Does Noradrenaline Influence the Extracellular Accumulation of Potassium, Sodium, Calcium, and Hydrogen Ions ([K+]e, [Na+]e, [Ca2+]e, [H+]e) during Global Ischemia in Isolated Rat Hearts?

Abstract

The influence of noradrenaline (NA) on net cation fluxes during global ischemia (gI) was investigated in isolated rat hearts. The hearts were perfused according to the Langendorff technique and left ventricular pressure (LVP), the first derivative of the LVP (dP/dtmax, dP/dtmin), coronary perfusion pressure (CPP), and heart rate (HF) were measured. In the control group, the perfusion medium was either Krebs-Henseleit's solution (KHS), or KHS and tetramethylammonium-chloride (TMA; 100 microM). In this study TMA was used as a marker to determine changes in the extracellular space (ECS) size during gI. The hearts were subjected to 40 min of gI. Changes in the size of the ECS, and net cation movements were calculated during the first 20 min of gI. In treated hearts, NA (50 nM) was added to the perfusate 15 min before the onset of gI. Extracellular concentrations of K+, Na+, Ca2+, H+, and TMA were measured using double-barreled polyvinyl-chloride (PVC) mini-electrodes. Relative changes in the ECS size and net cation movements were calculated from the extracellular TMA and cation concentrations. In separate experiments, the hemodynamics and lactate overflow of treated hearts were compared with control hearts prior to and following a brief period (1 min) of gI. Addition of NA to the perfusate significantly: 1) increased CPP, LVP, dP/dtmax, dP/dtmin, and HF prior to the onset of gI, and increased cell swelling during gI; 2) diminished K(+)-release from the cells, but significantly increased the influx of sodium and calcium into the intracellular space (ICS); 3) increased lactate overflow prior to and following 1 min of gI. We assume that catecholamines increase ECS shrinkage before and during gI, probably by increased lactate production. NA stimulates the Na+/K+ pump, thereby reducing [K+]e accumulation. The increased [Ca2+]i and intracellular acidification promote sodium entry into the cells during gI.