Anesthetic Effects on Mitochondrial ATP-sensitive K Channel

2001 ◽  
Vol 95 (6) ◽  
pp. 1435-1440 ◽  
Author(s):  
Shinji Kohro ◽  
Quinn H. Hogan ◽  
Yuri Nakae ◽  
Michiaki Yamakage ◽  
Zeljko J. Bosnjak
Keyword(s):  
Fluorescence Microscopy ◽  
Volatile Anesthetics ◽  
Cardioprotective Effect ◽  
K Channel ◽  
Myocardial Cells ◽  
Intravenous Anesthetics ◽  
Inhalational Anesthetics ◽  
Cardioprotective Effects ◽  
Cardiac Preconditioning ◽  
Dose Dependent

Background Volatile anesthetics show an ischemic preconditioning-like cardioprotective effect, whereas intravenous anesthetics have cardioprotective effects for ischemic-reperfusion injury. Although recent evidence suggests that mitochondrial adenosine triphosphate-regulated potassium (mitoK(ATP)) channels are important in cardiac preconditioning, the effect of anesthetics on mitoK(ATP) is unexplored. Therefore, the authors tested the hypothesis that anesthetics act on the mitoK(ATP) channel and mitochondrial flavoprotein oxidation. Methods Myocardial cells were isolated from adult guinea pigs. Endogenous mitochondrial flavoprotein fluorescence, an indicator of mitochondrial flavoprotein oxidation, was monitored with fluorescence microscopy while myocytes were exposed individually for 15 min to isoflurane, sevoflurane, propofol, and pentobarbital. The authors further investigated the effect of 5-hydroxydeanoate, a specific mitoK(ATP) channel antagonist, on isoflurane- and sevoflurane-induced flavoprotein oxidation. Additionally, the effects of propofol and pentobarbital on isoflurane-induced flavoprotein oxidation were measured. Results Isoflurane and sevoflurane induced dose-dependent increases in flavoprotein oxidation (isoflurane: R2 = 0.71, n = 50; sevoflurane: R2 = 0.86, n = 20). The fluorescence increase produced by both isoflurane and sevoflurane was eliminated by 5-hydroxydeanoate. Although propofol and pentobarbital showed no significant effects on flavoprotein oxidation, they both dose-dependently inhibited isoflurane-induced flavoprotein oxidation. Conclusions Inhalational anesthetics induce flavoprotein oxidation through opening of the mitoK(ATP) channel. This may be an important mechanism contributing to anesthetic-induced preconditioning. Cardioprotective effects of intravenous anesthetics may not be dependent on flavoprotein oxidation, but the administration of propofol or pentobarbital may potentially inhibit the cardioprotective effect of inhalational anesthetics.

scholarly journals Cardiac preconditioning with 4-h, 17°C ischemia reduces [Ca2+]i load and damage in part via KATP channel opening

2002 ◽  
Vol 282 (6) ◽  
pp. H1961-H1969 ◽  
Author(s):  
Qun Chen ◽  
Amadou K. S. Camara ◽  
Jianzhong An ◽  
Matthias L. Riess ◽  
Enis Novalija ◽  
...  
Keyword(s):  
Infarct Size ◽  
Potential Role ◽  
K Channel ◽  
Moderate Hypothermia ◽  
Channel Opening ◽  
Cardioprotective Effects ◽  
Hypothermic Storage ◽  
Cardiac Preconditioning

Brief ischemia before normothermic ischemia protects hearts against reperfusion injury (ischemic preconditioning, IPC), but it is unclear whether it protects against long-term moderate hypothermic ischemia. We explored in isolated guinea pig hearts 1) the influence of two 2-min periods of normothermic ischemia before 4 h, 17°C hypothermic ischemia on cardiac cytosolic [Ca2+], mechanical and metabolic function, and infarct size, and 2) the potential role of KATP channels in eliciting cardioprotection. We found that IPC before 4 h moderate hypothermia improved myocardial perfusion, contractility, and relaxation during normothermic reperfusion. Protection was associated with markedly reduced diastolic [Ca2+] loading throughout both hypothermic storage and reperfusion. Global infarct size was markedly reduced from 36 ± 2 (SE)% to 15 ± 1% with IPC. Bracketing ischemic pulses with 200 μM 5-hydroxydecanoic acid or 10 μM glibenclamide increased infarct size to 28 ± 3% and 26 ± 4%, respectively. These results suggest that brief ischemia before long-term hypothermic storage adds to the cardioprotective effects of hypothermia and that this is associated with decreased cytosolic [Ca2+] loading and enhanced ATP-sensitive K channel opening.

Protective effect of adenosine against a calcium paradox in the isolated frog heart

1992 ◽  
Vol 70 (1) ◽  
pp. 115-120 ◽  
Author(s):  
Maria Touraki ◽  
Antigone Lazou
Keyword(s):  
Protective Effect ◽  
Calcium Influx ◽  
Calcium Paradox ◽  
Mechanical Activity ◽  
Frog Heart ◽  
Dependent Manner ◽  
Myocardial Cells ◽  
Tissue Calcium ◽  
Maximum Protection ◽  
Dose Dependent

The effect of adenosine on the calcium paradox in the isolated frog heart was studied. Addition of adenosine during calcium depletion protected the frog heart against a calcium paradox. This protective effect was indicated by reduced protein and creatine kinase release, maintenance of electrical activity, and recovery of mechanical activity during reperfusion. Tissue calcium determination results showed that adenosine protected frog myocardial cells by reducing the massive calcium influx during reperfusion possibly through an action on calcium channels. Adenosine exerted its action in a dose-dependent manner; a concentration of 10 μM adenosine provided maximum protection of myocardial cells against the calcium paradox damage. Higher concentrations of adenosine produced side effects on both electrical and mechanical activity. These results are discussed in terms of the possible mechanism involved in the protective effect of adenosine.Key words: calcium paradox, adenosine, frog heart.

Abstract 272: Sex Differences in β-Adrenergic Responsiveness of Excitation-Contraction Coupling in Isolated Rabbit Hearts

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Gregory Hoeker ◽  
Ashleigh Hood ◽  
Rodolphe Katra ◽  
Steven Poelzing ◽  
Steven Pogwizd
Keyword(s):  
Sex Differences ◽  
Action Potentials ◽  
Adrenergic Receptor ◽  
Calcium Release ◽  
Dependent Manner ◽  
Ectopic Activity ◽  
Dose Threshold ◽  
Ectopic Beats ◽  
Cardioprotective Effects ◽  
Dose Dependent

Introduction: Sex differences in β-adrenergic receptor (β-AR) responsiveness are associated with female cardioprotection. We hypothesize that female (F) rabbits have reduced responsiveness to β-AR stimulation vs males (M), and that the degree and type of sex differences vary with the β-AR subtypes that are activated. Methods: Ventricular action potentials (AP) and intracellular calcium transients (CaT) were optically mapped from the epicardial surface of rabbit hearts during 3 Hz pacing. Spontaneous calcium release (SCR) and ectopic activity were elicited at 1, 3, and 5.5 Hz. β-responsiveness was assessed with the nonselective β-agonist isoproterenol (Iso, 1-316 nM), or β2-AR selective agonist zinterol (Zin, 10 nM). Results: At baseline, the time constant of CaT decay (τ) was faster in F than M (54.0±1.7 vs 62.1±3.0 ms; n=14, 14; p < 0.05), with no sex difference in CaT duration (CaD80). AP duration (APD90) was shorter in F than M (202.5±5.0 vs 218.2±5.7 ms; p < 0.05). Iso decreased τ, CaD80, and APD90 in a dose-dependent manner in both sexes (n = 5, 5 for F, M). Iso decreased τ to a lesser extent in F than M for 1 and 32-316 nM Iso (F = 11-32 ms, M = 23-48 ms; p < 0.05). The Iso-induced decrease in CaD80 was not significantly different in F than M at any dose. The Iso-induced decrease in APD90 was significantly less in F than M only at 316 nM Iso (75.5±8.7 ms vs 103.9±6.2 ms, p < 0.05). In contrast, there were no sex differences in the response to Zin for τ, CaD80, or APD90 (n = 6, 6 for F, M). Zin decreased τ by 7.2±2.0 ms in F vs 12.7±3.7 ms in M; CaD80 by 18.0±5.3% in F vs 21.1±8.0 ms in M; and APD90 by 24.9±8.5 ms in F vs 21.9±8.9 ms in M. SCR was observed in 50% (6/12) of hearts treated with Zin, whereas Iso elicited SCR in all hearts (10/10) with a dose threshold of 32 nM. No ectopic beats were observed with Zin (0/36 trials in 12 hearts). With Iso, ectopic activity was less frequent in F hearts (16%, 12/75 trials in 5 hearts) than in M hearts (41%, 26/68 trials in 5 hearts, p < 0.05). Conclusions: These results suggest that sex differences in AP and CaT depend on the dose of the agonist used and the β-AR subtypes that are activated. Elucidating nuances of sex differences in β-AR subtype physiology will provide a better understanding of the mechanisms of reduced β-responsiveness in F and its cardioprotective effects.

scholarly journals Cardioprotective effects of compound ALM-802 on subendocardial ischemia models

2021 ◽  
pp. 18-22
Author(s):  
I. B. Tsorin ◽  
V. V. Barchukov ◽  
M. B. Vititnova ◽  
A. M. Likhosherstov ◽  
G. V. Mokrov ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Cardioprotective Effect ◽  
Rat Models ◽  
Subendocardial Ischemia ◽  
Anesthetized Rats ◽  
St Segment ◽  
Cardioprotective Effects

The investigation purpose. N1-(2,3,4-trimethoxybenzyl)-N2-{2-[(2,3,4-trimethoxybenzyl)amino]ethyl}-1,2-ethanediamine (ALM-802 compounds) cardioprotective effect has been studied in rat models of subendocardial ischemia caused by isoproterenol and dobutamine. Material and methods. Acute subendocardial myocardial ischemia in anesthetized rats (urethane 1300 mg/kg, i.p.) was caused by infusion of isoproterenol (20 µg/kg/min i.v.) or dobutamine (80 µg/kg/min i.v.). Results. It was shown that in anesthetized rats, isoproterenol and dobutamine caused almost the same ST-segment depression in the II standard ECG lead. The compound ALM-802 (2 mg/kg i.v.), administered 2 minutes before the infusion start of isoproterenol or dobutamine, equally prevented the occurrence of ischemic changes on the ECG. Conclusion. The non-selective beta-adrenomimetic isoproterenol and the selective β1-adrenomimetic dobutamine cause subendocardial ischemia of the same intensity in anesthetized rats. The compound ALM-802 has a pronounced anti-ischemic effect on both models.

scholarly journals Metabolic inhibition impairs ATP-sensitive K+ channel block by sulfonylurea in pancreatic β-cells

1998 ◽  
Vol 274 (1) ◽  
pp. E38-E44 ◽  
Author(s):  
Eri Mukai ◽  
Hitoshi Ishida ◽  
Seika Kato ◽  
Yoshiyuki Tsuura ◽  
Shimpei Fujimoto ◽  
...  
Keyword(s):  
Metabolic Inhibition ◽  
K Channel ◽  
High Dose ◽  
Dependent Manner ◽  
Channel Activity ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Patch Clamp Technique ◽  
Channel Inhibition ◽  
Dose Dependent

The effect of metabolic inhibition on the blocking of β-cell ATP-sensitive K+ channels (KATP channels) by glibenclamide was investigated using a patch-clamp technique. Inhibition of KATP channels by glibenclamide was attenuated in the cell-attached mode under metabolic inhibition induced by 2,4-dinitrophenol. Under a low concentration (0.1 μM) of ATP applied in the inside-out mode, KATP channel activity was not fully abolished, even when a high dose of glibenclamide was applied, in contrast to the dose-dependent and complete KATP channel inhibition under 10 μM ATP. On the other hand, cibenzoline, a class Ia antiarrhythmic agent, inhibits KATP channel activity in a dose-dependent manner and completely blocks it, even under metabolic inhibition. In sulfonylurea receptor (SUR1)- and inward rectifier K+ channel (Kir6.2)-expressed proteins, cibenzoline binds directly to Kir6.2, unlike glibenclamide. Thus, KATPchannel inhibition by glibenclamide is impaired under the condition of decreased intracellular ATP in pancreatic β-cells, probably because of a defect in signal transmission between SUR1 and Kir6.2 downstream of the site of sulfonylurea binding to SUR1.

Adenosine Inhibits Tissue Factor Expression by LPS-stimulated Human Monocytes: Involvement of the A3 Adenosine Receptor

2002 ◽  
Vol 88 (07) ◽  
pp. 123-130 ◽  
Author(s):  
Matthieu Broussas ◽  
Pascale Cornillet-Lefèbvre ◽  
Gérard Potron ◽  
Philippe Nguyên
Keyword(s):  
Tissue Factor ◽  
Rank Order ◽  
Mrna Level ◽  
Dependent Manner ◽  
Human Monocytes ◽  
Extrinsic Pathway ◽  
A3 Adenosine Receptor ◽  
Factor Expression ◽  
Cardioprotective Effects ◽  
Dose Dependent

SummaryTissue Factor (TF), an integral membrane glycoprotein that initiates the extrinsic pathway of blood coagulation, is thought to play a major part in coronary acute events. Adenosine, an endogenous nucleoside produced by the degradation of intracellular adenosine triphosphate, has been shown to exert many cardioprotective effects via an inhibition of platelets and neutrophils. This study was conducted to determine whether adenosine (ADO) could modulate the expression of TF by human monocytes. We found that ADO inhibited TF antigen and activity on endotoxin-stimulated monocytes in a dose-dependent manner. The mechanism was at least pre-translational since ADO caused a change in the TF mRNA level. Using ADO receptor-specific analogs, we showed that highly selective A3 agonist N6-(3-iodobenzyl)-adenosine-5’-N’-methyluronamide (IB-MECA) inhibited LPSinduced TF activity expression more potently than A1 agonist R-phenylisopropyladenosine (R-PIA) and A2 agonist CGS 2180. Furthermore, A1/A3 antagonist, xanthine amine congener (XAC) blocked the effect of ADO whereas A2a, A2b and A1 antagonists were ineffective. In addition, we observed that ADO agonists inhibited monocyte TF expression in LPS-stimulated whole blood. The rank order of agonist potency suggested that A2 and A3 receptors might be involved (2-Cado > CGS = IB-MECA > R-PIA). This was supported by the fact that A2 and A3 antagonists reversed the action of 2-Cado. We conclude that TF inhibition by ADO on human purified monocytes involved A3 receptors.

scholarly journals Cardioprotective effects of a long acting K+ channel opener Y-27152 under in vivo conditions

1992 ◽  
Vol 58 ◽  
pp. 397
Author(s):  
Kenji Shinagawa ◽  
Atsushi Fukunari ◽  
Hisato Miyai ◽  
Tohru Nakajima
Keyword(s):  
K Channel ◽  
Channel Opener ◽  
Cardioprotective Effects ◽  
Long Acting ◽  
K Channel Opener

Region-specific and Agent-specific Dilation of Intracerebral Microvessels by Volatile Anesthetics in Rat Brain Slices 

1997 ◽  
Vol 87 (5) ◽  
pp. 1191-1198 ◽  
Author(s):  
Neil E. Farber ◽  
Christopher P. Harkin ◽  
Jennifer Niedfeldt ◽  
Antal G. Hudetz ◽  
John P. Kampine ◽  
...  
Keyword(s):  
Brain Slices ◽  
Volatile Anesthetics ◽  
Sprague Dawley ◽  
Cerebral Microvessels ◽  
Cerebrovascular Resistance ◽  
Institutional Review ◽  
Sprague Dawley Rats ◽  
Artificial Cerebrospinal Fluid ◽  
Dose Dependent ◽  
Brain Slice Preparation

Background Volatile anesthetics are potent cerebral vasodilators. Although the predominant site of cerebrovascular resistance is attributed to intracerebral arterioles, no studies have compared the actions of volatile anesthetics on intraparenchymal microvessels. The authors compared the effects of halothane and isoflurane on intracerebral arteriolar responsiveness in hippocampal and neocortical microvessels using a brain slice preparation. Method After Institutional Review Board approval, hippocampal or neocortical brain slices were prepared from anesthetized Sprague-Dawley rats and placed in a perfusion-recording chamber, superfused with artificial cerebrospinal fluid. Arteriolar diameters were monitored with videomicroscopy before, during, and after halothane or isoflurane were equilibrated in the perfusate. PGF2alpha preconstricted vessels before anesthetic administration. A blinded observer using a computerized videomicrometer analyzed diameter changes. Results Baseline microvessel diameter and the degree of preconstriction were not different between groups. In the hippocampus, the volatile agents produced similar, concentration-dependent dilation (expressed as percent of preconstricted control +/- SEM) of 68 +/- 6% and 79 +/- 9% (1 MAC) and 120 +/- 3% and 109 +/- 5% (2 MAC) (P &lt; 0.05) during halothane and isoflurane, respectively. In the cerebral cortex, isoflurane caused significantly less vasodilation than did similar MAC levels of halothane (84 +/- 9% vs. 42 +/- 5% dilation at 1 MAC; 121 +/- 4% vs. 83 +/- 5% dilation at 2 MAC halothane vs. isoflurane, respectively). Conclusion Halothane and isoflurane differentially produce dose-dependent dilation of intraparenchymal cerebral microvessels. These findings suggest that local effects of the volatile anesthetics on intracerebral microvessel diameter contribute significantly to alterations in cerebrovascular resistance and support previously described heterogeneous actions on cerebral blood flow produced by these agents.

Effects of Halothane and Isoflurane on Bradykinin-evoked Calcium2+Influx in Bovine Aortic Endothelial Cells

1996 ◽  
Vol 85 (2) ◽  
pp. 366-679 ◽  
Author(s):  
Claudie Simoneau ◽  
Dominique Thuringer ◽  
Shufen Cai ◽  
Line Garneau ◽  
Gilbert Blaise ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Patch Clamp ◽  
Direct Action ◽  
Volatile Anesthetics ◽  
K Channel ◽  
Resting Cells ◽  
Open Probability ◽  
Cell Potential ◽  
Fura 2 ◽  
Aortic Endothelial

Background Volatile anesthetics, such as halothane and isoflurane, have been reported to affect the endothelium mediated relaxation of vascular smooth muscle cells. Because the activity of the constitutive nitric oxide synthase in endothelial cells depends on the availability of intracellular Ca2+, there is a definite possibility that the observed inhibitory effect of volatile anesthetics involves an action on the agonist-evoked internal Ca2+ mobilization and/or Ca2+ influx in these cells. Therefore, a study was undertaken to determine how halothane and isoflurane affect the Ca2+ signalling process in vascular endothelial cells. Methods The effect of halothane and isoflurane on the Ca2+ response to bradykinin of bovine aortic endothelial (BAE) cells was investigated using the fluorescent Ca2+ indicator fura-2. Halothane or isoflurane was applied either to resting cells or after bradykinin stimulation. The agonist-evoked Ca2+ influx in BAE cells was estimated by measuring either the rate of fura-2 quenching induced by Mn2+ or the increase in cytosolic Ca2+ concentration initiated after readmission of external Ca2+ after a brief exposure of the cells to a Ca(2+)-free external medium. The effects of halothane on cell potential and intracellular Ca2+ concentration were measured in cell-attached patch-clamp experiments in which a calcium-activated K+ channel and an inward rectifying Ca(2+)-independent K+ channel were used as probes to simultaneously monitor the intracellular Ca2+ concentration and the cell transmembrane potential. In addition, combined fura-2 and patch-clamp cell-attached recordings were carried out, to correlate the variations in internal Ca2+ caused by halothane and the activity of the Ca(2+)-dependent K+ channels, which are known in BAE cells to regulate intracellular potential. Finally, a direct action of halothane and isoflurane on the gating properties of the Ca(2+)-activated K+ channel present in these cells was investigated in patch-excised inside-out experiments. Results The results of the current study indicate that the initial Ca2+ increase in response to bradykinin stimulation is not affected by halothane, but that pulse applications of halothane (0.4-2 mM) or isoflurane (0.5-1 mM) reversibly reduce the sustained cytosolic Ca2+ increase initiated either by bradykinin or by the Ca2+ pump inhibitor thapsigargin. In addition, halothane appeared to dose-dependently inhibit the Ca2+ influx evoked by bradykinin, and to cause, concomitant to a decrease in cytosolic Ca2+ concentration, a depolarization of the cell potential. Halothane failed, however, to affect internal Ca2+ concentration in thapsigargin-treated endothelial cells, which were depolarized using a high K+ external solution. Finally, halothane and isoflurane decreased the open probability of the Ca(2+)-dependent K+ channel present in these cells. Conclusions These observations suggest that the effects of halothane and isoflurane on Ca2+ homeostasis in BAE cells reflect, for the most part, a reduction of the thapsigargin- or bradykinin-evoked Ca2+ influx, which would be consequent to a cellular depolarization caused by an inhibition of the Ca(2+)-dependent K+ channel activity initiated after cell stimulation.

Effects of propofol and thiopentone on picrotoxin convulsive threshold in the rabbit

1995 ◽  
Vol 73 (6) ◽  
pp. 714-717 ◽  
Author(s):  
Zyheir Hasan ◽  
Said Khatib ◽  
Ayman Abu-Laban
Keyword(s):  
Intravenous Administration ◽  
Seizure Threshold ◽  
Intravenous Anesthetics ◽  
Threshold Test ◽  
Dose Dependent Increase ◽  
Convulsive Threshold ◽  
Dose Dependent ◽  
Higher Doses

The purpose of the present study was to examine the effect of intravenous administration of propofol and thiopentone on picrotoxin-induced seizures using the picrotoxin convulsive threshold test in the rabbit. Neither propofol nor thiopentone at a dose of 1.25 mg/kg had any significant effect on picrotoxin seizure threshold. However, at higher doses (2.5, 5, 10 mg/kg) both propofol and thiopentone produced a significant and dose-dependent increase in the picrotoxin convulsive threshold. These findings suggest that propofol is an effective anticonvulsant against picrotoxin-induced seizures in the rabbit.Key words: convulsions, intravenous anesthetics, picrotoxin, propofol, thiopentone.

Sign in / Sign up

Export Citation Format

Share Document