title: Reversing dobutamine-induced tachycardia using ivabradine increases stroke volume with neutral effect on cardiac energetics in left ventricular post-ischaemia dysfunction.
abstract: Compensatory tachycardia can potentially be deleterious in acute heart failure. In this study, we tested a therapeutic strategy of combined inotropic support (dobutamine) and selective heart rate (HR) reduction through administration of ivabradine.
  
  
  
  In an open-chest pig model (n = 12) with left ventricular (LV) post-ischaemia dysfunction, cardiac function was assessed by LV pressure catheter and sonometric crystals. Coronary flow and blood samples from the coronary sinus were used to measure myocardial oxygen consumption (MVO2 ). LV energetics was assessed by comparing MVO2 with cardiac work at a wide range of workloads.
  
  
  
  In the post-ischaemia heart, dobutamine (5 μg kg(-1)  min(-1) ) increased cardiac output (CO) by increasing HR from 102 ± 21 to 131 ± 16 bpm (beats per min; P < 0.05). Adding ivabradine (0.5 mg kg(-1) ) slowed HR back to 100 ± 9 bpm and increased stroke volume from 30 ± 5 to 36 ± 5 mL (P < 0.05) by prolonging diastolic filling time and increasing end-diastolic dimensions. Adding ivabradine had no adverse effects on CO, mean arterial pressure and cardiac efficiency. Similar findings on efficiency and LV function were also seen using an ex vivo working mouse heart protocol.
  
  
  
  A combined infusion of dobutamine and ivabradine had a neutral effect on post-ischaemia LV efficiency and increased left ventricular output without an increase in HR.
authors.affiliation: Cardiovascular Research Group, Institute of Medical Biology, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsø, Norway. jens.p.bakkehaug@uit.no.
authors.forename: J P
authors.initials: JP
authors.lastname: Bakkehaug
authors.affiliation: Institute of Clinical Medicine, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsø, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Naesheim
authors.affiliation: Cardiovascular Research Group, Institute of Medical Biology, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsø, Norway.
authors.forename: E
authors.initials: E
authors.lastname: Torgersen Engstad
authors.affiliation: Cardiovascular Research Group, Institute of Medical Biology, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsø, Norway.
authors.forename: A B
authors.initials: AB
authors.lastname: Kildal
authors.affiliation: Institute of Clinical Medicine, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsø, Norway.|Department of Cardiothoracic and Vascular Surgery, Heart and Lung Clinic, University Hospital of North Norway, Tromsø, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Myrmel
authors.affiliation: Cardiovascular Research Group, Institute of Medical Biology, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsø, Norway.
authors.forename: O-J
authors.initials: OJ
authors.lastname: How
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004280:Dobutamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D000077550:Ivabradine; D008297:Male; D051379:Mice; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D013318:Stroke Volume / Q000187:drug effects*; D013552:Swine; D013610:Tachycardia / Q000139:chemically induced* / Q000503:physiopathology; D018487:Ventricular Dysfunction, Left / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D001552:Benzazepines; D002316:Cardiotonic Agents; D000077550:Ivabradine; D004280:Dobutamine
keywords: acute heart failure; dobutamine; ivabradine; myocardial oxygen consumption