Comparison of pulmonary and extrapulmonary extraction of biogenic amines

Multiple indicator-dilution technique was used to study the effect of altered blood flow and imipramine (8 mg/kg) on extraction (E) of trace amounts of 5-hydroxy[14C]tryptamine (5-[14C]HT) and [3H]norepinephrine ([3H]NE) in pulmonary (n = 6) and hindlimb (n = 6) circulations of anesthetized dogs. Increasing cardiac output (via right-heart bypass) from 63 to 112 ml.min-1.kg-1 did not significantly affect pulmonary amine extraction [E(5-[14C]-HT), 73 +/- 4%; E([3H]NE), 51 +/- 3%], whereas decreasing cardiac output to 13 ml.min-1.kg-1 led to significant increases in extraction of either amine (P less than 0.05). Imipramine significantly decreased pulmonary amine extraction with greatest inhibition noted at the lowest cardiac output. Hindlimb E(5-[14C]HT) and E([3H]NE) was 49 +/- 6 and 33 +/- 3%, respectively, at hindlimb blood flow of 104 ml/min and was not affected by changes in hindlimb blood flow from 47 to 202 ml/min. Although hindlimb (5-[14C]HT) was significantly less than pulmonary E(5-[14C]-HT), it was similar in that imipramine significantly decreased hindlimb E(5][14C]HT) to 26% (P less than 0.01) suggesting that part of hindlimb 5-HT extraction may involve a drug-sensitive carrier-mediated process as has been shown in lung. The difference in magnitude between the two beds may be a function of decreased endothelial cell surface area in the hindlimb compared with lung. Since pulmonary and hindlimb extraction of trace amounts of these amines appears to be insensitive to changes in blood flow near normal regional blood flow, indicator-dilution techniques appear to be useful in evaluating alterations in the metabolic capacity of the microcirculation of intact animals.