HORIGUCHI Takashi Akita University School of Medicine, Department of Anesthesiology, instructor, 医学部, 助手 (70221570)
MITSUHATA Hiromasa Jichi Medical School, Department of Anesthesiology, assistant professor, 麻酔科, 講師 (70108934)
MASAKI Yoko Akita University School of Medicine, Department of Anesthesiology, instructor, 医学部, 助手 (30125744)
|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1991 : ¥300,000 (Direct Cost : ¥300,000)
Fiscal Year 1990 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1989 : ¥900,000 (Direct Cost : ¥900,000)
We designed this research to clear the mechanism which produce pulmonary hypertension after protamine reversal by the interaction of heparin protamine complexes(H-P complexes)with pulmonary intravascular macrophages(PIMs).
1)To study whether these responses are different among goats, rabbits pig, human, we compared the pulmonary arterial and airway pressures and thromboxane B2 changes(TxB2)among goat, rabbit, pig and human after protamine reversal. Pulmonary arterial and airway pressures and diromboxane B2(TxB2)increased in goats and pig after protamine reversal, whereas in rabbits and patients with open cardiac surgery did not change. Also, cyclooxygenase inhibitor(Inodomethacin)blocked completely the responses after protamine reversal in goats. From these data, we believe that thromoboxane plays an important roles in the responses after protamine reversal. Also, we can suppose that PIMs may play an important role in these responses, because goat and pig which have many PIMs had big re
sponses, whereas rabbit and human had less or no responses.
2)To study whether H-P complexes play an important role in the responses after protamine reversal, we separated H-P complexes with no heparin protamine complexes(no H-P complexes)by Shamberg's method. H-P complex caused increase in pulmonary arterial and airway pressures and TxB2, but no H-P complexes did not cause these response changes in goats. Also, indomethacin or thromboxane synthetase inhibitor(OKY046)blocked these responses to H-P complex in goats. Moreover, adult goats had big responses to H-P complex, but newborn goat had no responses. From these data, we believe that H-P complex is a major factor in the responses after protamine reversal. Also, both the responses to H-P complex and PIMs may be close related in goat, because adult goat had big responses, but newborn goat had no responses.
3)To study the interaction of H-P complex with PIMS, we did isolated lung perfusion experiment and histological study with electron microscopy. In isolated lung perfusion experiment, H-P complex caused the similar responses. It isclear that cells(PIMs)in the goat pulmonary circulation are produced TxB2 production. Also, according to electron microscopical study, goat lung has many phagocytic mononuclear cells(PIMs), but newborn goat has no PIMS. These mononuclear cells(PIMS)phagocyted some kinds of foreign particles in goats after H-P complexes, but did not foreign particles in goat after no H-P complexes.
We believe our data are consistent with the concept that after protamine reversal, H-P complex is produced and the H-P complex is reacting with the pulmonary intravascular macrophages which lead to the production of TxB2, the major cause of increases in pulmonary arterial and airway pressures in the goat.
For proof of our concept, we need to identify foreign particles which PIMs phagocyted after injection of H-P complexes in goats with H-P complexes. Less