Mechanism of morphine induced shifts in blood volume between extracorporeal reservoir and the systemic circulation of the dog under conditions of constant blood flow and vena caval pressures

The mechanism of a morphine-induced shift in blood volume between an extracorporeal reservoir and the systemic circulation of a dog under conditions of constant blood flow and vena caval pressure was investigated in 10 anesthetized dogs with the aid of right heart bypass. All blood returning to the heart was removed from the right atrial appendage and, after passing through a Starling resistor, drained by gravity into an extracorporeal reservoir. It then was pumped around a NaJ(Tl) scintillation crystal, through a heat exchanger and a flowmeter, and returned directly into the pulmonary artery. The following data (mean ± SE) were obtained with the pump flow set at 80 ml.min^-1.kg^-1. By the 5th minute following the administration of morphine, 4 mg/kg, arterial pressure fell from 99 ± 5 to 59 ± 6 mm Hg (P<0.001). Reservoir volume fell by 578 ± 86 ml, and central hematocrit increased from 0.41 ± 0.02 to 0.47 ± 0.01 (P<0.01) in 15 minutes. Plasma volume, determined by a ^113mIn-tagged plasma tracer, decreased by 317 ± 32 ml in 15 minutes. Thus, following the administration of morphine, 58% of the decrease in reservoir volume was accounted for by fluid lost from the circulatory system. This filtration was preceded by an immediate 30% rise in the counts/min obtained from a scintillation probe positioned over the liver, suggesting a similar rise in liver volume. These counts remained elevated throughout the experiment. Ascites volume determined by an indicator dilution technique steadily increased from 78 ± 24 ml at the time of morphine administration to 276 ± 44 ml (P<0.001) by the 60th minute following morphine. A mass balance calculated on the protein concentration of the ascites fluid suggested that the ascites produced by morphine resulted from the filtration of pure plasma. We conclude that morphine-induced decreases in extracorporeal reservoir volume at constant blood flow and vena caval pressure can be accounted for largely by blood trapped in the liver by constriction of the hepatic outflow vessels and plasma filtered at the liver sinusoids producing ascites.