Developmental changes in the geometry, function and responsiveness of the mouse heart to beta-adrenergic stimulation...

1. The mouse is the preferred species for gene targeting as a tool for research into the heart and heart development. The developmental features of the geometry and function of the heart in young mice are not well defined and cardiac functional responses following stimulation of beta-adrenoceptors have not been investigated. 2. Using the VisualSonic (Toronto, ON, Canada) high-resolution ultrasound system, we investigated male C57BL/6 mice at 0.5-18 weeks of age. Echocardiography was performed at baseline and repeated after administration of the beta-adrenoceptor agonist isoproterenol (4 microg/kg). 3. The geometry of the left ventricle became mature 2 weeks after birth. A significant decline in left ventricular contractile function occurred at 2-3 weeks of age. 4. Inotropic and chronotropic responses to isoproterenol were significantly weaker in mice at a weaning age < 2 weeks compared with adult mice (heart rate increment 3 +/- 3% vs 32 +/- 4%, respectively; fractional shortening increment 19 +/- 5% vs 78 +/- 8%, respectively; P < 0.001). 5. In conclusion, significant changes occur in mice from birth until weaning with respect to the topography, function and beta-adrenoceptor responsiveness of the heart. The results of the present study provide a reference point for future studies in genotyping cardiac function during the postnatal phase in genetically engineered mice.