**4. Pharmacology of other arterial grafts**

#### **4.1. Radial artery**

vasoconstriction in the IMA [44]. Further studies on this kind of substances may provide

Vascular endothelial growth factor (VEGF) has been studied in the human IMA and found to be a potent vasodilator through KDR receptors and NO -and PGI2 -mediated mechanisms [44,45]. However, VEGF has potent hypotensive effect due to systemic vasodilaton [44,45]. Therefore, the use of VEGF as a vasorelaxant agent may not be the primary consideration for

Albeit at least three distinct beta-adrenoceptors exist in IMA [105], β -receptor function is weak [31]. Consequently, it has been demonsted that use of β -adrenoceptor agonists is unlikely relax the IMA significantly [106]. Same study also indicated that beta-receptor agonist dobutamine exerts weak vasodilator effect in IMA. Dopamine-induced responses are complex and dosedependent, inasmuch as the complexity of interaction between dopamine and dopamine receptors as well as α1-adrenoceptors [107]. In IMA, dopamine induced a vasorelaxation on the norepinephrine contraction only at higher concentrations [107]. Similar to VEGF, the use of dopamine and dobutamine may not be the primary consideration for antispastic therapy. On the other hand, vasodilator effect of β-adrenoceptor agonists in IMA at high concentrations

TxA2 is one of the the most potent vasoconstrictors known and it is very potent in IMA as well [10,13]. Inasmuch as its importance in thrombosis together with its elevated plas‐ ma concentrations during cardiopulmonary bypass, specific TxA2 antagonists may be use‐ ful in the antispastic therapy of IMA. Accordingly, specific TxA2 antagonist GR30191 is a potent vasodilator for TxA2-mediated contraction in IMA [86]. However, to date, no clini‐

Studies on human IMA have shown that 5-HT directly contracts IMA through 5-HT1D and 5-HT2 receptors [33,108-110]. In IMA, 5-HT receptor mediated contractions are un‐ masked when endothelium is denuded [13,42]. Additionally, studies have shown 5-HT may interact synergistically with other vasoconstrictor substances, such as TxA2 released from platelets during thrombus formation, and 5-HT receptor mediated contractions may be unmasked or amplified [33,108-110]. 5-HT2A receptor antagonist ketanserin has antihy‐ pertensive properties and it's recently used to reduce the severity and frequency of the vasospasm in Raynaud's phenomenon [111]. Therefore, it may have potential to over‐

Testosterone may exert vasorelaxant effects on several vascular tissues [112-119]. We have studied effects of testosterone in the human IMA and found that vasorelaxant re‐

should be kept in mind when these agents are used primarily as inotropic agents.

development of new antispastic protocols.

**Vascular endothelial growth factor**

262 Artery Bypass

antispastic therapy in arterial grafts.

**TxA2 antagonists**

cal data are available.

**Testosterone**

**5-HT receptor antagonists**

come IMA spasm when it's applied topically.

**β-Adrenoceptor agonists: Dopamine and dobutamine**

The use of the RA as a graft for coronary revascularization was already introduced in the 1970s, but shortly thereafter it was abandoned due to high incidence of vasospasm and comparatively poorer short-term and long-term patency rates than IMA [27,122-124]. This was partly due to the inability to recognize RA spasm, but it was also due to lack of proper pharmacological tools to prevent this. It was later noted that radial grafts were indeed patent in patients long after their surgery. Thereafter, the RA was reassessed and its role as an alternative arterial graft was re-established.

Because of the dual blood supply to the hand, RA occlusion is not associated with major clinical sequelae but prevention is important. RA spasm rarely leads to serious vascular complications but can cause patient discomfort and can result in prolonging or failure of the procedure. Several studies now suggest that the vasospastic tendency of RA grafts has been countered in the operating room (immediately after harvest) by treating the artery with papaverine or milrinone, or both, and placing it in a bath of heparinized saline containing NTG or a combi‐ nation of NTG and a calcium channel blocker to prevent spasms. Similarly, protection from immediate postoperative and postdischarge vasospasm is sought through the use of intrave‐ nous or oral combinations of the aforementioned vasodilator drugs. However, clinical studies indicate that such vasodilatory precautions do not provide the expected protection from postoperative vasospasm of RA grafts. Although the patency rate of RA is debatable, mid-term and long-term patency rates may reach 90% and greater, that makes the RA a valuable addition in arterial grafting [125,126].

RA has less active endothelium compared to IMA and is stronger receptor-mediated contrac‐ tions can be evoked in the RA than in the IMA [49,127], which presumably predisposes it to higher incidences of spasm. Additionally, it was previously reported that RA grafts are more sensitive to TxA2 [13]. Furthermore, it has been reported that IMAs produce substantial amounts of both PGI2 and TxA2 [128]; nonetheless, the TxA2 to PGI2 ratio was significantly higher in the RA than in the IMA. Because PGI2 antagonizes the actions of TxA2, the higher TxA2 to PGI2 ratio implies that TxA2 would exert greater effects in the RA. Contraction to KCl in the RA is stronger than in the IMA or the GEA [16]. The RA is more reactive than the IMA to angiotensin II and ET-1, but the endothelial function of the RA is similar to the IMA [49].

**4.3. Inferior epigastric artery**

vasoconstrictors, such as ET, NE, K+

dependent relaxation is impaired.

**5. Conclusion**

preparation, and cost.

**Acknowledgements**

It has been demonstrated that there is no difference between the IEA and the IMA for some

IEA contracted less in response to histamine, but relaxed more in response to endotheliumdependent vasodilators, compared with the IMA [138]. Different contractile responses to TXA2 and NE between the IEA and the IMA have also been reported [139]. In general, it has been argued that the contractile response of the IEA is basically similar to that of the IMA [11].

It has been demonstrated that endothelium dependent relaxation is reduced in the IEA compared with the IMA [140]. Another report has shown that the non–receptor-mediated endothelium dependent relaxation (induced by calcium ionophore A23187) in the IEA is less than in the IMA, although the receptor-mediated endothelium-dependent relaxation induced by acetylcholine is similar [48]. This decreased endothelium-dependent relaxation may be an early sign of arteriosclerosis in the IEA [48], since non– receptor-mediated endothelium-

The problem of grafts spasm has become more obvious with the increasing use of new arterial grafts. Arterial spasm is a multifactor phenomenon modulated by different mechanism, such as drugs, temperature, endogenous catecholamine, and mechanical stimuli (surgical trauma), which is the most common cause. Surgical trauma can usually be minimized by harvesting the

Antispastic management is an important part of technical considerations during CABG surgery. There is extensive evidence that the use of appropriate vasodilators during CABG surgery can facilitate the operative procedure as well as improve graft flow and reduce structural damage to the graft conduit. Spasm of arterial graft conduits is best managed by prevention rather than treatment after it has occurred. There are many dilators of arterial grafts that vary in potency, rapidity of onset, and duration of action as shown in organ bath studies. Using these findings to make a rational choice of type of dilator and optimal concentration for clinical use requires an understanding of the reactivity of that particular type of graft to vasoconstrictor and vasodilator agents. In addition, clinical choice of grafts must be based on consideration of many additional factors, including the systemic effects of the agent if it enters the circulation, the effect of the agent and its vehicle on the endothelium, convenience of

artery as a pedicle rather than skeletonizing it by careful surgical technique.

The authors thank Enis Macit, PhD, for his contribution in preparing this chapter.

, and U46619 [48] However, a previous study showed that

Pharmacology of Arterial Grafts for Coronary Artery Bypass Surgery

http://dx.doi.org/10.5772/54723

265

Pharmacological and non-pharmacological strategies have been evaluated to prevent RA occlusion and RA spasm. A number of pharmacological 'cocktails' have been successfully tested but there is currently no agreement on the optimal combination of agents. RA studied in vitro was found to relax fully either to GV solution or to papaverine, but the relaxation to GV solution was more rapid in onset and of longer duration than for papaverine [62]. GV (GTN +Verapamil) solution has been found to be satisfactory when is used on the RA to dilate it during harvesting and preparation and it [11,129]. It can be argued that GV solution represents the optimum agent for RA spasm when used in the perioperative period [129]. It has been suggested that a 'cocktail' of agents may be given to counteract RA spasm before transradial coronary angiography or angioplasty [130]. A combination of heparin, NTG and verapamil seems to be associated with the best preventive outcome [130].
