The effects of sodium bicarbonate on thioridazine-induced cardiac dysfunction in the isolated perfused rat heart

To determine the site of thioridazine- induced cardiotoxicity and investiga te the effectiveness of sodium bicarbonate (NaHCO3) therapy, isolated rat h earts were perfused with Krebs-Henseleit-Bicarbonate buffer (KHB) at a cons tant coronary now of 10 mL/min and electrically paced at 300 bpm. Experimen tal protocol included 15 min intervals of KHB, thioridazine (TDZ), TDZ + Na HCO3, KHB. Left ventricular (LV) pressure was measured with a balloon-tippe d catheter placed in the LV via the mitral valve. Coronary perfusion pressu re was monitored continuously as an index of coronary vascular resistance ( CVR). LV generated pressure (LVCP) was used as our index of cardiac functio n and was calculated by subtracting LV end diastolic pressure (LVEDP) from LV peak systolic pressure (LVPSP). TDZ at 7500 mg/mL was chosen as the toxi c dose. NaHCO3 treatment was at an approximate sodium = 155mM and pH = 7.60 . Hearts perfused with TDZ resulted in a progressive decrease in LVGP. Afte r IS min of TDZ perfusion, LVGP decreased by 50%, and 75% at 30 min (n=5). TDZ increased LVEDP and decreased LVPSP. TDZ perfusion increased CVR by 83% . In another experiment, hearts were perfused with TDZ For IS min and then for an additional 15 min with TDZ + NaHCO3. NaHCO3 treatment transiently (s imilar to5 min) increased LVGP by 23% (n=5). During NaHCO3 treatment, LVPSP increased and LVEDP and CVR decreased during the first 5 min. During the r emainder of the NaHCO3 protocol, the hearts failed, similar to TDZ alone. T DZ diminished left ventricular function and promoted coronary artery vasoco nstriction. NaHCO3 temporarily reversed these toxic effects.