The observation that levels of the mitogenic peptide endothelin-1 are elevated in the human coronary sinus after percutaneous transluminal coronary angioplasty (PTCA) has implicated endothelin-1 in the etiology of vascular restenosis. The present study examined this hypothesis in both an in vitro and an in vivo rat model of neointimal formation by using the novel nonpeptide endothelin receptor antagonist SB 209670. In vitro, endothelin-1 (1 nmol/L) induced a ninefold increase in rat aortic vascular smooth muscle [3Hlthymidine incorporation. This endothelin A receptor-mediated effect was completely inhibited by SB 209670 (IC50, 6.2±2.2 nmol/L). In vivo, acute intra-arterial administration of exogenous endothelin-1 (5 to 500 pmol/kg over a 30-minute period immediately after angioplasty) dose-dependently augmented the degree of neointimal formation (by up to 150% when assessed 14 days after surgery). This response was evident as early as 7 days after angioplasty. Hemodynamic studies indicated that this action was unrelated to a systemic pressor action of the peptide. Administration of SB 209670 (2.5 mg/kg IP, twice a day for 3 days before and for 2 weeks after surgery) reduced neointimal formation by '50% relative to control animals. Thus, the data indicate for the first time that (1) endothelin-1 promotes neointimal formation in vivo and (2) tensin II and norepinephrine, endothelin-1 is now recognized as playing an intrinsic role in the endogenous control of systemic hemodynamics.3 Since levels of endothelin-1 are elevated in the human coronary sinus after PTCA, it has been suggested that endothelin-1 is involved in the pathogenesis of vascular restenosis.4In addition to its actions on vascular smooth muscle tonus, endothelin-1 is also a potent mitogen in several cultured cell lines of both cardiovascular and noncarReceived February 1, 1994; accepted March 21, 1994.

Vascular smooth muscle function in rats with glycerol-induced acute renal failure (ARF) was investigated by recording both the contractile responses of portal vein segments and the relaxant responses depressed contractile responses to the alpha 1-agonist methoxamine, the alpha 2-agonist B-HT 920 and to the calcium agonist BAY K 8644 when compared with controls. Both isoprenaline and nitroprusside produced 100% reversal of KCl induced tone in control aortic rings but in rings from rats with ARF complete reversal of of tone could not be obtained with either dilator drug. It is suggested that a defect in mitochondrial function and hence energy supply may account for the diminished ability of vascular preparations from rats with ARF to constrict and relax.

With the reduction in working hours brought on by Calmanisation and the European Working Time Directive there has been a simultaneous reduction in the number of hours of training received by SpRs. There are also plans to further shorten higher surgical training in the near future. In light of these facts it is important to identify any areas that can maximise training opportunities and learning. There are several papers evaluating training in the theatre and outpatient setting but very few of these include detailed information on the level of follow-up of SpRs' operative cases.

No abstract