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Zhongguo Yao Li Xue Bao = Acta... Nov 1993The effects of bretylium tosylate (BT) on the electrophysiologic properties of normal and digitalized papillary muscles isolated from guinea pigs were studied with...
The effects of bretylium tosylate (BT) on the electrophysiologic properties of normal and digitalized papillary muscles isolated from guinea pigs were studied with regular glass microelectrode. BT prolonged effective refractory period (ERP) and action potential duration (APD) of normal papillary muscles. The ERP and APD of papillary muscles were shortened by perfusion with ouabain (Oua) 0.2 mumol.L-1. No recovery was seen in perfusion without drug for 30 min. In digitalized papillary muscles with Oua, ERP, APD90, and APD50 were prolonged by BT 120 mumol.L-1 form 175 +/- 20, 187 +/- 20, and 146 +/- 21 ms to 222 +/- 21, 220 +/- 19, and 190 +/- 19 ms, respectively. The results demonstrated that BT can prolong ERP and APD of papillary muscles digitalized with Oua.
Topics: Action Potentials; Animals; Bretylium Tosylate; Electrophysiology; Female; Guinea Pigs; In Vitro Techniques; Male; Membrane Potentials; Ouabain; Papillary Muscles; Refractory Period, Electrophysiological
PubMed: 8010051
DOI: No ID Found -
Canadian Medical Association Journal Jul 1971Nine patients who had recurrent ventricular fibrillation following acute myocardial infarction or angina were given bretylium tosylate in a dose of 5 mg./kg....
Nine patients who had recurrent ventricular fibrillation following acute myocardial infarction or angina were given bretylium tosylate in a dose of 5 mg./kg. intramuscularly every eight hours after other measures had proved ineffective. Provided the patients were not in shock or in heart failure, there was a considerable reduction in the episodes of ventricular fibrillation.A second group of nine patients who developed recurrent ventricular fibrillation following open heart surgery were given bretylium intravenously, which controlled the arrhythmia in every instance.Bretylium did not completely abolish ventricular premature beats but the latter did not initiate ventricular fibrillation even when they occurred on the T wave.
Topics: Adult; Age Factors; Aged; Angina Pectoris; Aortic Valve Insufficiency; Aortic Valve Stenosis; Bretylium Compounds; Coronary Disease; Electrocardiography; Epinephrine; Female; Gluconates; Heart; Heart Septal Defects, Atrial; Heart Septal Defects, Ventricular; Humans; Injections, Intramuscular; Injections, Intravenous; Isoproterenol; Lidocaine; Male; Middle Aged; Myocardial Infarction; Phenytoin; Postoperative Complications; Potassium Chloride; Procainamide; Propranolol; Recurrence; Sex Factors; Ventricular Fibrillation
PubMed: 5556280
DOI: No ID Found -
Journal of Applied Physiology... May 2012Local administration of ascorbic acid (Asc) at a supraphysiological concentration inhibits the cutaneous vasoconstrictor response to local cooling (LC). However, whether... (Randomized Controlled Trial)
Randomized Controlled Trial
Local administration of ascorbic acid (Asc) at a supraphysiological concentration inhibits the cutaneous vasoconstrictor response to local cooling (LC). However, whether orally ingesting Asc inhibits the LC-induced vasoconstrictor response remains unknown. The purpose of the present study was to examine the acute influence of oral Asc on the adrenergic vasoconstrictor response to LC in human skin. In experiment 1, skin blood flow (SkBF) was measured by laser-Doppler flowmetry at three sites (forearm, calf, palm). The three skin sites were locally cooled from 34 to 24°C at -1°C/min and maintained at 24°C for 20 min before (Pre) and 1.5 h after (Post) oral Asc (2-g single dose) or placebo supplementation. Cutaneous vascular conductance (CVC) was calculated as the ratio of SkBF to blood pressure and expressed relative to the baseline value before LC. Oral Asc enhanced (P < 0.05) the reductions in CVC in the forearm (Pre, -50.3 ± 3.3%; Post, -57.8 ± 2.2%), calf (Pre, -52.6 ± 3.7%; Post, -66.1 ± 4.3%), and palm (Pre, -46.2 ± 6.2%; Post, -60.4 ± 5.6%) during LC. The placebo did not change the responses at any site. In experiment 2, to examine whether the increased vasoconstrictor response caused by oral Asc is due to the adrenergic system, the release of neurotransmitters from adrenergic nerves in forearm skin was blocked locally by iontophoresis of bretylium tosylate (BT). Oral Asc enhanced (P < 0.05) the reductions in CVC at untreated control sites but did not change the responses at BT-treated sites during LC. In experiment 3, to further examine whether adrenergically mediated vasoconstriction is enhanced by oral Asc, 0.1 mM tyramine was administered using intradermal microdialysis in the forearm skin at 34°C in the Pre and Post periods. Oral Asc increased (P < 0.05) the tyramine-induced reduction in CVC. These findings suggest that oral Asc acutely enhances the cutaneous vasoconstrictor responses to LC through the modification of adrenergic sympathetic mechanisms.
Topics: Administration, Cutaneous; Administration, Oral; Adrenergic Fibers; Analysis of Variance; Ascorbic Acid; Blood Flow Velocity; Blood Pressure; Blood Vessels; Bretylium Tosylate; Female; Humans; Hypothermia, Induced; Iontophoresis; Japan; Laser-Doppler Flowmetry; Male; Microdialysis; Regional Blood Flow; Skin; Skin Temperature; Time Factors; Tyramine; Vasoconstriction; Young Adult
PubMed: 22383508
DOI: 10.1152/japplphysiol.00043.2012 -
Journal of Applied Physiology... Mar 2003Reflex vasodilation is attenuated in aged skin during hyperthermia. We used laser-Doppler imaging (LDI) to test the hypothesis that the magnitude of conductance and the... (Clinical Trial)
Clinical Trial Comparative Study
Reflex vasodilation is attenuated in aged skin during hyperthermia. We used laser-Doppler imaging (LDI) to test the hypothesis that the magnitude of conductance and the spatial distribution of vasodilation are altered with aging. LDI of forearm skin was compared in 12 young (19- to 29-yr-old) and 12 older (64- to 75-yr-old) men during supine passive heating. Additionally, iontophoresis of bretylium tosylate was performed in a subset of subjects to explore the involvement of sympathetic vasoconstriction in limiting skin blood flow. Passive heating with water-perfused suits clamped mean skin temperature at 41.0 +/- 0.5 degrees C, causing a ramp increase in esophageal temperature (T(es)) to =38.5 degrees C. LDI scans were performed at baseline and at every 0.2 degrees C increase in T(es). LDI at bretylium and control sites was identical, suggesting no influence of noradrenergic vasoconstriction. Forearm vascular conductance (venous occlusion plethysmography) was reduced in the older men (P = 0.001) at every elevated T(es). Mean cutaneous vascular conductance (CVC) of the scanned area was reduced in the older men at 0.2 degrees C = DeltaT(es) = 0.8 degrees C. Early in heating (0.2 degrees C = DeltaT(es) = 0.6 degrees C), older men also responded with a reduced vasodilated area (P = 0.05), implying a slower recruitment or filling of skin microvessels. The results indicate that the area of vasodilation and CVC within the vasodilated area are reduced in aged skin during early passive heating, but only CVC is reduced at DeltaT(es) = 0.8 degrees C.
Topics: Adult; Aged; Aging; Anaerobic Threshold; Bretylium Compounds; Fever; Forearm; Humans; Image Processing, Computer-Assisted; Iontophoresis; Laser-Doppler Flowmetry; Male; Osmolar Concentration; Regional Blood Flow; Skin; Vasodilation
PubMed: 12433866
DOI: 10.1152/japplphysiol.00274.2002 -
The Journal of Physiology Aug 19751. Stimulation of left atrial receptors by distension of the junctions between the pulmonary veins and the left atrium is known to cause a reflex increase in heart rate....
1. Stimulation of left atrial receptors by distension of the junctions between the pulmonary veins and the left atrium is known to cause a reflex increase in heart rate. It was suggested that the efferent path of this reflex was solely in the sympathetic nerves to the heart but more recently the existence of a vagal efferent component has been postulated by Albrook, Bennion & Ledsome (1972). 3. The junctions between the pulmonary veins and the levt atrium were distended before and after the administration of I.C.I. 66082 and bretylium tosylate. The response of an increase in heart rate was significantly decreased after the administration of I.C.I. 66082 (5 mg/kg) and abolished after the administration of bretylium tosylate (10 mg/kg). 3. It is concluded that the efferent pathway of the reflex is solely in the sympathetic nerves to the heart.
Topics: Animals; Atenolol; Bretylium Compounds; Dogs; Heart Atria; Heart Rate; Neurons; Neurons, Efferent; Reflex; Sensory Receptor Cells; Sympathetic Nervous System
PubMed: 1177105
DOI: 10.1113/jphysiol.1975.sp011031 -
Journal of Applied Physiology... Feb 2006Epidemiological evidence suggests decreased heat tolerance in patients with Type 2 diabetes mellitus (T2DM), but it is not known whether the mechanisms involved in... (Comparative Study)
Comparative Study
Epidemiological evidence suggests decreased heat tolerance in patients with Type 2 diabetes mellitus (T2DM), but it is not known whether the mechanisms involved in thermoregulatory control of skin blood flow are altered in these patients. We tested the hypothesis that individuals with T2DM have a delayed internal temperature threshold for active cutaneous vasodilation during whole body heating compared with healthy control subjects. We measured skin blood flow using laser-Doppler flowmetry (LDF), internal temperature (T or) via sublingual thermocouple, and mean arterial pressure via Finometer at baseline and during whole body heating in 9 T2DM patients and 10 control subjects of similar age, height, and weight. At one LDF site, sympathetic noradrenergic neurotransmission was blocked by local pretreatment with bretylium tosylate (BT) to isolate the cutaneous active vasodilator system. Whole body heating was conducted using a water-perfused suit. There were no differences in preheating T(or) between groups (P > 0.10). Patients with T2DM exhibited an increased internal temperature threshold for the onset of vasodilation at both untreated and BT-treated sites. At BT-treated sites, T or thresholds were 36.28 +/- 0.07 degrees C in controls and 36.55 +/- 0.05 degrees C in T2DM patients (P < 0.05), indicating delayed onset of active vasodilation in patients. Sensitivity of vasodilation was variable in both groups, with no consistent difference between groups (P > 0.05). We conclude that altered control of active cutaneous vasodilation may contribute to impaired thermoregulation in patients with T2DM.
Topics: Adrenergic Antagonists; Body Temperature; Body Temperature Regulation; Bretylium Tosylate; Diabetes Mellitus, Type 2; Hot Temperature; Humans; Laser-Doppler Flowmetry; Middle Aged; Regional Blood Flow; Skin; Sympathetic Nervous System; Vasodilation
PubMed: 16210432
DOI: 10.1152/japplphysiol.00943.2005 -
The Journal of Physiology Jan 2002The venoarteriolar response causes vasoconstriction to skin and muscle via local mechanisms secondary to venous congestion. The purpose of this project was to...
The venoarteriolar response causes vasoconstriction to skin and muscle via local mechanisms secondary to venous congestion. The purpose of this project was to investigate whether this response occurs through alpha-adrenergic mechanisms. In supine individuals, forearm skin blood flow was monitored via laser-Doppler flowmetry over sites following local administration of terazosin (alpha(1)-antagonist), yohimbine (alpha(2)-antagonist), phentolamine (non-selective alpha-antagonist) and bretylium tosylate (inhibits neurotransmission of adrenergic nerves) via intradermal microdialysis or intradermal injection. In addition, skin blood flow was monitored over an area of forearm skin that was locally anaesthetized via application of EMLA (2.5 % lidocaine (lignocaine) and 2.5 % prilocaine) cream. Skin blood flow was also monitored over adjacent sites that received the vehicle for the specified drug. Each trial was performed on a minimum of seven subjects and on separate days. The venoarteriolar response was engaged by lowering the subject's arm from heart level such that the sites of skin blood flow measurement were 34 +/- 1 cm below the heart. The arm remained in this position for 2 min. Selective and non-selective alpha-adrenoceptor antagonism and presynaptic inhibition of adrenergic neurotransmission did not abolish the venoarteriolar response. However, local anaesthesia blocked the venoarteriolar response without altering alpha-adrenergic mediated vasoconstriction. These data suggest that the venoarteriolar response does not occur through adrenergic mechanisms as previously reported. Rather, the venoarteriolar response may due to myogenic mechanisms associated with changes in vascular pressure or is mediated by a non-adrenergic, but neurally mediated, local mechanism.
Topics: Adult; Arterioles; Female; Humans; Laser-Doppler Flowmetry; Male; Receptors, Adrenergic, alpha; Regional Blood Flow; Skin; Veins
PubMed: 11790822
DOI: 10.1113/jphysiol.2001.013060 -
American Journal of Physiology.... Jan 2006The purpose of this study was to evaluate the possible differences in the postexercise cutaneous vasodilatory response between men and women. Fourteen subjects (7 men... (Comparative Study)
Comparative Study
The purpose of this study was to evaluate the possible differences in the postexercise cutaneous vasodilatory response between men and women. Fourteen subjects (7 men and 7 women) of similar age, body composition, and fitness status remained seated resting for 15 min or cycled for 15 min at 70% of peak oxygen consumption followed by 15 min of seated recovery. Subjects then donned a liquid-conditioned suit. Mean skin temperature was clamped at approximately 34 degrees C for 15 min. Mean skin temperature was then increased at a rate of 4.3 +/- 0.8 degrees C/h while local skin temperature was clamped at 34 degrees C. Skin blood flow was measured continuously at two forearm skin sites, one with (UT) and without (BT) (treated with bretylium tosylate) intact alpha-adrenergic vasoconstrictor activity. The exercise threshold for cutaneous vasodilation in women (37.51 +/- 0.08 degrees C and 37.58 +/- 0.04 degrees C for UT and BT, respectively) was greater than that measured in men (37.33 +/- 0.06 degrees C and 37.35 +/- 0.06 degrees C for UT and BT, respectively) (P < 0.05). Core temperatures were similar to baseline before the start of whole body warming for all conditions. Postexercise heart rate (HR) for the men (77 +/- 4 beats/min) and women (87 +/- 6 beats/min) were elevated above baseline (61 +/- 3 and 68 +/- 4 beats/min for men and women, respectively), whereas mean arterial pressure (MAP) for the men (84 +/- 3 mmHg) and women (79 +/- 3 mmHg) was reduced from baseline (93 +/- 3 and 93 +/- 4 mmHg for men and women, respectively) (P < 0.05). A greater increase in HR and a greater decrease in the MAP postexercise were noted in women (P < 0.05). No differences in core temperature, HR, and MAP were measured in the no-exercise trial. The postexercise threshold for cutaneous vasodilation measured at the UT and BT sites for men (37.15 +/- 0.03 degrees C and 37.16 +/- 0.04 degrees C, respectively) and women (37.36 +/- 0.05 degrees C and 37.42 +/- 0.03 degrees C, respectively) were elevated above no exercise (36.94 +/- 0.07 degrees C and 36.97 +/- 0.05 degrees C for men and 36.99 +/- 0.09 degrees C and 37.03 +/- 0.11 degrees C for women for the UT and BT sites, respectively) (P < 0.05). A difference in the magnitude of the thresholds was measured between women and men (P < 0.05). We conclude that women have a greater postexercise onset threshold for cutaneous vasodilation than do men and that the primary mechanism influencing the difference between men and women in postexercise skin blood flow is likely the result of an altered active vasodilatory response and not an increase in adrenergic vasoconstrictor tone.
Topics: Adult; Blood Pressure; Body Temperature; Exercise; Female; Humans; Male; Sex Characteristics; Skin; Time Factors; Vasodilation
PubMed: 16123228
DOI: 10.1152/ajpregu.00428.2005 -
The Journal of Physiology Jan 19971. Our aim was to determine if sympathetic vasodilatation occurs in the human forearm, and if the vasodilating substance nitric oxide contributes to this dilatation. We... (Clinical Trial)
Clinical Trial
1. Our aim was to determine if sympathetic vasodilatation occurs in the human forearm, and if the vasodilating substance nitric oxide contributes to this dilatation. We also sought to determine if the nitric oxide might be released as a result of cholinergic stimulation of the vascular endothelium. 2. Blood flow was measured in the resting non-dominant forearm with venous occlusion plethysmography. To increase sympathetic traffic to the resting forearm, rhythmic handgrip exercise to fatigue followed by post-exercise ischaemia was performed by the dominant forearm. A brachial artery catheter in the non-dominant arm was used to selectively infuse drugs. 3. During control conditions, there was mild vasodilatation in the resting forearm during exercise followed by constriction during post-exercise ischaemia. When exercise was performed after brachial artery administration of bretylium (to block noradrenaline release) and phentolamine (an alpha-adrenergic antagonist), profound vasodilatation was seen in the resting forearm during both exercise and post-exercise ischaemia. 4. When the nitric oxide synthase blocker NG-monomethyl-L-arginine (L-NMMA) was administered in the presence of bretylium and phentolamine prior to another bout of handgripping, little or no vasodilatation was seen either during exercise or post-exercise ischaemia. Atropine also blunted the vasodilator responses to exercise and post-exercise ischaemia after bretylium and phentolamine. 5. These results support the existence of active sympathetic vasodilatation in the human forearm and the involvement of nitric oxide in this phenomenon. They also suggest nitric oxide might be released as a result of cholinergic stimulation of the vascular endothelium.
Topics: Adrenergic Agents; Adrenergic alpha-Antagonists; Adult; Bretylium Tosylate; Enzyme Inhibitors; Exercise; Female; Forearm; Hemodynamics; Humans; Ischemia; Male; Nitric Oxide; Nitric Oxide Synthase; Norepinephrine; Phentolamine; Regional Blood Flow; Sympathectomy, Chemical; Sympathetic Nervous System; Vasodilation; omega-N-Methylarginine
PubMed: 9032700
DOI: 10.1113/jphysiol.1997.sp021879 -
The Journal of Physiology Dec 19981. In humans, a deep breath is known to induce cutaneous vasoconstriction in the warm state, and vasodilatation in the cold state. To investigate whether vasodilatation...
1. In humans, a deep breath is known to induce cutaneous vasoconstriction in the warm state, and vasodilatation in the cold state. To investigate whether vasodilatation in the cold state is related to reduction of sympathetic vasoconstrictor nerve traffic, we studied the effect of a deep breath on vascular resistance in a skin area on the dorsum of the hand, in which release of noradrenaline from sympathetic nerves was blocked by iontophoretic pretreatment with bretylium tosylate. Simultaneous measurements were made in two control areas. In eight healthy subjects, data were obtained from deep breaths taken before bretylium in the warm state, after general cooling to a finger skin temperature below 25 C and after rewarming to above 32 C. 2. In the warm state before bretylium pretreatment, the deep breath evoked short-lasting vasoconstrictions at all sites. In the cold state there was no change of vascular resistance in the bretylium-pretreated area, whereas in the control areas an initial tendency towards vasoconstriction was followed by a significant transient vasodilatation. After rewarming, transient vasoconstrictions reappeared at the control sites, whereas only a transient vasodilatation occurred at the bretylium-pretreated site. 3. In six healthy subjects we also monitored the effects of a deep breath on skin sympathetic nerve activity (recorded by microneurography in the peroneal nerve), and skin vascular resistance within the innervation zone of the impaled nerve fascicle in the foot. Data from thirty deep breaths per subject were averaged. 4. In the cold state, the deep breath induced a strong increase in neural discharge, followed by a transient reduction of nerve traffic lasting approximately 15 s and associated with a subsequent reduction of vascular resistance. 5. We conclude that the deep breath-induced vasodilatation in the cold state is due to reduction of sympathetic vasoconstrictor nerve traffic. The vasodilatation after bretylium treatment in the warm state raises the possibility that a deep breath induces two simultaneous neural reactions, a vasoconstrictor and an active vasodilator component, the latter being weaker and normally masked by the strong vasoconstrictor component.
Topics: Adult; Cold Temperature; Female; Fingers; Foot; Hot Temperature; Humans; Male; Nervous System Physiological Phenomena; Norepinephrine; Respiration; Skin; Skin Temperature; Sympathetic Nervous System; Vascular Resistance; Vasoconstriction; Vasodilation
PubMed: 9807004
DOI: 10.1111/j.1469-7793.1998.559bb.x