Heart function challenged with beta-receptor agonism or antagonism in a heart failure model.
We have shown that chronic treatment with carteolol, a non-selective beta-adrenergic receptor antagonist, improved left ventricular (LV) function and survival in an avian model of dilated cardiomyopathy (DCM). The aim of the present study was to compare ex vivo heart function with and without beta-agonist and antagonist challenge. We investigated whether intracoronary infusion of a beta-blocker, carteolol or beta-agonist, isoproterenol decreased contractility. In the DCM group, isoproterenol resulted in a significantly greater increase in heart rate (71% vs. 28% compared to control hearts). To investigate the mechanism for the increase in heart rate, we exposed spontaneously beating neonatal cardiomyocytes to serum immunoglobulin (IgG) isolated from DCM animals. Serum IgG resulted in a significant increase in spontaneous beating rate in neonatal rat cardiomyocytes that was blocked by pre-treatment with a beta-blocker. Carteolol challenge did not significantly change heart rate but did significantly increase LV peak pressure in DCM hearts (62%) while coronary artery flow remained unchanged (2.7+/-0.1 vs 2.7+/-0.5 ml/min/g). These results show that 1) beta-receptor stimulation results in a greater tachycardic response in DCM animals, and 2) carteolol challenge improves myocardial contractility in hearts from DCM animals independent of heart rate or changes in coronary artery flow.
Washington
B
B
Department of Biological Sciences, Tennessee State University, Nashville 37209, USA. BWashington@picard.tnstate.edu
Butler
K
K
Doye
A A
AA
Jang
M
M
Hajjar
R J
RJ
Gwathmey
J K
JK
D000318:Adrenergic beta-Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy / Q000503:physiopathology; D002354:Carteolol / Q000494:pharmacology / Q000627:therapeutic use; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D007074:Immunoglobulin G / Q000378:metabolism / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology / Q000627:therapeutic use; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D051381:Rats; D014422:Turkeys; D016277:Ventricular Function, Left / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D007074:Immunoglobulin G; D002354:Carteolol; D007545:Isoproterenol