Russell A. Van Dyke

Halothane impairs the hemodynamic influence of endothelium-derived nitric oxide

Background The endogenous vasodilator endothelium‐derived nitric oxide (EDNO) contributes to the regulation of vascular tone and organ perfusion. It has been suggested that some volatile anesthetics may diminish the influence of EDNO and thereby decrease regional blood flow. Methods Radioactive microspheres were used to determine regional hemodynamics in rats. The authors tested the hypothesis that halothane inhibits EDNO and, therefore, should diminish the response to nitric oxide synthesis inhibition by NW ‐nitro‐L‐arginine methyl ester (L‐NAME) compared with either conscious or barbiturate‐anesthetized rats. Results NW ‐nitro‐L‐arginine methyl ester decreased blood flow to the brain by 23% (P < 0.005) in conscious rats to a level similar to that seen with either anesthetic agent. In both conscious and barbiturate‐anesthetized rats, L‐NAME increased blood pressure (BP) by 24 plus/minus 2 (P < 0.001) and 20 plus/minus 1 (P < 0.001) mmHg and total peripheral resistance (TPR) by 132% (P < 0.001) and 105% (P < 0.001), respectively. In contrast, during halothane anesthesia, both the pressor response (only 7 plus/minus 1 mmHg) and the increase in TPR (only 22%) were greatly diminished (P < 0.001). NW ‐nitro‐L‐arginine methyl ester decreased cardiac output (CO) by 47% (P < 0.001) and heart rate (HR) by 28% (P < 0.001) in conscious rats. In barbiturate‐anesthetized rats, L‐NAME decreased CO by 38% (P < 0.005) and HR by 13% (P < 0.001). In halothane‐anesthetized rats, L‐NAME changed neither CO nor HR. Thus halothane anesthesia largely eliminated the systemic response to EDNO synthesis inhibition. In conscious rats, L‐NAME decreased blood flow to the heart (30%) and kidneys (47%). In barbiturate‐anesthetized rats, L‐NAME did not alter blood flow to the heart but decreased renal blood flow by 35% (P < 0.005). In halothane‐anesthetized rats, L‐NAME did not alter blood flow to either the heart or the kidneys. Overall, halothane blunted or blocked the systemic and regional hemodynamic responses to EDNO synthesis inhibition seen in conscious and barbiturate‐anesthetized rats. Conclusions Halothane anesthesia greatly diminished or eliminated all systemic and regional hemodynamic responses to L‐NAME. These data indicate that halothane anesthesia inhibits EDNO‐mediated regulation of systemic and organ hemodynamics.

The effects of anesthetic agents and techniques on canine cerebral ATP and lactate levels.

Cerebral ATP, lactate, and pyruvate were measured in 64 dogs during seven anesthetic circumstances. In the presence of anesthetic agents associated with even twofold differences in cerebral oxygen consumption (CMRo2), there were no differences in cerebral ATP and lactate levels or lactate-pyruvate ratios. Similar values were observed after induction of hypothermia (30 C). However, in dogs made hypocapnic (Paco2 = 10 mm Hg), a threefold increase in cerebral lactate content and a significant reduction in cerebral ATP content (5 per cent) were observed. In hypocapnic, anemic dogs (Hb = 5.0 gm/100 ml), a greater reduction in cerebral ATP content (12 per cent) was observed. EEGs of all dogs were active. The EEGs of hypocapnic dogs could not be distinguished from those of hypocapnic, anemic dogs. The increases in cerebral lactate content induced by hypocapnia were not associated with increased differences between lactate levels in arterial and sagittal sinus blood.

Sympathoadrenal and Hemodynamic Effects of Isoflurane, Halothane, and Cyclopropane in Dogs

The sympathoadrenal response and its relation to the hemodynamic effects of isoflurane, halothane, and cyclopropane were studied in ten dogs. Each animal was used as its own control. At weekly intervals, the changes in plasma epinephrine and norepinephrine concentrations and in cardiac output (), wh

Venomotor changes caused by halothane acting on the sympathetic nerves.

Experiments were performed to determine whether depression of venomotor responses with halothane results from interference with sympathetic activation or from an effect on venous smooth muscle cells. Changes in isometric tension of isolated canine saphenous-vein strips were recorded. Adrenergic activation was achieved by transmural electrical stimulation, by addition of tyramine, and by addition of norepinephrine. Halothane (0.5 to 3 per cent) did not significantly alter basal tension. It lessened the reaction of the veins to electrical stimulation but not their response to norepinephrine; it increased the response to tyramine. Since the responses to norepinephriae and tyramine were not decreased, halothane appears to act on the nerve terminal to prevent release of neurotransmitter associated with nerve-terminal depolarization. Thus, halothane causes inhibition of electrically induced venoconstriction in cutaneous veins, probably by interfering with the release of norepinephrine from nerve terminals rather than by an inhibitory effect on the smooth-muscle cells.

Hepatic oxygen supply and consumption in rats exposed to thiopental, halothane, enflurane, and isoflurane in the presence of hypoxia.

Hepatic oxygen supply and uptake were assessed in phenobarbital-pretreated male Sprague-Dawley rats receiving subanesthetic doses of thiopental, halothane, enflurane, or isoflurane combined with hypoxia (approximately 0.5 MAC and 12% oxygen) for the purpose of evaluating the role of these combinations in hepatic blood flow alterations and the concomitant hepatic oxygen supply and uptake. Hepatic blood flow was measured using microspheres; hepatic oxygen supply and consumption was calculated from measured hepatic blood flow and oxygen content in hepatic arterial, portal venous, and hepatic venous blood. In all anesthetic groups, total hepatic blood flow did not change from the control value. Oxygen supply to the liver was decreased from air control values in all anesthetic groups, but there were no significant differences among anesthetic groups. Hepatic oxygen consumption was significantly lower in animals exposed to halothane and isoflurane versus air controls, whereas it was not significantly decreased in animals receiving thiopental or enflurane. The hepatic oxygen supply/consumption ratio was higher in the air control and the isoflurane groups than in other groups; however, no significant differences in this ratio were observed among the thiopental, halothane, and enflurane groups. Oxygen content in hepatic venous blood correlated well with hepatic oxygen supply/consumption ratio in all five groups. These results show that, during exposure to mild hypoxia, a sub-MAC dose of isoflurane maintains the relationship of hepatic oxygen supply to uptake better than thiopental, halothane, or enflurane. However, a subanesthetic dose of halothane did not aggravate liver hypoxia specifically, compared with thiopental or enflurane.

The effects of sevoflurane on intracellular Ca2+ regulation in rat hepatocytes

The effects of sevoflurane, a new volatile anesthetic agent undergoing clinical trial, on the mobilization of intracellular Ca2+ in isolated rat hepatocytes was studied. This agent produced a dose-dependent release of 45Ca2+ from internal, non-mitochondrial stores of permeabilized hepatocytes (saponin treated). However, the administration of sevoflurane to aequorin-loaded intact hepatocytes had little or no effect on intracellular [Ca2+] (i.e., short transient or no increases in luminescence: no toxic effect). These data may indicate that because of the low solubility of sevoflurane, it has a selective effect on endoplasmic reticulum, i.e., mobilizing internal stores of Ca2+ relative to increasing transmembrane fluxes.

The effects of halothane and succinylcholine on oxygen uptake of the canine gracilis muscle.

The effects of halothane and sueeinylcholine (SCh) on Vo, and blood flow of the canine graci-lis muscle were determined and compared with previous findings for the gastrocnemius muscle. Because halothane decreased and SCh increased the Vo2s of the two muscles to approximately the same extent, the responses of the two muscles were averaged and used to estimate the contribution of change in skeletal muscle Vo, to change in whole-body Vo,. These projections suggested that increasing halothane from 0.1 to 0.8 per cent would reduce skeletal muscle Vo, approximately 12 per cent and comprise a decrease of 4 per cent in whole-body Vo,. Infusion of SCh, 0.3 mg/kg/min, was estimated to increase skeletal muscle Vo, approximately 30 and 14 per cent during the first and second hours, respectively, and to contribute increases in whole-body Vo, of 11 and 5 per cent, respectively. The accuracy of the latter estimates was supported by previous direct determinations of the effects of SCh on whole-body Vo,. Whereas the gracilis and gastrocaemius muscles were similar in these responses, actual resting Vo, and blood flow were significantly less for the gracilis muscle, as were cytochreme e concentration, succinic dehydrogenase activity, and Vo, in citro.