EFFECT OF TREPPE ON ISOVOLUMIC FUNCTION IN THE ISOLATED BLOOD-PERFUSED MOUSE HEART

The effects of treppe on left ventricular function in the isolated mou se heart perfused with physiological buffer or with erythrocyte-rich b uffer were compared. Left ventricular systolic and diastolic pressures were measured in the isovolumically contracting (balloon in the left ventricle) mouse hearts. Hearts were isolated from 12 adult Swiss-Webs ter mice and perfused at constant pressure (approximately 85 mmHg) via the aorta. Perfusate consisted of non-recirculating oxygenated Krebs- Henseleit (KH) solution without or with washed cow red blood cells at a hematocrit of 20% (KH-RBC(20)). The measured ionized calcium concent ration of the perfusates were adjusted to 2.2 mmol/l and the temperatu re held constant at 37 degrees C. Left ventricular systolic pressure, its derivative and diastolic pressures were recorded via a pressure tr ansducer attached to a small latex balloon which was placed in the lef t ventricle through a left atrial incision. The balloon volume was adj usted to achieve an end-diastolic pressure of 4-8 mmHg. Left ventricul ar (LV) developed pressure averaged 111+/-4 (mean+/-S.E.M.) with KH al one and 108+/-4 mmHg with KH-RBC(20) while the coronary flows were 3.1 +/-0.18 and 0.95+/-0.15 ml/min, respectively. In both KH solution alon e and KH-RBC(20), developed pressure remained relatively stable from 3 to 5 Hz while +/-dP/dt increased approximately 10% above values obser ved at 3 Hz. During KH perfusion with increasing stimulation rates, le ft ventricular pressure and +/-dP/dt, to a lesser extent, decreased wh ile end-diastolic pressure markedly increased at stimulation rates hig her than 5 Hz. However, KH-RBC(20) perfusion prevented the marked incr ease in diastolic pressure with increasing stimulation rates (from 5 t o 10 Hz). No significant difference in left ventricular developed pres sure or +/-dP/dt response to treppe were in evidence between groups. T hese results demonstrate that diastolic function of the isovolumically contracting mouse heart is sensitive to treppe and different techniqu es of perfusion. Buffer perfusion alone may limit accurate measurement of left ventricular diastolic properties and exacerbate changes in di astolic function, particularly under conditions of increased oxygen de mand. The erythrocyte perfused mouse heart provides an in vitro model for determining cardiac function which is physiologically superior to buffer perfusion, and may be useful to investigators to assess gene in fluence on left ventricular function in genetically altered mice. (C) 1996 Academic Press Limited