770-1 Exogenously Administered Growth Hormone and IGF-1 Alter Intracellular Calcium Handling and Enhance Cardiac Performance

To further elucidate the mechanisms by which growth hormone (GH) and IGF-l modulate cardiac function, we studied isolated, isovolumic, bufferperfused rat hearts after 4 weeks of treatment with high doses of GH, IGF-l or combination of both (G+I). Flow rate was 10ml/min/g heart wt., baseline perfusate Ca2+ was 1.0mmol/l. Functional parameters including systolic and diastolic pressure (Psys, Pdias,mmHg), maximal+dP/dt/DevP (sec-1) and (calculated) peak systolic circumferential wall stress (σsys, kdyn/m2) were measured at 50% of the intracardiac balloon volume at which maximal developed pressure (DevP) occurred. EC50 (μmol/l) of the force Ca2+ relationship and maximum Ca2+ activated force (σsysmx, kdyn/cm2) were assessed by stepwise increase of Ca2+ in the perfusate and plotting σsys vs. intracellular peak systolic Ca2+ measured by the aequorin bio-Iuminescence method. Results at baseline and Ca2+ response were as follows:Psysσsys+dP/dt/DevPEC50σsysmxControl139±5#68±515.4±0.10.67±00178±5IGF-1169±6#*68±217.7±0.2#*0.73±0.02*103±4*GH162±5#*67±316.5±0.2*0.74±0.01*107±4*G+I153±4*69±3156±0.30.72±0.02*106±2*Data are mean±SEM:*p<0.05 vs. control.#vs. G+IPdias, Casys, Cadias, shape and duration of the Ca2+ transient were not influenced by the treatments. All treatmenls caused a similar increase of heart wt. although the heart wt. to body wt. ratio remained unchanged. asys was unchanged by the treatments despite increasing Psys, suggesting a concenlric growth pattern. In addition to the increased Psys enhanced systolic performance was demonstrated by an increased σsysmx, although this effect is not seen on σsys at baseline due to an increased EC50.These data support the hypothesis, that both IGF-l and GH have a direct effect on cardiac performance by influencing geometry and maximum Ca2+ activated force capacity