The effect of ischemia reperfusion or hypoxia reoxygenation on pulmonary vascular permeability and resistance was studied in 25 isolated blood-perfused dog lungs. Vascular permeability, assessed by determining filtration coefficient (Kf), and vascular resistances were measured at the beginning and end of the experiment. Ischemia reperfusion was produced by occluding blood flow to the lung for 3 h and reperfusing for 1 h, whereas hypoxia reoxygenation was obtained by ventilating the lung with 95% N2-5% CO2 for 3 h and then ventilating with 95% O2-5% CO2 for 1 h with no interruption of perfusion. There was a significant increase in Kf in both ischemia reperfusion and hypoxia reoxygenation groups (51 and 85%, respectively), and total vascular resistance increased greatly in both groups (386 and 532%, respectively). Two additional groups were also studied in which the ischemia reperfusion or hypoxia reoxygenation lungs were pretreated with allopurinol (20 micrograms/ml). The Kf did not significantly increase in either the allopurinol ischemia reperfusion or the allopurinol hypoxia reoxygenation groups (22 and 6%, respectively). However, total vascular resistance significantly increased in both groups (239 and 224%, respectively). Although vascular permeability is modestly increased by both ischemia reperfusion and hypoxia reoxygenation, the predominant change in these conditions is the increased vascular resistance, which predominantly affects the postcapillary resistance and would result in a greater tendency for edema to develop in these slightly damaged lungs. Allopurinol, which inhibits xanthine oxidase, attenuated the permeability changes in both groups and may be useful in preventing ischemia reperfusion injury in certain conditions.
The action of histamine (H), serotonin (5-HT), and norepinephrine (NE) on the lung vasculature was evaluated in isolated blood-perfused dog lung lobes using isogravimetric techniques. Pre- and postcapillary resistances, isogravimetric capillary pressure (Pc,i), capillary filtration pressure (Pc,f), capillary filtration coefficient (Kf,c), and vascular pressure-volume relationships were measured. For constant-flow conditions, all drugs induced marked increases in both pre- and postcapillary resistances and increased Pc,f. The rise in Pc,f was most pronounced for H and least marked for NE and 5-HT. For constant-pressure perfusion, Pc,f increased slightly for H but not for NE and 5-HT, while total vascular resistance increased 4-5 times for all drugs. Vascular distensibility and volumes decreased markedly for NE and 5-HT but only slightly for H. None of the drugs appeared to alter capillary permeability because Kf,c and Pc,i measured during the infusions were not different from control.
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