Monitoring of pulmonary endothelial enzyme function: an animal model for a simplified clinically applicable procedure.
The authors present a simple and clinically applicable method for the serial monitoring of pulmonary microvascular enzyme function in vivo. This method requires the intravenous injection of trace amounts of a radiolabelled substrate and the collection of a single arterial blood sample. Simultaneous measurement of pulmonary blood flow, (e.g., by dye- or thermo-dilution) and the determination of blood hematocrit are also needed for the calculations. This method was compared to the multiple blood sample indicator dilution method in normal anesthesized rabbits. Both methods gave identical results for the metabolism of the synthetic, hemodynamically inactive tripeptide, 3H-benzoyl-Phe-Ala-Pro (3H-BPAP), by pulmonary microvascular endothelial angiotensin converting enzyme. The parameters measured were: 1) substrate utilization, expressed linearly and logarithmically, and 2) the apparent first order reaction constant. The new method was also used for the simultaneous measurement of single pass, transpulmonary metabolism of 3H-BPAP by angiotensin converting enzyme and of 5'-adenosine monophosphate by 5'-nucleotidase in rabbits in vivo. The authors propose that similar enzyme kinetic measurements could be used in clinical studies to test their usefulness as an aid in the early diagnosis of incipient pulmonary endothelial dysfunction, e.g., adult respiratory distress syndrome.
Toivonen
H J
HJ
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912.
Makari
N
N
Catravas
J D
JD
D015720:5'-Nucleotidase; D000818:Animals; D004730:Endothelium, Vascular / Q000201:enzymology*; D008168:Lung / Q000098:blood supply*; D008297:Male; D008991:Monitoring, Physiologic / Q000379:methods*; D009708:Nucleotidases / Q000097:blood; D009842:Oligopeptides; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011817:Rabbits; D014316:Tritium
D009842:Oligopeptides; D014316:Tritium; C029689:benzoylphenylalanyl-alanyl-proline; D009708:Nucleotidases; D015720:5'-Nucleotidase; D007703:Peptidyl-Dipeptidase A