Intravenous emulsified halogenated anesthetics produce acute and delayed preconditioning against myocardial infarction in rabbits.
BACKGROUND
Preconditioning against myocardial infarction by volatile anesthetics is well known. The authors tested the hypothesis that new emulsified formulations of halogenated anesthetics administered intravenously reduce myocardial infarct size when administered either 1 or 24 h before prolonged ischemia and reperfusion.


METHODS
Pentobarbital-anesthetized rabbits (n = 39) were instrumented for measurement of hemodynamics and randomly assigned to receive intravenous saline (control), lipid vehicle, or infusions (3.5 ml . kg . h for 30 min) of emulsified isoflurane (6.9%), enflurane (7.1%), or sevoflurane (7.5%). Infusions were discontinued 30 min before a 30-min coronary occlusion and 3 h of reperfusion. In three additional groups, conscious rabbits (n = 21) received saline, lipid vehicle, or emulsified sevoflurane (7.5%) infusions (3.5 ml . kg . h for 30 min) 24 h before ischemia and reperfusion. Infarct size was determined using triphenyltetrazolium staining.


RESULTS
Lipid vehicle produced transient increases in heart rate, whereas emulsified volatile anesthetics had no effect on hemodynamics before coronary occlusion. Lipid vehicle did not affect infarct size (38 +/- 2% of the area at risk; mean +/- SEM) as compared with saline control (41 +/- 4%). In contrast, emulsified isoflurane, enflurane, and sevoflurane reduced infarct size (20 +/- 3%, 20 +/- 3%, and 21 +/- 2% of the area at risk, respectively; P < 0.05). Administration of lipid vehicle or emulsified sevoflurane did not produce sedation or respiratory depression in conscious rabbits. Emulsified sevoflurane (18 +/- 2%) but not lipid vehicle (44 +/- 2%) reduced infarct size as compared with control in delayed preconditioning experiments.


CONCLUSIONS
Intravenous emulsified halogenated anesthetics produce acute and delayed preconditioning against myocardial infarction.
Chiari
Pascal C
PC
Department of Anesthesiology and Pharmacology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Pagel
Paul S
PS
Tanaka
Katsuya
K
Krolikowski
John G
JG
Ludwig
Lynda M
LM
Trillo
Raul A
RA
Puri
Navneet
N
Kersten
Judy R
JR
Warltier
David C
DC
D018685:Anesthetics, Inhalation / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001784:Blood Gas Analysis; D002626:Chemistry, Pharmaceutical; D004655:Emulsions; D004737:Enflurane / Q000008:administration & dosage / Q000494:pharmacology; D005079:Excipients; D006439:Hemodynamics / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D007530:Isoflurane / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage / Q000494:pharmacology; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control; D009206:Myocardium / Q000473:pathology; D011817:Rabbits; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D004655:Emulsions; D005079:Excipients; D008738:Methyl Ethers; D000077149:Sevoflurane; D004737:Enflurane; D007530:Isoflurane