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Am. J. Respir. Crit. Care Med., Volume 162, Number 3, September 2000, 850-856

Comparison of Phosphodiesterase Inhibitors of Differing Isoenzyme Selectivity Added to St. Thomas' Hospital Cardioplegic Solution Used for Hypothermic Preservation of Rat Lungs

ROLAND L. FEATHERSTONE, DAVID J. CHAMBERS, and FRANK J. KELLY

Cardiovascular Research and Cardiac Surgical Research, The Rayne Institute, St. Thomas' Hospital, London, United Kingdom

Raising intracellular cAMP or cGMP concentrations protects lungs from ischemia-reperfusion injury. These nucleotides are catabolized by a number of distinct phosphodiesterase (PDE) isoenzyme subfamilies. We examined the ability of PDE inhibitors of differing selectivities to protect lungs from the effects of prolonged hypothermic storage. Rat lungs were perfused with bicarbonate buffer mixed with rat blood (4:1 vol/vol, 37° C), ventilated, and vascular resistance, airway compliance, and resistance, and gas exchange measured. Lungs were then flushed with, and immersed in, St. Thomas' Hospital Solution (STH) (4° C) or STH containing rolipram, milrinone, zaprinast, or theophylline. After 8 h storage, function was reassessed during 40 min reperfusion. Lungs stored in STH containing rolipram or theophylline had improved function on reperfusion. After 40 min reperfusion, pulmonary compliance (Cstat) was 0.07 ± 0.01 ml/cm H2O in lungs stored in STH alone. Adding rolipram (100 µM) or theophylline (3,000 µM) to the STH used for flushing and storage improved Cstat after reperfusion to 0.17 ± 0.02 ml/cm H2O (p < 0.05) and 0.17 ± 0.02 ml/cm H2O (p < 0.05), respectively. Theophylline also improved the increase in perfusate PO2 on transit through the lung after storage to 25.16 ± 2.33 compared with 4.72 ± 2.18 mm Hg in lungs stored in STH alone (p < 0.05). Of the selective PDE inhibitors tested, rolipram (type IV inhibitor) was most effective. However, the nonselective agent, theophylline, provided the best protection of function after storage and reperfusion of rat lungs.




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