Kaoru Izumi

The Action of Sevoflurane on Vascular Smooth Muscle of Isolated Mesenteric Resistance Arteries (Part 1)Role of Endothelium

Background The direct action of sevoflurane on systemic resistance arteries is not fully understood. Methods Isometric force was recorded in isolated rat small mesenteric arteries. Results Sevoflurane (2–5%) enhanced contractile response to norepinephrine only in the presence of endothelium, but inhibited it in its absence. Sevoflurane still enhanced the norepinephrine response after inhibitions of the nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase and lipoxygenase pathways, or after blockade of either endothelin-1 ET-1), angiotensin-II, or sevotonin receptors. Sevoflurane (3–5%) inhibited contractile response to potassium chloride only in the absence of endothelium but did not influence it in its presence. In the endothelium-intact strips, inhibition of the norepinephrine response, which was enhanced during application of sevoflurane, was observed after washout of sevoflurane and persisted for approximately 15 min. In the endothelium-denuded strips, the inhibition of norepinephrine response was similarly prolonged after washout of sevoflurane. However, no significant inhibitions of potassium chloride response were observed after washout of sevoflurane in both the endothelium-intact and the endothelium-denuded strips. Conclusions The action of sevoflurane on norepinephrine contractile response consists of endothelium-dependent vasoconstricting and endothelium-independent vasodilating components. In the presence of endothelium, the former predominates over the latter, enhancing the norepinephrine response. The endothelium-independent component persisted after washout of sevoflurane, leading to prolonged inhibition of the norepinephrine response. The mechanisms behind the sevoflurane-induced inhibition of norepinephrine response are at least in part different from those behind its inhibition of potassium chloride response. Nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase products, lipoxygenase products, endothelin-1, angiotensin-II, and serotonin are not involved in the vasoconstricting action.

Comparison of volatile anesthetic actions on intracellular calcium stores of vascular smooth muscle: Investigation in isolated systemic resistance arteries

Background Volatile anesthetic actions on intracellular Ca2+ stores (i.e., sarcoplasmic reticulum [SR]) of vascular smooth muscle have not been fully elucidated. Methods Using isometric force recording method and fura-2 fluorometry, the actions of four volatile anesthetics on SR were studied in isolated endothelium-denuded rat mesenteric arteries. Results Halothane (≥ 3%) and enflurane (≥ 3%), but not isoflurane and sevoflurane, increased the intracellular Ca2+ concentration ([Ca2+]i) in Ca2+-free solution. These Ca2+-releasing actions were eliminated by procaine. When each anesthetic was applied during Ca2+ loading, halothane (≥ 3%) and enflurane (5%), but not isoflurane and sevoflurane, decreased the amount of Ca2+ in the SR. However, if halothane or enflurane was applied with procaine during Ca2+ loading, both anesthetics increased the amount of Ca2+ in the SR. The caffeine-induced increase in [Ca2+]i was enhanced in the presence of halothane (≥ 1%), enflurane (≥ 1%), and isoflurane (≥ 3%) but was attenuated in the presence of sevoflurane (≥ 3%). The norepinephrine-induced increase in [Ca2+]i was enhanced only in the presence of sevoflurane (≥ 3%). Not all of these anesthetic effects on the [Ca2+]i were parallel with the simultaneously observed anesthetic effects on the force. Conclusions In systemic resistance arteries, the halothane, enflurane, isoflurane, and sevoflurane differentially influence the SR functions. Both halothane and enflurane cause Ca2+ release from the caffeine-sensitive SR. In addition, both anesthetics appear to have a stimulating action on Ca2+ uptake in addition to the Ca2+-releasing action. Halothane, enflurane, and isoflurane all enhance, while sevoflurane attenuates, the Ca2+-induced Ca2+-release mechanism. However, only sevoflurane stimulates the inositol 1,4,5-triphosphate–induced Ca2+ release mechanism. Isoflurane and sevoflurane do not stimulate Ca2+ release or influence Ca2+ uptake.

Changes in body temperature following deflation of limb pneumatic tourniquet

Abstract Study Objectives : To investigate changes in both core and peripheral skin-surface temperatures during and after application of a unilateral leg pneumatic tourniquet in adult patients. Design : Prospective, observational clinical study. Setting : University hospital. Patients : 21 ASA physical status I and II adult patients scheduled for elective leg orthopedic surgery with lumbar epidural anesthesia. Interventions : Rectal and fingertip skin-surface temperatures were recorded every minute after steady-state lumbar epidural anesthesia was established. Measurements and Main Results : Significant ( p p Conclusions : Limb tourniquets appear to cause thermal perturbations during epidural anesthesia. The progressive increases in core temperature during tourniquet application presumably resulted from constraint of metabolic heat to the core thermal compartment, and the greater increases in the skin-surface temperature during tourniquet application appear to represent vasodilation in response to the core hyperthermia. On the other hand, redistribution of body heat and the efflux of hypothermic venous blood from the tourniqueted area into systemic circulation following tourniquet deflation probably decreased the core temperature, which might switch off the thermoregulatory vasodilation, leading to the decreases in skin-surface temperature. Recognition of these thermal perturbations are useful in diagnosing intraoperative thermal perturbations.

Role of Endothelium in the Action of Isoflurane on Vascular Smooth Muscle of Isolated Mesenteric Resistance Arteries

BackgroundIt is believed that isoflurane decreases blood pressure predominantly by decreasing systemic vascular resistance with modest myocardial depression. Nevertheless, little information is available regarding the direct action of isoflurane on systemic resistance arteries. MethodsWith use of the isometric force recording method, the action of isoflurane on contractile response to norepinephrine, a neurotransmitter that plays a central role in sympathetic maintenance of vascular tone in vivo, was investigated in isolated rat small mesenteric arteries. ResultsIn the endothelium-intact strips, the norepinephrine response was initially enhanced after application of isoflurane (2–5%), but it was subsequently almost normalized to the control level during exposure to isoflurane. However, the norepinephrine response was notably inhibited after washout of isoflurane. In the endothelium-denuded strips, the norepinephrine response was gradually inhibited during exposure to isoflurane (≥ 3%), and the inhibition was prolonged after washout of isoflurane. The isoflurane-induced enhancement of norepinephrine response was still observed after inhibitions of the nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase and lipoxygenase pathways, or after blockade of endothelin-1, angiotensin-II, and serotonin receptors; however, it was prevented by superoxide dismutase. ConclusionsIn isolated mesenteric resistance artery, the action of isoflurane on contractile response to norepinephrine consists of two distinct components: an endothelium-dependent enhancing component and an endothelium-independent inhibitory component. During exposure to isoflurane, the former counteracted the latter, preventing the norepinephrine response from being strongly inhibited. However, only the endothelium-independent component persists after washout of isoflurane, causing prolonged inhibition of the norepinephrine response. Superoxide anions may be involved in the enhanced response to norepinephrine.

Sevoflurane and bradykinin-induced calcium mobilization in pulmonary arterial valvular endothelial cells in situ: sevoflurane stimulates plasmalemmal calcium influx into endothelial cells.

Kinins locally synthesized in the cardiovascular tissue are believed to contribute to the regulation of cardiovascular homeostasis by stimulating the endothelial cells to release nitric oxide, prostacyclin, or a hyperpolarizing factor via autocrine-paracrine mechanisms. This study was designed to investigate the action of sevoflurane on bradykinin-induced Ca2+ mobilization in endothelial cells in situ. Utilizing fura-2-loaded rat pulmonary arterial valve leaflets, the effects of sevoflurane were examined on bradykinin-induced increases in intracellular Ca2+ concentration ([Ca2+]i) in endothelial cells in situ. In the presence of extracellular Ca2+ (1.5 m M), bradykinin (3–30 &mgr;M) produced an initial phasic and a subsequent tonic increase in [Ca2+]i in a concentration-dependent manner. However, it produced only the phasic increase in [Ca2+]i in the absence of extracellular Ca2+. Sevoflurane (5%, 0.67 m M) inhibited both the phasic and tonic responses to bradykinin. In these experiments, sevoflurane (3–5%) generated sustained increases (approximately 20–40% of the bradykinin-induced maximal increase in [Ca2+]i) in the resting [Ca2+]i level. Sevoflurane still increased [Ca2+]i after depletion of the intracellular Ca2+ stores with ionomycin (0.1 &mgr;M). However, the sevoflurane-induced increase in [Ca2+]i was eliminated by removal of the extracellular Ca2+ and attenuated by NiCl2 (1–3 m M). In conclusion, in the pulmonary arterial valvular endothelial cells, sevoflurane inhibits both bradykinin-induced Ca2+ release from the intracellular stores and bradykinin-induced plasmalemmal Ca2+ influx. In addition, sevoflurane appears to stimulate the plasmalemmal Ca2+ influx and thereby increase the endothelial [Ca2+]i level. Sevoflurane might influence the pulmonary vascular tone through its direct action on the pulmonary arterial valvular endothelial cells.

Diabetes-associated Alterations in Volatile Anesthetic Actions on Contractile Response to Norepinephrine in Isolated Mesenteric Resistance Arteries

Background:Clinical concentrations of volatile anesthetics significantly influence contractile response to the sympathetic neurotransmitter norepinephrine although its precise mechanisms remain unclarified. In this study, we investigated its possible alterations in diabetes, as well as its underlying mechanisms. Methods:Isometric force was recorded in small mesenteric arteries from streptozotocin-induced diabetic and age-matched control rats. Results:The concentration–response curve for acetylcholine-induced endothelium-dependent relaxation was shifted to the right in diabetic arteries compared with controls. The concentration–response curve for norepinephrine-induced contraction was shifted to the left and upward by both endothelial denudation and diabetic induction. In the presence of endothelium, isoflurane or sevoflurane enhanced norepinephrine-induced contraction in control arteries but not in diabetic arteries; however, in its absence, both anesthetics identically inhibited norepinephrine-induced contraction in both groups. In control arteries, the isoflurane- or sevoflurane-induced enhancement was not affected by adrenomedullin22–52, calcitonin gene-related peptide8–37, 18&bgr;-glycyrrhetinic acid, NG-nitro l-arginine, ouabain, Ba2+, indomethacin, losartan, ketanserin, BQ-123, and BQ-788. Conclusions:In diabetes, vascular responses to acetylcholine, norepinephrine, and volatile anesthetics are altered in mesenteric resistance arteries, presumably reflecting endothelial dysfunction and possibly underlying circulatory instability during administration of either anesthetic. Some endothelial mechanisms that are impaired in diabetes would be involved in the anesthetic-induced enhancement of norepinephrine-induced contraction. However, the vasoregulatory mechanism mediated by adrenomedullin, calcitonin gene-related peptide, myoendothelial gap junction, nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase products, angiotensin II, serotonin, or endothelin-1, all of which have been suggested to be impaired in diabetes, would not be involved in the enhancement.

Changes in Body Temperature Following Deflation of Limb Pneumatic Tourniquet

STUDY OBJECTIVES To investigate changes in both core and peripheral skin-surface temperatures during and after application of a unilateral leg pneumatic tourniquet in adult patients. DESIGN Prospective, observational clinical study. SETTING University hospital. PATIENTS 21 ASA physical status I and II adult patients scheduled for elective leg orthopedic surgery with lumbar epidural anesthesia. INTERVENTIONS Rectal and fingertip skin-surface temperatures were recorded every minute after steady-state lumbar epidural anesthesia was established. MEASUREMENTS AND MAIN RESULTS Significant (p < 0.05) increases in both rectal and fingertip temperatures were observed during tourniquet application for 91 +/- 6 minutes from 36.5 +/- 0.14 degrees C to 37.0 +/- 0.17 degrees C and from 32.6 +/- 0.79 degrees C to 35.5 +/- 0.44 degrees C, respectively. In contrast, both rectal and fingertip temperatures progressively decreased following tourniquet release; significant (p < 0.05) decreases in the rectal and fingertip temperatures were observed 6 and 5 minutes after tourniquet release, respectively. Decreases (approximately maximum) in the rectal and fingertip temperatures 15 minutes after tourniquet release were 0.25 +/- 0.05 degrees C and 1.26 +/- 0.26 degrees C, respectively. In each case, changes in fingertip temperature were approximately six times greater than those in the rectal temperature. CONCLUSIONS Limb tourniquets appear to cause thermal perturbations during epidural anesthesia. The progressive increases in core temperature during tourniquet application presumably resulted from constraint of metabolic heat to the core thermal compartment, and the greater increases in the skin-surface temperature during tourniquet application appear to represent vasodilation in response to the core hyperthermia. On the other hand, redistribution of body heat and the efflux of hypothermic venous blood from the tourniqueted area into systemic circulation following tourniquet deflation probably decreased the core temperature, which might switch off the thermoregulatory vasodilation, leading to the decreases in skin-surface temperature. Recognition of these thermal perturbations are useful in diagnosing intraoperative thermal perturbations.

Limb tourniquet causes thermal perturbations under various types of anesthesia: a report of seven cases

Pneumatic tourniquets are frequently used during limb operations to decrease blood loss and to provide a bloodless surgical field. Deflation of the limb tourniquet is known to cause a number of adverse systemic responses such as systemic hypotension, tachycardia, systemic acidosis with increases in arterial CO2 pressure (Pac%) and lactate, and decreases in arterial oxygen pressure (Pao2) [1-4]. Although Bloch et al. previously demonstrated progressive increases in central temperature following tourniquet application in pediatric patients under general anesthesia [5], little information is available regarding changes in body temperature following tourniquet release. In this report of seven patients who underwent limb surgery under various types of anesthesia, we demonstrate gradual increases in both central and peripheral temperatures during tourniquet application, and progressive decreases in both central and peripheral temperatures following tourniquet release.