| Title | Cardioprotective effects of propofol and sevoflurane in ischemic and reperfused rat hearts: role of K(ATP) channels and interaction with the sodium-hydrogen exchange inhibitor HOE 642 (cariporide). | | Author(s) | Mathur S, Farhangkhgoee P, Karmazyn M | | Institution | Department of Pharmacology, University of Western Ontario, London, Canada. | | Source | Anesthesiology 1999 Nov; 91(5):1349-60. | | MeSH | Adenosine Triphosphate
Anesthetics, Inhalation
Anesthetics, Intravenous
Animals
Biotransformation
Drug Interactions
Energy Metabolism
Glyburide
Guanidines
Hemodynamic Processes
In Vitro
Male
Methyl Ethers
Myocardial Reperfusion Injury
Potassium Channels
Propofol
Rats
Rats, Sprague-Dawley
Research Support, Non-U.S. Gov't
Sodium-Hydrogen Antiporter
Sulfones
Ventricular Function, Left
| | Abstract | BACKGROUND: Sodium ion-hydrogen ion (Na(+)-H(+)) exchange inhibitors are effective cardioprotective agents. The N(+)-H(+) exchange inhibitor HOE 642 (cariporide) has undergone clinical trials in acute coronary syndromes, including bypass surgery. Propofol and sevoflurane are also cardioprotective via unknown mechanisms. The authors investigated the interaction between propofol and HOE 642 in the ischemic reperfused rat heart and studied the role of adenosine triphosphate-sensitive potassium (K(ATP)) channels in the myocardial protection associated with propofol and sevoflurane.
METHODS: Isolated rat hearts were perfused by the Langendorff method at a constant flow rate, and left ventricular function and coronary pressures were assessed using standard methods. Energy metabolites were also determined. To assess the role of K(ATP) channels, hearts were pretreated with the K(ATP) blocker glyburide (10 microM). Hearts were then exposed to either control buffer or buffer containing HOE 642 (5 microM), propofol (35 microM), sevoflurane (2.15 vol%), the K(ATP) opener pinacidil (1 microM), or the combination of propofol and HOE 642. Each heart was then subjected to 1 h of global ischemia followed by 1 h of reperfusion.
RESULTS: Hearts treated with propofol, sevoflurane, pinacidil, or HOE 642 showed significantly higher recovery of left ventricular developed pressure and reduced end-diastolic pressures compared with controls. The combination of propofol and HOE 642 provided superior protection toward the end of the reperfusion period. Propofol, sevoflurane, and HOE 642 also attenuated the onset and magnitude of ischemic contracture and preserved high-energy phosphates (HEPs) compared with controls. Glyburide attenuated the cardioprotective effects of sevoflurane and abolished the protection observed with pinacidil. In contrast, glyburide had no effect on the cardioprotection associated with propofol treatment.
CONCLUSION: HOE 642, propofol, and sevoflurane provide cardioprotection via different mechanisms. These distinct mechanisms may allow for the additive and superior protection observed with the combination of these anesthetics and HOE 642. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 10551586 |
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