title: Effects of changing heart rate on electrophysiological and hemodynamic function in the dog.
abstract: Cardiovascular parameters were measured in dogs after RR interval was changed from 0.25 s to 1.2 s with atropine and graded doses of zatebradine, an I(f)-channel blocker. Left ventricular (LV) pre-ejection period (PEP), systemic vascular resistance, tau (an estimate of myocardial stiffness), PQ, QTc, dLVP/dt(max) and dLVP/dt(min), aortic pressure, and right atrial pressure did not change when each parameter was plotted against RR interval (r(2)'s < or = 0.5). LV end-diastolic pressure, stroke volume index, LV ejection time (ET), and QT all increased either linearly or curvilinearly as RR interval prolonged. Cardiac output index and PEP/ET decreased curvilinearly. When heart rate (HR) was fixed by pacing, and graded doses of zatebradine were given, changes in cardiovascular function were minimal. Thus zatebradine affects cardiovascular function principally by changing HR and not by affecting function directly. This study provides data on the effects of changing HR, alone, on cardiovascular parameters measured frequently during pharmacological and toxicological studies. It should prove useful when physiological variables, including HR, change, and there is need to know what change in HR, alone, contributes.
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, 1900 Coffey Road, Columbus 43212-1092, USA. hamlin.1@osu.edu
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hamlin
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakayama
authors.forename: Hitomi
authors.initials: H
authors.lastname: Nakayama
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Carnes
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D002304:Cardiac Pacing, Artificial; D002316:Cardiotonic Agents / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D004594:Electrophysiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D001552:Benzazepines; D002316:Cardiotonic Agents; D018727:Muscarinic Antagonists; D001285:Atropine; C043636:zatebradine