Cardiac contractile function and electrolyte regulation during hyperosmolal stress: an experimental study in the isolated rabbit heart.

Perturbations of the extracellular osmotic environment leads to cell volume changes. The aim of the present study was to evaluate the effects of hyperosmolality on cardiac contractile function and in particular the role of ionic mechanisms anticipated to be operative during hyperosmolal exposure. Paced rabbit hearts were perfused in the Langendorff mode and were exposed to 330, 370, 410, 450 and 600 mOsm kg-1 in 10 min. intervals intervened by 15 min. isosmolal buffer perfusion (by adding mannitol). Thereafter, 370 and 600 mOsm kg-1 perfusates were chosen for investigation of the effects of inhibition of the Na-K-2Cl co-transporter (bumetanide 1 microM and 10 microM), the Na+/H+ exchanger (5-(N-ethyl-N-isopropyl amiloride (EIPA) 100 nM) and the Na+/K(+)-ATPase (ouabain 50 nM). After a rapid and transient decrease in left ventricular developed pressure, all perfusates up to 450 mOsm kg-1 increased LVDP. The 600 mOsm kg-1 perfusate initially reduced LVDP by 50%, but LVDP increased to 85% of initial value at the end of the 10 min. perfusion. EIPA attenuated the recovery of LVDP during perfusion with 600 mOsm kg-1, whereas bumetanide did not affect cardiac contractile function. A net uptake of potassium was observed during hyperosmolal perfusion. Inhibition of the Na+/H+ exchanger resulted in a continued release of cardiac water throughout hyperosmolal perfusion. Isolated perfused rabbit hearts tolerate considerable elevations in perfusate osmolality. Our results suggest that the Na+/H+ antiporter is activated on hyperosmolal exposure with a secondary activation of the Na+/K(+)-ATPase. Since inhibition with bumetanide did not affect contractility or electrolyte movements, the Na-K-2Cl co-transporter does not seem to play an important role in cardiac response to hyperosmolality in rabbits.