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Biomedical subjects

Judy R Kersten

Publications and source records attributed to Judy R Kersten.

At least 55 records · Page 3Linked to original sources
PubMed2003

Influence of isoflurane on left atrial function in dogs with pacing-induced cardiomyopathy: evaluation with pressure-volume relationships.

OBJECTIVE: The actions of volatile anesthetics on left ventricular (LV) function in normal and failing hearts have been previously evaluated, but the effects of these agents on left atrial (LA) function in the presence of LV dysfunction are unknown. The hypothesis was tested that isoflurane alters LA mechanics evaluated with pressure-volume relations. DESIGN: Prospective. SETTING: Laboratory. PARTICIPANTS: Barbiturate-anesthetized dogs (n = 8) were instrumented for measurement of aortic, LA, and LV pressures (micromanometers), and LA volume (epicardial orthogonal sonomicrometers) after 3 weeks of rapid ventricular pacing (220 beats/min). INTERVENTIONS: LA myocardial contractility (E(es)) was assessed with end-systolic pressure-volume relations. LA stroke work and reservoir function were assessed by A and V loop area, respectively, from the steady-state pressure-volume diagram. LA-LV coupling was determined by the ratio of E(es) to LV elastance (E(LV)). Dogs received 0.6, 0.9, and 1.2 minimum alveolar concentration isoflurane in a random manner, and LA function was determined after a 20-minute equilibration at each dose. MEASUREMENTS AND MAIN RESULTS: Isoflurane significantly (p < 0.05) decreased heart rate, mean arterial pressure, LV end-systolic pressure, and LV +dP/dt(max). Isoflurane produced dose-related reductions in E(es) and E(es)/E(LV). Declines in LA stroke work, emptying fraction, reservoir volume, V loop area, and the active LA contribution to LV filling also occurred. CONCLUSIONS: The results indicate that isoflurane depresses LA myocardial contractility, impairs LA-LV coupling, and reduces active LA contribution to LV filling in dogs with pacing-induced cardiomyopathy. The impact of isoflurane on LA function in the presence of LV dysfunction has profound effects on cardiac performance.

Anesthetics, Inhalation↗
PubMed2003

Morphine enhances pharmacological preconditioning by isoflurane: role of mitochondrial K(ATP) channels and opioid receptors.

BACKGROUND: Adenosine triphosphate-regulated potassium channels mediate protection against myocardial infarction produced by volatile anesthetics and opioids. We tested the hypothesis that morphine enhances the protective effect of isoflurane by activating mitochondrial adenosine triphosphate-regulated potassium channels and opioid receptors. METHODS: Barbiturate-anesthetized rats (n = 131) were instrumented for measurement of hemodynamics and subjected to a 30 min coronary artery occlusion followed by 2 h of reperfusion. Myocardial infarct size was determined using triphenyltetrazolium staining. Rats were randomly assigned to receive 0.9% saline, isoflurane (0.5 and 1.0 minimum alveolar concentration [MAC]), morphine (0.1 and 0.3 mg/kg), or morphine (0.3 mg/kg) plus isoflurane (1.0 MAC). Isoflurane was administered for 30 min and discontinued 15 min before coronary occlusion. In eight additional groups of experiments, rats received 5-hydroxydecanoic acid (5-HD; 10 mg/kg) or naloxone (6 mg/kg) in the presence or absence of isoflurane, morphine, and morphine plus isoflurane. RESULTS: Isoflurane (1.0 MAC) and morphine (0.3 mg/kg) reduced infarct size (41 +/- 3%; n = 13 and 38 +/- 2% of the area at risk; n = 10, respectively) as compared to control experiments (59 +/- 2%; n = 10). Morphine plus isoflurane further decreased infarct size to 26 +/- 3% (n = 11). 5-HD and naloxone alone did not affect infarct size, but abolished cardioprotection produced by isoflurane, morphine, and morphine plus isoflurane. CONCLUSIONS: Combined administration of isoflurane and morphine enhances the protection against myocardial infarction to a greater extent than either drug alone. This beneficial effect is mediated by mitochondrial adenosine triphosphate-regulated potassium channels and opioid receptors in vivo.

Adenosine Triphosphate↗
PubMed2003

Mitochondrial adenosine triphosphate-regulated potassium channel opening acts as a trigger for isoflurane-induced preconditioning by generating reactive oxygen species.

BACKGROUND: Whether the opening of mitochondrial adenosine triphosphate-regulated potassium (K(ATP)) channels is a trigger or an end effector of anesthetic-induced preconditioning is unknown. We tested the hypothesis that the opening of mitochondrial K(ATP) channels triggers isoflurane-induced preconditioning by generating reactive oxygen species (ROS) in vivo. METHODS: Pentobarbital-anesthetized rabbits were subjected to a 30-min coronary artery occlusion followed by 3 h reperfusion. Rabbits were randomly assigned to receive a vehicle (0.9% saline) or the selective mitochondrial K(ATP) channel blocker 5-hydroxydecanoate (5-HD) alone 10 min before or immediately after a 30-min exposure to 1.0 minimum alveolar concentration (MAC) isoflurane. In another series of experiments, the fluorescent probe dihydroethidium was used to assess superoxide anion production during administration of 5-HD or the ROS scavengers N-acetylcysteine or N-2-mercaptopropionyl glycine (2-MPG) in the presence or absence of 1.0 MAC isoflurane. Myocardial infarct size and superoxide anion production were measured using triphenyltetrazolium staining and confocal fluorescence microscopy, respectively. RESULTS: Isoflurane (P < 0.05) decreased infarct size to 19 +/- 3% (mean +/- SEM) of the left ventricular area at risk as compared to the control (38 +/- 4%). 5-HD administered before but not after isoflurane abolished this beneficial effect (37 +/- 4% as compared to 24 +/- 3%). 5-HD alone had no effect on infarct size (42 +/- 3%). Isoflurane increased fluorescence intensity. Pretreatment with N-acetylcysteine, 2-MPG, or 5-HD before isoflurane abolished increases in fluorescence, but administration of 5-HD after isoflurane only partially attenuated increases in fluorescence produced by the volatile anesthetic agent. CONCLUSIONS: The results indicate that mitochondrial K(ATP) channel opening acts as a trigger for isoflurane-induced preconditioning by generating ROS in vivo.

Adenosine Triphosphatases↗
PubMed2003

N-acetylcysteine restores isoflurane-induced preconditioning against myocardial infarction during hyperglycemia.

BACKGROUND: Hyperglycemia generates reactive oxygen species and prevents isoflurane-induced preconditioning. The authors tested the hypothesis that scavenging reactive oxygen species with N-acetylcysteine will restore protection against myocardial infarction produced by isoflurane in vivo. METHODS: Barbiturate-anesthetized dogs (n = 45) were instrumented for measurement of systemic hemodynamics. Myocardial infarct size and coronary collateral blood flow were measured with triphenyltetrazolium staining and radioactive microspheres, respectively. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Dogs were randomly assigned to receive an infusion of 0.9% saline or 15% dextrose in water to increase blood glucose concentrations to 600 mg/dl (hyperglycemia) in the absence or presence of isoflurane (1.0 minimum alveolar concentration) with or without pretreatment with N-acetylcysteine (150 mg/kg i.v.) in six experimental groups. Isoflurane was discontinued, and blood glucose concentrations were allowed to return to baseline values before left anterior descending coronary artery occlusion. RESULTS: Myocardial infarct size was 27 +/- 2% (n = 8) of the left ventricular area at risk in control experiments. Isoflurane significantly (P < 0.05) decreased infarct size (13 +/- 2%; n = 7). Hyperglycemia alone did not alter infarct size (29 +/- 3%; n = 7) but abolished the protective effect of isoflurane (25 +/- 2%; n = 8). N-Acetylcysteine alone did not affect infarct size (28 +/- 2%; n = 8) but restored isoflurane-induced cardioprotection during hyperglycemia (10 +/- 1%; n = 7). CONCLUSIONS: Acute hyperglycemia abolishes reductions in myocardial infarct size produced by isoflurane, but N-acetylcysteine restores these beneficial effects. The results suggest that excessive quantities of reactive oxygen species generated during hyperglycemia impair isoflurane-induced preconditioning in dogs.

Acetylcysteine↗
PubMed2003

Three-dimensional computational fluid dynamics modeling of alterations in coronary wall shear stress produced by stent implantation.

Rates of coronary restenosis after stent implantation vary with stent design. Recent evidence suggests that alterations in wall shear stress associated with different stent types and changes in local vessel geometry after implantation may account for this disparity. We tested the hypothesis that wall shear stress is altered in a three-dimensional computational fluid dynamics (CFD) model after coronary implantation of a 16 mm slotted-tube stent during simulations of resting blood flow and maximal vasodilation. Canine left anterior descending coronary artery blood flow velocity and interior diameter were used to construct CFD models and evaluate wall shear stress proximal and distal to and within the stented region. Channeling of adjacent blood layers due to stent geometry had a profound affect on wall shear stress. Stagnation zones were localized around stent struts. Minimum wall shear stress decreased by 77% in stented compared to unstented vessels. Regions of low wall shear stress were extended at the stent outlet and localized to regions where adjacent axial strut spacing was minimized and the circumferential distance between struts was greatest within the stent. The present results depict alterations in wall shear stress caused by a slotted-tube stent and support the hypothesis that stent geometry may be a risk factor for restenosis by affecting local wall shear stress distributions.

Adenosine↗
PubMed2002

Stent implantation alters coronary artery hemodynamics and wall shear stress during maximal vasodilation.

Coronary stents improve resting blood flow and flow reserve in the presence of stenoses, but the impact of these devices on fluid dynamics during profound vasodilation is largely unknown. We tested the hypothesis that stent implantation affects adenosine-induced alterations in coronary hemodynamics and wall shear stress in anesthetized dogs (n = 6) instrumented for measurement of left anterior descending coronary artery (LAD) blood flow, velocity, diameter, and radius of curvature. Indexes of fluid dynamics and shear stress were determined before and after placement of a slotted-tube stent in the absence and presence of an adenosine infusion (1.0 mg/min). Adenosine increased blood flow, Reynolds (Re) and Dean numbers (De), and regional and oscillatory shear stress concomitant with reductions in LAD vascular resistance and segmental compliance before stent implantation. Increases in LAD blood flow, Re, De, and indexes of shear stress were observed after stent deployment (P < 0.05). Stent implantation reduced LAD segmental compliance to zero and potentiated increases in segmental and coronary vascular resistance during adenosine. Adenosine-induced increases in coronary blood flow and reserve, Re, De, and regional and oscillatory shear stress were attenuated after the stent was implanted. The results indicate that stent implantation blunts alterations in fluid dynamics during coronary vasodilation in vivo.

Adenosine↗
PubMed2002

Reactive oxygen species contribute to contractile dysfunction following rapid ventricular pacing in dogs.

BACKGROUND: Ventricular tachyarrhythmias may produce subsequent myocardial dysfunction through the formation of oxygen-derived free radicals. We tested the hypothesis that the antioxidant N-acetylcysteine enhances recovery of contractile function after rapid ventricular pacing. METHODS: Barbiturate-anesthetized dogs were instrumented for measurement of systemic and coronary hemodynamics and subendocardial segment shortening (%SS). All dogs were subjected to 3 h of rapid ventricular pacing (230 beats/min) followed by a 2 h recovery period. In three groups (n=8 each), dogs received intravenous 0.9% saline or N-acetylcysteine (50 or 150 mg/kg over 60 min) in a random manner before pacing. RESULTS: N-acetylcysteine did not affect systemic and coronary hemodynamics or alter regional myocardial contractility. Rapid ventricular pacing significantly (P<0.05) increased rate-pressure product and left ventricular end-diastolic pressure and decreased +dP/dt(max). Rapid ventricular pacing produced equivalent degrees of contractile dysfunction in dogs receiving saline or N-acetylcysteine (e.g. %SS of 14.7+/-1.8 to -3.8+/-2.7% before and during pacing in saline-pretreated dogs). Dogs receiving the 150 mg/kg dose of N-acetylcysteine demonstrated greater recovery of contractile function than those pretreated with saline or the 50 mg/kg dose (e.g. %SS of 12.3+/-1.7% compared to 7.0+/-2.0% 2 h after pacing in dogs receiving saline). No differences in systemic and coronary hemodynamics were observed between groups during recovery from pacing. CONCLUSIONS: The results indicate that the N-acetylcysteine enhances recovery of contractile function after rapid ventricular pacing independent of alterations in systemic and coronary hemodynamics and imply that reactive oxygen species are an important component of the contractile dysfunction following rapid pacing in vivo.

Acetylcysteine↗
PubMed2002

The role of mitochondrial and sarcolemmal K(ATP) channels in canine ethanol-induced preconditioning in vivo.

UNLABELLED: Chronic consumption of small doses of ethanol protects myocardium from ischemic injury. We tested the hypothesis that mitochondrial and sarcolemmal adenosine triphosphate-dependent potassium (K(ATP)) channels mediate these beneficial effects. Dogs (n = 76) were fed with ethanol (1.5 g/kg) or water mixed with dry food bid for 6 or 12 wk, fasted overnight before experimentation, and instrumented for measurement of hemodynamics. Dogs received intracoronary saline (vehicle), 5-hydroxydecanoate (a mitochondrial K(ATP) channel antagonist; 6.75 mg/kg over 45 min), or HMR-1098 (a sarcolemmal K(ATP) channel antagonist; 45 microg/kg over 45 min) and were subjected to a 60 min coronary artery occlusion followed by 3 h of reperfusion. A final group of dogs was pretreated with ethanol and chow for 6 wk before occlusion and reperfusion. Myocardial infarct size and transmural coronary collateral blood flow were measured with triphenyltetrazolium chloride staining and radioactive microspheres, respectively. The area at risk of infarction was similar between groups. A 12-wk pretreatment with ethanol significantly reduced infarct size to 13% +/- 2% (mean +/- SEM; n = 8) of the area at risk compared with control experiments (25% +/- 2%; n = 8), but a 6-wk pretreatment did not (21% +/- 2%; n = 8). 5-hydroxydecanoate and HMR-1098 abolished the protective effects of 12-wk ethanol pretreatment (24% +/- 2% and 29% +/- 3%, respectively; n = 8 for each group) but had no effect in dogs that did not receive ethanol (22% +/- 2% and 23% +/- 4%, respectively; n = 8 for each group). No differences in hemodynamics or transmural coronary collateral blood flow were observed between the groups. The results indicate that mitochondrial and sarcolemmal K(ATP) channels mediate ethanol-induced preconditioning in dogs independent of alterations in systemic hemodynamics or coronary collateral blood flow. IMPLICATIONS: Mitochondrial and sarcolemmal K(ATP) channels mediate ethanol-induced preconditioning independent of alterations in systemic hemodynamics or coronary collateral perfusion in vivo.

Adenosine Triphosphate↗
PubMed2002

Propofol alters left atrial function evaluated with pressure-volume relations in vivo.

UNLABELLED: The effects of IV anesthetics on left atrial (LA) function in vivo are unknown. We tested the hypothesis that propofol alters LA mechanics evaluated with pressure-volume relations in barbiturate-anesthetized dogs (n = 9) instrumented for measurement of aortic, LA, and left ventricular (LV) pressures (micromanometers) and LA volume (epicardial orthogonal sonomicrometers). LA myocardial contractility (E(es)) and dynamic chamber stiffness were assessed with end-systolic and end-reservoir pressure-volume relations, respectively. Relaxation was determined from the slope of LA pressure decline after contraction corrected for peak LA pressure. LA stroke work and reservoir function were assessed by A and V loop area, respectively, from the steady-state pressure-volume diagram. LA-LV coupling was determined by the ratio of E(es) to LV elastance. Dogs received propofol (5, 10, 20, or 40 mg. kg(-1). h(-1)) in a random manner, and LA function was determined after a 15-min equilibration at each dose. Propofol decreased heart rate, mean arterial blood pressure, and the maximal rate of increase of LV pressure. Propofol caused dose-related reductions in E(es), dynamic chamber stiffness, and E(es)/LV elastance. An increase in V loop area and declines in LA stroke work, emptying fraction, and the active LA contribution to LV filling also occurred. Relaxation was unchanged. The results indicate that propofol depresses LA myocardial contractility, reduces dynamic chamber stiffness, maintains reservoir function, and impairs LA-LV coupling but does not alter LA relaxation in vivo. IMPLICATIONS: Propofol depresses contractile function of left atrial (LA) myocardium, impairs mechanical matching between the LA and the left ventricular (LV), and reduces the active LA contribution to LV filling in vivo. Compensatory decreases in chamber stiffness contribute to relative maintenance of LA reservoir function during the administration of propofol.

Anesthesia↗
PubMed2002

Isoflurane does not produce a second window of preconditioning against myocardial infarction in vivo.

UNLABELLED: The administration of a volatile anesthetic shortly before a prolonged ischemic episode exerts protective effects against myocardial infarction similar to those of ischemic preconditioning. A second window of preconditioning (SWOP) against myocardial infarction can also be elicited by brief episodes of ischemia when this occurs 24 h before prolonged coronary artery occlusion. Whether remote exposure to a volatile anesthetic also causes delayed myocardial protection is unknown. We tested the hypothesis that the administration of isoflurane 24 h before ischemia produces a SWOP against infarction. Barbiturate-anesthetized dogs (n = 25) were instrumented for measurement of hemodynamics, including aortic and left ventricular (LV) pressures and LV +dP/dt(max), and subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Myocardial infarct size and coronary collateral blood flow were assessed with triphenyltetrazolium chloride staining and radioactive microspheres, respectively. Two groups of dogs received 1.0 minimum alveolar anesthetic concentration isoflurane for 30 min or 6 h that was discontinued 30 min (acute) or 24 h (delayed) before ischemia and reperfusion, respectively. A control group of dogs did not receive isoflurane. Infarct size was 27% +/- 3% of the LV area at risk in the absence of pretreatment with isoflurane. Acute, but not remote, administration of isoflurane reduced infarct size (12% +/- 1% and 31% +/- 3%, respectively). No differences in hemodynamics or transmural myocardial perfusion during or after occlusion were observed between groups. The results indicate that isoflurane does not produce a SWOP when administered 24 h before prolonged myocardial ischemia in vivo. IMPLICATIONS: Isoflurane mimics the beneficial effects of ischemic preconditioning by protecting myocardium against infarction when it is administered shortly before a prolonged ischemic episode. However, unlike ischemic preconditioning, isoflurane does not produce a second window of protection 24 h after administration in dogs.

Anesthetics, Inhalation↗
PubMed2002

Hyperglycemia prevents isoflurane-induced preconditioning against myocardial infarction.

BACKGROUND: Volatile anesthetics stimulate but hyperglycemia attenuates activity of mitochondrial adenosine triphosphate-regulated potassium channels. The authors tested the hypothesis that acute hyperglycemia interferes with isoflurane-induced preconditioning in vivo. METHODS: Barbiturate-anesthetized dogs (n = 79) were instrumented for measurement of hemodynamics. Myocardial infarct size and collateral blood flow were assessed with triphenyltetrazolium chloride staining and radioactive microspheres, respectively. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Dogs were randomly assigned to receive an infusion of normal saline (normoglycemic controls) or 15% dextrose in water to increase blood glucose concentrations to 300 or 600 mg/dl in the absence or presence of isoflurane (0.5 or 1.0 minimum alveolar concentration [MAC]) in separate experimental groups. Isoflurane was discontinued, and blood glucose concentrations were allowed to return to baseline values before left anterior descending coronary artery occlusion. RESULTS: Myocardial infarct size was 26 +/- 1% of the left ventricular area at risk in control experiments. Isoflurane reduced infarct size (15 +/- 2 and 13 +/- 1% during 0.5 and 1.0 MAC, respectively). Hyperglycemia alone did not alter infarct size (26 +/- 2 and 33 +/- 4% during 300 and 600 mg/dl, respectively). Moderate hyperglycemia blocked the protective effects of 0.5 MAC (25 +/- 2%) but not 1.0 MAC isoflurane (13 +/- 2%). In contrast, severe hyperglycemia prevented reductions of infarct size during both 0.5 MAC (29 +/- 3%) and 1.0 MAC isoflurane (28 +/- 4%). CONCLUSIONS: Acute hyperglycemia attenuates reductions in myocardial infarct size produced by isoflurane in dogs.

Anesthetics, Inhalation↗
PubMed2002

Is isoflurane-induced preconditioning dose related?

BACKGROUND: Volatile anesthetics precondition against myocardial infarction, but it is unknown whether this beneficial action is threshold- or dose-dependent. The authors tested the hypothesis that isoflurane decreases myocardial infarct size in a dose-dependent fashion in vivo. METHODS: Barbiturate-anesthetized dogs (n = 40) were instrumented for measurement of systemic hemodynamics including aortic and left ventricular pressures and rate of increase of left ventricular pressure. Dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion and were randomly assigned to receive either 0.0, 0.25, 0.5, 1.0, or 1.25 minimum alveolar concentration (MAC) isoflurane in separate groups. Isoflurane was administered for 30 min and discontinued 30 min before left anterior descending coronary artery occlusion. RESULTS: Infarct size (triphenyltetrazolium staining) was 29 +/- 2% of the area at risk in control experiments (0.0 MAC). Isoflurane produced significant (P < 0.05) reductions of infarct size (17 +/- 3, 13 +/- 1, 14 +/- 2, and 11 +/- 1% of the area at risk during 0.25, 0.5, 1.0, and 1.25 MAC, respectively). Infarct size was inversely related to coronary collateral blood flow (radioactive microspheres) in control experiments and during low (0.25 or 0.5 MAC) but not higher concentrations of isoflurane. Isoflurane shifted the linear regression relation between infarct size and collateral perfusion downward (indicating cardioprotection) in a dose-dependent fashion. CONCLUSIONS: Concentrations of isoflurane as low as 0.25 MAC are sufficient to precondition myocardium against infarction. High concentrations of isoflurane may have greater efficacy to protect myocardium during conditions of low coronary collateral blood flow.

Anesthetics, Inhalation↗
PubMed2002

Increases in coronary collateral blood flow produced by sevoflurane are mediated by calcium-activated potassium (BKCa) channels in vivo.

BACKGROUND: Sevoflurane enhances coronary collateral blood flow independent of adenosine triphosphate-regulated potassium channels. The authors tested the hypothesis that this volatile anesthetic increases coronary collateral blood flow by either opening calcium-activated potassium channels or by directly stimulating nitric oxide synthesis in the canine coronary collateral circulation. METHODS: Twelve weeks after left anterior descending coronary artery ameroid constrictor implantation, barbiturate-anesthetized dogs (n = 22) were instrumented for measurement of hemodynamics and retrograde coronary flow. Dogs received sevoflurane ([0.5 and 1.0 minimum alveolar concentration [MAC]) during intracoronary infusions of drug vehicle (0.9% saline), the calcium-activated potassium channel antagonist iberiotoxin (13 microg/min), or the nitric oxide synthase inhibitor -nitro-l-arginine methyl ester (l-NAME, 300 microg/min). Retrograde coronary collateral blood flow was measured under baseline conditions, during and after administration of sevoflurane, and during intracoronary infusion of bradykinin. Data are mean +/- SEM. RESULTS: Sevoflurane increased (* < 0.05) retrograde coronary collateral blood flow (from 65 +/- 11 during control to 67 +/- 12* and 71 +/- 12* ml/min during 0.5 and 1.0 MAC, respectively). Iberiotoxin but not l-NAME attenuated these sevoflurane-induced increases in retrograde flow (6 +/- 1*, 7 +/- 2*, and 3 +/- 2 ml/min during vehicle, l-NAME, and iberiotoxin, respectively). After discontinuation of sevoflurane, retrograde flow returned to baseline values in each group. Bradykinin increased retrograde flow in vehicle- (63 +/- 12 to 69 +/- 12* ml/min) but not in iberiotoxin- (61 +/- 7 to 62 +/- 5 ml/min) or l-NAME-treated dogs (64 +/- 11 to 63 +/- 10 ml/min). CONCLUSIONS: The results demonstrate that sevoflurane increases coronary collateral blood flow, in part, through activation of calcium-activated potassium channels. This action occurs independent of nitric oxide synthesis.

Anesthetics, Inhalation↗
PubMed2002

Mechanism of preconditioning by isoflurane in rabbits: a direct role for reactive oxygen species.

BACKGROUND: Reactive oxygen species (ROS) contribute to myocardial protection during ischemic preconditioning, but the role of the ROS in protection against ischemic injury produced by volatile anesthetics has only recently been explored. We tested the hypothesis that ROS mediate isoflurane-induced preconditioning in vivo. METHODS: Pentobarbital-anesthetized rabbits were instrumented for measurement of hemodynamics and were subjected to a 30 min coronary artery occlusion followed by 3 h reperfusion. Rabbits were randomly assigned to receive vehicle (0.9% saline), or the ROS scavengers N-acetylcysteine (NAC; 150 mg/kg) or N-2-mercaptopropionyl glycine (2-MPG; 1 mg. kg(-1).min(-1)), in the presence or absence of 1.0 minimum alveolar concentration (MAC) isoflurane. Isoflurane was administered for 30 min and then discontinued 15 min before coronary artery occlusion. A fluorescent probe for superoxide anion production (dihydroethidium, 2 mg) was administered in the absence of the volatile anesthetic or 5 min before exposure to isoflurane in 2 additional groups (n = 8). Myocardial infarct size and superoxide anion production were assessed using triphenyltetrazolium staining and confocal fluorescence microscopy, respectively. RESULTS: Isoflurane (P < 0.05) decreased infarct size to 24 +/- 4% (mean +/- SEM; n = 10) of the left ventricular area at risk compared with control experiments (43 +/- 3%; n = 8). NAC (43 +/- 3%; n = 7) and 2-MPG (42 +/- 5%; n = 8) abolished this beneficial effect, but had no effect on myocardial infarct size (47 +/- 3%; n = 8 and 46 +/- 3; n = 7, respectively) when administered alone. Isoflurane increased superoxide anion production as compared with control experiments (28 +/- 12 -6 +/- 9 fluorescence units; P < 0.05). CONCLUSIONS: The results indicate that ROS produced following administration of isoflurane contribute to protection against myocardial infarction in vivo.

Analysis of Variance↗
PubMed2002

Isoflurane-induced preconditioning is attenuated by diabetes.

Volatile anesthetics stimulate, but hyperglycemia attenuates, the activity of mitochondrial ATP-regulated K(+) channels. We tested the hypothesis that diabetes mellitus interferes with isoflurane-induced preconditioning. Acutely instrumented, barbiturate-anesthetized dogs were randomly assigned to receive 0, 0.32, or 0.64% end-tidal concentrations of isoflurane in the absence or presence of diabetes (3 wk after administration of alloxan and streptozotocin) in six experimental groups. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Myocardial infarct size (triphenyltetrazolium staining) was 29 +/- 3% (n = 8) of the left ventricular area at risk in control experiments. Isoflurane reduced infarct size (15 +/- 2 and 13 +/- 1% during 0.32 and 0.64% concentrations; n = 8 and 7 dogs, respectively). Diabetes alone did not alter infarct size (30 +/- 3%; n = 8) but blocked the protective effects of 0.32% (27 +/- 2%; n = 7) and not 0.64% isoflurane (18 +/- 3%; n = 7). Infarct size was directly related to blood glucose concentrations in diabetic dogs, but this relationship was abolished by higher concentrations of isoflurane. The results indicate that blood glucose and end-tidal isoflurane concentrations are important determinants of infarct size during anesthetic-induced preconditioning.

Anesthetics, Inhalation↗