1030-9 An Acute Increase in Hemodynamic Load Produces Plasma Membrane Wounding of Cardiac Myocytes In Vivo

Myocyte-derived basic fibroblast growth factor (bFGF) has been proposed as one of several autocrinelparacrine growth factors that mediate the hypertrophic response to increased cardiac load. However, a linkage between a hemodynamic stimulus and bFGF release has not yet been reported. Since reversible plasma membrane disruption- wounding has been demonstrated to be a possible release mechanism for bFGF in skeletal muscle, we tested the hypothesis that membrane wounding can be detected in cardiac myocytes in response to a pressure overload. In an acute rat model of aortic banding plasma membrane wounding was analyzed by measuring the uptake of extracellular albumin into the myocyte cytosol. Baseline systolic and mean aortic pressures in the banded rats increased immediately from 142±6 to 219±10mmHg, and from 118±6 to 152±4mmHg, respectively (n=5, p<0.001 vs baseline). In separate experiments, analysis of hemodynamics after banding showed a significant rise in left ventricular end-diastolic pressure in banded rats compared to sham-operated rats (14.2±1.5mmHg vs 2.8±1.1mmHg, n=4, P<0.05). One hour after banding the hearts were perfused in situ with phosphate buffered saline, followed by formalin fixation. Frozen sections were immunostained with a polyclonal antibody specific for rat serum albumin, the wound event marker. Digital image analysis revealed an excess of wounded cardiac myocytes in the pressure overloaded hearts (45.6±7.01% vs 7.9±2.5%, n=5, p<0.01). A trend toward a thinner left ventricular wall (0.16±0.02 vs 0.19±0.02cm, n=3 for each group) in the banded rats paralleled the increase in left ventricular volume, perhaps due to profound myocyte slippage in the banded animals. These data show that membrane disruptions occur in ventricular myocytes in vivo in response to an acute increase in hemodynamic load and may provide a route for bFGF release from ventricular myocytes