Functional Analysis of Myocardial Performance in Murine Hearts Overexpressing the Humanβ2-Adrenergic Receptor,

Transgenic mice overexpressing the humanβ2-adrenergic receptor gene were compared with wild mice type in terms of cardiac function, using a modified work-performing isolated murine heart preparation and on-line computer analysis. A preload-dependent experiment was performed, in which venous return was gradually increased in 5 mmHg increments from 5 mmHg to 25 mmHg. At each preload, aortic flow, left atrial pressure and aortic pressure were measured in all hearts, and from these parameters stroke volume, contractility, and cardiac index (cardiac output divided by body weight in g) were calculated and compared between groups. At increasing preload levels, the heart rates ranged from 322 beats/min (±29) to 369 beats/min (±39) in control mice and from 469 beats/min (±36) to 540 beats/min (±39) in transgenic mice. Cardiac index increased from 138μl/min/g (±13) and 48μl/min/g (±5) for transgenic and control mice, respectively at 5 mmHg preload to 262μl/min/g (±51) and 167μl/min/g (±15), respectively at 20 mmHg preload. The contractility in the transgenic mice were significantly increased at lower preload levels compared to control mice (1420 mmHg/s ±204v1187 mmHg/s ±127). An increase in myocardial adrenergic receptor density (100–200 fold) leads to significantly higher indices of cardiac function in transgenic mice compared to control mice. The increased heart rate leading to a positive inotropic effect in the hearts of transgenic mice is, at least in part, due to the overexpression of adrenergic receptors. These findings suggest a possible alternative method of establishing a positive chronotropic and inotropic state without the use of pharmacological agents.