v. injection of morphine on supraspinally- and spinally-mediated tachycardiac reflex responses of heart rate (HR) and cardiac sympathetic nerve reflex activity were examined following electrical stimulation of either a non-segmental hindlimb (tibial) or a segmental (3rd or 4th intercostal, IC3–4) afferent nerve. In central nervous system (CNS)-intact rats, the supraspinally-mediated reflex increase in HR in response to tibial afferent nerve stimulation was augmented by morphine, whereas the increase in response to IC3–4 afferent nerve stimulation was variable. Both the supraspinally-mediated myelinated (A) and unmyelinated (C) reflex discharges in the cardiac sympathetic nerve elicited by tibial afferent nerve stimulation were augmented by morphine. The effects of morphine on A- and C-sympathetic reflex discharges elicited by IC3–4 afferent nerve stimulation varied depending upon whether the discharge was of supraspinal or spinal origin. In spinal rats (spinalized at the cervical level), tibial afferent nerve stimulation did not produce any HR response, whereas IC3–4 afferent nerve stimulation produced a reflex increase in both HR and sympathetic reflex discharges of spinal origin. Furthermore, these spinal HR and sympathetic nerve reflex responses were inhibited by morphine. In conclusion, morphine depressed somatocardiac sympathetic reflexes at the spinal level, but enhanced these reflexes at the supraspinal level, leading to different effects of morphine on somatically-induced HR responses of supraspinal and spinal origins depending upon the segmental levels of afferent nerves stimulated.