Hyperosmotic perfusion of the beating rat heart and the role of the Na+/K+/2Cl- co-transporter and the Na+/H+ exchanger.

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The aim of the present study was to investigate the role of the Na+/K+/2Cl- co-transporter and the Na+/H+ exchanger on contractile function and electrolyte regulation during hyperosmotic perfusion of the heart. Langendorff perfused rat hearts were subjected to hyperosmolal perfusion in 10-min intervals. Perfusates were made hyperosmotic by adding mannitol to the buffer (370, 450 and 600 mOsmol/kg H2O). Cardiac contractile function was monitored with a balloon in the left ventricle (LV) coupled to a pressure transducer. Cardiac effluent was sampled repeatedly throughout and after hyperosmotic perfusion and analysed for content of Na+, K+, and Cl-. All three hyperosmotic perfusates initially reduced LV developed pressure (LVDP), but for 370 and 450 mOsmol/kg H2O, LVDP recovered to baseline within 4 min of perfusion. With 600 mOsmol/kg H2O, LVDP recovered slowly and was 50% below baseline after 10 min of hyperosmotic perfusion. Inhibition of the Na+/H+ exchanger with 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and 3-methylsulfonyl-4-piperidinobenzoyl-guanidine methanesulfonate (HOE 694) abolished the recovery of LVDP to the 600 mOsmol/kg H2O perfusate, whereas inhibition of the Na+/K+/2Cl- co-transporter had no impact on LVDP. Potassium was taken up by the heart during hyperosmotic perfusion and this uptake was significantly reduced with inhibition of the Na+/H+ exchanger. Intracellular pH was assessed with 31p magnetic resonance spectroscopy and hyperosmolality induced a significant alkalosis that was dependent upon the Na+/H+ exchanger. The rat heart responds to moderate elevations in osmolality with a transient reduction in contractile function, whereas an elevation of 300 mOsmol/kg H2O persistently reduces contractile function. The Na+/H+ exchanger, but not the Na+/K+/2Cl- co-transporter, is of importance in contractile recovery and electrolyte regulation during hyperosmotic perfusion in the rat heart.