Lusitrophic effects of dobutamine in young and aged mice in vivo

Abstract

Aged individuals have impaired diastolic relaxation-lusitropic function. Dobutamine, a selective B1-adrenergic agonist, is used to augment systolic cardiac function at the termination of cardiopulmonary bypass (CPB). However, our question is whether dobutamine will also enhance the lusitropic function in the aged individual. The myocyte mechanism for the rate of ventricular relaxation is dependent on the velocity of calcium removal from the myocyte contractile elements by sarcoplasmic reticulum (SR) Ca 2+-ATPase (SERCA2a), which is regulated by an inhibitory protein, phospholamban (PLB). Ventricular tissues harvested from young (4 month) and aged (20 months) mice were analyzed to compare the protein levels of SERCA2a and PLB with immunoblot and gene expression for PLB with reverse-transcriptase- polymerase chain reaction. The molecular analyses were compared with in vivo left ventricular function in the young and old mice before and during an intravenous infusion of dobutamine (5 μg/kg/min). The SERCA2a levels were not different between the groups; however, there was a 2-fold increase in PLB in the aged group compared with the young group (p < .05). The gene expression for PLB was increased by 5-fold in the aged group compared with the young group (p