Reduced mitochondrial Ca2+ loading and improved functional recovery after ischemia-reperfusion injury in old vs. young guinea pig hearts
| Autor: | Mohammed Aldakkak, David F. Stowe, Amadou K.S. Camara, Samhita S. Rhodes, James S. Heisner, Matthias L. Riess |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Aging
Digoxin medicine.medical_specialty Cardiotonic Agents Physiology Dopamine Guinea Pigs Myocardial Infarction Ischemia Diastole Myocardial Reperfusion Injury Guinea pig Coronary circulation Integrative Cardiovascular Physiology and Pathophysiology Cytosol Coronary Circulation Physiology (medical) Internal medicine Animals Medicine Calcium metabolism business.industry Myocardium Recovery of Function Anatomy NAD medicine.disease Myocardial Contraction Mitochondria medicine.anatomical_structure Endocrinology Ventricular pressure Calcium Cardiology and Cardiovascular Medicine business Reperfusion injury medicine.drug |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 302:H855-H863 |
| ISSN: | 1522-1539 0363-6135 |
| Popis: | Oxidative damage and impaired cytosolic Ca2+ concentration ([Ca2+]cyto) handling are associated with mitochondrial [Ca2+] ([Ca2+]mito) overload and depressed functional recovery after cardiac ischemia-reperfusion (I/R) injury. We hypothesized that hearts from old guinea pigs would demonstrate impaired [Ca2+]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 Ca2+ concentration at 37°C). Left ventricular pressure (LVP, mmHg) was measured with a balloon, and NADH, [Ca2+]mito (nM), and [Ca2+]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 [Ca2+]cyto was higher during ischemia (837 ± 39 vs. 541 ± 39), but [Ca2+]mito was lower (545 ± 62 vs. 975 ± 38); 5) [Ca2+]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 [Ca2+]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 [Ca2+]mito loading after I/R injury despite higher [Ca2+]cyto load during ischemia in old vs. young hearts. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|