RESUMEN
OBJECTIVE: Surgical treatment choice for coronary artery disease is coronary artery bypass grafting (CABG) surgery. Left internal mammary artery (LIMA) is frequently used as an arterial graft in CABG operations. Perioperative spasm of LIMA can result in increased morbidity and mortality. Pharmacological interventions are routinely used for prevention and treatment of LIMA spasm. In this study, we aimed to investigate the effects of carvedilol, an alpha- and beta-adrenergic receptor blocker, on responses to endogenous vasoconstrictors which play a role in graft spasm and the possible interaction between carvedilol and diltiazem/papaverine which are vasodilators commonly used in CABG surgery. PATIENTS AND METHODS: Isolated LIMA rings collected from patients undergoing CABG operation were suspended in an organ bath. Concentration-dependent responses to norepinephrine (NE), serotonin (5-HT) and diltiazem were examined before and after carvedilol incubation (10-6 M, 1 hour). Maximum relaxation response to papaverine (10-4 M) was compared in LIMA rings incubated with 0.05% dimethyl sulfoxide (DMSO, placebo) or carvedilol (10-6 M). RESULTS: Carvedilol did not affect the maximal contractile response to NE; however, it significantly reduced the sensitivity of LIMA to NE. Carvedilol increased contractile response and sensitivity to 5-HT. Promisingly, carvedilol increased the vasodilatory effects of diltiazem and papaverine. CONCLUSIONS: Our study suggests that carvedilol may be administered perioperatively in combination with diltiazem or papaverine to prevent or resolve LIMA graft spasm.
Asunto(s)
Antagonistas Adrenérgicos beta/farmacología , Carbazoles/farmacología , Arterias Mamarias/efectos de los fármacos , Propanolaminas/farmacología , Vasoconstricción/efectos de los fármacos , Antagonistas Adrenérgicos beta/uso terapéutico , Anciano , Carbazoles/uso terapéutico , Carvedilol , Puente de Arteria Coronaria , Enfermedad Coronaria/tratamiento farmacológico , Humanos , Técnicas In Vitro , Arterias Mamarias/metabolismo , Norepinefrina/farmacología , Propanolaminas/uso terapéutico , Serotonina/farmacologíaRESUMEN
Placing a silicone collar around the rabbit carotid artery induces intimal thickening, an early stage in atherosclerosis and restenosis. We investigatedwhethertreatment with oral pranidipine, a new potent, long-lasting dihydropyridine calcium channel blocker (CCB), inhibited collar-induced intimal thickening in addition to the changes in vascular reactivity usually observed in this model. Pranidipine treatment did not inhibit collar-induced intimal thickening. Placing the collar around the carotid artery resulted in the characteristic changes in vascular reactivity, such as increased sensitivity to 5-hydroxytryptamine. Treatment with Nomega-nitro-L-arginine (100 microM) and pranidipine, however, did not affect collar-induced changes in vascular reactivity. From results of this and previous studies, we conclude that pranidipine does not prevent collar-induced intimal thickening or collar-induced changes in vascular reactivity. Not all CCBs prevent collar-induced intimal thickening, suggesting that the effects of these agents are not related to their chemical structure and/or their calcium channel-blocking actions.
