David P. Taggart

Objective: To assess platelet activating factor (PAF) antagonists, potent neuroprotective agents in experimental cerebral dysfunction, in clinical practice. Design: Double blind, minimised, placebo controlled trial of low and high dose PAF antagonist (lexipafant). Setting: Cardiac surgery unit. Patients: 150 patients undergoing coronary artery bypass graft (CABG) surgery using cardiopulmonary bypass. Interventions: Randomisation to placebo, low dose (10 mg) or high dose (100 mg) lexipafant. Main outcome measures: Incidence of impairment on four established cognitive tests, undertaken before, five days, and three months after CABG, examined by three methods for defining impairment. Results: The three groups were similar with respect to preoperative and intraoperative factors. Observed levels of cognitive impairment were less than had been predicted from previous studies. There was no difference in the groups in cognitive change scores at five days or three months. Group mean analysis showed significant time factors for all four tests but not for interactions or for the lexipafant group. A composite cognitive index, based on the aggregate of four normally distributed tests, showed a significant effect for timing of the test but not for the lexipafant group or interaction. Age, but not duration of bypass, was the most important determinant of postoperative cognitive impairment. Conclusions: The neuroprotective PAF antagonist lexipafant did not differentially reduce the level of cognitive impairment after CABG as determined by power estimates derived from published studies. The strongest predictors of cognitive impairment were age and timing of the test after operation.

There is an increasing use of arterial conduits for coronary artery bypass grafting, and the radial artery is commonly used as the third graft. The major drawback of the radial artery is its proclivity to spasm. Both papaverine and phenoxybenzamine have been recommended as topical vasodilators in clinical practice. We compared the efficacy of both drugs to prevent radial artery spasm and their ability to preserve endothelial function. The ability of both drugs to prevent alpha-adrenoreceptor mediated constriction was tested in vitro in an organ bath in radial artery segments obtained from 20 patients. Vessel viability was determined by potassium (K(+)) constriction, and endothelial function was assessed by observing endothelium-dependent relaxation by a synthetic analogue of acetylcholine, carbachol. Papaverine consistently abolished and prevented spasm for up to a maximum of 30 min in all segments. In contrast, phenoxybenzamine consistently abolished and prevented radial artery spasm in all segments for at least 6 h. Whereas papaverine damaged the endothelium of 70% of vessels, there was no evidence of endothelial damage in any arterial segments after exposure to phenoxybenzamine. Phenoxybenzamine more effectively prevents alpha-adrenoreceptor mediated spasm of the human radial artery than papaverine. It is also less harmful to the endothelium.