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

Abstract

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.

Effects of levosimendan on isolated human internal mammary artery and saphenous vein: concurrent use with conventional vasodilators

“…One of the most serious problems in CABG surgery is that the bypass grafts often go into spasm after implantation into coronary arterial circulation, which may contribute to early myocardial ischemia and increased perioperative morbidity and mortality. Endogenous vasoconstrictors like NA and 5‐HT are among some of the factors contributing to the development of graft spasm . The calcium sensitizing agent levosimendan is an inodilator with cardioprotective properties and phosphodiesterase 3 (PDE3) inhibitory effects .…”

“…Coronary artery bypass grafting (CABG) surgery is the first‐line treatment of advanced coronary artery disease and internal mammary artery (IMA) and saphenous vein (SV) are the conduits of choice in most of the cases. However, coronary bypass graft materials can go into spasm during or after the operation increasing the risk of patient morbidity and mortality . Apart from the well‐known risk factors, such as surgical technique, endogenous vasoconstrictors like noradrenaline (NA) and serotonin (5‐hydroxytryptamine, 5‐HT) can provoke graft spasm .…”

“…Reversal of vasospasm needs urgent treatment and is often challenging. Papaverine, nitroglycerin (NG), and calcium channel blockers have generally been used clinically for the treatment of this phenomenon . The search for ideal vasodilators for the treatment of graft spasm is still ongoing as almost every agent has its disadvantages like potential of papaverine to impair endothelial relaxation , progression of tolerance against NG , and moderate vasodilatory properties of calcium channel blockers such as diltiazem .…”

“…In addition to its positive inotropic effect, it exerts vasodilatory actions on several vasculatures . It has been demonstrated that levosimendan has vasodilatory effect on human coronary arteries , umbilical artery , portal vein as well as human IMA and SV . Moreover, there are some studies showing protective effects of levosimendan against cardiac ischemia possibly through pharmacological preconditioning .…”

Levosimendan has a prolonged antispasmodic effect in isolated human radial artery bypass grafts and inhibits thrombin-induced aggregation of human platelets in vitro

“…Following pre-incubation with levosimendan, the maximum contractile capacity, endothelial function, and maximum relaxation of the isolated RA segments were comparable to those obtained in physiologic saline (see Table 4 and 5). In this respect, levosimendan seems to be safer than papaverine that impairs endothelial function [29,[61][62][63]68,69]. Furthermore, graft segments stored in heparinized whole blood improved endothelium-dependent relaxation to Ach [27], but these blood-stored RA grafts revealed markedly increased smooth muscle contractions [28].…”