Organ preservationNitroglycerin Reperfusion Reduces Ischemia-Reperfusion Injury in Non-Heart-Beating Donor Lungs
Section snippets
Isolated Perfused Lung Model
The IPRLM first described by Gaar et al29 and modified by Drake et al30 provides a sensitive and reproducible method to assess alterations in the permeability of the pulmonary microcirculation, the critical initial phase of lung IRI. After determining Kfc in rat lungs,31 investigators have used this preparation to further characterize lung reperfusion injury.32, 33, 34, 35 The specific details of our preparation have been outlined previously.4
Briefly, male Sprague-Dawley rats weighing 250 to
Kfc
Changes in microvascular permeability as measured by Kfc are shown in Figure 1. Kfc increased in lungs as the post-mortem ischemic time increased. The elevation in Kfc was slightly attenuated in lungs retrieved 120 minutes post-mortem with O2 ventilation alone. Reperfusion with NTG resulted in substantially decreased Kfc of lungs retrieved 120 minutes post-mortem, regardless of cadaver ventilation. Kfc could not be determined in lungs retrieved >2 hours post-mortem unless they were reperfused
Discussion
Endothelium-derived NO is a product of L-arginine conversion to citrulline. NO acts as a signaling molecule to maintain endothelial capillary permeability, reduce platelet aggregation, and inhibit neutrophil adhesion to the endothelial surface.25, 38 Endogenous and exogenous NO stimulate soluble guanylate cyclase to produce cGMP.23, 39 Increased levels of cGMP induce smooth muscle relaxation and vasodilation23, 40 via changes in smooth muscle cytosolic calcium.41, 42
Pinsky et al and other
Conclusion
Increased capillary permeability of lungs retrieved from NHBD rat lungs can be almost completely ameliorated after up to 120 minutes of post-mortem ischemic time if the lungs are reperfused with a NTG-supplemented solution. Marginal yet significant attenuation of IRI was also observed in NTG-reperfused lungs beyond 2 hours of pre-harvest ventilation with O2. The mechanism through which this occurs appears to involve an increase in intracellular cGMP concentration. Stimulation of cGMP pathways
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Cited by (0)
This study was supported by NIH R01 HL63159-01A2.