Early anti-remodeling effect of labetalol in the congestive heart failure model induced by aortic constriction in the guinea pig.
We investigated the effects of the beta1-beta2-alpha1-blocker, labetalol, in the congestive heart failure (CHF) model induced by aortic constriction in the guinea pig. One hundred days after aortic constriction, 52 animals were given either placebo, labetalol 2 mg/kg/d, or labetalol 20 mg/kg/d for 60 days. Eighteen sham-operated animals were used as controls. Investigations were performed at the end of the treatment period. Compared with sham-operated animals, banded animals receiving placebo showed signs of overt CHF with cardiac, systemic and regional (mesenteric and femoral) hemodynamic dysfunction, and pulmonary and hepatic congestion. An increase in whole heart, atria, and left and right ventricle weights associated with left ventricular cavity enlargement and left and right ventricular wall thickening indicated a remodeling process. Compared with placebo, labetalol did not significantly modify cardiac, systemic, or regional hemodynamic variables but significantly decreased pulmonary and hepatic congestion. Labetalol significantly reduced left ventricular cavity area (-10 and -20% after 2 and 20 mg/kg, respectively) and left ventricular (-4 and -16%) and right ventricular (-4 and -19%) wall thickness. In conclusion, labetalol induced partial regression of cardiac remodeling before hemodynamic improvement. This early anti-remodeling effect could play a role in the favorable effects observed with beta1-beta2-alpha1-blockers in humans.
Pape
Danielle
D
Laboratoire de Pharmacologie Expérimentale et Clinique, UPRES EA 3194, Groupe de Recherche Cardio-Vasculaire, Faculté de Médecine, Rennes, France. Danielle.Pape@univ-rennes1.fr
Goineau
Sonia
S
Guillo
Pascal
P
Ramée
Marie-Paule
MP
Bellissant
Eric
E
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D001024:Aortic Valve Stenosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006333:Heart Failure / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D007741:Labetalol / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009929:Organ Size / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D007741:Labetalol