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Erschienen in: Cardiovascular Drugs and Therapy 5/2009

01.10.2009

Comparison of the Effects of Levosimendan and Papaverine on Human Internal Mammary Artery and Saphenous Vein

verfasst von: Hossein Mirkhani, Masih Shafa, Hajar Khazraei

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 5/2009

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Abstract

Purpose

Internal mammary artery (IMA) and saphenous vein (SV) are two most common vessels used in coronary artery bypass grafting (CABG). In the present study, the effect of levosimendan (a novel inotropic/vasodilator compound) and papaverine are compared, using IMA and SV obtained from CABG patients.

Methods

Unused segments of IMA and SV of each patient were cut into two rings of 3 mm length. Four rings (two from IMA, two from SV) were suspended in an organ bath, contracted with norepinephrine and then the responses to the cumulative concentrations of levosimendan and papaverine were recorded.

Results

Levosimendan relaxed IMA but failed to relax SV completely. In addition, its IC50 value (concentration which reduced 50% of initial contraction) to relax SV was about 300 times higher than the IC50 value for IMA. Its arteriodilating concentration was in the range of its clinically effective inotropic concentration. Papaverine relaxed both vascular preparations completely. Its IC50 value was about 2.4 times higher toward SV in comparison to that of IMA.

Conclusions

It is concluded that levosimendan is much more potent to relax norepinephrine-induced contraction of human IMA in comparison to its effect on human SV. It may have the potential to be used as a mixed inotropic/arteriodilator compound in several clinical settings including CABG in which it can increase cardiac contractility and prevent IMA vasospasm.
Literatur
1.
Zurück zum Zitat Jett GK, Arcidi JM Jr, Dorsey LM, Hatcher CR Jr, Guyton RA. Vasoactive drug effects on blood flow in internal mammary artery and saphenous vein grafts. J Thorac Cardiovasc Surg. 1987;94:2–11.PubMed Jett GK, Arcidi JM Jr, Dorsey LM, Hatcher CR Jr, Guyton RA. Vasoactive drug effects on blood flow in internal mammary artery and saphenous vein grafts. J Thorac Cardiovasc Surg. 1987;94:2–11.PubMed
2.
Zurück zum Zitat Formica F, Ferro O, Brustia M, Corti F, Colagrande L, Bosisio E, et al. Effects of papaverine and glycerylnitrate-verapamil solution as topical and intraluminal vasodilators for internal thoracic artery. Ann Thorac Surg. 2006;81:120–4.CrossRefPubMed Formica F, Ferro O, Brustia M, Corti F, Colagrande L, Bosisio E, et al. Effects of papaverine and glycerylnitrate-verapamil solution as topical and intraluminal vasodilators for internal thoracic artery. Ann Thorac Surg. 2006;81:120–4.CrossRefPubMed
3.
Zurück zum Zitat Mahmoudian M, Shafiei M, Mirkhani H, Omrani GR. Effects of different vasodilators on human internal mammary artery in vitro. Adv Exp Med Biol. 1999;471:419–26.PubMed Mahmoudian M, Shafiei M, Mirkhani H, Omrani GR. Effects of different vasodilators on human internal mammary artery in vitro. Adv Exp Med Biol. 1999;471:419–26.PubMed
4.
Zurück zum Zitat Uydeş-Doğan BS, Nebigil M, Aslamaci S, Onuk E, Kanzik I, Akar F. The comparison of vascular reactivities of arterial and venous grafts to vasodilators: management of graft spasm. Int J Cardiol. 1996;53:137–45.CrossRefPubMed Uydeş-Doğan BS, Nebigil M, Aslamaci S, Onuk E, Kanzik I, Akar F. The comparison of vascular reactivities of arterial and venous grafts to vasodilators: management of graft spasm. Int J Cardiol. 1996;53:137–45.CrossRefPubMed
5.
Zurück zum Zitat He GW, Rosenfeldt FL, Buxton BF, Angus JA. Reactivity of human isolated internal mammary artery to constrictor and dilator agents. Implications for treatment of internal mammary artery spasm. Circulation. 1989;80:I141–50.PubMed He GW, Rosenfeldt FL, Buxton BF, Angus JA. Reactivity of human isolated internal mammary artery to constrictor and dilator agents. Implications for treatment of internal mammary artery spasm. Circulation. 1989;80:I141–50.PubMed
6.
Zurück zum Zitat DiNardo JA, Bert A, Schwartz MJ, Johnson RG, Thurer RL, Weintraub RM. Effects of vasoactive drugs on flows through left internal mammary artery and saphenous vein grafts in man. J Thorac Cardiovasc Surg. 1991;102:730–5.PubMed DiNardo JA, Bert A, Schwartz MJ, Johnson RG, Thurer RL, Weintraub RM. Effects of vasoactive drugs on flows through left internal mammary artery and saphenous vein grafts in man. J Thorac Cardiovasc Surg. 1991;102:730–5.PubMed
7.
Zurück zum Zitat Holley AD, Ziegenfuss M. Levosimendan: a new option in acute cardiac failure. Emerg Med Australas. 2006;18:505–9.CrossRefPubMed Holley AD, Ziegenfuss M. Levosimendan: a new option in acute cardiac failure. Emerg Med Australas. 2006;18:505–9.CrossRefPubMed
8.
Zurück zum Zitat Yildiz O, Seyrek M, Yildirim V, Demirkilic U, Nacitarhan C. Potassium channel-related relaxation by levosimendan in the human internal mammary artery. Ann Thorac Surg. 2006;81:1715–9.CrossRefPubMed Yildiz O, Seyrek M, Yildirim V, Demirkilic U, Nacitarhan C. Potassium channel-related relaxation by levosimendan in the human internal mammary artery. Ann Thorac Surg. 2006;81:1715–9.CrossRefPubMed
9.
Zurück zum Zitat Höhn J, Pataricza J, Petri A, Tóth GK, Balogh A, Varró A, et al. Levosimendan interacts with potassium channel blockers in human saphenous veins. Basic Clin Pharmacol Toxicol. 2004;94:271–3.PubMed Höhn J, Pataricza J, Petri A, Tóth GK, Balogh A, Varró A, et al. Levosimendan interacts with potassium channel blockers in human saphenous veins. Basic Clin Pharmacol Toxicol. 2004;94:271–3.PubMed
10.
Zurück zum Zitat Rang HP, Dale MM, Ritter M, Flower RJ. Rang & Dale’s pharmacology. 6th ed. Churchill Livingston; 2007. Rang HP, Dale MM, Ritter M, Flower RJ. Rang & Dale’s pharmacology. 6th ed. Churchill Livingston; 2007.
11.
Zurück zum Zitat Montes FR, Echeverri D, Buitrago L, Ramírez I, Giraldo JC, Maldonado JD, et al. The vasodilatory effects of levosimendan on the human internal mammary artery. Anesth Analg. 2006;103:1094–8.CrossRefPubMed Montes FR, Echeverri D, Buitrago L, Ramírez I, Giraldo JC, Maldonado JD, et al. The vasodilatory effects of levosimendan on the human internal mammary artery. Anesth Analg. 2006;103:1094–8.CrossRefPubMed
12.
Zurück zum Zitat Antila S, Kivikko M, Lehtonen L, Eha J, Heikkilä A, Pohjanjousi P, et al. Pharmacokinetics of levosimendan and its circulating metabolites in patients with heart failure after an extended continuous infusion of levosimendan. Br J Clin Pharmacol. 2004;57:412–5.CrossRefPubMed Antila S, Kivikko M, Lehtonen L, Eha J, Heikkilä A, Pohjanjousi P, et al. Pharmacokinetics of levosimendan and its circulating metabolites in patients with heart failure after an extended continuous infusion of levosimendan. Br J Clin Pharmacol. 2004;57:412–5.CrossRefPubMed
13.
Zurück zum Zitat Giessler C, Wangemann T, Silber RE, Dhein S, Brodde OE. Norepinephrine-induced contraction of human saphenous vein and human internal mammary artery: involvement of different alpha-adrenoceptor subtypes. Naunyn Schmiedebergs Arch Pharmacol. 2002;366:104–9.CrossRefPubMed Giessler C, Wangemann T, Silber RE, Dhein S, Brodde OE. Norepinephrine-induced contraction of human saphenous vein and human internal mammary artery: involvement of different alpha-adrenoceptor subtypes. Naunyn Schmiedebergs Arch Pharmacol. 2002;366:104–9.CrossRefPubMed
14.
Zurück zum Zitat Pataricza J, Hõhn J, Petri A, Balogh A, Papp JG. Comparison of the vasorelaxing effect of cromakalim and the new inodilator, levosimendan, in human isolated portal vein. J Pharm Pharmacol. 2000;52:213–7.CrossRefPubMed Pataricza J, Hõhn J, Petri A, Balogh A, Papp JG. Comparison of the vasorelaxing effect of cromakalim and the new inodilator, levosimendan, in human isolated portal vein. J Pharm Pharmacol. 2000;52:213–7.CrossRefPubMed
15.
Zurück zum Zitat Nieminen MS, Akkila J, Hasenfuss G, Kleber FX, Lehtonen LA, Mitrovic V, et al. Hemodynamic and neurohumoral effects of continuous infusion of levosimendan in patients with congestive heart failure. J Am Coll Cardiol. 2000;36:1903–12.CrossRefPubMed Nieminen MS, Akkila J, Hasenfuss G, Kleber FX, Lehtonen LA, Mitrovic V, et al. Hemodynamic and neurohumoral effects of continuous infusion of levosimendan in patients with congestive heart failure. J Am Coll Cardiol. 2000;36:1903–12.CrossRefPubMed
16.
Zurück zum Zitat Slawsky MT, Colucci WS, Gottlieb SS, Greenberg BH, Haeusslein E, Hare J, et al. Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure. Circulation. 2000;102:2222–7.PubMed Slawsky MT, Colucci WS, Gottlieb SS, Greenberg BH, Haeusslein E, Hare J, et al. Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure. Circulation. 2000;102:2222–7.PubMed
17.
Zurück zum Zitat Poelzl G, Zwick RH, Grander W, Metzler B, Jonetzko P, Frick M, et al. Safety and effectiveness of levosimendan in patients with predominant right heart failure. Herz. 2008;33:368–73.CrossRefPubMed Poelzl G, Zwick RH, Grander W, Metzler B, Jonetzko P, Frick M, et al. Safety and effectiveness of levosimendan in patients with predominant right heart failure. Herz. 2008;33:368–73.CrossRefPubMed
18.
Zurück zum Zitat Hurax C, Makita T, Montes F, Szlam F, Levy JH. Comparative evaluation of the effects of multiple vasodilators on human internal mammary artery. Anesthesiology. 1998;88:1654–9.CrossRef Hurax C, Makita T, Montes F, Szlam F, Levy JH. Comparative evaluation of the effects of multiple vasodilators on human internal mammary artery. Anesthesiology. 1998;88:1654–9.CrossRef
19.
Zurück zum Zitat Gao YJ, Yang H, Teoh K, Lee RM. Detrimental effects of papaverine on the human internal thoracic artery. J Thorac Cardiovasc Surg. 2003;126:179–85.CrossRefPubMed Gao YJ, Yang H, Teoh K, Lee RM. Detrimental effects of papaverine on the human internal thoracic artery. J Thorac Cardiovasc Surg. 2003;126:179–85.CrossRefPubMed
Metadaten
Titel
Comparison of the Effects of Levosimendan and Papaverine on Human Internal Mammary Artery and Saphenous Vein
verfasst von
Hossein Mirkhani
Masih Shafa
Hajar Khazraei
Publikationsdatum
01.10.2009
Verlag
Springer US
Erschienen in
Cardiovascular Drugs and Therapy / Ausgabe 5/2009
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-009-6197-0

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