AMRINONE COMBINED WITH DOBUTAMINE IMPROVES HEMODYNAMICS AND OXYGEN DELIVERY WITHOUT DOWNREGULATION OF CARDIAC βADRENERGIC RECEPTOR DENSITY IN PORCINE ENDOTOXEMIA

Autor: Jones, Jana L., Gengo, Peter J., Dodam, John R., Hellyer, Peter W.
Zdroj: Shock; March 1995, Vol. 3 Issue: 3 p224-224, 1p
Abstrakt: Effects of amrinone (AMR), a phosphodiesterase inhibitor, alone and in combination with dobutamine (DOB), on hemodynamics and O2delivery were studied during porcine endotoxemia. Pentobarbital-anesthetized pigs were randomly administered either Escherichia colilipopolysaccharide (endotoxin) or equivolumetric .9 NaCl (control) as a continuous infusion for 4 h. From 2 to 4 h (T120–240 min) of endotoxin infusion, pigs were randomly administered one of the following treatments; AMR infusion (40 μg/kg/min) (AMRlow); DOB (10 μg/kg/min) (DOB); AMR infusion (40 μg/kg/min) DOB (AMRlow DOB); AMR bolus (.75 mg/kg) followed by AMR infusion (40 μg/kg/min) (AMRhigh); or AMR bolus (.75 mg/kg) followed by infusion (40 μg/kg/min) DOB (AMRhigh DOB). Myocardial samples were obtained at the end of the experiment and flash-frozen for β-adrenergic receptor analysis. Endotoxin significantly (p< .05) decreased cardiac index, right ventricular ejection fraction, stroke volume index, maximum rate of rise of left ventricular pressure (dP/dtmaxmean arterial pressure, and O2delivery, and increased pulmonary vascular resistance and mean pulmonary arterial pressure (p< .05). AMRlow DOB significantly (p< .05) increased cardiac index, dP/dtmax, right ventricular ejection fraction, stroke volume index, O2delivery and consumption, and decreased mean pulmonary arterial pressure, pulmonary vascular resistance, mean arterial pressure, and systemic vascular resistance. β-Adrenergic receptor density (Bmax) and binding equilibrium dissociation constant (KD) for [3H]dihydroalprenolol were not affected by endotoxin or any treatment (p< .05). Endotoxin-induced hemodynamic deterioration and decreased O2delivery was attenuated by AMRlow DOB. Potential applications of this combination may exist in treatment of septic patients with inadequate myocardial performance and reduction in O2delivery complicated by pulmonary hypertension.
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