title: Effect of the calcium sensitizer levosimendan on the performance of ischaemic myocardium in anaesthetised pigs.
abstract: The calcium sensitizer levosimendan (LEV) improves the function of stunned myocardium, cardiac performance in heart failure, and possibly the efficiency of myocardial work. The present experiments investigated the effect of LEV on myocardial contraction and metabolism of acutely ischaemic myocardium distal to a functionally effective coronary artery stenosis. Anaesthetised open chest pigs (n = 14) were instrumented to assess heart rate (HR), aortic pressure (AoP), cardiac output (CO), blood flow in the left descending (QLAD) and circumflex (QLCX) coronary artery, myocardial end-diastolic segment length and systolic shortening (edL, MSS by sonomicrometry) in the LAD- and LCX-territory. Systemic vascular resistance (SVR), and a myocardial power index (PowI) for the LAD- and LCX-region were calculated. Following obstruction of QLAD by an external snare proximal to the first diagonal branch LEV was given intravenously (10 + 20 + 30 microg/kg 15 min apart, n = 8) or the vehicle of LEV (n = 6). Following LEV haemodynamics and regional myocardial performance changed significantly: HR +22 min(-1), AoP -6 mmHg, CO +17%, SVR -21%; intact myocardium: QLCX +15%, RLCX -24%, PowILCX + 39%; ischaemic myocardium: QLAD -7%, MSSLAD -42%, PowILAD -27%. The data confirm the pharmacological profile of LEV: positive chronotropy, positive inotropy, and vasodilatation. The pump function of acutely ischaemic myocardium worsened following LEV. The efficiency of myocardial performance did not improve. A beneficial effect of LEV on the function of ischaemic myocardium was possibly outmanoeuvred by the increase in heart rate.
authors.affiliation: Department of Anaesthesiology, German Heart Centre Munich, Lazarettstr 36, D-80636 München, Germany. tassani@dhm.mhn.de
authors.forename: Peter
authors.initials: P
authors.lastname: Tassani
authors.forename: Hubert
authors.initials: H
authors.lastname: Schad
authors.forename: Werner
authors.initials: W
authors.lastname: Heimisch
authors.forename: Angelika
authors.initials: A
authors.lastname: Bernhard-Abt
authors.forename: Ursula
authors.initials: U
authors.lastname: Ettner
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Mendler
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Lange
mesh_terms: D000758:Anesthesia / Q000379:methods; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D023921:Coronary Stenosis / Q000188:drug therapy / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006835:Hydrazones / Q000494:pharmacology* / Q000627:therapeutic use; D007275:Injections, Intravenous; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage; D011724:Pyridazines / Q000494:pharmacology* / Q000627:therapeutic use; D012039:Regional Blood Flow / Q000187:drug effects; D000077464:Simendan; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014690:Venous Pressure / Q000187:drug effects
chemical_list: D006835:Hydrazones; D014677:Pharmaceutical Vehicles; D011724:Pyridazines; D014665:Vasodilator Agents; D000077464:Simendan