Effects of niguldipine, a new dihydropyridine calcium antagonist, on regional blood flow, cardiac performance and myocardial metabolism in anaesthetized open-chest dogs.
The haemodynamic and metabolic effects of niguldipine (0.01, 0.025 and 0.5 mumol/kg i.v.), a novel dihydropyridine calcium antagonist, were evaluated in 18 anaesthetized open-chest dogs. The following parameters were continuously measured: heart rate, arterial and pulmonary arterial blood pressure, left and right atrial pressure, left ventricular dp/dtmax, cardiac output, regional blood flow in the circumflex branch of the left coronary artery, and in 1 renal and 1 femoral artery. At predetermined intervals, contents of O2, CO2, H+ ions, glucose, lactate and free fatty acids were determined in blood drawn from the left atrium and a regional cardiac vein. Niguldipine induced a dose-dependent decrease in both systolic and diastolic arterial blood pressure, which led to an increase in heart rate and cardiac output. Mean left atrial pressure was markedly reduced by all doses. Coronary blood flow increased dose-dependently and persistently. Perfusion in the renal and femoral vascular beds also increased, but only transiently and to a lesser extent. Calculation of vascular conductances revealed a preferred vasodilating drug effect on the coronary vascular bed. Right atrial and systolic and diastolic pulmonary artery pressures were not noteworthy altered. Balances of metabolic substrates, O2, CO2 and H+ ions did not indicate any major drug effect of niguldipine on myocardial metabolism.
Pharmakologisches Institut Universität Wien, Austria.
G
G
Fischer
W
W
Schneider
G
G
Krumpl
J G
JG
Grohs
G
G
Raberger
D000758:Anesthesia; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology*; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D011652:Pulmonary Circulation / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D005230:Fatty Acids, Nonesterified; D007773:Lactates; D005947:Glucose; C054074:niguldipine