Faculty Collaboration Database

Reduced reactive O2 species formation and preserved mitochondrial NADH and [Ca2+] levels during short-term 17 degrees C ischemia in intact hearts. Cardiovasc Res 2004 Feb 15;61(3):580-90

Date

02/14/2004

Pubmed ID

14962488

DOI

10.1016/j.cardiores.2003.09.016

Scopus ID

2-s2.0-1142285436 (requires institutional sign-in at Scopus site)   104 Citations

Abstract

OBJECTIVE: Different cardioprotective strategies such as ischemic or pharmacologic preconditioning lead to attenuated ischemia/reperfusion (I/R) injury with less mechanical dysfunction and reduced infarct size on reperfusion. Improved mitochondrial function during ischemia as well as on reperfusion is a key feature of cardioprotection. The best reversible cardioprotective strategy is hypothermia. We investigated mitochondrial protection before, during, and after hypothermic ischemia by measuring mitochondrial (m)Ca2+, NADH, and reactive oxygen species (ROS) by online spectrophotofluorometry in intact hearts.

METHODS: A fiberoptic cable was placed against the left ventricle of Langendorff-prepared guinea pig hearts to excite and record transmyocardial fluorescence at the appropriate wavelengths during 37 and 17 degrees C perfusion and during 30 min ischemia at 37 and 17 degrees C before 120 min reperfusion/rewarming.

RESULTS: Cold perfusion caused significant reversible increases in m[Ca2+], NADH, and ROS. Hypothermia prevented a further increase in m[Ca2+], excess ROS formation and NADH oxidation/reduction imbalance during ischemia, led to a rapid return to preischemic values on warm reperfusion, and preserved cardiac function and tissue viability on reperfusion.

CONCLUSIONS: Hypothermic perfusion at 17 degrees C caused moderate and reversible changes in mitochondrial function. However, hypothermia protects during ischemia, as shown by preservation of mitochondrial NADH energy balance and prevention of deleterious increases in m[Ca2+] and ROS formation. The close temporal relations of these factors during cooling and during ischemia suggest a causal link between mCa2+, mitochondrial energy balance, and ROS production.

Author List

Riess ML, Camara AK, Kevin LG, An J, 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
Cold Temperature
Guinea Pigs
Ischemic Preconditioning, Myocardial
Mitochondria, Heart
Myocardial Contraction
Myocardial Ischemia
NAD
Perfusion
Reactive Oxygen Species