MEASUREMENT OF INTRAVENTRICULAR PRESSURE AND CARDIAC-PERFORMANCE IN THE INTACT CLOSED-CHEST ANESTHETIZED MOUSE

To fully utilize the potential of newly developed mouse models with sp ecific genetic mutations, it is necessary to study the functional cons equences of genetic manipulation in the fully intact animal. To this e nd, the purpose of the present study was to develop and validate a met hodology for the study of myocardial performance in the fully intact, closed-chest mouse. Left ventricular function was evaluated in euthyro id, hypothyroid, and hyperthyroid mice, animals with well-documented a lterations in myocardial function. The mice were anesthetized and inst rumented with polyethylene catheters in the right femoral artery and v ein and with a Millar MIKRO-TIP transducer in the left, ventricle via the right carotid artery. Structural and functional evidence suggested that the instrumentation procedure did not cause myocardial damage, v alvular insufficiency, or aortic obstruction. Isovolumic indexes of my ocardial contractility derived from the left ventricular pressure puls e and its first derivative demonstrated a 40% increase in contractilit y in the hyperthyroid animals and a 40% decrease in contractility in t he hypothyroid animals. Similar differences in the indexes of relaxati on were observed. Furthermore, isoproterenol dose-response relationshi ps of these contractile parameters were blunted in the hypothyroid ani mals and augmented in the hyperthyroid animals compared with euthyroid control animals. Given the small size of the mouse and the high frequ ency of the cardiac cycle, these data demonstrate the feasibilty of co mbining a high-fidelity, microtip manometer with a high-speed data-acq uisition system to obtain faithful recordings of cardiac performance i n the fully intact mouse.