Faculty Collaboration Database

ROS scavenging before 27 degrees C ischemia protects hearts and reduces mitochondrial ROS, Ca2+ overload, and changes in redox state. Am J Physiol Cell Physiol 2007 Jun;292(6):C2021-31

Date

02/09/2007

Pubmed ID

17287367

DOI

10.1152/ajpcell.00231.2006

Scopus ID

2-s2.0-34447548815 (requires institutional sign-in at Scopus site)   39 Citations

Abstract

We have shown that cold perfusion of hearts generates reactive oxygen and nitrogen species (ROS/RNS). In this study, we determined 1) whether ROS scavenging only during cold perfusion before global ischemia improves mitochondrial and myocardial function, and 2) which ROS leads to compromised cardiac function during ischemia and reperfusion (I/R) injury. Using fluorescence spectrophotometry, we monitored redox balance (NADH and FAD), O(2)(*-) levels and mitochondrial Ca(2+) (m[Ca(2+)]) at the left ventricular wall in 120 guinea pig isolated hearts divided into control (Con), MnTBAP (a superoxide dismutase 2 mimetic), MnTBAP (M) + catalase (C) + glutathione (G) (MCG), C+G (CG), and N(G)-nitro-L-arginine methyl ester (L-NAME; a nitric oxide synthase inhibitor) groups. After an initial period of warm perfusion, hearts were treated with drugs before and after at 27 degrees C. Drugs were washed out before 2 h at 27 degrees C ischemia and 2 h at 37 degrees C reperfusion. We found that on reperfusion the MnTBAP group had the worst functional recovery and largest infarction with the highest m[Ca(2+)], most oxidized redox state and increased ROS levels. The MCG group had the best recovery, the smallest infarction, the lowest ROS level, the lowest m[Ca(2+)], and the most reduced redox state. CG and L-NAME groups gave results intermediate to those of the MnTBAP and MCG groups. Our results indicate that the scavenging of cold-induced O(2)(*-) species to less toxic downstream products additionally protects during and after cold I/R by preserving mitochondrial function. Because MnTBAP treatment showed the worst functional return along with poor preservation of mitochondrial bioenergetics, accumulation of H(2)O(2) and/or hydroxyl radicals during cold perfusion may be involved in compromised function during subsequent cold I/R injury.

Author List

Camara AK, Aldakkak M, Heisner JS, Rhodes SS, Riess ML, An J, Heinen A, Stowe DF

Authors

Amadou K. Camara PhD Professor in the Anesthesiology department at Medical College of Wisconsin
David F. Stowe MD, PhD Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Calcium
Catalase
Female
Free Radical Scavengers
Glutathione
Guinea Pigs
Ischemia
Male
Manganese
Mitochondria, Heart
NG-Nitroarginine Methyl Ester
Oxidation-Reduction
Reactive Oxygen Species
Temperature
Time Factors