Haemodynamic effects of hypotension induced by KRN2391 and nicardipine in isoflurane anaesthetized dogs.
OBJECTIVE
The investigational agent, KRN2391, is a potassium channel opener with a nitrate moiety which possesses potent vasodilatory action. We compared the haemodynamic effect of KRN2391. Induced hypotension with those of nicardipine.


METHODS
Sixteen dogs were anaesthetized with isoflurane 1.3% in oxygen (1 MAC). After the baseline period. mean arterial pressure (MAP) was decreased to 60 mmHg for 60 min with an infusion nicardipine (n = 8).


RESULTS
The KRN2391- and nicardipine-induced hypotension resulted in maximal decreased systemic vascular resistance of 35% and 25%, increases in cardiac index of 145% and 197%, and stroke volume index of 150% and 212%, respectively, (P < 0.01). There was no change in heart rate. Nicardipine was associated with increases (P < 0.01) in both right atrial and mean pulmonary artery pressures, whereas these variables remained unchanged with KRN2391. Pulmonary capillary wedge pressure decreased with KRN2391 (P < 0.01), but not with nicardipine.


CONCLUSIONS
While both drugs were equally able of inducing hypotension, our results show that the haemodynamic profile of KRN2391- and nicardipine-induced hypotension was a hyperdynamic state expressed by the marked increase in cardiac index with varying changes in right and left ventricular filling pressures, and suggest that KRN2391 may be a useful vasodilator for induced hypotension.
Takeda
S
S
Department of Anesthesiology, Showa University Fujigaoka Hospital, Yokohama, Japan.
Ozawa
Y
Y
Tomaru
T
T
D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation / Q000008:administration & dosage*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016280:Atrial Function, Right / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007023:Hypotension, Controlled; D007262:Infusions, Intravenous; D007530:Isoflurane / Q000008:administration & dosage*; D008297:Male; D009529:Nicardipine / Q000008:administration & dosage / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D011651:Pulmonary Artery / Q000187:drug effects; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects; D016278:Ventricular Function, Right / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D018685:Anesthetics, Inhalation; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D015221:Potassium Channels; D011725:Pyridines; D014665:Vasodilator Agents; C070492:N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide methanesulfonate; D007530:Isoflurane; D009529:Nicardipine