Cardiovascular effects of verapamil and quinidine at normal and elevated ambient pressure

Cardiovascular parameters were measured in rats before and after administra tion of verapamil and quinidine, a slow Ca2+ and fast Na+ channel blocker, respectively, at normal and elevated ambient pressure [5 bar (500 kPa)]. Le ft ventricular pressure (P-ivt), maximal velocity of P-ivt rise (+dP/dt) an d Fall (-dP/dt), and heart rate (HR), arterial systolic pressure (P-asys), and mean arterial pressure (MAP) were measured in all animals using cathete rs connected to pressure transducers. Cardiac output ((Q) over dot), and my ocardial blood flow (MBF) were detected by the microsphere technique. Total peripheral vascular resistance (TPVR) myocardial vascular resistance (MVR) and oxygen consumption of the heart ((V) over dot (O2)) was calculated. In Groups 1a (control group; 1 bar) and 1b (test group; 1-5 bar), verapamil ( 1.5 mg(.)kg(-1)) caused a reduction in P-ivt, +dP/dt, -dP/dt, P-asys, MAP, (V) over dot O-2, TPVR, and MVR in both groups at 1 bar(100 kPa), and these parameters remained depressed for at least 50 min in Group la. However, MB F increased after verapamil injection. After compression to 5 bar (500 kPa) , Plvt, dP/dt, P-asys, (V) over dot (O2), and MBF were markedly elevated (G roup Ib). No change in HR, SV, or (Q) over dot was found in either of the g roups. In Groups 2a (control group; 1 bar) and 2b (test group; 1-5 bar), qu inidine (5 mg(.)kg(-1)), infused over a period of 10 min, reduced P-ivt, +d P/dt, -dP/dt, MAP, Pasys, (V) over dot (O2), (Q) over dot, stroke volume (S V), TPVR and MBF at 1 bar (100 kPa). These parameters remained depressed fo r almost the whole experimental period in Group 2a, while P-ivt, +/- dP/dt, Pasys, MAP and (V) over dot (O2), were enhanced during exposure to 5 bar ( 500 kPa) in Group 2b. The HR was unchanged by quinidine in Group 2a, but wa s increased at elevated ambient pressure in Group 2b, whereas the MBF was u nchanged in both groups. The present results show that verapamil and quinid ine have a depressant effect on cardiac function, arterial pressure and (V) over dot (O2) at normal atmospheric pressure, whereas MBF was enhanced onl y in the verapamil group. During exposure to elevated ambient pressure, car diac function, arterial pressure and (V) over dot (O2) increased despite ad equate inhibition of slow Ca2+ and fast Na+ channels.