Current Review
Pharmacology of coronary artery bypass grafts

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Abstract

Spasm of arterial and venous graft conduits can occur both during harvesting and after the graft is connected. Attempts to overcome spasm during harvesting by probing or hydraulic distension can cause structural damage to the graft, which may impair short- and long-term patency. After a coronary artery bypass graft is connected, spasm can cause major problems with myocardial perfusion. To select the best pharmacologic agent to prevent or reverse vasoconstriction in a graft requires an understanding of the reactivity of that particular type of graft to vasoconstrictor and vasodilator agents. The pharmacologic reactivity of venous and arterial graft conduits has been documented through extensive studies of isolated vessels in the organ bath and of in situ grafts in the body. In this review we summarize the current state of knowledge of the reactivity of arterial and venous grafts to vasoconstrictor and vasodilator agents and describe the practical application of this knowledge in the operating room and in the postoperative period.

Section snippets

In vitro pharmacology of blood vessels

Isolated blood vessel pharmacology allows the scientist to explore mechanisms of drug action and establish concentration–response relationships for analysis of potency and range (efficacy) more readily than is possible in in vivo experiments. In vitro blood vessel assays provide information in a controlled environment without blood flow and shear stress, extrinsic neural activity, or hormonal influences. Therefore, although scientists gain quantitation and analytical power with an in vitro

Contraction

Spasm of the GEA is a well-described clinical phenomenon [52]. Dignan and associates [7] have found that the GEA is more reactive than the IMA to K+, NE, and 5-HT, whereas others have suggested that the GEA and the IMA have similar response to NE, phenylephrine, and 5-HT 34, 53, and that the IMA is more reactive to the TXA2 mimetic, U46619 [54]. The diverse results from different groups may reflect the variation of techniques used in the studies. In general, the GEA has a stronger contractility

Guidelines for the use of vasodilators for arterial grafts during CABG

  • 1.

    There is no perfect vasodilator that is effective in every situation. Vasoconstriction (or spasm) is caused by multiple mechanisms. Vasodilators relax vascular smooth muscles through a specific mechanism or mechanisms. Selective vasodilators, such as calcium antagonists, are more potent when the vessel is constricted by agents, such as potassium, which act indirectly to open VOCCs, but are less potent when the vessel is constricted through a receptor-operated mechanism, such as for TX

Importance of protecting the saphenous vein during harvesting

The two situations in which spasm of the SV may occur are during harvesting and during the postoperative period. Postoperative spasm is a rarity and can be readily reversed by GTN [63]. However, spasm of the SV during harvesting is a common phenomenon. Therefore it is important to appreciate the detrimental effects of spasm and to be aware of techniques that can be used to prevent or reverse this spasm.

The occlusion rate of SV grafts in the first year is between 15% and 26% [64]. By 10 years,

Method of application of solution

Having selected the optimal venodilator(s) on the basis of organ bath studies, the next question arises as to the best method of application to the SV during harvesting. Ideally the dilator solution would be applied early enough during the procedure to prevent spasm before it occurs. LoGerfo and associates [72] recommended injecting papaverine subcutaneously along the track of the saphenous vein before cutting the skin. This technique has the potential disadvantage that it is difficult to

Conclusions

There are many possible causes of graft spasm during CABG but undoubtedly the most common is surgical trauma. In the case of arterial grafts, surgical trauma can usually be minimized by careful surgical technique and by harvesting the artery as a pedicle rather than skeletonizing it. In the case of the SV, the vessel is always skeletonized during harvesting and is often subjected to surgical trauma especially during minimally invasive harvesting techniques. Thus unless specific pharmacologic

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      Citation Excerpt :

      Actually, there is no a perfect vasodilator drug, because arterial spasm is often a multifactorial phenomenon modulated by different mechanism, such as mechanical stimuli, drugs, temperature, and endogenous catecholamine.5 In order to prevent LITA spasm, several vasodilatory agents, such as papaverine,7,13–15 calcium-channel blockers13,17 sodium nitroprusside,18 nitroglycerine,17,19 milrinone,19,20 and phenoxibenzamine,17,21 have been studied, compared, and used both topically and intraluminally to treat perioperative spasm of the arterial conduits. Papaverine is most commonly used agent,6,7 which initially was proposed to be injected intraluminally.

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    Copyright © 1999 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.