Z J Bosnjak

The Inhibitory Action of Halothane on Reflex Constriction in Mesenteric Capacitance Veins

Potent inhalational anesthetics depress autonomic reflex responses at multiple sites. Most studies emphasize cardiac chronotropic changes and changes in systemic blood pressure. Recently, active reflex venoconstriction of 500-1,000 microns O.D. mesenteric veins has been demonstrated. In the current study, the effects of halothane on the reflex responses of similar mesenteric veins were measured. Mesenteric vein diameter and intravenous pressure were measured in 500-1,000 microns O.D. veins from the mesentery of segments of terminal ileum externalized in situ from 27 New Zealand white rabbits anesthetized with alpha-chloralose. Mean arterial pressure was measured with femoral arterial cannulation, and heart rate was determined from the arterial pressure signal. In a separate group of six animals, sympathetic efferent nerve activity was measured from a postganglionic splanchnic nerve. Reflex venoconstriction and increases in mean arterial pressure and mesenteric vein pressure in response to bilateral carotid occlusion were attenuated by 0.5% and 1% inhaled halothane but not by superfusate equilibrated with 3% halothane. Decreases in mesenteric vein diameter and increases in mesenteric vein pressure in response to celiac ganglion stimulation were unaffected by both 0.5% inhaled halothane and superfusate equilibrated with 5% halothane. The bilateral carotid occlusion reflex-mediated increase in sympathetic efferent nerve activity was depressed by both 0.5% and 1% inhaled halothane. The effect of inhaled halothane on prestimulation baseline vein diameter was inconsistent. Superfusate equilibrated with 5% but not 3% halothane caused baseline venodilation. These results suggest a mechanism whereby control of venous tone is inhibited by halothane proximal to the postganglionic neuron. This could involve central or ganglionic inhibition.

A Comparison of the Effects of Halothane and Tetrodotoxin on the Regional Repolarization Characteristics of Canine Purkinje Fibers

The effects of halothane, tetrodotoxin (TTX), veratridine (VTD), and alterations of extracellular calcium ion concentration [Ca++]0) on regional differences of canine Purkinje fiber action potential duration (APD50 and APD90) were investigated in vitro at a paced rate of 75 beats per min. Under control conditions (n = 15 hearts) APD90 of proximal (false tendon) fibers (289 +/- 6 ms) always exceeded (P less than or equal to 0.01) that of distal (apical) fibers (213 +/- 4 ms). Halothane (0.35-1.07 mM) reduced regional differences of APD90 by producing dose-dependent decreases of proximal APD90 without decreases of distal APD90. The regional actions of halothane were similar to those of low (0.33-1.0 microM) concentrations of the Na+ channel antagonist TTX, which also decreased proximal APD90 more than distal APD90. The actions of halothane in combination with TTX further decreased proximal APD90, whereas the Na+ channel agonist VTD, which increased proximal APD90 more than distal APD90, reversed the regional actions of halothane. Decreasing Ca++ influx by reducing [Ca++]0 from 1.8 to 0.6 mM increased proximal APD90 more than distal APD90 in a manner opposite to the regional actions of halothane. Although there was no difference between the values of APD90 obtained for each region in the presence of halothane at 0.6, 1.8, and 3.6 mM [Ca++]0, the action of halothane decreasing APD90 of proximal fibers was more prominent at 0.6 mM [Ca++]0 because of the increased APD90 of fibers under this condition. The findings are consistent with, but do not definitively prove, the hypothesis that halothane may decrease APD90 of proximal Purkinje fibers by a mechanism similar to that of TTX involving inhibition of plateau-phase inward Na+ current.

Effects of Isoflurane on Regulation of Capacitance Vessels under Normotensive and Chronically Hypertensive Conditions

Publisher Summary This chapter summarizes several studies that demonstrate that significant differences exist in the reflex regulation of mesenteric capacitance veins in chronic renal wrap hypertensive versus normotensive rabbits. The heart rate response to aortic depressor nerve stimulation and to graded hypoxia has also been equally attenuated by isoflurane in both groups of animals. The two groups of animals also differ significantly in the baseline responses to isoflurane administration. In both groups of animals, 1.5% inhaled isoflurane significantly reduces heart rate and mean arterial pressure and dilated mesenteric capacitance vein diameter. However, in the hypertensive animals, the isoflurane-mediated reduction in arterial pressure has been significantly greater and the isoflurane-mediated increase in mesenteric vein diameter has been significantly less than that observed in the normotensive animals. The present study of the interaction between a volatile anesthetic and the hypertensive condition focused on changes in reflex responses that are mediated primarily by an elevation of sympathetic neural efferent activity. It has been observed that an inhibition of baroreflex and chemoreflex changes in heart rate, blood pressure, and mesenteric vein diameter during the administration of 0.75 minimum alveolar concentration (MAC) isoflurane in normotensive control animals. In addition, isoflurane has been shown to inhibit the relaxation effect of endothelium-derived nitric oxide on vascular smooth muscle cells in in vitro mesenteric vein ring preparations. In the hypertensive animals, the inhibitory effect of isoflurane on the heart rate responses to chemoreflex activation, on the blood pressure responses to both baroreflex and chemoreflex activation and on the mesenteric venodilation in response to aortic depressor nerve stimulation has been the same as in the normotensive control animals. Finally, it should be noted that the action of different anesthetic agents on sympathetically mediated reflex responses, particularly reflex regulation of venous tone, may vary.