Age-related changes in ischemic tolerance in male and female mouse hearts

Willems, Laura, Zatta, Amanda, Holmgren, Kirsten, Ashton, Kevin J., and Headrick, John P. (2005) Age-related changes in ischemic tolerance in male and female mouse hearts. Journal of Molecular and Cellular Cardiology, 38 (2). pp. 245-256.

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Abstract

Aging is associated with reduced tolerance to ischemic insult, and genesis of this intolerant phenotype is poorly understood. We characterized effects of aging and gender on cardiovascular function and cell damage during 20 min ischemia and 60 min reperfusion in isolated hearts from young adult (2–4 months), mature adult (8 months), middle-aged (12 months), aged (18 months), and senescent (24–28 months) C57/Bl6 mice. Aging substantially impaired recovery of ventricular contractility, with this change primarily evident within 12 months of age. In males ventricular developed pressure recovered to 72 ± 8 mmHg in young hearts vs. only 44 ± 7, 30 ± 3, 24 ± 5, and 27 ± 4 mmHg in mature, middle-aged, aged and senescent hearts, respectively. This pattern was largely due to worsened diastolic dysfunction. Coronary flow recovered to below pre-ischemic levels in all ages, correlating with contractile recovery. However, coronary dysfunction (impaired responses to 2-chloroadenosine and ADP) was unaltered by senescence. Lactate dehydrogenase (LDH) loss, a marker for oncosis, increased to middle-age (approximately twofold), then fell with further aging to a value no longer different from that in young adult hearts. Similar patterns of change were observed in female hearts, although LDH efflux was significantly lower in mature adult and middle-aged female vs. male hearts, with functional tolerance also tending to be greater at these ages (though not achieving significance). Overall, our data reveal age-related ischemic intolerance develops well before senescence, being primarily evident by “middle-age”. Phenotypic changes appear selective for myocardial vs. vascular injury, and functional vs. oncotic injury. Similar changes occur in males and females, though there is evidence of a protected phenotype in mature to middle-aged female vs. male hearts.

Item ID: 10025
Item Type: Article (Refereed Research - C1)
Keywords: aging; gender; ischemia–reperfusion; oncosis; senescence; coronary dysfunction
ISSN: 1095-8584
Date Deposited: 15 Apr 2010 23:35
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1199 Other Medical and Health Sciences > 119999 Medical and Health Sciences not elsewhere classified @ 50%
06 BIOLOGICAL SCIENCES > 0606 Physiology > 060699 Physiology not elsewhere classified @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 50%
97 EXPANDING KNOWLEDGE > 970102 Expanding Knowledge in the Physical Sciences @ 50%
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