Changes Of NPY,CGRP In Plasma, And TXB₂,6-keto-PG1α In Urine With Autologous-blood-clots-induced Pulmonary Embolism In Canine Model

Objective : 1. To establish an ideal canine model of autologous-blood-clots-induced pulmonary embolism. 2. To investigate the changes of neuropeptide Y(NPY), calcitonin-gene-related peptide(CGRP) and angiotensin II (AT-II) with acute pulmonary thromboembolism, and to evaluate the in vivo production of thromboxane A2(TXA2) and prostacyclin(PGI2) during the initial phase of experimental PTE, respectively, by determinations of urine thromboxane B2(TXB2) and 6-ketoprostaglandin F1 (6-keto-PGF 1 ).Methods: 14 healthy canines were randomly divided into two groups: pulmonary thromboembolism(PTE) group and non-PTE one as control. Made of the veinal blood by natural coagulation and heat treatment, the atologous blood clots(0.04g/Kg) were injected to the right jugular vein of the canines in the PTE group, while in the control group 20 ml warm saline was injected. The hemodynamic markers were recorded before PTE and 0.5h, 1h, 2h, 4h and 6h afterPTE, at the same time, arterial blood and urine were collected for blood gas analysis and measurement later by radio-immunity assay. Results: Blood gases and hemodynamic profile: PaO2 decreased significantly immediately after the clots injection (P<0.05). MPAP of the PTE group remained elevated after PTE (P<0.05), while cardiac index(CI) immediately decreased significantly(P<0.05). The changes of pathology: The pathologic changes in PTE group were examined and it accorded with the characteristic of the pathology of PTE. The changes of vasoactive substance: In PTE group, plasma CGRP decreased persistently from the baseline of 62.2 21.2pg/ml, and reached its maximum of 26.1 22.1pg/ml at the end of the experiment, while NPY and AT-II increased transiently from 150.7卤32pg/ml up to 260.3卤103pg/ml and from 25.5卤12.7ng/ml up to 45.3卤22.6ng/ml, respectively. Plasma TXB2 and urine TXB2 changed at the same step, and reached their peak at 1 hour after the injection of clots. Plasma 6-keto-PGFl and urine 6-keto-PGFl also changed at the same step, and reached their peak at 30 minutes after the injection of clots.Conclusion: 1. We succeeded in making the ideal canine model of autologous-blood-clots-induced pulmonary embolism to investigate hemodynamics and vasoactive substance in PTE. 2. The data suggest that the NPY, CGRP and AT-II may be involved in pathophysiologic course of APTE. The observed hemodynamic effects may be associated with the changed relation of TXA2/PGI2.The in vivo production of TXA2 and PGI2 can be evaluated byurine TXB2 and 6-keto-PG1α, respectively.