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Ann Thorac Surg 1997;64:1219-1220
© 1997 The Society of Thoracic Surgeons
Baglan cad Orgen Apt 18/3, 16090 Cekirge, Bursa, Turkey
To the Editor:
We have recently read with pleasure Dr Bilgen and associates' interesting article regarding the use of normothermic papaverine solution in relieving internal thoracic artery (ITA) spasm [1]. The ITA free flow had been measured before and after a median of 16 minutes of spraying 4 mL of normal saline solution at 20°C, 6 mg of papaverine in 4 mL at 20°C, and the same amount of papaverine at 37°C in three randomly assigned similar groups of patients. More favorable vasodilating effects of normothermic papaverine (37°C) over papaverine at ambient temperature (20°C) were documented. In connection with this observation, Bilgen and associates postulate as the explanatory mechanism for the significant difference that "papaverine-induced relaxation involves inhibition of enzyme activity, which is a temperature-dependent process." We think this might not be the only mechanism; additional inferences could also be drawn from the data presented.
Internal thoracic artery spasm during harvesting seems to be an extremely complex phenomenon, depending on an unsteady balance between the many vasodilator and constrictor variables involved. These variables are not completely clarified yet. In this particular study, during the 16 minutes' time, dynamic changes in the cumulative vasoconstrictor effects might be calming down, and the intervening vasodilator factors seem to cause less resistance to IMA free flow in all three groups. As an exogenously applied vasodilator, the papaverine solution at ambient temperature might indeed cause decreased activity at lower temperatures, but at the same time, being a mild hypothermic solution, it might also take part in the vasoconstrictor side—causing a net effect of delayed or decreased vasodilation—by altering the response to various neurohumoral constrictor and dilator factors that are already in charge.
There has been some evidence that hypothermia could induce vasoconstriction by increasing the responsiveness of 
2-adrenoceptors [2] and serotonergic receptors [3], reducing noradrenaline reuptake in autonomic nerves [4], and increasing release of adenosine triphosphate or related purines from sympathetic nerves acting as cotransmitters [5]. Concerning the vasomotor function in hypothermic exposure, some other vasoconstrictive and on the opposing scale vasodilatory mechanisms—which seems paradoxical but may exist to counterbalance the constrictor effects—have also been suggested, but these discussions and the citation of the related literature are beyond the limits of this letter format.
The vasomotor response to hypothermia is known to be variable among different vascular segments, even in the same organism, depending on different locational and constitutional properties. Of course, the models that have been previously studied do not fully resemble the unique situation of Dr Bilgen and associates' in vivo human study under general anesthesia, in which the autonomic innervation of the ITA was preserved and a small amount of hypothermic solution was locally sprayed. In this context, the effects on ITA free flow 16 minutes after harvesting of spraying such a mild hypothermic solution might be speculative. However, this hypothetical effect of hypothermia causing a delayed vasorelaxation by other mechanisms, if it exists, might have been shown in this model by another group given pure saline solution at 37°C, which would be a control for 20°C saline solution.
In our opinion the exact mechanisms causing the better vasodilatory effects of normothermic papaverine versus papaverine at ambient temperature remain obscure, but the treatment of ITA spasm is symptomatic and directed toward the easiest and fastest technique. Whatever the mechanisms involved, for presenting a more effective method to achieve this goal, Dr Bilgen and associates should be congratulated.
References
erbetçio
lu A, Tarhan IA, Çoruh T, Özler A. Effect of normothermic papaverine to relieve intraoperative spasm of the internal thoracic artery. Ann Thorac Surg 1996;62:769–71.This article has been cited by other articles:
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  A. Tarhan, T. Kehlibar, F. Yapici, M. Yilmaz, Y. Arslan, N. Yapici, and A. Ozler Role of physiological state 'normothermia' in internal thoracic artery spasm after harvesting Eur. J. Cardiothorac. Surg., November 1, 2006; 30(5): 749 - 752. [Abstract] [Full Text] [PDF]
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