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ORIGINAL ARTICLE

Desferoxamine and its protective effect in pulmonary preservation

Luiz Sérgio FragomeniI; Robert S BonserII; Brian EdwardsII; Stuard W JamiesonII; Michael P KayeII

DOI: 10.1590/S0102-76381989000300009

ABSTRACT

There is increasing evidence that oxygen derived free radicals are involved in the injury that occurs following the reperfusion of ischaemic tissue. Deferoxamine by preventing hydroxyl radical production and scavenging superoxide anion may attenuate this injury and its effects were evaluated following 4 hours of static hypothermic pulmonary preservation. Left lung autotransplantation was performed in 12 mongrel dogs. The autograft was initially flushed with 1000 cc of modified Collins solution and then stored in an inflated state for 4 hours in 4ºC saline. Six dogs received deferoxamine 500 mg intravenously infused before and immediately after the time of reperfusion. Following reimplantation, contralateral pulmonary artery ligation was performed and the animals were then maintained on a fixed FiO2 (40%) and monitored for 6 hours. During the first hour of reperfusion arterial pO2 was significantly better in the deferoxamine treated dogs (p < 0.05). Alveolar-arterial oxygen gradients were also lower (p < 0.05). Pulmonary vascular resistance was not different between groups. We conclude that deferoxamine improves gas exchange in the immediate reperfusion period and that further investigation of its use is warranted.

RESUMO

Há recentes evidências de que radicais livres derivados do oxigênio estáo envolvidos na lesão tecidual decorrente de isquemia e subseqüente reperfusão. A desferoxamina (DF), evitando a produção de radicais hidroxila e eliminando o ânion superóxido, pode atenuar este dano, sendo seus efeitos aqui avaliados após quatro horas de preservação pulmonar hipotérmica. O auto-transplante pulmonar esquerdo foi realizado em 12 cães mestiços. O pulmão foi, inicialmente, perfurado com 1000 ml de solução de Collins modificada e mantido insuflado, colocado sob refrigeração (4ºC) em solução salina durante quatro horas. Seis cães receberam 500 mg de DF administrados E.V. durante o período isquémico e imediatamente após iniciar a reperfusão. Após reimplante e ligadura da artéria pulmonar direita, os animais foram mantidos numa FiO2 fixa (49%) e monitorizados por quatro horas. Durante a primeira hora pós-reperfusão, o pO2 arterial foi sifnif¡cativamente superior no grupo tratado com DF (p < 0.05). O gradiente alvéolo-arterial foi também inferior (p < 0.05). A resistência vascular pulmonar foi semelhante em ambos os grupos. Concluímos que a desferoxamina permite melhor troca gasosa no período imediatamente após reperfusão e que sua investigação, na área da preservação pulmonar, deve ser estimulada.
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REFERENCES

1. AMBROSIO, G.; WEISFELDT, M. L.; JACOBUS, W. E.; FLAHERTY, J. T. - Evidence for a reversible, oxygen radical mediated component of reperfusion damage: reduction by recombinant human superoxide dismutase administered at the time of reflow. Circulation. 75: 282-291, 1987. [MedLine]

2. AMBROSIO, G.; ZWEIER, J. L.; JACOBUS, W. E.; WEISFELDT, M. L.; FLAHERTY, J. T. - Improvement of postischemic myocardial function and metabolism induced by administration of deferoxamine at the time of reflow: the role of iron in the pathogenesis of reperfusion injury. Circulation, 76: 906-915, 1987. [MedLine]

3. AMBROSIO, G.; ZWEIER, J. L.; WEISFELDT, M. L.; FLAHERTY, J. T. - Early toxic effects of oxygen free radicals on myocardial energy metabolism following reperfusion. J. Am. Coll. Cardiol., 9: 125A, 1987. [MedLine]

4. AUST, S. D.; MOREHOUSE, L. A.; THOMAS, C. E. - Role of metals in oxygen radical ractions. J. Free Radicals Biol. Med., 1: 3-25, 1985.

5. AUST, S. D. & WHITE, B. C. - Iron chelation prevents tissue injury following ischemia. Adv. Free Radicals Biol., 1: 1-17, 1985.

6. BANDO, K.; TAGO, M.; TERAMOTO, S. - Prevention of free radical-induced myocardial injury by allopurinol. J. Thorac Cardiovasc. Surg., 95: 465-473, 1988. [MedLine]

7. CASALE, A. A.; BUKLEY, G. B.; BULKLEY, B. H.; FLAHERTY, J. T.; GOTT, V. L.; GARDNER, T. J. - Oxygen free-radical scavengers protect the arrested, globally ischemic heart upon reperfusion. Surg. Forum, 34: 313-316, 1983.

8. FRIDOVICH, I- The biology of oxygen radicals. Science, 210: 875-880, 1978.

9. GRAF, E.; MAHONEY, J. R.; BRYANT, R. G.; EATON, J. W. - Iron-catalyzed hydroxyl radical formation: stringent requirement for free iron coordination site. J. Biol. Chem., 259: 3620-3624, 1987.

10. GRANGER, D. N.; HOLLWARTH, M. A.; PARKS, D. A. - Ischemia reperfusion injury: role of oxygen-derived free radicals. Acta Physiol. Scand., 126 (Supl. 1): 47-63, 1986.

11. HAVERICH, A.; SCOTT, W. C.; JAMIESON, S. W. - Twenty years of lung preservation: a review. Heart Tranplant., 4: 234-240, 1985.

12. HESS, M. L. & MANSON, N. H. - Molecular oxygen: friend and foe. The role of the oxygen free radical system in the calcium paradox, the oxygen paradox and ischemia/reperfusion injury. J. Mol. Cell. Cardiol., 16: 969-985, 1984. [MedLine]

13. JURMANN, M. J.; SCHAEFERS, H. J.; DAMMENHAYN, L.; HAVERICH, A. - Oxygen-derived free radical scavengers for amelioration of reperfusion damage in heart transplantation. J. Thorac. Cardiovasc. Surg., 95: 368-377, 1988. [MedLine]

14. McCORD, J. M. - Oxygen-devised free radicals in post-ischemic tissue injury. N. Engl. J. Med., 312: 159-163, 1985. [MedLine]

15. McCORD, J. M. & FRIDOVICH, I. - Superoxide dismutase: an enzymic function for erythrocuprein (hemocuprein). J. Biol. Chem., 244: 6049-6065, 1969.

16. MENASCHE, P.; GROUSSET, C.; GAUDUEL, Y.; MOVAS, C.; PIWNICA, A. - Prevention of hydroxyl radical formation. A critical concept for improving cardioplegia: protective effects of deferoxamine. Circulation, 76 (Supl. 5): 180-185, 1988.

17. MYERS, C. L.; WEISS, S. J.; KIRSH, M. M.; SHLAFER, M. - Involvement of hydrogen peroxide and hydroxyl radical in the "oxygen paradox" rduction of creatine kinase release by catelase, allopurinol or deferoxamine but not by superoxide dismutase. J. Moll. Cell Cardiol., 17: 675-684, 1985.

18. SHLAFER, M.; KANE, P. F.; WIGGINS, V. Y.; KIRSH, M. M. - Possible role for cytotoxic oxygen metabolites in the pathogenesis of cardiac ischemic injury. Circulation., 66 (Supl. 1): 85-92, 1982.

19. SIMPSON, P.; MICKELSON, J. K.; LUCCHESI, B. R. - Free radical scavengers in myocardial ischemia. Fed. Proc., 46: 2413-2421, 1987. [MedLine]

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