JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS
AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
A&A International Anesthesia Research Society
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (6)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gross, E. R.
Right arrow Articles by Pagel, P. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gross, E. R.
Right arrow Articles by Pagel, P. S.
Anesth Analg 2001;92:299-305
© 2001 International Anesthesia Research Society

CARDIOVASCULAR ANESTHESIA

Ethanol Enhances the Functional Recovery of Stunned Myocardium Independent of KATP Channels in Dogs

Eric R. Gross, MS*, Meir Gare, MD{dagger}, Wolfgang G. Toller, MD§, Judy R. Kersten, MD*, David C. Warltier, MD, PhD*{dagger}{ddagger}, and Paul S. Pagel, MD, PhD*{ddagger}

Departments of *Anesthesiology, {dagger}Medicine (Division of Cardiovascular Diseases), and {ddagger}Pharmacology and Toxicology, the Medical College of Wisconsin; the Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin; and the §Department of Anesthesiology, University of Graz, Graz, Austria

Address correspondence and reprint requests to Paul S. Pagel, MD, PhD, Medical College of Wisconsin, MEB-M4280, 8701 Watertown Plank Rd., Milwaukee, WI 53226. Address e-mail to pspagel @mcw.edu.


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Chronic, intermittent exposure to small amounts of ethanol reduces myocardial infarct size in vivo. We tested the hypothesis that acute administration of ethanol enhances the functional recovery of stunned myocardium and that adenosine triphosphate-dependent potassium (KATP) channels mediate this beneficial effect. Barbiturate-anesthetized dogs were instrumented for measurement of aortic and left ventricular pressure, +dP/dtmax, and subendocardial segment shortening (%SS) and were subjected to five 5-min periods of coronary artery occlusion, each separated by 5 min of reperfusion followed by a 3-h final reperfusion. In four groups (n = 7 each), dogs received 0.9% saline or ethanol (0.25, 0.5, or 1.0 g/kg over 30 min) in a random manner before occlusions and reperfusions. In other groups (n = 7 each), dogs received the KATP channel antagonist glyburide (0.3 mg/kg, IV) 30 min before saline or ethanol (0.25 g/kg) was administered. Dogs receiving saline or glyburide alone demonstrated poor recovery of contractile function during reperfusion (%SS = 0.9% ± 2.0% and 1.6% ± 1.2% at 3 h, respectively). Recovery of %SS was enhanced in dogs receiving the 0.25- and 0.5-g/kg doses of ethanol (10.0% ± 1.8% and 8.6% ± 2.2% at 3 h, respectively) independent of alterations in hemodynamics or coronary collateral blood flow (radioactive microspheres). Glyburide did not affect improvement of recovery of stunned myocardium produced by ethanol (11.8% ± 2.2% at 3 h). The results indicate that ethanol enhances the functional recovery of stunned myocardium independent of KATP channels in vivo.

Implications: Small amounts of ethanol improve the functional recovery of postischemic, reperfused myocardium in barbiturate-anesthetized dogs. These beneficial effects are not related to adenosine triphosphate-dependent potassium channels.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Adenosine triphosphate-dependent potassium (KATP) channels mediate the protective effects of ischemic preconditioning (IPC) (1) through a signal transduction cascade linking adenosine type 1 (A1) receptors (2), inhibitory guanine nucleotide binding proteins (3), and protein kinase C (PKC) (4). Activation of KATP channels and adenosine receptors also enhances the functional recovery of postischemic, reperfused ("stunned") myocardium in vivo (5). These data indicate that KATP channels are important in the protection of myocardium against both irreversible and reversible ischemic injury. Chronic ingestion of small doses of ethanol also protects myocardium from ischemic damage (6,7) by stimulating A1 (7) or {alpha}1-adrenergic (8) receptors and translocating the {epsilon} isoform of PKC (9) in rats and guinea pigs. These data suggest that the signal transduction pathways responsible for chronic "ethanol-induced preconditioning" and IPC may be similar. We have recently demonstrated (10) that blockade of KATP channels with the nonselective antagonist glyburide abolishes this salutary effect of chronic ethanol ingestion in dogs, indicating that KATP channels are involved in this process as well. Small doses of ethanol also exert protective effects against anoxia (11) or prolonged ischemia (12–14) during acute exposure by a mechanism that may involve {epsilon}PKC (14) or pertussis toxin-sensitive G protein-mediated, inwardly rectifying potassium (GIRK) channels (15). However, another study failed to demonstrate that ethanol reduces myocardial injury associated with prolonged ischemia (16). Thus, we tested the hypothesis that acute administration of ethanol immediately before a series of brief coronary artery occlusions and reperfusions enhances the functional recovery of stunned myocardium, and that KATP channels mediate this beneficial effect in dogs.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
All experimental procedures and protocols used in this investigation were reviewed and approved by the Animal Care and Use Committee of the Medical College of Wisconsin. All conformed to the "Guiding Principles in the Care and Use of Animals" of the American Physiological Society and the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health (Revised, 1996).

The implantation of instruments has been described previously (17). Briefly, dogs were anesthetized with sodium barbital (200 mg/kg) and sodium pentobarbital (15 mg/kg) and ventilated with an air and oxygen mixture (fraction of inspired oxygen = 0.25) after endotracheal intubation. Arterial blood gas tensions and acid-base status were maintained within a physiologic range by adjustment of tidal volume and respiratory rate. Temperature was maintained with a heating blanket. A double pressure transducer-tipped catheter was inserted into the aorta and left ventricle (LV) through the left carotid artery for measurement of arterial and LV pressures and the maximal rate of increase of LV pressure (+dP/dtmax). The femoral artery and vein were cannulated for the withdrawal of reference blood flow samples and fluid administration, respectively. A thoracotomy was performed in the left fifth intercostal space and a heparin-filled catheter was inserted into the left atrial appendage for the administration of radioactive microspheres. A silk ligature was placed around the left anterior descending coronary artery (LAD) immediately distal to the first diagonal branch for production of occlusion and reperfusion. Two pairs of ultrasonic segment length transducers (5 MHz) used to measure changes in regional contractile function (percent segment shortening [%SS]) were implanted in the subendocardium of the LAD (ischemic zone) and left circumflex coronary artery (LCCA; normal zone). End-systolic segment length (ESL) was determined 10 ms before maximal negative left ventricular dP/dt, and end-diastolic segment length (EDL) was determined immediately before the onset of LV isovolumic contraction. %SS was calculated in the LAD and LCCA zones by using the following formula: %SS = (EDL - ESL) x 100/EDL. Hemodynamics were monitored continuously on a polygraph and digitized by using a computer interfaced with an analog-to-digital converter.

The experimental design is illustrated in Figure 1. Baseline hemodynamics and regional contractile function were recorded 90 min after instrumentation was completed. All dogs were subjected to five 5-min periods of LAD occlusion separated by 5-min periods of reperfusion and a 3-h period of final reperfusion. In four separate experimental groups, dogs received IV 0.9% saline or ethanol infusions (0.25, 0.5, or 1.0 g/kg over 30 min) in a random manner before brief LAD occlusions and reperfusions. Blood ethanol concentrations were determined by using a standard enzymatic assay (18) at selected intervals throughout each experiment. In two additional groups of experiments, dogs received the KATP channel antagonist glyburide (0.3 mg/kg in polyethylene glycol and 0.1 N NaOH, IV) 30 min before saline or ethanol (0.25 g/kg) was administered. This dose of glyburide blocks the enhanced functional recovery of stunned myocardium produced by KATP channel agonists (19) without affecting systemic hemodynamics, coronary collateral blood flow, or postischemic recovery. Blood glucose concentrations (Tracer II glucometer, Boehringer Mannheim, Indianapolis, IN) were measured at selected intervals in dogs treated with glyburide in the presence and absence of ethanol. Transmural myocardial blood flow in the ischemic (LAD) and normal (LCCA) regions was measured by using the radioactive microsphere technique (17) immediately before brief LAD occlusions were initiated, during the fifth LAD occlusion, and after 60 and 180 min of reperfusion.



View larger version (9K):
[in this window]
[in a new window]
  		Figure 1. Schematic illustration of the experimental protocol (see text). OCC = occlusion.

 
Statistical analysis of data within and among groups was performed with multiple analysis of variance with repeated measures followed by Student’s t-test with Bonferroni’s correction for multiplicity. A P value < 0.05 was considered significant. All data were expressed as mean ± SEM.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Fifty-eight dogs were instrumented to obtain 42 successful experiments (n = 7 in each group). Ten dogs were excluded from data analysis because transmural coronary collateral blood flow during the fifth LAD occlusion was >25% of the baseline value (one saline, two 0.25-g/kg dose of ethanol, two 0.5-g/kg dose of ethanol, one 1.0-g/kg dose of ethanol, two glyburide alone, and two ethanol plus glyburide). Six other dogs were excluded because of problems with instrumentation or intractable ventricular fibrillation during LAD occlusions or reperfusion.

No differences in baseline systemic hemodynamics were observed among experimental groups ( Table 1). The ratio of myocardial area at risk to total LV mass was also similar among groups (saline 30 ± 2; ethanol [0.25 g/kg] 32 ± 2; ethanol [0.5 g/kg] 31 ± 4; ethanol [1.0 g/kg] 30 ± 3; glyburide alone 32 ± 3; and ethanol plus glyburide 35% ± 2% of the LV). LAD occlusions caused a significant increase in LV end-diastolic pressure and a decrease in +dP/dtmax. Reductions in global myocardial contractility were also observed during the final reperfusion. Heart rate and mean arterial and LV systolic pressures were unchanged. Systolic aneurysmal bulging of ischemic myocardium occurred during each 5-min LAD occlusion ( Fig. 2). %SS in the LAD perfusion territory was also decreased from baseline during each 5-min reperfusion and during the entire 3 h of the final reperfusion. Dogs receiving saline showed poor recovery of contractile function (0.9% ± 2.0% at 3 h reperfusion) (Fig. 2). No changes in %SS were observed in the normal (LCCA) zone during LAD occlusions and reperfusions.


View this table:
[in this window]
[in a new window]
  		Table 1. Systemic Hemodynamics
 


View larger version (27K):
[in this window]
[in a new window]
  		Figure 2. Segment shortening in the ischemic and reperfused zone in dogs receiving saline (CON; control) or 0.25, 0.5, and 1.0 mg/kg ethanol (ETOH). *P < 0.05 versus CON.

 
The peak blood ethanol concentrations were 47 ± 4, 116 ± 9, 289 ± 26 mg/dL (10 ± 1, 25 ± 2, and 63 ± 6 mM) at the completion of the 0.25-, 0.5-, and 1.0-g/kg ethanol infusions, respectively (Table 1). The 0.25- and 0.5-g/kg doses of ethanol did not affect systemic hemodynamics. In contrast, the 1.0-g/kg dose of ethanol increased LV end-diastolic pressure and decreased +dP/dtmax and %SS consistent with a direct negative inotropic effect. An increase in LV end-diastolic pressure and a decrease in +dP/dtmax were observed during the fifth LAD occlusion in dogs receiving ethanol. Equivalent degrees of systolic dyskinesia were produced by LAD occlusions in dogs receiving ethanol compared with those receiving saline (Fig. 2). Ischemic zone %SS was significantly more during the first and second 5-min reperfusion periods in dogs treated with ethanol. Enhanced recovery of %SS during reperfusion occurred in dogs receiving the 0.25- and 0.5-g/kg doses of ethanol (10.0% ± 1.8% and 8.6% ± 2.2% at 3-h reperfusion, respectively). However, improved recovery of contractility was not observed in dogs pretreated with the 1.0-g/kg dose of ethanol (6.3% ± 2.6% at 3-h reperfusion) compared with those receiving saline. Glyburide did not alter hemodynamics in the presence or absence of ethanol (0.25 g/kg). Recovery of contractile function was poor after the administration of glyburide alone (1.6% ± 1.2% at 3-h reperfusion) ( Fig. 3). Glyburide did not affect ethanol-induced improvement of recovery of stunned myocardium (11.8% ± 2.2% at 3-h reperfusion).



View larger version (26K):
[in this window]
[in a new window]
  		Figure 3. Segment shortening in the ischemic and reperfused zone in dogs receiving saline (CON; control), ethanol (ETOH; 0.25 g/kg), glyburide (GLB; 0.3 mg/kg), or ethanol plus glyburide. *P < 0.05 versus CON; {dagger}P < 0.05 versus GLB.

 
No differences in baseline myocardial perfusion before and transmural coronary collateral blood flow during the fifth LAD occlusion were observed among groups ( Table 2). Transmural blood flow recovered to baseline values at 60 min after reperfusion in all groups. Perfusion of normal myocardium (LCCA region) remained constant during LAD occlusion and reperfusion in all experimental groups. There were no differences among groups in blood flow to ischemic and normal myocardium during reperfusion.


View this table:
[in this window]
[in a new window]
  		Table 2. Transmural Myocardial Blood Flow in the Ischemic and Normal Regions (mL · min-1 · g-1)
 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
Several epidemiological studies have demonstrated that regular consumption of a moderate amount of ethanol reduces the incidence of coronary artery disease (20) and decreases mortality after acute myocardial infarction (21). These beneficial effects in humans have been attributed to favorable alterations in lipid metabolism and platelet function (22). More recently, investigations conducted in experimental animals (7–10) indicate that moderate ethanol consumption may exert direct protective effects against ischemic injury by activating an endogenous myocardial signal transduction pathway involving adenosine A1 receptors, {epsilon}PKC, and KATP channels that also appears to be responsible for IPC and volatile anesthetic-induced preconditioning (23). These clinical and experimental data clearly identify beneficial cardiovascular actions associated with chronic, intermittent ingestion of small amounts of ethanol, but the acute effects of ethanol on reversible or irreversible myocardial ischemic injury remain more controversial. Acute administration of amounts of ethanol that result in peak blood concentrations substantially more than the intoxicating level (defined as 100 mg/dL [22 mM]) did not alter myocardial infarct size in a canine model of prolonged coronary artery occlusion (16) and reduced global LV performance (24) and exercise capacity before the onset of angina or ST segment changes in patients with coronary artery disease (25,26). In contrast, ethanol (approximately 20 mM) markedly reduced histologic evidence of myocardial cell injury, decreased intracellular calcium accumulation, and preserved ATP concentrations in isolated rat hearts exposed to anoxia and reoxygenation (11). More recently, Chen et al. (14) demonstrated that ethanol concentrations as small as 10 mM exert protective effects against ischemic damage in ventricular myocytes and isolated rat hearts. These beneficial actions were blocked by an isozyme-selective inhibitor of {epsilon}PKC (14). Other investigations performed in rats also suggest that acute administration of ethanol (0.5 to 6.0 g/kg) may reduce the extent of myocardial infarction associated with supply (12) or demand (13) ischemia. Like structurally related volatile anesthetics, aliphatic alcohols, including ethanol, produce direct negative inotropic effects in vitro by partially inhibiting calcium (Ca2+) uptake and release by the sarcoplasmic reticulum (27). Such an attenuation of the Ca2+ transient by ethanol may also theoretically protect against ischemic injury by reducing intracellular Ca2+ overload during and after coronary artery occlusion.

The results of the present investigation indicate that the 0.25- and 0.5-g/kg doses of ethanol produced mildly intoxicating peak blood concentrations immediately before multiple, brief LAD occlusions and reperfusions and enhanced the contractile function of stunned myocardium. The beneficial effects of ethanol occurred independently of alterations in systemic hemodynamics or transmural coronary collateral blood flow. These results support the previous studies indicating that smaller concentrations of ethanol produce direct cardioprotective effects (11,14). In contrast to the findings with smaller doses, the 1.0-g/kg dose of ethanol increased LV end-diastolic pressure and reduced global and regional myocardial contractility but did not provide significant protective effects in postischemic, reperfused myocardium. The hemodynamic findings with the 1.0-g/kg dose of ethanol support previous results demonstrating pronounced LV systolic and diastolic dysfunction in dogs (28) with a dose of ethanol that produced a peak blood concentration exceeding the intoxicating level. The results with the 1.0-g/kg dose of ethanol also support previous findings indicating that blood ethanol concentrations between 150 and 300 mg/dL immediately before prolonged coronary artery occlusion do not reduce myocardial infarct size in rats (12) and dogs (16). Acute administration of larger concentrations of ethanol may increase the formation of oxygen-derived free radicals in cardiac muscle (29). For example, intracellular myocardial damage (evaluated with electron microscopy) produced by a single 2-g/kg dose of ethanol was attenuated by the free radical scavenger vitamin E in rats (30). Reactive oxygen species play a central role in the pathogenesis of stunned myocardium (31). Thus, the 1-g/kg dose of ethanol may not have provided protection against reversible ischemic injury in the present investigation because increases in oxygen-derived free radical production by ethanol contributed to myocardial damage. This hypothesis will require further investigation to confirm, however.

Ethanol opens cardiac-type GIRK channels in vitro (15). The KATP channel is a GIRK channel subtype that is an important mediator of protection against ischemic injury (23). These observations suggest that KATP channels may be opened by acute ethanol exposure in vivo. Several chemically different KATP channel agonists enhance and antagonists abolish the functional recovery of postischemic, reperfused myocardium (5,32). The present results with glyburide indicate that this nonselective KATP channel antagonist does not alter improvements in the recovery of stunned myocardium produced by the 0.25-g/kg dose of ethanol (peak blood concentration = 50 ± 4 mg/dL [11 ± 1 mM]). These data suggest that acute ethanol-induced protection against reversible ischemic injury occurs independent of KATP channels. The dose of glyburide (0.3 mg/kg) used in the present investigation abolishes the enhanced recovery of postischemic, reperfused myocardium produced by KATP channel agonists (19) and volatile anesthetics (23), and inhibits IPC and anesthetic-induced preconditioning (17). The administration of glyburide reduced blood glucose concentration in the presence (107 ± 8 to 73 ± 7 mg/dL) and absence (119 ± 9 to 75 ± 15 mg/dL) of ethanol to similar degrees consistent with closure of pancreatic ß cell KATP channels, and facilitated insulin secretion (33). Thus, it appears unlikely that the present dose of glyburide would be insufficient to attenuate ethanol-enhanced recovery of stunned myocardium if this process was mediated by KATP channel opening, because direct physiologic evidence of KATP channel blockade was observed in response to this dose. Nevertheless, ethanol may have affected the pharmacokinetics of glyburide or altered the efficacy of this KATP channel antagonist at the sulfonylurea binding site. In contrast to the present findings with acute ethanol exposure, we (10) have recently demonstrated that reductions in myocardial infarct size produced by chronic, intermittent ingestion of small amounts of ethanol, resulting in peak blood concentrations of 52 ± 4 mg/dL (11 ± 1 mM), were abolished by glyburide. These findings indicate that KATP channel opening is involved in chronic ethanol-induced preconditioning. Taken together, the present and previous (10) results suggest that ethanol-induced, KATP channel-mediated protection against ischemic injury does not occur immediately but requires temporal adaptation.

Chronic ethanol consumption produces sustained translocation of the {epsilon} isoform of PKC (9). A role for {epsilon}PKC is also implicated in IPC (4), but is not firmly established in the pathogenesis of stunned myocardium (31). KATP channel opening is linked to PKC stimulation (34), but PKC may also exert protective effects in ischemic myocardium by other mechanisms, including modification of protein-tyrosine or mitogen-activated protein kinase activity, favorable alterations in adenosine metabolism, or decreases in sarcolemmal Ca2+ influx (31). Thus, although acute administration of ethanol may be protective by activating {epsilon}PKC (14), these salutary actions may not necessarily be mediated by KATP channels. Ethanol may also produce differential effects on several signal transduction elements, including protein-tyrosine and mitogen-activated protein kinases and phospholipase D in vitro (35). Whether these actions contribute to ethanol-induced myocardial protection from ischemia represents an important goal of future research.

In summary, the present results demonstrate that acute administration of doses of ethanol that produce blood concentrations less than or equal to the intoxicating level immediately before a series of brief coronary artery occlusions and reperfusions enhances the functional recovery of stunned myocardium independent of alterations in systemic hemodynamics or transmural coronary collateral blood flow. Pretreatment with the KATP channel antagonist glyburide did not alter these beneficial effects, indicating that KATP channel opening is not required for acute ethanol-induced protection against reversible ischemic injury in barbiturate anesthetized dogs.


   Acknowledgments
 
This work was supported in part by the Medical Scientist Training Program of the Medical College of Wisconsin (ERG), an American Heart Association Postdoctoral Fellowship (MG), a Max Kade Research Fellowship from the Austrian Science Foundation (WGT), and Grants AA-12331 (PSP), HL-03690 (JRK), HL-54820 (DCW), and GM-08377 (DCW) from the United States Public Health Service, Bethesda, MD.

The authors thank Mr. David A. Schwabe and Mr. John P. Tessmer for technical assistance and Dr. Joseph J. Barboriak for his helpful suggestions.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Gross GJ, Auchampach JA. Blockade of ATP-sensitive potassium channels prevents myocardial preconditioning in dogs. Circ Res 1992; 70: 223–33.[Abstract/Free Full Text]
  2. Auchampach JA, Gross GJ. Adenosine A1 receptors, KATP channels and ischemic preconditioning in dogs. Am J Physiol 1993; 33: H1327–36.
  3. Schultz JE, Hsu AK, Barbieri JT, et al. Pertussis toxin abolishes the cardioprotective effect of ischemic preconditioning in the intact rat heart. Am J Physiol 1998; 44: H495–500.
  4. Ping P, Zhang J, Qiu Y, et al. Ischemic preconditioning induces selective translocation of protein kinase C isoforms {epsilon} and {eta} in the heart of conscious rabbits without subcellular redistribution of total protein kinase C activity. Circ Res 1997; 81: 404–14.[Abstract/Free Full Text]
  5. Yao Z, Gross GJ. Glibenclamide antagonizes adenosine A1 receptor-mediated cardioprotection in stunned canine myocardium. Circulation 1993; 88: 235–44.[Abstract/Free Full Text]
  6. McDonough KH. Chronic alcohol consumption causes accelerated myocardial preconditioning to ischemia-reperfusion injury. Alcohol Clin Exp Res 1997; 21: 869–73.[Web of Science][Medline]
  7. Miyamae M, Diamond I, Weiner MW, et al. Regular alcohol consumption mimics cardiac preconditioning by protecting against ischemia-reperfusion injury. Proc Natl Acad Sci USA 1997; 94: 3235–9.[Abstract/Free Full Text]
  8. Miyamae M, Camacho SA, Zhou H-Z, et al. Alcohol consumption reduces ischemia-reperfusion injury by species-specific signaling in guinea pigs and rats. Am J Physiol 1998; 44: H50–6.
  9. Miyamae M, Rodriguez MM, Camacho SA, et al. Activation of {epsilon} protein kinase C correlates with a cardioprotective effect of regular ethanol consumption. Proc Natl Acad Sci USA 1998; 95: 8262–7.[Abstract/Free Full Text]
  10. Pagel PS, Toller WG, Gross EG, et al. KATP channels mediate the beneficial effects of chronic ethanol ingestion. Am J Physiol 2000; 279: H2574–9.
  11. Kobayashi H, Ashraf M, Rahamathulla PM, Minami M. Moderating effect of low doses of ethanol on reoxygenation injury in the anoxic myocardium. Pathol Res Pract 1987; 182: 810–6.[Web of Science][Medline]
  12. Bernauer W. The effect of ethanol on arrhythmias and myocardial necrosis in rats with coronary artery occlusion and reperfusion. Eur J Pharmacol 1986; 126: 179–87.[Web of Science][Medline]
  13. Mallov S, Gilmour RF. Inhibition of epinephrine-induced myocardial necrosis in rats by administration of single doses of ethanol. Drug Alcohol Depend 1977; 2: 397–407.[Web of Science][Medline]
  14. Chen CH, Gray MO, Mochly-Rosen D. Cardioprotection from ischemia by a brief exposure to physiological levels of ethanol: role of epsilon protein kinase C. Proc Natl Acad Sci USA 1999; 96: 12784–9.[Abstract/Free Full Text]
  15. Kobayashi T, Ikeda K, Kojima H, et al. Ethanol opens G-protein-activated inwardly rectifying K+ channels. Nat Neurosci 1999; 2: 1091–7.[Web of Science][Medline]
  16. Itoya M, Morrison JD, Downey HF. Effect of ethanol on myocardial infarct size in a canine model of coronary artery occlusion-reperfusion. Mol Cell Biochem 1998; 186: 35–41.[Web of Science][Medline]
  17. Kersten JR, Schmeling TJ, Pagel PS, et al. Isoflurane mimics ischemic preconditioning via activation of KATP channels: reduction of myocardial infarct size with an acute memory phase. Anesthesiology 1997; 87: 361–70.[Web of Science][Medline]
  18. Jung G, Ferard G. Enzyme-coupled measurement of ethanol in whole blood and plasma with a centrifugal analyzer. Clin Chem 1978; 24: 873–6.[Abstract/Free Full Text]
  19. Auchampach JA, Maruyama M, Cavero I, Gross GJ. Pharmacological evidence for a role of ATP-dependent potassium channels in myocardial stunning. Circulation 1992; 86: 311–9.[Abstract/Free Full Text]
  20. Rimm EB, Giovannucci EL, Willett WC, et al. Prospective study of alcohol consumption and risk of coronary artery disease in men. Lancet 1991; 338: 464–8.[Web of Science][Medline]
  21. Wannamethee G, Whincup PH, Shaper AG, et al. Factors determining case fatality in myocardial infarction "who dies in a heart attack"? Br Heart J 1995; 74: 324–31.[Abstract/Free Full Text]
  22. Gaziano JM, Buring JE, Breslow JL, et al. Moderate alcohol intake, increased levels of high-density lipoprotein and its subfractions, and decreased risk of myocardial infarction. N Engl J Med 1993; 329: 1829–34.[Abstract/Free Full Text]
  23. Kersten JR, Gross GJ, Pagel PS, Warltier DC. Activation of adenosine triphosphate-regulated potassium channels: mediation of cellular and organ protection. Anesthesiology 1998; 88: 495–513.[Web of Science][Medline]
  24. Conway N. Haemodynamic effects of ethyl alcohol in patients with coronary heart disease. Br Heart J 1968; 30: 638–44.[Free Full Text]
  25. Orlando J, Aronow WS, Cassidy J, Prakash R. Effect of ethanol on angina pectoris. Ann Intern Med 1976; 84: 652–5.
  26. Ahlawat S, Siwach SB, Jagdish . Indirect assessment of acute effects of ethyl alcohol on coronary circulation in patients with chronic stable angina. Int J Cardiol 1991; 33: 385–91.[Web of Science][Medline]
  27. Lynch C III. Alcohol and anesthetic actions on myocardial contractility: evidence for a lipophilic/electrophilic sarcoplasmic reticulum site. Adv Exp Med Biol 1991; 301: 155–67.[Medline]
  28. Cheng CP, Shihabi Z, Little WC. Acute effects of mildly intoxicating levels of alcohol on left ventricular function in conscious dogs. J Clin Invest 1990; 85: 1858–65.
  29. McDonough KH. The role of alcohol in the oxidant antioxidant balance in the heart. Front Biosci 1999; 4: D601–6.[Medline]
  30. Redetzki JE, Griswold KE, Nopajaroonsri C, Redetzki HM. Amelioration of cardiotoxic effects of alcohol by vitamin E. J Toxicol Clin Toxicol 1983; 20: 319–31.[Web of Science][Medline]
  31. Kloner RA, Bolli R, Marban E, et al. Medical and cellular implications of stunning, hibernation, and preconditioning: an NHLBI workshop. Circulation 1998; 97: 1848–67.[Free Full Text]
  32. Grover GJ. Protective effects of ATP-sensitive potassium-channel openers in experimental myocardial ischemia. J Cardiovasc Pharmacol 1994; 24: S18–27.
  33. Dunne MJ, Petersen OH. Potassium selective ion channels in insulin-secreting cells: physiology, pharmacology and their role in stimulus-secretion coupling. Biochim Biophys Acta 1991; 1071: 67–82.[Medline]
  34. Hu K, Duan D, Li G-R, Nattel S. Protein kinase C activates ATP-sensitive K+ current in human and rabbit ventricular myocytes. Circ Res 1996; 78: 492–8.[Abstract/Free Full Text]
  35. Levine GH, Maglio JJ, Horwitz J. Differential effects of ethanol on signal transduction. Alcohol Clin Exp Res 2000; 24: 93–101.[Web of Science][Medline]
Accepted for publication October 10, 2000.




This article has been cited by other articles:


Home page
 Ther Adv Cardiovasc DisHome page
E. N. Churchill, M.-H. Disatnik, G. R. Budas, and D. Mochly-Rosen
Ethanol for cardiac ischemia: the role of protein kinase c
Therapeutic Advances in Cardiovascular Disease, December 1, 2008; 2(6): 469 - 483.
[Abstract] [PDF]

Home page
 CirculationHome page
R. A. Kloner and S. H. Rezkalla
To Drink or Not to Drink? That Is the Question
Circulation, September 11, 2007; 116(11): 1306 - 1317.
[Abstract] [Full Text] [PDF]

Home page
 Anesth. Analg.Home page
T. P. Weber, M. A. G.{b.}e Hartlage, N. Rolf, M. Booke, E. Berendes, H. Van Aken, and A. Meissner
Short-Term Administration of Ethanol Does Not Affect Functional Recovery from Myocardial Stunning in Awake Dogs
Anesth. Analg., March 1, 2003; 96(3): 665 - 672.
[Abstract] [Full Text] [PDF]

Home page
 Anesth. Analg.Home page
P. S. Pagel, J. G. Krolikowski, F. Kehl, B. Mraovic, J. R. Kersten, and D. C. Warltier
The Role of Mitochondrial and Sarcolemmal KATP Channels in Canine Ethanol-Induced Preconditioning In Vivo
Anesth. Analg., April 1, 2002; 94(4): 841 - 848.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (6)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gross, E. R.
Right arrow Articles by Pagel, P. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gross, E. R.
Right arrow Articles by Pagel, P. S.

Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press