Abstract 15506: Hyponatremia Increases Expression of Apoptosis Related Proteins and Infarct Size
Hyponatremia (Na < 135mEq/L) is the most common electrolyte disorder in clinical practice. Hyponatremia increases mortality in patients with heart disease; however, the mechanisms remain unclear. We postulated that hyponatremia impairs tolerance to myocardial ischemia by increasing oxidative injury and apoptosis. Rat hearts (n=3/group) were divided into two groups: A) Control: normal sodium levels and B) Hyponatremia: low sodium levels. Hyponatremia was induced by the subcutaneous infusion of DDAVP at a rate of 5 ng/hr with an osmotic mini-pump and liquid diet for 14 days. Myocardial infarction was induced in rats by ligation of the left anterior descending coronary artery (LAD) for 24 hrs. Echocardiography was performed before and after LAD ligation. Infarct size was measured by TTC staining. P53 and Bcl-2 expressions were measured in infarcted and non-infarcted tissues by western blot. ROS production was measured by the expression of myocardial 3-nitrotyrosine. Serum sodium was 108 ± 1 mEq/L in Hyponatremia rats vs. 138 ± 0.4 mEq/L in Control (p<0.05). Infarct size was larger after LAD ligation in hyponatremia rats than control rats (47 ± 2% vs. 38 ± 3% of area at risk, p<0.05). Left ventricular ejection fraction was reduced by 21 ± 2% in control rats vs. 23 ± 3% in hyponatremia rats. The expression of p53 and 3-nitrotyrosine proteins were higher in infarct area than non-infarct area in both control and hyponatremia hearts. The expression of Bcl-2 protein was higher in non-infarct area as compared to infarct area. Hyponatremia hearts had increased p53 and 3-nitrotyrosine expression and lower Bcl-2 in the infarct area. This study demonstrated that hyponatremia has direct deleterious effects on myocardial tolerance to MI. Hyponatremia increases myocardial infarct size after LAD ligation. The increase in infarct size results from increased peroxynitrite production and increased expression of apoptotic proteins and decreased expression of antiapoptotic proteins.
- © 2012 by American Heart Association, Inc.