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1 Division of Cardiovascular Diseases, Department of Medicine and 2 Departments of Anesthesiology and 3 Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226; The Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin 53295 and 4 Department of Anesthesiology, University of Graz, Graz, Austria
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Chronic ingestion of low doses of ethanol protects the myocardium from ischemic injury by activating adenosine receptors and protein kinase C. We tested the hypothesis that ATP-dependent potassium (KATP) channels mediate these beneficial effects. Dogs were fed with ethanol (1.5 g/kg) or water mixed with dry food twice per day for 12 wk. After they were acutely instrumented for measurement of hemodynamics, dogs received saline (vehicle) or glyburide (0.1 mg/kg iv) and were subjected to 60 min of coronary artery occlusion followed by 3 h of reperfusion. Infarct size (through triphenyltetrazolium chloride staining) was significantly (P < 0.05) reduced to 14 ± 1% of the left ventricular area at risk in ethanol-pretreated dogs compared with controls (25 ± 2%). Glyburide alone did not affect infarct size (25 ± 3%) but abolished the protective effects of ethanol pretreatment (28 ± 3%). No differences in hemodynamics or coronary collateral blood flow (through radioactive microspheres) were observed among groups. The results indicate that KATP channels mediate the protective effects of chronic consumption of ethanol.
myocardial infarction; infarct size; prolonged coronary occlusion; myocardial ischemia
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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ATP-DEPENDENT
POTASSIUM (KATP) channels mediate the protective
effects of ischemic preconditioning (IPC) (7) through a signal transduction pathway that involves adenosine subtype-1 (A1) inhibitory guanine (Gi) nucleotide-binding
proteins (27) and protein kinase C (PKC)
(25). Recent evidence obtained in rats and guinea pigs
indicates that chronic consumption of low doses of ethanol also
protects the myocardium from ischemic injury (18, 20) by
activating A1 (20) or
1-adrenergic (19) receptors and the
-isoform of PKC (21). These data suggest the signal transduction pathways responsible for chronic ethanol-induced preconditioning (CEPC) and IPC may be similar. Whether KATP
channel activation plays a role in CEPC is unknown. Thus we tested the hypothesis that KATP channels mediate CEPC in a canine
model of chronic, intermittent ethanol ingestion.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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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).
Model of chronic, intermittent ethanol consumption. Mongrel dogs weighing between 25 and 30 kg were randomly assigned to receive dry dog chow (Lab Canine Diet, Richmond, IN) mixed with ethanol (1.5 g/kg) or an equal volume of water twice a day for 12 wk (4). Blood ethanol concentrations were determined using a standard enzymatic assay (11) 45 min after eating on random days. Drinking water was provided ad libitum. Dogs that failed to consume the chow-ethanol mix or lost weight during the 12-wk pretreatment period were excluded from further experimentation. Dogs were fasted overnight before and did not receive ethanol on the day of experimentation.
Surgical preparation. Implantation of instruments has been previously described (13). Briefly, dogs were anesthetized with barbital sodium (200 mg/kg) and pentobarbital sodium (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 physiological range by adjustment of the tidal volume and respiratory rate. 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 inserted into the left atrial appendage for administration of radioactive microspheres. A silk ligature was placed around the left anterior descending coronary artery (LADCA) immediately distal to the first diagonal branch for production of occlusion and reperfusion. Regional myocardial perfusion was measured in the ischemic (LADCA) and normal (left circumflex coronary artery) zones using radioactive microspheres at selected intervals (13). Myocardial infarct size was determined with triphenyltetrazolium chloride staining at the completion of each experiment (29). Hemodynamics were continuously monitored on a polygraph and digitized using a computer interfaced with an analog-to-digital converter.
Experimental protocol.
Baseline hemodynamics were recorded 90 min after instrumentation was
completed. All dogs were subjected to a 60 min LADCA occlusion followed
by 3 h of reperfusion. In four separate groups of experiments,
dogs that consumed ethanol or water (control) mixed with dog chow for
12 wk were randomly assigned to receive 0.9% saline or the
KATP channel antagonist glyburide (0.1 mg/kg iv) 60 min
before LADCA occlusion and reperfusion, as shown in Fig.
1. This dose of glyburide has been
previously shown to block volatile anesthetic-induced preconditioning
and IPC (13). Plasma glucose concentrations (Tracer II
glucometer) were measured at selected intervals. Dogs that developed
intractable ventricular fibrillation and those with a subendocardial
coronary collateral blood flow 
0.15
ml · min
1 · g1 were
excluded from subsequent data analysis (7).
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Statistical analysis. Statistical analysis of data within and among groups was performed with analysis of variance (ANOVA) with repeated measures followed by Student's t-test with Bonferroni's correction for multiplicity. Linear regression analysis was performed to determine the relationship between transmural collateral blood flow and infarct size expression as a percentage of LV area at risk (AAR). Changes within and among groups were considered statistically significant when P < 0.05. Data are expressed as means ± SE.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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All dogs consumed the assigned diet during the 12-wk pretreatment
period. The average blood-ethanol concentration was 52 ± 4 mg/dl
45 min after consumption of the chow-ethanol mix. Forty dogs were used
to obtain 32 successful experiments. Three dogs were excluded from
analysis because of intractable ventricular fibrillation during LADCA
occlusion or reperfusion (1 dog from the control group, 1 dog from the
glyburide alone group, and 1 dog from the ethanol and glyburide group).
The number of dogs requiring defibrillation (5 dogs from the control
group, 4 dogs from the glyburide alone group, 4 dogs from ethanol
pretreatment group, and 5 dogs from ethanol and glyburide group) and
the number of defibrillation attempts (1.9 ± 0.5 from the control
group, 2.1 ± 0.5 from the glyburide alone group, 1.8 ± 0.4 from ethanol pretreatment group, and 2.3 ± 0.5 from the ethanol
and glyburide group) during LADCA occlusion and reperfusion were
similar among groups. Four dogs were excluded because subendocardial
coronary collateral blood flow exceeded 0.15 ml · min1 · g1 (1 dog from
the control group, 1 dog from the glyburide alone group, 1 dog from the
ethanol pretreatment group, and 1 dog from the ethanol and glyburide
group). Another dog receiving the chow-ethanol mix died of an unrelated
illness during the 12-wk pretreatment period.
Systemic hemodynamics.
No differences in baseline systemic hemodynamics were observed between
experimental groups (Table 1). Twice
daily consumption of ethanol for 12 wk did not affect hemodynamics.
Glyburide produced no hemodynamic effects but reduced blood glucose
concentration in the presence (79 ± 4 to 43 ± 4 mg/dl) or
absence (74 ± 4 to 46 ± 4 mg/dl) of ethanol pretreatment.
Significant (P < 0.05) increases in LV end-diastolic
pressure and decreases in +dP/dtmax were
observed during LADCA occlusion and reperfusion in all groups. There
were no hemodynamic differences among groups during LADCA occlusion or
reperfusion.
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Infarct size and coronary collateral blood flow.
The AAR was similar among groups (control group 37 ± 2%,
glyburide group 42 ± 2%, ethanol group 41 ± 2%, and
ethanol and glyburide group 38 ± 2% of the LV). Twelve-week
pretreatment with ethanol significantly reduced myocardial infarct size
to 14 ± 1% of the AAR (Figs. 2,
3, and 4)
compared with control experiments (25 ± 2%). Glyburide abolished
the protective effects of ethanol pretreatment (28 ± 3%) but had
no effect in dogs that did not receive ethanol (25 ± 3%).
Consumption of ethanol for 12 wk did not affect baseline regional
myocardial perfusion. No differences in subepicardial, midmyocardial,
subendocardial, or transmural coronary collateral blood flow (Table
2) were observed among groups.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Clinical studies have demonstrated that regular consumption of small amounts of ethanol reduces the incidence of coronary artery disease (26) and decreases mortality after acute myocardial infarction (28), in part by producing beneficial alterations in lipid metabolism and platelet function (6, 24). Several recent investigations (19-21) provide intriguing evidence that chronic, moderate ethanol consumption may also mimic the protective effects of IPC by a receptor-mediated mechanism. Isolated hearts from guinea pigs receiving ethanol (2.5-5%) in drinking water ad libitum for 12 wk before experimentation demonstrated improved functional recovery and decreased myocardial necrosis after 45 min of no-flow ischemia (19, 20). These salutary effects were similar to those obtained with IPC in the absence of ethanol pretreatment and were inhibited by adenosine A1 but not A2 receptor antagonists (19, 20). Ethanol has been shown to activate A1 receptors (3) and increase extracellular adenosine concentration by nucleoside transportor inhibition (23). Adenosine mimics IPC by activating A1 receptors (1) and is coupled to KATP channels through Gi proteins in ventricular myocytes (14). Pharmacological blockade of A1 receptors (1) and Gi proteins (27) abolishes the beneficial actions of IPC (1).
Chronic ethanol consumption produces sustained translocation of the
-isoform of PKC (21). A role for PKC - and
-isoforms has also been strongly implicated in IPC
(25), and KATP channel opening has been linked
to PKC stimulation (8). This latter action is
synergistically enhanced by concomitant administration of adenosine
(17). Ethanol also activates pertussis toxin-sensitive G
protein-linked inwardly rectifying potassium (Kir) channels in vitro (15). The KATP channel is a
Kir channel subtype (9) that has been shown to
be an important endogenous mediator of myocardial protection and has
been proposed to be the putative end-effector of a signal transduction
cascade responsible for the beneficial effects of IPC and
anesthetic-induced preconditioning (12). KATP
channel agonists mimic (22) and antagonists prevent (7) IPC in vivo. Taken together, these data indicate that
the signaling pathways responsible for CEPC and IPC share many common features and further suggest that KATP channels may play a
central role in reduction of ischemic injury associated with chronic
ingestion of low doses of ethanol.
The present results in dogs confirm and extend previous experimental
(18-21) and clinical (28) findings
indicating that chronic ethanol consumption reduces myocardial ischemic
injury. This beneficial effect was blocked by glyburide, demonstrating
that this preconditioning effect is mediated by KATP
channels. The reduction in infarct size produced by chronic ethanol
ingestion occurred independent of alterations in systemic hemodynamics
and transmural coronary collateral blood flow. Consumption of the
ethanol-chow mix during the 12-wk pretreatment period consistently
produced subintoxicating blood ethanol concentrations in dogs. Although
the pharmacokinetics of ethanol appear to be similar in dogs and
humans, the present results should be qualified because oral ingestion
of the dose of ethanol used in this investigation may produce greater
blood ethanol concentrations in humans than those observed here in
dogs. Previous studies conducted in small mammals
(18-21) did not measure blood ethanol concentrations
during the pretreatment period nor quantify regional myocardial
perfusion during acute experimentation. In contrast to the findings
with chronic ethanol ingestion, intravenous administration of ethanol
immediately before coronary artery occlusion did not affect infarct
size in a similar canine model (10). These data support
the contention that the advantageous effect of chronic, modest ethanol
consumption observed in the present investigation represents a temporal
adaptation of signaling elements involved in protection from
irreversible ischemic injury. Miyamae et al (20) have
provided compelling evidence for a role for A1 receptor
activation in this time-dependent process. A strong link between
A1 receptors and KATP channels has been
established in ventricular myocardium during IPC (1), and
it is highly likely that a similar mechanism may also be activated to
produce CEPC. In addition, chronic ethanol ingestion has been shown to activate the PKC -isoform (21), another important
component of intracellular signaling during IPC (25) that
has been directly linked to KATP channels
(16). Sarcolemmal and mitochondrial KATP
channels have been identified, and recent evidence (2, 5)
suggests that mitochondrial KATP channels play an essential role in IPC. The present data indicate that KATP channels
are clearly involved in CEPC, but the precise subcellular location of
these channels remains to be defined.
In summary, the present results demonstrate that chronic, intermittent consumption of subintoxicating amounts of ethanol reduces myocardial infarct size. This protective effect was abolished by the nonselective KATP channel antagonist glyburide, indicating that KATP channels mediate CEPC in dogs.
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ACKNOWLEDGEMENTS |
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The authors thank David A. Schwabe and John P. Tessmer for technical assistance and Dr. James J. Henderson for helpful comments and suggestions about the experimental model. The authors also thank Dr. Joseph J. Barboriak for assistance.
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FOOTNOTES |
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This work was supported in part by the National Institute on Alcohol Abuse and Alcoholism Grant AA-12331 (to P. S. Pagel), National Heart, Lung, and Blood Institute Grants HL-03690 (to J. R. Kersten) and HL-54820 (to D. C. Warltier), and National Institute of General Medical Sciences Anesthesiology Research Training Grant GM-08377 (to D. C. Warltier).
Address for reprint requests and other correspondence: P. S. Pagel, Medical College of Wisconsin, MEB-M4280, 8701 Watertown Plank Rd., Milwaukee, WI 53226 (E-mail: pspagel{at}mcw.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 5 May 2000; accepted in final form 21 June 2000.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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1.
Auchampach, JA,
and
Gross GJ.
Adenosine A1 receptors, KATP channels, and ischemic preconditioning in dogs.
Am J Physiol Heart Circ Physiol
264:
H1327-H1336,
1993
2.
Baines, CP,
Liu GS,
Birincioglu M,
Critz SD,
Cohen MV,
and
Downey JM.
Ischemic preconditioning depends on interaction between mitochondrial KATP channels and actin cytoskeleton.
Am J Physiol Heart Circ Physiol
276:
H1361-H1368,
1999
3.
Diamond, I,
and
Gordon AS.
Cellular and molecular neuroscience of alcoholism.
Physiol Rev
77:
1-20,
1997
4.
Ferguson, ER,
Blachley JD,
Carter NW,
and
Knochel JP.
Derangements of muscle composition, ion transport, and oxygen consumption in chronically alcoholic dogs.
Am J Physiol Renal Fluid Electrolyte Physiol
246:
F700-F709,
1984.
5.
Garlid, KD,
Paucek P,
Yarov-Yarovoy V,
Murray HN,
Darbenzio RB,
D'Alonzo AJ,
Lodge NJ,
Smith MA,
and
Grover GJ.
Cardioprotective effect of diazoxide and its interaction with mitochondrial ATP-sensitive K+ channels. Possible mechanism of cardioprotection.
Circ Res
81:
1072-1082,
1997
6.
Gaziano, JM,
Buring JE,
Breslow JL,
Goldhaber SZ,
Rosner B,
VanDenburgh M,
Willett W,
and
Hennekens CH.
Moderate alcohol intake, increased levels of high-density lipoprotein and its subfractions, and decreased risk of myocardial infarction.
N Engl J Med
329:
1829-1834,
1993
7.
Gross, GJ,
and
Auchampach JA.
Blockade of ATP-sensitive potassium channels prevents myocardial preconditioning in dogs.
Circ Res
70:
223-233,
1992
8.
Hu, K,
Duan D,
Li GR,
and
Nattel S.
Protein kinase C activates ATP-sensitive K+ current in human and rabbit ventricular myocytes.
Circ Res
78:
492-498,
1996
9.
Inagaki, N,
Gonoi T,
Clement IVJP,
Namba N,
Inazawa J,
Gonzalez G,
Aguilar-Bryan L,
Seino S,
and
Bryan J.
Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor.
Science
270:
1166-1170,
1995
10.
Itoya, M,
Morrison JD,
and
Downey HF.
Effect of ethanol on myocardial infarct size in a canine model of coronary artery occlusion-reperfusion.
Mol Cell Biochem
186:
35-41,
1998[ISI][Medline].
11.
Jung, G,
and
Ferard G.
Enzyme-coupled measurement of ethanol in whole blood and plasma with a centrifugal analyzer.
Clin Chem
24:
873-876,
1978
12.
Kersten, JR,
Gross GJ,
Pagel PS,
and
Warltier DC.
Activation of adenosine triphosphate-regulated potassium channels. Mediation of cellular and organ protection.
Anesthesiology
88:
495-513,
1998[ISI][Medline].
13.
Kersten, JR,
Schmeling TJ,
Pagel PS,
Gross GJ,
and
Warltier DC.
Isoflurane mimics ischemic preconditioning via activation of KATP channels. Reduction of myocardial infarct size with an acute memory phase.
Anesthesiology
87:
361-370,
1997[ISI][Medline].
14.
Kirsch, GE,
Codina J,
Birnbaumer L,
and
Brown AM.
Coupling of ATP-sensitive K+ channels to A1 receptors by G proteins in rat ventricular myocytes.
Am J Physiol Heart Circ Physiol
259:
H820-H826,
1990
15.
Kobayashi, T,
Ikeda K,
Kojima H,
Niki H,
Yano R,
Yoshioka T,
and
Kumanishi T.
Ethanol opens G-protein-activated inwardly rectifying K+ channels.
Nat Neurosci
2:
1091-1097,
1999[ISI][Medline].
16.
Light, PE,
Sabir AA,
Allen BG,
Walsh MP,
and
French RJ.
Protein kinase C-induced changes in the stoichiometry of ATP binding activate cardiac ATP-sensitive K+ channels. A possible mechanistic link to ischemic preconditioning.
Circ Res
79:
399-406,
1996
17.
Liu, Y,
Gao WD,
O'Rourke B,
and
Marban E.
Synergistic modulation of ATP-sensitive K+ currents by protein kinase C and adenosine. Implications for ischemic preconditioning.
Circ Res
78:
443-454,
1996
18.
McDonough, KH.
Chronic alcohol consumption causes accelerated myocardial preconditioning to ischemia-reperfusion injury.
Alcohol Clin Exp Res
21:
869-873,
1997[ISI][Medline].
19.
Miyamae, M,
Camacho SA,
Zhou HZ,
Diamond I,
and
Figueredo VM.
Alcohol consumption reduces ischemia-reperfusion injury by species-specific signaling in guinea pigs and rats.
Am J Physiol Heart Circ Physiol
275:
H50-H56,
1998
20.
Miyamae, M,
Diamond I,
Weiner MW,
Camacho SA,
and
Figueredo VM.
Regular alcohol consumption mimics cardiac preconditioning by protecting against ischemia-reperfusion injury.
Proc Natl Acad Sci USA
94:
3235-3239,
1997
21.
Miyamae, M,
Rodriguez MM,
Camacho SA,
Diamond I,
Mochly-Rosen D,
and
Figueredo VM.
Activation of protein kinase C correlates with a cardioprotective effect of regular ethanol consumption.
Proc Natl Acad Sci USA
95:
8262-8267,
1998
22.
Mizumura, T,
Nithipatikom K,
and
Gross GJ.
Bimakalim, an ATP-sensitive potassium channel opener, mimics the effects of ischemic preconditioning to reduce infarct size, adenosine release, and neutrophil function in dogs.
Circulation
92:
1236-1245,
1995
23.
Nagy, LE,
Diamond I,
Casso DJ,
Franklin C,
and
Gordon AS.
Ethanol increases extracellular adenosine by inhibiting adenosine uptake via the nucleoside transporter.
J Biol Chem
265:
1946-1951,
1990
24.
Pikaar, NA,
Wedel M,
van der Beek EJ,
van Dokkum W,
Kempen HJM,
Kluft C,
Ockhuizen T,
and
Hermus RJJ
Effects of moderate alcohol consumption on platelet aggregation, fibrinolysis, blood lipids.
Metabolism
36:
538-543,
1987[ISI][Medline].
25.
Ping, P,
Zhang J,
Qiu Y,
Tang XL,
Manchikalapudi S,
Cao X,
and
Bolli R.
Ischemic preconditioning induces selective translocation of protein kinase C isoforms and in the heart of conscious rabbits without subcellular redistribution of total protein kinase C activity.
Circ Res
81:
404-414,
1997
26.
Rimm, EB,
Giovannucci EL,
Willett WC,
Colditz GA,
Ascherio A,
Rosner B,
and
Stampfer MJ.
Prospective study of alcohol consumption and risk of coronary artery disease in men.
Lancet
338:
464-468,
1991[ISI][Medline].
27.
Schultz, JE,
Hsu AK,
Barbieri JT,
Li PL,
and
Gross GJ.
Pertussis toxin abolishes the cardioprotective effect of ischemic preconditioning in the intact rat heart.
Am J Physiol Heart Circ Physiol
275:
H495-H500,
1998
28.
Wannamethee, G,
Whincup PH,
Shaper AG,
Walker M,
and
MacFarlane PW.
Factors determining case fatality in myocardial infarction "Who dies in a heart attack?".
Br Heart J
74:
324-331,
1995
29.
Warltier, DC,
Zyvoloski MG,
Gross GJ,
Hardman HF,
and
Brooks HL.
Determination of experimental myocardial infarct size.
J Pharmacol Methods
6:
199-210,
1981[ISI][Medline].
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significantly (P < 0.05) different from GLB; §significantly (P < 0.05)
different from ETOH + GLB.
