Reactivity of the human internal thoracic artery to vasodilators in coronary artery bypass grafting

We read with great interest the article by Takeuchi and colleagues on the effects of papaverine hydrochloride, isosorbide dinitrate (ISDN) and phosphodiesterase III inhibitor (PDE III-I) on the free blood flow in human internal thoracic artery (ITA) conduits [1]. The authors found that PDE III-I was most effective for increasing the free blood flow of the ITA graft and that papaverine had no effect at all. The free ITA blood flow increased only from around 37ml/min before medical treatment to 40ml/min after papaverine, 48ml/min after ISDN and 57ml/min after PDE III-I. These results are in contrast to previous work in this area [2,3]. In a similar study, we compared the free flow between pedicled and skeletonized ITA grafts before and after intraluminal injection of papaverine [3]. Although we found similar baseline free flows in the ITA conduits (skeletonized: 51ml/min and pedicled: 69ml/min), the flow significantly increased after treatment with papaverine (skeletonized: 197ml/min and pedicled: 147ml/min). Why was the ITA free flow post-pharmacological treatment in our study over three folds higher than that achieved in Takeuchi's work? Takeuchi and colleagues used an interval of only 1min after vasodilator injection to measure graft flow, whereas we assessed graft flow 15min after papaverine injection. Is a 1min time interval after treatment with papaverine too short to assess for maximum vasodilation of the ITA? In addition, the period of time which was used to calculate free blood flow per minute was only 10s in Takeuchi's study compared to 20s in our investigation. This may have some statistical implications. In both studies papaverine was injected intraluminally. However, the concentration of papaverine used in our study was only 2.5mg/ml, whereas Takeuchi et al. used concentrations of 4mg/ml. It could be that the higher concentrations induced endothelial damage of the ITA which then reduced free flow [4]. There is no mention in the methodology of the technique of ITA preparation. There is a significant difference in flow rates between pedicled and skeletonized grafts after injection of papaverine (see earlier). It would therefore be interesting to see if PDE III-I has a significantly different effect in skeletonized compared to pedicled ITAs. Finally, low flow rates in ITA grafts have important clinical implications, especially if they are to be used for instance as ‘T’-grafts in complex arterial revascularizations. In this type of configuration, total coronary bypass flow is dependent on the flow in the proximal ITA. If this is low, either as a result of poor harvesting technique or suboptimal treatment with vasodilator, hypoperfusion syndrome with global ischemia can ensue [5].