Proceedings of The Physiological Society

University of Oxford (2011) Proc Physiol Soc 23, PC281

Poster Communications

Protective effect of hypercapnia on warm ischemia induced free radical damage of lungs retrieved from non-heart-beating donors

D. Hodyc1,2, P. Vaněk1,2, K. Dušková1,2, J. Herget1,2

1. Department of Physiology, Charles University in Prague, 2nd Medical School, Prague, Czech Republic. 2. Centre for Cardiovascular Research, Prague, Czech Republic.

Lungs retrieved from non-heart-beating donors (NHBD) might alleviate the shortage of suitable organs for transplantation. The critical point is the preservation of lungs during warm ischemia, when damage is caused by free radicals [1-2]. We have demonstrated previously that ventilation during warm ischemia worsens lung free radical damage. Also, pre arrest administration of radical scavenger, tempol, reduces warm ischemic damage of lung functions [3]. Hypercapnia has protective effect on free radical damage [4-5]. In present study we investigated a possible protective effect of ventilation using hypercapnic gas mixture during warm ischemia on free radical damage in lungs retrieved from non-heart-beating donors. Four groups (n = 8) of Wistar male rats were used - 3 experimental and 1 control group. All the experimental groups underwent the protocol of NHBD lung harvesting - the tracheal cannula was introduced under thiopental anaesthesia (50mg/kg, administered intraperitoneally) and the animals were killed by overdosing of sodium thiopental (250mg/kg, administered intraperitoneally). Then the animals were kept in room temperature for 60 minutes - warm ischemia. The groups were: V - ventilated during warm ischemia with room air; H - ventilated during warm ischemia with hypercapnic gas mixture (7% CO2, 21%O2, 72% N2); N - non ventilated during warm ischemia; C-controls, lungs isolated immediately after thiopental anaesthesia without warm ischemia. Then in isolated rat lungs we measured perfusion pressure, weight, and arterio-venous difference in oxygen partial pressure in time intervals of 30, 60 90 and 120 minutes after reperfusion. For statistical evaluation we used ANOVA for repeated measures, Games/Howell post hoc test, p ≤ 0,05; values are presented as means ± SEM. We found that ventilation with the room-air caused severe pulmonary oedema within 30 minutes after reperfusion in 3 of 8 animals and also in the rest of V group we found significant increase of lung weight (0; 0.23±0.15; 0,43±0.19; 0,53±0,22) compared to controls (C; 0; 0.03±0.07; 0.08±0.1; 0.04±0.13; p≤0.05) or non-ventilated animals, (N; 0; 0.05±0.09; 0.04±0.14; -0.06±0.14; p≤0.05). In contrast to this after ventilation with hypercapnic gas mixture (H) we did not observe any signs of pulmonary oedema and the lung weight gain (0; 0.05±0.01; 0.12±0.02; 0.2±0.04) did not differ compared to non-ventilated (N) and controls (C). The perfusion pressure and gas transport ability did not differ significantly among the groups. In lungs retrieved from non-heart-beating donors hypercapnia has protective effect against free radical damage caused by room air ventilation during warm ischemia.

Where applicable, experiments conform with Society ethical requirements