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Department of Cardiac Surgery, Alder Hey Hospital, Liverpool, United Kingdom, drrajashahzad@hotmail.com
To the Editor:
Katai et al. (1) and the editorial staff of Anesthesia & Analgesia deserve credit for carrying out and publishing an important study on the variable effects of dopamine among human isolated arteries commonly used for coronary bypass grafts. The study is timely and of extreme clinical significance in the present era of total arterial myocardial revascularization. I will particularly highlight the clinical implications of their laboratory findings related to the effects of dopamine on radial artery.
The increasing use of multiple arterial conduits in coronary artery bypass grafting (CABG) has followed the superior results initially achieved with a single internal thoracic artery (ITA) and more recently with bilateral ITAs (2). Most patients undergoing CABG need three or more grafts, and the radial artery has become the conduit of choice for the third graft (3). First used as an aorta-coronary graft in 1971, (4) it was subsequently abandoned because of high rates (35%) of postoperative narrowing or occlusion on angiography possibly secondary to vasospasm. Interest in the radial artery has been rekindled because it can be harvested easily and safely, reaches any coronary target comfortably, and can be used as either free or composite grafts. Five-year patency rates between 85% and 92% have been reported (5). Despite its attractive handling characteristics, and improvements in harvesting technique, perioperative graft vasospasm, however, continues to be a major concern (3).
Several topical and systemic pharmacologic preparations have been used to reduce radial artery graft vasospasm. Papaverine, verapamil/nitroglycerin solution (VG solution), and phenoxybenzamine are in clinical use as topical radial artery antispasmodic agents (5). However, there is still no consensus among cardiac surgeons as to which of these antispasmodic agents is the best. The study of Katai et al. (1) at last provides a solution to this controversial issue. In the peripheral vasculature, the effects of dopamine are mediated by D1 and 
-adrenoceptors, with resultant vasodilatation and vasoconstriction, respectively (1). Blockade of -adrenoceptors by phenoxybenzamine may unmask its D1-mediated effects. Hence, phenoxybenzamine’s ability to prevent dopamine-mediated vasoconstriction makes it an ideal antispasmodic agent and increases the safety of using radial artery conduits in CABG. Furthermore, as vasoconstriction of radial artery is -adrenoceptor-mediated, phenoxybenzamine, being a nonselective -adrenoceptor antagonist, with a long duration of action resulting from alkylation of the target receptors, can be effective against other catecholamines.
In an era of evidence-based medicine, there is no denying the fact that randomized controlled trials are the best judge of the efficacy of any therapy. However, until prospective, randomized studies of various topical antispasmodic agents are conducted, the study of Katai et al. (1) provides enough evidence to suggest that phenoxybenzamine, being a nonselective -adrenoceptor antagonist, is a more effective agent to prevent -adrenergic spasm in radial artery than VG solution or papaverine, especially in patients requiring inotropic support with epinephrine, norepinephrine, or dopamine.
References
Department of Anesthesiology and Critical Care Medicine, Kagoshima University School of Medicine, Sakuragaoka, Kagoshima, Japan
In Response:
We would like to thank Dr. Raja for his interest in our work (1) as well as for his comments. We used human arteries—including radial artery (RA), gastroepiploic artery, and internal mammary artery, obtained directly from patients undergoing CABG—and thus our results may reflect the functional status of grafts actually inserted into the body. In the arterial rings examined in our study (1), dopamine substantially increased tone, especially in RA, an effect that was largely prevented by the -adrenoreceptor antagonist prazosin, suggesting that dopamine may directly contract the smooth muscle of human RA grafts via stimulation of -adrenoreceptors. In this respect, phenoxybenzamine, an -adrenoreceptor blocker, is useful for preventing radial artery spasms mediated by dopaminergic stimulation. Moreover, the effect of this drug is irreversible, and thus the possible avoidance of the need for repeated application is another obvious gain (2). However, several other vasoconstrictors—including endothelium-derived contractile factors such as endothelin-1, endogenous vasoactive hormones such as vasopressin, and renin-angiotensin system-related substances such as angiotensin II—are also released as a result of surgery and are implicated in the genesis of vasospasm (3). These vasospasm-inducing substances exert their effects via their own high-affinity plasma-membrane receptors, which are distinct from -adrenoceptors. These results in turn suggest that administration of phenoxybenzamine alone may not be sufficient to eliminate any worry of vasospastic activity. Indeed, Conant et al. (4) have recently reported that the phenoxybenzamine-treated human radial artery failed to respond to norepinephrine, but did respond to vasopressin, angiotensin II, KCl, and endothelin-1. Overall, additional strategies may be required to completely prevent vasospasm. More data or more valid trials are needed. Further work in our laboratory is in progress to test the use of phosphodiesterase inhibitors in the treatment of radial artery spasm.
References
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