R. Shibata et al., HEMODYNAMIC-EFFECTS OF NICARDIPINE AND PHENTOLAMINE IN COMBINATION WITH NOREPINEPHRINE IN A CANINE LOW-OUTPUT-STATE MODEL, Japanese Heart Journal, 38(5), 1997, pp. 729-739
Norepinephrine (NE) is one of the most potent positive inotropic drugs
available for the treatment of low-output state following open-heart
surgery. However, its inotropic effect is often masked by a significan
t increase of peripheral vascular resistance due to marked vasoconstri
ction. The purpose of the present study was to investigate whether the
use of nicardipine (Nc) and phentolamine (Ph) in combination with NE
could ameliorate the adverse vasoconstrictive action of NE. A low-outp
ut-state (LOS) model was produced by global myocardial ischemia due to
electrically induced intermittent ventricular fibrillations in open-c
hest dogs. Twenty-eight dogs were divided into 6 groups according to t
he drugs infused after producing LOS. In the control group, hemodynami
c changes similar to the clinical low-output state were observed, e.g.
, a decrease in cardiac output (CO) and left ventricular dp/dt, and an
increase in the systemic vascular resistance (SVR). The use of NE alo
ne produced marked increases in tile systemic arterial pressure (SAP),
heart rate, and SVR, with a slight increase in CO. The infusion of Nc
alone produced decreases in SVR and SAP with a slight increase in CO.
The concomitant infusion of NE and Nc produced increases in SV and CO
, and decreases in SAP and SVR. The infusion of Ph alone produced no s
ignificant hemodynamic changes. The combined use of NE and Ph produced
increases in CO, SAP and heart rate, but not to a significant extent.
These results suggest that there are major advantages in the concomit
ant use of NE and Nc for the control of LOS.