Improved mitochondrial bioenergetics by anesthetic preconditioning during and after 2 hours of 27 degrees C ischemia in isolated hearts.

Abstract

We examined if sevoflurane given before cold ischemia of intact hearts (anesthetic preconditioning, APC) affords additional protection by further improving mitochondrial energy balance and if this is abolished by a mitochondrial KATP blocker. NADH and FAD fluorescence was measured within the left ventricular wall of 5 groups of isolated guinea pig hearts: (1) hypothermia alone; (2) hypothermia+ischemia; (3) APC (4.1% sevoflurane)+cold ischemia; (4) 5-HD+cold ischemia, and (5) APC+5-HD+cold ischemia. Hearts were exposed to sevoflurane for 15 minutes followed by 15 minutes of washout at 37 degrees C before cooling, 2 hours of 27 degrees C ischemia, and 2 hours of 37 degrees C reperfusion. The KATP channel inhibitor 5-HD was perfused before and after sevoflurane. Ischemia caused a rapid increase in NADH and a decrease in FAD that waned over 2 hours. Warm reperfusion led to a decrease in NADH and an increase in FAD. APC attenuated the changes in NADH and FAD and further improved postischemic function and reduced infarct size. 5-HD blocked the cardioprotective effects of APC but not APC-induced alterations of NADH and FAD. Thus, APC improves redox balance and has additive cardioprotective effects with mild hypothermic ischemia. 5-HD blocks APC-induced cardioprotective effects but not improvements in mitochondrial bioenergetics. This suggests that mediation of protection by KATP channel opening during cold ischemia and reperfusion is downstream from the APC-induced improvement in redox state or that these changes in redox state are not attenuated by KATP channel antagonism.

• Authors: Jianzhong An, Amadou K S Camara, Matthias L Riess, Samhita S Rhodes, Srinivasan G Varadarajan, David F Stowe
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 46 Issue 3 Pg. 280-7 (Sep 2005) ISSN: 0160-2446 [Print] United States
• PMID: 16116332 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• ATP-Binding Cassette Transporters
• Anesthetics
• Anesthetics, Inhalation
• KATP Channels
• Methyl Ethers
• Potassium Channels, Inwardly Rectifying
• uK-ATP-1 potassium channel
• NAD
• Flavin-Adenine Dinucleotide
• Sevoflurane

Topics

• ATP-Binding Cassette Transporters (drug effects)
• Anesthetics (pharmacology)
• Anesthetics, Inhalation (pharmacology)
• Animals
• Blood Pressure (drug effects)
• Coronary Circulation (drug effects)
• Energy Metabolism (drug effects)
• Flavin-Adenine Dinucleotide (metabolism)
• Guinea Pigs
• Heart Rate (drug effects)
• In Vitro Techniques
• Ischemic Preconditioning, Myocardial
• KATP Channels
• Methyl Ethers (pharmacology)
• Mitochondria, Heart (drug effects)
• NAD (metabolism)
• Oxidation-Reduction
• Oxygen Consumption (drug effects)
• Potassium Channels, Inwardly Rectifying (drug effects)
• Reperfusion Injury (metabolism, prevention & control)
• Sevoflurane
• Ventricular Function, Left (drug effects)