Effects of intravascular volume expansion on the cardiovascular response to naloxone in a canine model of severe endotoxin shock.
The specific opiate receptor antagonist, naloxone, can produce haemodynamic improvement and increased survival in experimental shock. The efficacy of naloxone therapy in a canine model of endotoxin shock has been evaluated both with and without intravascular volume replacement. Animals were anaesthetized with alpha-chloralose and allowed to breathe spontaneously. A large bolus dose of endotoxin was followed by a continuous infusion and treatment was instituted one hour after the endotoxin bolus. In the absence of volume replacement, naloxone caused only limited and transient increases in mean arterial pressure (MAP) and left ventricular (LV) dp/dt max, with little effect on cardiac index (CI). Total peripheral resistance index (TPRI) tended to rise in both control and naloxone-treated dogs. In volume-replaced animals, naloxone produced substantial and sustained increases in the MAP and LV dp/dt max with an associated rise in the CI. TPRI rose initially in this series and then fell progressively. Further analysis of the improvements in the CI showed an increase in stroke index with a tendency for heart rate to fall. These findings suggest a myocardial action of naloxone in endotoxin shock, which is augmented by volume replacement. An initial, transient vasoconstrictor effect cannot, however, be excluded. Further work is required to determine the mechanism of the effects described.
D000818:Animals; D001772:Blood Cell Count; D001794:Blood Pressure / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology*; D010952:Plasma Substitutes / Q000008:administration & dosage; D011652:Pulmonary Circulation / Q000187:drug effects; D012772:Shock, Septic / Q000503:physiopathology* / Q000628:therapy; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D010952:Plasma Substitutes; D009270:Naloxone