Cardiovascular effects of verapamil and quinidine at normal and elevated ambient pressure.
Cardiovascular parameters were measured in rats before and after administration of verapamil and quinidine, a slow Ca2+ and fast Na+ channel blocker, respectively, at normal and elevated ambient pressure [5 bar (500 kPa)]. Left ventricular pressure (Pivt), maximal velocity of Plvt rise (+dP/dt) and fall (-dP/dt), and heart rate (HR), arterial systolic pressure (Pasys), and mean arterial pressure (MAP) were measured in all animals using catheters connected to pressure transducers. Cardiac output (Q), and myocardial blood flow (MBF) were detected by the microsphere technique. Total peripheral vascular resistance (TPVR), myocardial vascular resistance (MVR) and oxygen consumption of the heart (VO2) was calculated. In Groups 1a (control group; 1 bar) and 1b (test group; 1-5 bar), verapamil (1.5 mg x kg(-1)) caused a reduction in Plvt, +dP/dt, -dP/dt, Pasys, MAP, VO2, TPVR, and MVR in both groups at 1 bar (100 kPa), and these parameters remained depressed for at least 50 min in Group 1a. However, MBF increased after verapamil injection. After compression to 5 bar (500 kPa), Plvt, dP/dt, Pasys, VO2, and MBF were markedly elevated (Group 1b). No change in HR, SV, or Q was found in either of the groups. In Groups 2a (control group; 1 bar) and 2b (test group; 1-5 bar), quinidine (5 mg x kg(-1)), infused over a period of 10 min, reduced Plvt, +dP/dt, -dP/dt, MAP, Pasys, VO2, Q, stroke volume (SV), TPVR and MBF at 1 bar (100 kPa). These parameters remained depressed for almost the whole experimental period in Group 2a, while Plvt, +/-dP/dt, Pasys, MAP and VO2 were enhanced during exposure to 5 bar (500 kPa) in Group 2b. The HR was unchanged by quinidine in Group 2a, but was increased at elevated ambient pressure in Group 2b, whereas the MBF was unchanged in both groups. The present results show that verapamil and quinidine have a depressant effect on cardiac function, arterial pressure and VO2 at normal atmospheric pressure, whereas MBF was enhanced only in the verapamil group. During exposure to elevated ambient pressure, cardiac function, arterial pressure and VO2 increased despite adequate inhibition of slow Ca2+ and fast Na+ channels.
Stuhr
L E
LE
Department of Physiology, University of Bergen, Norway. linda.stuhr@pki.uib.no
Risberg
J
J
Bergø
G W
GW
Tyssebotn
I
I
D000399:Air Pressure; D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001274:Atmospheric Pressure; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics; D008297:Male; D015221:Potassium Channels / Q000187:drug effects*; D011802:Quinidine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D015221:Potassium Channels; D014700:Verapamil; D011802:Quinidine