Comparison of Milrinone, Phenoxybenzamine, and Mixture of Nitroglycerin and Verapamil for the Prevention and Treatment of Human Radial Artery Spasm_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

ZHU Yan , WANG Huishan , LI Xinmin , WANG Lihui , WANG Zengwei.

PLA Cardiovascular Surgery Institute，Department of Cardiovascular Surgery，General Hospital of Shenyang Military District，Shenyang 110016，P. R. China;

Corresponding author：

Keywords：

Coronary artery bypass grafting; Radial artery; Spasm; Milrinone; Phenoxybenzamine; Nitroglycerin; Verapamil

DOI：

10.7507/1007-4848.20130059

Video：

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Objective To compare milrinone （MIN）, Phenoxybenzamine （PHE），and mixture of nitroglycerin and verapamil(NVC) for the prevention and treatment of human radial artery spasm. Methods Residuary radial arteries from 30 patients undergoing coronary artery bypass grafting （CABG） using autologous radial artery from March to September of 2012 in General Hospital of Shenyang Military District were collected. All the artery specimens were cut into 60 vessel rings of 3 mm in width and hanged in the Organ-Bath. Using a random number table，all the vessel rings were divided into 4 groups：PHE group，NVC group，MIN group and blank group （control group）. Firstly，20 vessel rings were used for spasm relaxation experiment with 5 rings in each group. Phenylephrine was added into the Organ-Bath to reach final concentration of 10-3 mol/L　in order to cause vessel rings spasm. PHE of 1 mmol/L，NVC of both 30 μmol/L，MIN of 30 μmol/L and Krebs-Ringer’s　solution were added respectively into above groups to compare the relaxant effect of these vasodilators on radial artery spasm. Secondly，the other 40 vessel rings were used for spasm prevention experiment with 10 rings in each group. All the 40 vessel rings were dipped in above 4 groups. After 30 minutes，phenylephrine was added to the Organ-Bath to reach final concentration　of 10-3 mol/L. Time-dependent constriction of the vessel rings were compared to examine the prevention effect of these vasodilators on radial artery spasm. Results In the spasm relaxation experiment, vessel ring spasm relaxed most quickly in NVC group （P＜ 0.01）. Vessel rings in MIN group relaxed more slowly but steadily （P＜ 0.05）. Vessel rings in PHE group relaxed most slowly （P＜0.01）. And there was no relaxation in the control group. In the spasm prevention experiment，vessel rings in the control group contracted （spasm） 100% immediately after phenylephrine administration. Vessel rings in MIN group contracted immediately after phenylephrine administration too，but slower than the control group（P＜0.01）. Vessel rings in NVC group did not contract right after phenylephrine administration，but the sedentary tension of these vessel　rings gradually increased 120 minutes after phenylephrine administration，and vessel ring contraction reached 46.89% 240 minutes after phenylephrine administration. There was no vessel ring contraction in PHE group. Conclusions All the vasodilators in our experiment are effective for the prevention and treatment of radial artery spasm to different degree，but each medication has its own characteristics，vasodilatation result and time-dependent effect. NVC is most effective to dilate radial artery which has been in spasm state, while radial artery pretreated by PHE is least to become spasm after being stimulated.

Citation： ZHU Yan,WANG Huishan,LI Xinmin,WANG Lihui,WANG Zengwei.. Comparison of Milrinone, Phenoxybenzamine, and Mixture of Nitroglycerin and Verapamil for the Prevention and Treatment of Human Radial Artery Spasm. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2013, 20(2): 198-203. doi: 10.7507/1007-4848.20130059 Copy

1.	Tranbaugh RF， Dimitrova KR， Friedmann P， et al. Coronary artery bypass grafting using the radial artery：clinical outcomes， patency， and need for reintervention. Circulation， 2012， 126 （11 Suppl 1）：S170-S175.
2.	Schwann TA， Engoren M， Bonnell M， et al. Comparison of late coronary artery bypass graft survival effects of radial artery versus saphenous vein grafting in male and female patients. Ann Thorac Surg， 2012， 94 （5）：1485-1491.
3.	Carpentier A， Guermonprez JL， Deloche A， et al. The aorta-to-coronary radial artery bypass graft. A technique avoiding pathological changes in grafts. Ann Thorac Surg， 1973， 16 （2）：111-121.
4.	Kristi　 I， Lukenda J. Radial artery spasm during transradial coronary procedures. J Invasive Cardiol， 2011， 23 （12）：527-531.
5.	Pérez de Prado A， Cuellas C， Diego A， et al. Vasomotor response to different endothelium-dependent vasodilators in an animal model. J Invasive Cardiol， 2012， 24 （7）：320-323.
6.	Tveita T， Sieck GC. Effects of milrinone on left ventricular cardiac function during cooling in an intact animal model. Cryobiology， 2012， 65 （1）：27-32.
7.	Huang MH， Wu Y， Nguyen V， et al. Heart protection by combination　therapy with esmolol and milrinone at late-ischemia and early reperfusion. Cardiovasc Drugs Ther， 2011， 25 （3）：223-232.
8.	Kishi T， Sunagawa K. Baroreflex sensitivity might predict responders　to milrinone in patients with heart failure. Int Heart J， 2010， 51 （6）：411-415.
9.	Na S， Oh YJ， Shim YH， et al. Effects of milrinone on blood flow of the Y-graft composed with the radial and the internal thoracic artery in patients with coronary artery disease. Eur J Cardiothorac Surg， 2006， 30 （2）：324-328.
10.	Rabbani G， Vijay V， Sarabu MR， et al. Regulation of human internal　mammary and radial artery contraction by extracellular and intracellular Calcium channels and cyclic adenosine 3’， 5’ monophosphate. Ann Thorac Surg， 2007， 83 （2）：510-515.
11.	Taggart DP， Dipp M， Mussa S， et al. Phenoxybenzamine prevents spasm in radial artery conduits for coronary artery bypass grafting. J Thorac Cardiovasc Surg， 2000， 120 （4）：815-817.
12.	Ning YM， Sánchez ER. Evidence for a functional interaction　between calmodulin and the glucocorticoid receptor. Biochem Biophys　Res Commun， 1995， 208 （1）：48-54.
13.	Mueed I， Tazzeo T， Liu C， et al. Isoprostanes constrict human radial　artery by stimulation of thromboxane receptors， Ca2+ release， and RhoA activation. J Thorac Cardiovasc Surg， 2008， 135 （1）：131-138.
14.	Harrison WE， Mellor AJ， Clark J， et al. Vasodilator pre-treatment of human radial arteries； comparison of effects of phenoxybenzamine vs papaverine on norepinephrine-induced contraction in vitro. Eur Heart J， 2001， 22 （23）：2209-2216.
15.	Tsuchida A， Liu Y， Liu GS， et al. Alpha 1-adrenergic agonists precondition rabbit ischemic myocardium Independent of adenosine by direct activation of protein kinase C. Circ Res， 1994， 75 （3）：576-585.
16.	Velez DA， Morris CD， Muraki S， et al. Brief pretreatment of radial artery conduits with phenoxybenzamine prevents vasoconstriction long term. Ann Thorac Surg， 2001， 72 （6）：1977-1984.
17.	Dipp MA， Nye PC， Taggart DP. Phenoxybenzamine is more effective　and less harmful than papaverine in the prevention of radial artery vasospasm. Eur J Cardiothorac Surg， 2001， 19 （4）：482-486.
18.	Roubos N， Rosenfeldt FL， Richards SM， et al. Improved preservation of saphenous vein grafts by the use of glyceryl trinitrate-verapamil solution during harvesting. Circulation， 1995， 92 （9 Suppl）：II31-II36.
19.	Dogan OF， Tatar I， Duman U， et al. Comparison of the pretreatment effects of mixed vasodilators （3-D solution） on radial and internal thoracic arteries by using a 3-dimensional anaglyph electron microscope technique. Heart Surg Forum， 2006， 9 （3）：E643-E649.

1. 　Tranbaugh RF， Dimitrova KR， Friedmann P， et al. Coronary artery bypass grafting using the radial artery：clinical outcomes， patency， and need for reintervention. Circulation， 2012， 126 （11 Suppl 1）：S170-S175.
2. 　Schwann TA， Engoren M， Bonnell M， et al. Comparison of late coronary artery bypass graft survival effects of radial artery versus saphenous vein grafting in male and female patients. Ann Thorac Surg， 2012， 94 （5）：1485-1491.
3. 　Carpentier A， Guermonprez JL， Deloche A， et al. The aorta-to-coronary radial artery bypass graft. A technique avoiding pathological changes in grafts. Ann Thorac Surg， 1973， 16 （2）：111-121.
4. 　Kristi　 I， Lukenda J. Radial artery spasm during transradial coronary procedures. J Invasive Cardiol， 2011， 23 （12）：527-531.
5. 　Pérez de Prado A， Cuellas C， Diego A， et al. Vasomotor response to different endothelium-dependent vasodilators in an animal model. J Invasive Cardiol， 2012， 24 （7）：320-323.
6. 　Tveita T， Sieck GC. Effects of milrinone on left ventricular cardiac function during cooling in an intact animal model. Cryobiology， 2012， 65 （1）：27-32.
7. 　Huang MH， Wu Y， Nguyen V， et al. Heart protection by combination　therapy with esmolol and milrinone at late-ischemia and early reperfusion. Cardiovasc Drugs Ther， 2011， 25 （3）：223-232.
8. 　Kishi T， Sunagawa K. Baroreflex sensitivity might predict responders　to milrinone in patients with heart failure. Int Heart J， 2010， 51 （6）：411-415.
9. 　Na S， Oh YJ， Shim YH， et al. Effects of milrinone on blood flow of the Y-graft composed with the radial and the internal thoracic artery in patients with coronary artery disease. Eur J Cardiothorac Surg， 2006， 30 （2）：324-328.
10. 　Rabbani G， Vijay V， Sarabu MR， et al. Regulation of human internal　mammary and radial artery contraction by extracellular and intracellular Calcium channels and cyclic adenosine 3’， 5’ monophosphate. Ann Thorac Surg， 2007， 83 （2）：510-515.
11. 　Taggart DP， Dipp M， Mussa S， et al. Phenoxybenzamine prevents spasm in radial artery conduits for coronary artery bypass grafting. J Thorac Cardiovasc Surg， 2000， 120 （4）：815-817.
12. 　Ning YM， Sánchez ER. Evidence for a functional interaction　between calmodulin and the glucocorticoid receptor. Biochem Biophys　Res Commun， 1995， 208 （1）：48-54.
13. 　Mueed I， Tazzeo T， Liu C， et al. Isoprostanes constrict human radial　artery by stimulation of thromboxane receptors， Ca2+ release， and RhoA activation. J Thorac Cardiovasc Surg， 2008， 135 （1）：131-138.
14. 　Harrison WE， Mellor AJ， Clark J， et al. Vasodilator pre-treatment of human radial arteries； comparison of effects of phenoxybenzamine vs papaverine on norepinephrine-induced contraction in vitro. Eur Heart J， 2001， 22 （23）：2209-2216.
15. 　Tsuchida A， Liu Y， Liu GS， et al. Alpha 1-adrenergic agonists precondition rabbit ischemic myocardium Independent of adenosine by direct activation of protein kinase C. Circ Res， 1994， 75 （3）：576-585.
16. 　Velez DA， Morris CD， Muraki S， et al. Brief pretreatment of radial artery conduits with phenoxybenzamine prevents vasoconstriction long term. Ann Thorac Surg， 2001， 72 （6）：1977-1984.
17. 　Dipp MA， Nye PC， Taggart DP. Phenoxybenzamine is more effective　and less harmful than papaverine in the prevention of radial artery vasospasm. Eur J Cardiothorac Surg， 2001， 19 （4）：482-486.
18. 　Roubos N， Rosenfeldt FL， Richards SM， et al. Improved preservation of saphenous vein grafts by the use of glyceryl trinitrate-verapamil solution during harvesting. Circulation， 1995， 92 （9 Suppl）：II31-II36.
19. 　Dogan OF， Tatar I， Duman U， et al. Comparison of the pretreatment effects of mixed vasodilators （3-D solution） on radial and internal thoracic arteries by using a 3-dimensional anaglyph electron microscope technique. Heart Surg Forum， 2006， 9 （3）：E643-E649.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Comparison of Milrinone, Phenoxybenzamine, and Mixture of Nitroglycerin and Verapamil for the Prevention and Treatment of Human Radial Artery Spasm

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