Faculty Collaboration Database

Reduced mitochondrial Ca2+ loading and improved functional recovery after ischemia-reperfusion injury in old vs. young guinea pig hearts. Am J Physiol Heart Circ Physiol 2012 Feb 01;302(3):H855-63

Date

12/06/2011

Pubmed ID

22140052

Pubmed Central ID

PMC3353793

DOI

10.1152/ajpheart.00533.2011

Scopus ID

2-s2.0-84856446031 (requires institutional sign-in at Scopus site)   16 Citations

Abstract

Oxidative damage and impaired cytosolic Ca(2+) concentration ([Ca(2+)](cyto)) handling are associated with mitochondrial [Ca(2+)] ([Ca(2+)](mito)) overload and depressed functional recovery after cardiac ischemia-reperfusion (I/R) injury. We hypothesized that hearts from old guinea pigs would demonstrate impaired [Ca(2+)](mito) handling, poor functional recovery, and a more oxidized state after I/R injury compared with hearts from young guinea pigs. Hearts from young (∼4 wk) and old (>52 wk) guinea pigs were isolated and perfused with Krebs-Ringer solution (2.1 mM Ca(2+) concentration at 37°C). Left ventricular pressure (LVP, mmHg) was measured with a balloon, and NADH, [Ca(2+)](mito) (nM), and [Ca(2+)](cyto) (nM) were measured by fluorescence with a fiber optic probe placed against the left ventricular free wall. After baseline (BL) measurements, hearts were subjected to 30 min global ischemia and 120 min reperfusion (REP). In old vs. young hearts we found: 1) percent infarct size was lower (27 ± 9 vs. 57 ± 2); 2) developed LVP (systolic-diastolic) was higher at 10 min (57 ± 11 vs. 29 ± 2) and 60 min (55 ± 10 vs. 32 ± 2) REP; 3) diastolic LVP was lower at 10 and 60 min REP (6 ± 3 vs. 29 ± 4 and 3 ± 3 vs. 21 ± 4 mmHg); 4) mean [Ca(2+)](cyto) was higher during ischemia (837 ± 39 vs. 541 ± 39), but [Ca(2+)](mito) was lower (545 ± 62 vs. 975 ± 38); 5) [Ca(2+)](mito) was lower at 10 and 60 min REP (129 ± 2 vs. 293 ± 23 and 122 ± 2 vs. 234 ± 15); 6) reduced inotropic responses to dopamine and digoxin; and 7) NADH was elevated during ischemia in both groups and lower than BL during REP. Contrary to our stated hypotheses, old hearts showed reduced [Ca(2+)](mito), decreased infarction, and improved basal mechanical function after I/R injury compared with young hearts; no differences were noted in redox state due to age. In this model, aging-associated protection may be linked to limited [Ca(2+)](mito) loading after I/R injury despite higher [Ca(2+)](cyto) load during ischemia in old vs. young hearts.

Author List

Rhodes SS, Camara AK, Heisner JS, Riess ML, Aldakkak M, Stowe DF

Author

Amadou K. Camara PhD Professor in the Anesthesiology department at Medical College of Wisconsin

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

Aging
Animals
Calcium
Cardiotonic Agents
Coronary Circulation
Cytosol
Digoxin
Dopamine
Guinea Pigs
Mitochondria
Myocardial Contraction
Myocardial Infarction
Myocardial Reperfusion Injury
Myocardium
NAD
Recovery of Function