Lung dismissal of HIPDM: a new index of lung disfunction for clinical experimental studies.

It has been shown that the lung, in addition to its function in the exchange of gases, can play an important non-respiratory role in the uptake and metabolism of many circulating substances such as amines, peptides and pro- staglandins. The uptake and dismissal of cir- culating vasoactive amines, such as noradre- naline and serotonin have been found to be im- paired in the course of several conditions of lung injury 1"3. Moreover, a reduced pul- monary removal of vasoactive amines, as studied in man by indicator dilution methods, was observed after cardiopulmonary bypass and in patients with pulmonary hypertension 4'6. We studied in rabbit and man the pulmonary kinetics of N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-l,3-propanediamine (HIPDM), a tracer currently evaluated for brain perfusion studies7. After intravenous injection, radioiodinated HIPDM is rapidly cleared from the blood and most of the activi- ty is found in the lungs where a fairly homo- geneous distribution, resembling that of lung perfusion is observed8'9. In rabbit, 95% of in- jected HIPDM is kept whithin the lungs and is then released with a mean time (t) of several hours as assessed both in vivo, by gamma camera external counting (n=5; t=7.0 hours), and in vitro, by measuring activity in lung homogenates at various times after injection (n=56; t=7.6 hours). In 10 healthy non smok- ing subjects, t was 6.4 ±1 hours, whereas it was 12.1 ±2 hours in 10 asymptomatic smok- ers of 20 cigarettes/day with normal pulmo- nary function tests. Preliminary clinical studies showed that HIPDM lung dismissal is delayed in non smoking patients with primary pulmonary hypertension (n=4; t=11.5±2 hours), and to a greater extent in patients with adult respiratory dystress syndrome (n=4; t=25.8±5 hours), whereas it was not signi- ficantly affected in patients with cardiogenic pulmonary edema (n=4; 1=8.8 ±2 hours). Results of our study show that both smoke exposure and injury to the lung microcircula- tion may impair HIPDM lung kinetics. HIPDM external counting may therefore provide a new index of lung dysfunction in man. In rabbit, lung kinetics of HIPDM, as assessed by exter- nal counting, is almost identical to that obtain- ed by counting of lung homogenates. Further- more, the mean time of dismissal of HIPDM in rabbit is very similar to that of normal non smoking man. Hence, rabbit can be used as a model to evaluate HIPDM lung kinetics in ex- perimentally induced lung injury.