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Biomedical subjects

J Roughan

Publications and source records attributed to J Roughan.

5 recordsLinked to original sources

Modulation of reperfusion injury after single lung transplantation by pentoxifylline, inositol polyanions, and sin-1.

OBJECTIVE: Previous studies have suggested reductions in lung reperfusion injury with pentoxifylline, inositol polyanions, and the nitric oxide donor, SIN-1, but these agents have never been directly compared to ascertain which is superior. We investigated these agents in a porcine model of left single lung transplantation. METHODS: Donor lungs were preserved with modified Euro-Collins solution for a mean ischemic time of 18.4 hours. Neutrophil trapping in the graft, pulmonary vascular resistance, free radical release (measured by malonaldehyde levels) and gas exchange were assessed over a 12-hour period. All groups were reperfused at an initial pulmonary artery pressure of 20 mm Hg. Group A (n = 5) was a control group with no interventions added; group B was reperfused with the addition of intravenous inositol polyanions (0.02 mg/kg/h), and group C was reperfused with intravenous SIN-1 (0.02 mg/kg/h). Group D was reperfused with the addition of intravenous pentoxifylline (2 mg/kg/h). RESULTS: Neutrophil sequestration was observed within 10 minutes of reperfusion in group A. This was attenuated significantly by interventions in groups B, C, and D. In group D, malonaldehyde levels were significantly lower than in other groups and was associated with superior oxygenation. Pulmonary vascular resistance was reduced in groups B, C, and D compared with group A. CONCLUSIONS: Pentoxifylline, when administered only to recipient animals was superior to the other interventions studied. Inositol polyanions are promising as a possible therapeutic intervention but were not as effective as the other agents studied.

Animals↗

Controlled reperfusion and pentoxifylline modulate reperfusion injury after single lung transplantation.

OBJECTIVE: Rodent models have suggested that initial low-pressure reperfusion of transplanted lungs reduces injury after ischemia. We investigated this phenomenon and the use of pentoxifylline in a porcine model of left single lung transplantation. METHODS: Donor lungs were preserved with Euro-Collins solution for a mean ischemic time of 18.4 hours. Neutrophil trapping in the graft, pulmonary artery pressure, and gas exchange were assessed over a 12-hour period. Partial occlusion of the contralateral pulmonary artery allowed manipulation of the pulmonary artery pressure in the transplanted lung. Group A (n = 5) was perfused at a mean pulmonary artery pressure of 20 mm Hg, group B was reperfused at a mean pulmonary artery pressure of 45 mm Hg for 10 minutes before reducing the pressure to the same as group A, and group C was reperfused at a mean pressure of 20 mm Hg for 10 minutes, then increased to a mean of 45 mm Hg for the remainder of the experiment. Group D was reperfused as in group A with the addition of intravenous pentoxifylline. RESULTS: Leukocyte sequestration was observed in the first 10 minutes after reperfusion in groups A, B, and C, with maximal sequestration at 2 minutes. Significantly more sequestration was observed in the first 6 minutes in group B than in groups A and C, which were similar. Pentoxifylline significantly reduced leukocyte sequestration. Pulmonary venous oxygen tension in the allograft lung was worst in group B. Groups A and C were similar, but group D was superior to all other groups (p < 0.001). CONCLUSIONS: Low-pressure reperfusion, even when limited to the first 10 minutes, modulates reperfusion injury possibly through a leukocyte-dependent mechanism. The addition of pentoxifylline in the recipient confers significant additional benefit.

Animals↗

Influence of oral buprenorphine, oral naltrexone or morphine on the effects of laparotomy in the rat.

The effects of oral administration of buprenorphine ('buprenorphine jello'), a partial mu opioid agonist, oral naltrexone, a mu antagonist and morphine, a mu agonist, were investigated in rats following laparotomy. Food and water consumption and body weight were reduced in rats that underwent surgery. Rats undergoing anaesthesia alone showed only a small reduction in water consumption. Administration of oral buprenorphine (0.5 mg/kg in flavoured gelatin) decreased the effects of surgery on body weight and water intake when compared to untreated (vehicle alone) controls. The magnitude of this beneficial effect was similar to that seen in previous studies using subcutaneous administration of buprenorphine. The fall in body weight and food and water intake following surgery was similar in the groups which received morphine and the control group which received vehicle (jelly). Neither the magnitude of the fall in body weight, and food and water intake, nor the behavioural scores differed between naltrexone and control (vehicle alone) rats following surgery. This suggests that the beneficial effects of partial agonist analgesics are mediated by a reduction in pain rather than by antagonism of endogenous opioids. Both anaesthesia and surgery caused changes in behaviour, but the major effects of buprenorphine in normal (unoperated) rats severely limited the value of behavioural parameters as a means of assessing possible beneficial effects of analgesic administration.

Administration, Oral↗