Document Detail

Reduced mitochondrial Ca2+ loading and improved functional recovery after ischemia-reperfusion injury in old vs. young guinea pig hearts.
MedLine Citation:
PMID:  22140052     Owner:  NLM     Status:  MEDLINE    
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.
Samhita S Rhodes; Amadou K S Camara; James S Heisner; Matthias L Riess; Mohammed Aldakkak; David F Stowe
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2011-12-02
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  302     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-01     Completed Date:  2012-03-20     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H855-63     Citation Subset:  IM    
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MeSH Terms
Aging / metabolism*
Calcium / metabolism*
Cardiotonic Agents / pharmacology
Coronary Circulation / physiology
Cytosol / metabolism
Digoxin / pharmacology
Dopamine / pharmacology
Guinea Pigs
Mitochondria / metabolism*
Myocardial Contraction / physiology
Myocardial Infarction / drug therapy,  metabolism
Myocardial Reperfusion Injury / drug therapy,  metabolism*
Myocardium / metabolism*
NAD / metabolism
Recovery of Function / drug effects,  physiology
Grant Support
Reg. No./Substance:
0/Cardiotonic Agents; 0U46U6E8UK/NAD; 73K4184T59/Digoxin; SY7Q814VUP/Calcium; VTD58H1Z2X/Dopamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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