Propofol attenuates ischaemia-reperfusion injury in the rat heart in vivo.

BACKGROUND: We have previously demonstrated, in the isolated rat heart, that propofol attenuates hydrogen peroxide-induced damage and ischaemia-reperfusion injury, and that the beneficial effect of propofol is correlated with reduction of the lipid peroxidation. This study was designed to evaluate whether propofol has a cardioprotective effect against ischaemia-reperfusion injury in a rat model in vivo. METHODS: Adult rats were anaesthetized with pentobarbital 10 mg kg(-1) h(-1) alone (control group), pentobarbital 10 or 20 mg kg(-1) h(-1) + Intralipid as a vehicle (Pent-10, Pent-20 group), propofol 10 or 20 mg kg(-1) h(-1) (Prop-10, Prop-20 group) intravenously throughout the experiment. The left anterior descending coronary artery was occluded for 30 min followed by 120 min of reperfusion. Infarct size was determined at the end of reperfusion. The tissue concentration of malondialdehyde was measured at 30 min after reperfusion to evaluate lipid peroxidation. RESULTS: The infarct sizes (% of area at risk) were significantly smaller in the Prop-10 (54 +/- 11%; P < 0.01 vs. control) and Prop-20 (39 +/- 8%; P < 0.01 vs. control) groups than in the control (68 +/- 9%), Pent-10 (69 +/- 13%) and Pent-20 (68 +/- 14%) groups (n = 12). In the Pent-10 and Pent-20 groups, ischaemia-reperfusion produced significant increases in the values for tissue malondialdehyde (0.72 +/- 0.24 micromol mg protein-1; P < 0.05 and 0.63 +/- 0.33 micromol mg protein-1; P < 0.05 vs. 0.46 +/- 0.22 micromol mg protein-1 in non-ischaemic hearts, n = 8). However, the values of malondialdehyde in the Prop-10 and -20 groups were suppressed by 41% and 63%, respectively, compared with the Pent-10 group (P < 0.01). CONCLUSION: Our results suggest that propofol could be cardioprotective against ischaemia-reperfusion injury dose dependently in a rat model in vivo and that the beneficial action of propofol may be correlated with its antioxidant effect.

Mechanisms of isoflurane-mediated hyperpolarization of vascular smooth muscle in chronically hypertensive and normotensive conditions.

BACKGROUND: The purpose of this study was to compare the effects of isoflurane on membrane and intracellular mechanisms that regulate vascular smooth muscle (VSM) transmembrane potential (Em; which is related to VSM tone) in the spontaneously hypertensive rat (SHR) model of essential hypertension and its normotensive Wistar-Kyoto (WKY) control. METHODS: Vascular smooth muscle Em values were measured in situ in locally denervated, superfused, intact, small (200-300-microm OD) mesenteric arteries and veins in anesthetized 9-12-week-old SHR and WKY. Effects of 1.0 minimum alveolar concentration (0.60 mM) superfused isoflurane on VSM Em were measured before and during superfusion with specific inhibitors of VSM calcium-activated (KCa) and adenosine triphosphate-regulated (KATP) potassium channels, and with endogenous mediators of vasodilatation (nitric oxide, cyclic guanosine monophosphate, protein kinase G, cyclic adenosine monophosphate, and protein kinase A). RESULTS: Isoflurane significantly hyperpolarized small arteries (5 +/- 3.4 mV) and veins (6 +/- 4.7 mV) (pooled SHR and WKY, mean +/- SD). Inhibition of KCa and KATP channels, cyclic adenosine monophosphate, and protein kinase A, but not nitric oxide, cyclic guanosine monophosphate, and protein kinase G, abolished such hyperpolarization equally in SHR and WKY vessels. CONCLUSIONS: Isoflurane-induced in situ VSM hyperpolarization in denervated, small mesenteric vessels involves a similar activation of KCa and KATP channels and cyclic adenosine monophosphate, but not nitric oxide or cyclic guanosine monophosphate, second messenger pathways in both SHR and WKY. A greater isoflurane-induced VSM hyperpolarization (observed previously in neurally intact SHR vessels) suggests enhanced inhibition of elevated sympathetic neural input as a major mechanism underlying such hyperpolarization (and coupled relaxation) in this neurogenic model of hypertension.

Effect of isoflurane on in situ vascular smooth muscle transmembrane potential in spontaneous hypertension.

BACKGROUND: Administration of general anesthetics to patients with chronic hypertension often causes hemodynamic instability that has been attributed in part to a poorly understood increased loss of control of peripheral vascular smooth muscle tone. The purpose of the current study was to determine if such an increased loss occurs in the spontaneously hypertensive (SH) rat neurogenic model of chronic hypertension, as reflected by a greater volatile anesthetic-induced in situ vascular smooth muscle hyperpolarization compared with normotensive Wistar-Kyoto (WKY) rat controls. METHODS: Vascular smooth muscle transmembrane potentials (E(m)s) were measured in situ using glass microelectrodes in externalized small mesenteric resistance- and capacitance-regulating blood vessels in 10- to 12-week-old SH and WKY rats before, during and after administration of 1 minimum alveolar concentration levels (1.5%) of inhaled or 0.60 mM superfused isoflurane. Vascular smooth muscle E(m)s were also measured in vessels after local sympathetic denervation with superfused 6-hydroxydopamine. RESULTS: Local sympathetic denervation caused a significant hyperpolarization of arterial and venous vascular smooth muscle in SH but not WKY rats. Hyperpolarization induced by either inhaled or superfused isoflurane was significantly greater in innervated than in denervated arterial and venous vascular smooth muscle, particularly in SH rats. In addition, for innervated (but not denervated) arterial and venous vascular smooth muscle, hyperpolarization induced by inhaled (but not superfused) isoflurane was significantly greater in SH than in WKY rats. CONCLUSIONS: In the neurogenic SH rat model of human hypertension, a primary mechanism underlying elevated isoflurane-induced vascular smooth muscle hyperpolarization (and reduced vascular smooth muscle tone) in both resistance- and capacitance-regulating blood vessels is a central neural inhibition of excitatory sympathetic input. Peripheral neural and nonneurally mediated hyperpolarization by isoflurane is similar in SH and WKY rat vascular smooth muscles.

Potassium channel-mediated hyperpolarization of mesenteric vascular smooth muscle by isoflurane.

BACKGROUND: A primary source of calcium (Ca2+) necessary for excitation contraction in vascular smooth muscle (VSM) is influx via voltage-dependent Ca2+ channels. Thus, force generation in VSM is coupled closely to resting transmembrane potential, which itself is primarily a function of potassium conductance. Previously, the authors reported that volatile anesthetics hyperpolarize VSM of small mesenteric resistance arteries and capacitance veins. The current study was designed to determine whether isoflurane-mediated hyperpolarization is the result of specific effects on one or more of four types of potassium channels known to exist in VSM. METHODS: Transmembrane potentials (Em) were recorded from in situ mesenteric capacitance and resistance vessels in Sprague-Dawley rats weighing 250-300 g. In separate experiments, selective inhibitors of each of four types of potassium channels known to exist in VSM were administered in the superfusate of the vessel preparations to assess their effects on isoflurane-mediated hyperpolarization. RESULTS: Resting VSM Em ranged from -38 to -43 mV after local sympathetic denervation. Isoflurane produced a significant hyperpolarization (2.7-4.3 mV), whereas each potassium channel inhibitor significantly depolarized (2.8-8.5 mV) the VSM. Both 100 nM iberiotoxin (inhibitor of high conductance calcium-activated potassium channels) and 1 microM glybenclamide (inhibitor of adenosine triphosphatase-sensitive potassium channels) significantly inhibited VSM hyperpolarization induced by 1 MAC (minimum alveolar concentration) levels of inhaled isoflurane (0.1-0.9 mV Em change, which was not significant). In contrast, isoflurane hyperpolarized the VSM significantly despite the presence of 3 mM 4 aminopyridine (inhibitor of voltage-dependent potassium channels) or 10 microM barium chloride (an inhibitor of inward rectifier potassium channels) (3.7-8.2 mV change in VSM Em). CONCLUSIONS: These results suggest that isoflurane-mediated hyperpolarization (and associated relaxation) of VSM can be attributed in part to an enhanced (or maintained) opening of calcium-activated and adenosine triphosphate-sensitive potassium channels but not voltage-dependent or inward rectifier potassium channels.

Propofol improves functional and metabolic recovery in ischemic reperfused isolated rat hearts.

UNLABELLED: Propofol attenuates mechanical dysfunction, metabolic derangement, and lipid peroxidation by exogenous administration of H2O2 in the Langendorff rat heart. In this study, we examined the effects of propofol on mechanical and metabolic changes, as well as on lipid peroxidation induced by ischemia-reperfusion, in isolated, working rat hearts. Rat hearts (in control-modified Krebs-Henseleit bicarbonate buffer) were treated with two doses (25 microM and 50 microM) of propofol in an intralipid vehicle. In the first protocol, propofol was administered during the preischemic and reperfusion period, whereas in the second, it was only administered during the reperfusion period. Ischemia (15 min) decreased peak aortic pressure (PAOP), heart rate (HR), rate-pressure product (RPP), coronary flow (CF), and tissue concentrations of adenosine triphosphate (ATP) and creatine phosphate. After postischemic reperfusion (20 min), the CF and tissue concentration of ATP recovered incompletely; however, PAOP, HR, and RPP did not. Ischemia-reperfusion also increased the tissue concentration of malondialdehyde (MDA). In both protocols, both doses of propofol enhanced recovery of PAOP, HR, RPP, CF, and tissue concentration of ATP during reperfusion, and inhibited the tissue accumulation of MDA. These results indicate that propofol improves recovery of mechanical function and the energy state in ischemic reperfused isolated rat hearts, and the mechanism may involve the reduction of lipid peroxidation during postischemic reperfusion. IMPLICATIONS: We evaluated the possible cardioprotective effects of propofol in isolated, working rat hearts subjected to 15-min ischemia, followed by 20-min reperfusion. We observed that propofol attenuated mechanical dysfunction, metabolic derangement, and lipid peroxidation during reperfusion. This latter finding seems to be one mechanism for cardioprotective effects of propofol.

Lidocaine attenuates mechanical and metabolic derangements induced by palmitoyl-L-carnitine in the isolated perfused rat heart.

The effect of lidocaine on the palmitoyl-L-carnitine (PALCAR)-induced mechanical and metabolic derangements was studied in Langendorff rat hearts, perfused aerobically at a constant flow rate and paced electrically. PALCAR (5 mumol/l) increased the left ventricular end-diastolic pressure, decreased the left ventricular developed pressure (i.e., mechanical dysfunction), and decreased the tissue levels of adenosine triphosphate and creatine phosphate (i.e., metabolic change). These mechanical and metabolic alterations induced by PALCAR were concentration-dependently attenuated by lidocaine (20, 50 or 100 mumol/l). Nevertheless, lidocaine (20, 50 or 100 mumol/l) did not affect the mechanical function and energy metabolism of the normal (PALCAR-untreated) heart. These results indicate that lidocaine has a cardioprotective action against the PALCAR-induced mechanical and metabolic derangements.

Effects of thoracic epidural anesthesia on changes in ischemic myocardial metabolism induced by intracoronary injection of endothelin in dogs.

OBJECTIVE: Thoracic epidural anesthesia (TEA) has been reported to alleviate ischemic damage to the myocardium. Endothelin, an endothelium-derived peptide and a potent coronary vasoconstrictor, may contribute to poor cardiac perfusion and ischemia. The objective was to examine regional myocardial metabolism during ischemia caused by intracoronary injection of endothelin with and without TEA. DESIGN: The three experimental groups and three treatments were randomized. SETTING: All studies were conducted in a university research laboratory. PARTICIPANTS: Thirty anesthetized dogs comprised the study groups. INTERVENTIONS: Study animals were divided into three groups of 10 animals each identified as normal saline (NS); TEA; and TEA + blood pressure controlled (TEA + BPC). The NS group had 0.5 mL/kg of normal saline injected into the T4-5 epidural space. The TEA group had 0.5 mL/kg of saline containing 1% lidocaine injected into the T4-5 space. The TEA + BPC group had blood pressure and heart rate maintained at pre-epidural injection values by partially occluding the descending aorta and by atrial pacing. Endothelin (15 pmol/kg) was bolus injected into the left anterior descending (LAD) artery of each heart. Systolic and diastolic blood pressure, heart rate, and LAD coronary blood flow (CBF) were monitored. Three minutes after injection of endothelin, myocardial tissue was sampled from the distribution of the LAD artery and from the control, left circumflex (LCx) artery. ATP, ADP, AMP, lactate, and pyruvate were measured by enzymatic methods. MEASUREMENTS AND MAIN RESULTS: It was found that in each group endothelin consistently decreased LAD CBF, but the decrease was less in the TEA + BPC group. In the tissue distribution of the LAD, the levels of ATP and energy charge potential were lower, and the level of lactate was higher in the NS group than in the TEA or the TEA + BPC groups (p < 0.01). CONCLUSIONS: These results confirm that (1) endothelin injected into the LAD artery decreases CBF and causes selective myocardial ischemia in a fashion similar to intravascular stenosis of the LAD rather than to mechanical occlusion and (2) TEA, with or without pressure support, lessens the degree of regional ischemia induced by injection of endothelin in the LAD.

Propofol attenuates hydrogen peroxide-induced mechanical and metabolic derangements in the isolated rat heart.

BACKGROUND: Oxygen-derived free radicals are involved in tissue damage during myocardial ischemia and reperfusion. Recent in vitro studies have demonstrated that a beneficial effect of propofol lies on its free radical scavenging properties. The current study, therefore, examined whether propofol is effective against the mechanical and metabolic damage induced by exogenously administered hydrogen peroxide in the isolated rat heart. METHODS: Rat hearts were perfused aerobically with Krebs-Henseleit bicarbonate buffer at a constant flow rate according to Langendorff's technique, while being paced electrically. Hearts were studied in control Krebs-Henseleit bicarbonate buffer, with Intralipid vehicle, with 25 microM or 50 microM propofol for 40 min, and with 50 microM propofol for 30 min followed by Intralipid for 10 min. A similar set of hearts was treated with hydrogen peroxide for 4 min, either in the absence of or beginning 10 min after Intralipid or propofol infusion. Left ventricular pressure was recorded as an index of mechanical function. The tissue concentrations of adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, and creatine phosphate were measured as indices of energy metabolism. The tissue concentration of malondialdehyde was measured to evaluate lipid peroxidation. RESULTS: Hydrogen peroxide (600 microM) significantly increased the left ventricular end-diastolic pressure, decreased the left ventricular developed pressure (i.e., it produced mechanical dysfunction), and decreased tissue concentrations of adenosine triphosphate and creatine phosphate (i.e., metabolic damage). Hydrogen peroxide also increased the tissue concentration of malondialdehyde. These mechanical and metabolic alterations induced by hydrogen peroxide were significantly attenuated by propofol (25 microM or 50 microM), while the increase in malondialdehyde was completely suppressed by propofol. CONCLUSIONS: The current study demonstrates that in the isolated heart, propofol attenuates both mechanical and metabolic changes induced by exogenously applied hydrogen peroxide. The beneficial action of propofol is probably correlated with reduction of the hydrogen peroxide-induced lipid peroxidation.

[Cardiopulmonary resuscitation with continuous veno-venous hemofiltration for intraoperative cardiac arrest owing to hypothermia--a case report].

A 77-year-old female was scheduled for an exploratory laparotomy under nitrous oxide-oxygen-neurolept anesthesia. At the time of admission to the operating room, the rectal temperature was 36.0 degrees C. From the beginning of operation, the body temperature dropped slowly despite constant efforts of warming with a blanket and warm intravenous fluids. At 5 hours and 15 minutes after the beginning of operation, she developed cardiac arrest due to hypothermia. At this time the rectal temperature was 31.8 degrees C. In spite of cardioversion and intravenous administration of epinephrine, we could not resuscitate her successfully. Immediately, rewarming was started with continuous veno-venos hemofiltration (CVVH). When the rectal temperature rose to 32.9 degrees C one hour after the rewarming, cardioversion was performed again and spontaneous heart beat was observed. As soon as the rectal temperature rose to 34.0 degrees C, CHF was stopped. Her consciousness recovered 2 hours and 10 minutes after cardiopulmonary resuscitation, we conclude that rewarming with CVVH can be an effective method of cardiopulmonary resuscitation in a patient suffering cardiac arrest due to hypothermia.

[Two cases of diffuse pulmonary lymphangiomyomatosis].

We cared 2 patients with diffuse pulmonary lymphangiomyomatosis (LAM) through the perioperative period. LAM is a disease of uncertain origin and poor prognosis because of respiratory failure. Therefore, it is important to provide not only a good anesthetic care but also a good preoperative respiratory care. In the first case (a 35-yr-old woman), an open lung biopsy was performed after dyspnea and sputum had disappeared with preoperative medications of a bronchodilator and some antibiotics. In the second case (a 35-yr-old woman), oophorectomy was performed after FEV1.0% had remarkably increased with preoperative medication of a bronchodilator. Both patients did well through the perioperative period without any trouble or complications, such as pneumonia or severe hypoxemia, presumably owing to our perioperative management system.