Alterations in electrical and mechanical activity in Langendorff-perfused guinea pig hearts exposed to decreased external sodium concentration with or without hypotonic insult

In order to examine electrical and mechanical effects of hyponatremia and hypotonicity, relevant to those in patients with 'water intoxication' syndrome, Langendorff-perfused guinea pig hearts were exposed to reduced NaCl concentrations (hypotonic [NaCl]₀-reduction) under the monitoring of left ventricular developed pressure (LVDP) and epicardial ECG. In some hearts, hyponatremia (from 140 to 80 mEq/l) was compensated for by adding mannitol to maintain osmolarity at a constant level (isotonic [NaCl]₀-reduction) or tetraethylammonium chloride to maintain both osmolarity and chloride concentrations at a constant level (isotonic [Na⁺]₀-reduction). Progressive isotonic [NaCl]₀-reduction increased LVDP, which was abolished in the presence of KB-R7943, a novel inhibitor of Na⁺/Ca²⁺-exchange. LVDP was reduced in hypotonic [NaCl]₀-reduction in which myocardial water content was increased. PQ interval and QRS duration were prolonged with both hypotonic and isotonic [NaCl]₀-reduction and these changes tended to be more pronounced with hypotonic than with isotonic [NaCl]₀-reduction. Similar ECG changes were also evident with isotonic [Na⁺]₀-reduction. Gd³⁺ (1-5 μM), a blocker of stretch-activated nonspecific cation channels, had no substantial effects on the electrical or mechanical changes seen with hypotonic [NaCl]₀-reduction. In conclusion, isotonic [NaCl]₀-reduction produced a positive inotropism by modulating Na⁺/Ca²⁺-exchange, whereas hypotonic [NaCl]₀-reduction led to negative inotropism, due in part to hypotonic myocardial swelling. In addition, [Na⁺]₀-reduction, irrespective of the concomitant [Cl^-]₀ or osmotic changes, depressed atrioventricular as well as intraventricular conduction.