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.
All Science Journal Classification (ASJC) codes
- Pathology and Forensic Medicine
- Physiology (medical)