Amrinone combined with dobutamine improves hemodynamics and oxygen delivery without down-regulation of cardiac beta-adrenergic receptor density in porcine endotoxemia.
Effects of amrinone (AMR), a phosphodiesterase inhibitor, alone and in combination with dobutamine (DOB), on hemodynamics and O2 delivery were studied during porcine endotoxemia. Pentobarbital-anesthetized pigs were randomly administered either Escherichia coli lipopolysaccharide (endotoxin) or equivolumetric .9% NaCl (control) as a continuous infusion for 4 h. From 2 to 4 h (T = 120-240 min) of endotoxin infusion, pigs were randomly administered one of the following treatments; AMR infusion (40 micrograms/kg/min) (AMRlow); DOB (10 micrograms/kg/min) (DOB); AMR infusion (40 micrograms/kg/min) + DOB (AMRlow+DOB); AMR bolus (.75 mg/kg) followed by AMR infusion (40 micrograms/kg/min) (AMRhigh); or AMR bolus (.75 mg/kg) followed by infusion (40 micrograms/kg/min) + DOB (AMRhigh+DOB). Myocardial samples were obtained at the end of the experiment and flash-frozen for beta-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/dtmax), mean arterial pressure, and O2 delivery, 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, O2 delivery and consumption, and decreased mean pulmonary arterial pressure, pulmonary vascular resistance, mean arterial pressure, and systemic vascular resistance. beta-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 O2 delivery was attenuated by AMRlow+DOB. Potential applications of this combination may exist in treatment of septic patients with inadequate myocardial performance and reduction in O2 delivery complicated by pulmonary hypertension.
Jones
J L
JL
Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University.
Gengo
P J
PJ
Dodam
J R
JR
Hellyer
P W
PW
D000676:Amrinone / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004280:Dobutamine / Q000494:pharmacology*; D015536:Down-Regulation; D004359:Drug Therapy, Combination; D006439:Hemodynamics / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D010101:Oxygen Consumption / Q000187:drug effects*; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D012772:Shock, Septic / Q000188:drug therapy* / Q000503:physiopathology; D017693:Sodium Bicarbonate / Q000097:blood; D013552:Swine; D016278:Ventricular Function, Right / Q000187:drug effects
D011943:Receptors, Adrenergic, beta; D004280:Dobutamine; D017693:Sodium Bicarbonate; D000676:Amrinone