Hyperosmotic pretreatment reduces infarct size in the rat heart

Preconditioning of the heart can be achieved by an ischemia/reperfusion sti mulus, but also by stretching of the heart by an acute volume overload. Sin ce manipulations of the extracellular osmolality affects cell size, we hypo thesized that hyperosmotic pretreatment of the isolated perfused rat heart could reduce infarct size following regional ischemia (RI). Langendorff per fused rat hearts were subjected to 30 min RI by ligature of the main branch of the left coronary artery followed by 120 min reperfusion (control group ). Ischemic preconditioning (IP-5') was achieved by 5 min total global isch emia and 5 min reperfusion prior to RI. Hyperosmotic pretreatment was accom plished by perfusion with a hyperosmotic buffer (600 mOsm/kg H2O by adding mannitol) for 1 min, 2 min or 5 min. At the end of the experiments, the hea rts were cut into 2 mm slices, incubated with triphenyltetrazoliumchloride before scanning and computerized for estimation of infarct size. The averag e infarct size (as percentage of area at risk) in the control group was 42 % and was significantly reduced to 16 % by ischemic preconditioning and to 17 % by 2 min hyperosmotic pretreatment. Neither 1 min nor 5 min hyperosmot ic pretreatment reduced infarct size as compared to the controls. The infar ct reducing effect of 2 min hyperosmotic pretreatment was not blunted by in hibition of protein kinase C (chelerytrine chloride), the Na+/H+-exchanger (HOE 694) or stretch-activated anion channels (gadolinium chloride). The re sults indicate that shortlasting hyperosmotic perturbations of the extracel lular environment may precondition the heart to a subsequent ischemic insul t.