Vasodilatory Efficacy and Impact of Papaverine on Endothelium in Radial Artery Predilatation for CABG Surgery: in Search for Optimal Concentration

Abstract

Objective: The aim of this study was to compare the efficacy of two different papaverine concentrations (0.5 mg/ml and 2 mg/ml) for vasospasm prevention and their impact on endothelium integrity.

Methods: We have studied distal segments of radial arteries obtained by no-touch technique from coronary artery bypass graft (CABG) patients (n=10). The vasodilatory effect of papaverine (concentrations of 0.5 mg/ml and 2 mg/ml) was assessed in vitro, in isometric tension studies using ex vivo myography (organ bath technique) and arterial rings precontracted with potassium chloride (KCl) and phenylephrine. The impact of papaverine on endothelial integrity was studied by measurement of the percentage of vessel's circumference revealing CD34 endothelial marker.

Results: 2 mg/ml papaverine concentration showed stronger vasodilatatory effect than 0.5 mg/ml, but it caused significantly higher endothelial damage. Response to KCl was 7.35±3.33 mN for vessels protected with papaverine 0.5 mg/ml and 2.66±1.96 mN when papaverine in concentration of 2 mg/ml was used. The histological examination revealed a significant difference in the presence of undamaged endothelium between vessels incubated in papaverine 0.5 mg/ml (72.86±9.3%) and 2 mg/ml (50.23±13.42%), P=0.002.

Conclusion: Papaverine 2 mg/ml caused the higher endothelial damage. Concentration of 0.5 mg/ml caused better preservation of the endothelial lining.

Fig. 1

Vasodilatation of potassium chloride (KCl) precontracted radial artery segments induced by papaverine 0.5 mg/ml (n=12) and 2 mg/ml (n=12). Mean±SD. ***P<0.001; SD=standard deviation

Fig. 2

Potassium chloride (KCl) and phenylephrine induced contraction of radial artery segments predilated by papaverine 0.5 mg/ml (n=12) and 2 mg/ml (n=12). ***P=0.083.

Fig. 3

Representative micrographs showing endothelium (red) of radial artery after treatment with papaverine 0.5 mg/ml (a) and 2 mg/ml (b). Note progressive damage to the endothelial lining. Cell nuclei counterstained by DAPI (blue). Bar = 200 µm.