Compared peripheral vascular responses to intravenous and intra-arterial administrations of positive inotropic agents in conscious dogs.
In addition to their direct effects on cardiac contractility, a number of positive inotropic agents also induce, through direct peripheral vasodilation, a reduction in afterload which is of major importance in their beneficial effects in the treatment of congestive heart failure. However, the induced increase in cardiac output can indirectly improve perfusion of peripheral vessels through a flow-mediated mechanism. Thus, the goal of the present study was to compare the direct peripheral vasomotor effects assessed in the iliac vascular bed of four positive inotropic agents: DPI 201-106, ouabain, milrinone and dobutamine, in the presence and absence of simultaneous changes in cardiac function. These drugs were administered either through intravenous or intra-arterial (aorto-iliac catheter) routes in 6 conscious dogs, chronically instrumented for the measurement of heart rate, arterial pressure, left ventricular dP/dt, iliac artery blood flow and iliac artery diameter (sonomicrometry). Intravenous doses were selected as those inducing equipotent positive inotropic responses whereas intra-arterial doses were below those required to induce any significant change in systemic hemodynamics. Ouabain decreased and milrinone increased both iliac blood flow and diameter after either intravenous or intra-arterial administrations. In contrast, iliac blood flow did not change after intra-arterial administration of DPI 201-106 and dobutamine whereas iliac diameter was not modified by DPI 201-106 and even decreased with dobutamine. After intravenous administration, DPI 201-106 but not dobutamine, increased both iliac blood flow and diameter. Thus, this experimental preparation can differentiate inotropic agents with direct vasodilating (milrinone) or constricting (ouabain) properties and those (DPI 201-106 and dobutamine) with indirect vasodilating effects most likely mediated by the improvement in cardiac function.
Gosgnach
M
M
Département de pharmacologie, Faculté de médecine Paris-Sud, Le Kremlin-Bicêtre, France.
Gérard
J L
JL
Berdeaux
A
A
Giudicelli
J F
JF
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004280:Dobutamine / Q000008:administration & dosage / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D020105:Milrinone; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010042:Ouabain / Q000008:administration & dosage / Q000494:pharmacology; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D011728:Pyridones / Q000008:administration & dosage / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014666:Vasomotor System / Q000187:drug effects*
D002316:Cardiotonic Agents; D010879:Piperazines; D011728:Pyridones; D004280:Dobutamine; D010042:Ouabain; C046261:DPI 201-106; D005996:Nitroglycerin; D020105:Milrinone; D000109:Acetylcholine; D009638:Norepinephrine