|Durgan, David -|
|Young, Martin -|
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: March 17, 2008
Publication Date: May 17, 2008
Citation: Durgan, D.J., Young, M.E. 2008. Diurnal variation in myocardial ischemia/reperfusion tolerance; mediation by the circadian clock within the cardiomyocyte [abstract]. Proceeding, Society for Research on Biological Rhythms.May 17-21, 2008 San Delia, Florida, p. 83. Technical Abstract: Circadian rhythms in cardiovascular physiology (e.g. blood pressure and heart rate) and pathophysiology (e.g. myocardial infarction (MI)) exist. Humans exhibit a marked increase in MI frequency during the early hours of the morning. However, MIs occurring during the evening are more likely to result in subsequent heart failure (i.e. decreased tolerance). These phenomena have largely been attributed to rhythms in neurohumoral factors. Recent studies suggest a role for intracellular circadian clocks in modulating cardiovascular function. Therefore, we hypothesized that the cardiomyocyte circadian clock regulates tolerance of the heart to ischemia/reperfusion (I/R). Wild-type (WT) and cardiomyocyte-specific clock mutant (CCM) mice were subjected to 45 minutes of ischemia (through left anterior descending coronary artery occlusion) followed by reperfusion. The closed chest model was utilized to minimize acute influence of an immune response. I/R and sham interventions were performed either at ZT0, 6, 12 or 18. 24-hours following I/R or sham intervention, hearts were isolated and infarct size (i.e. region of nonviable tissue) measured. A marked diurnal variation in I/R-induced infarct size was observed in WT hearts (p=0.037), with a 3.8-fold greater infarct size at ZT12 (peak) versus ZT0 (trough; p=0.024). This diurnal variation was absent in CCM hearts, which exhibit lower infarct sizes relative to WT hearts, independent of time (p=0.035). For example, at ZT12 infarct size in WT hearts was 5.3-fold greater than that of CCM hearts (p=0.034). These data reveal a diurnal variation in myocardial I/R tolerance that is mediated by the circadian clock within the cardiomyocyte.