title: Altered LV inotropic reserve and mechanoenergetics early in the development of heart failure.
abstract: To test the hypothesis that alterations in left ventricular (LV) mechanoenergetics and the LV inotropic response to afterload manifest early in the evolution of heart failure, we examined six anesthetized dogs instrumented with LV micromanometers, piezoelectric crystals, and coronary sinus catheters before and after 24 h of rapid ventricular pacing (RVP). After autonomic blockade, the end-systolic pressure-volume relation (ESPVR), myocardial O(2) consumption (MVO(2)), and LV pressure-volume area (PVA) were defined at several different afterloads produced by graded infusions of phenylephrine. Short-term RVP resulted in reduced preload with proportionate reductions in stroke work and the maximum first derivative of LV pressure but with no significant reduction in baseline LV contractile state. In response to increased afterload, the baseline ESPVR shifted to the left with maintained end-systolic elastance (E(es)). In contrast, after short-term RVP, in response to comparable increases in afterload, the ESPVR displayed reduced E(es) (P < 0.05) and significantly less leftward shift compared with control (P < 0.05). Compared with the control MVO(2)-PVA relation, short-term RVP significantly increased the MVO(2) intercept (P < 0.05) with no change in slope. These results indicate that short-term RVP produces attenuation of afterload-induced enhancement of LV performance and increases energy consumption for nonmechanical processes with maintenance of contractile efficiency, suggesting that early in the development of tachycardia heart failure, there is blunting of length-dependent activation and increased O(2) requirements for excitation-contraction coupling, basal metabolism, or both. Rather than being adaptive mechanisms, these abnormalities may be primary defects involved in the progression of the heart failure phenotype.
authors.affiliation: Department of Medicine, University of Texas Health Science Center at San Antonio, and South Texas Veterans Health Care System-Audie Murphy Division, San Antonio, Texas 78284, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Prabhu
authors.forename: G L
authors.initials: GL
authors.lastname: Freeman
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001794:Blood Pressure; D002303:Cardiac Output, Low / Q000503:physiopathology*; D002304:Cardiac Pacing, Artificial; D002316:Cardiotonic Agents; D004285:Dogs; D004734:Energy Metabolism; D005260:Female; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption; D010656:Phenylephrine / Q000008:administration & dosage; D013599:Systole; D016277:Ventricular Function, Left
chemical_list: D002316:Cardiotonic Agents; D010656:Phenylephrine