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

Abstract

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 10 ml/min/g heart wt., baseline perfusate Ca 2+ was 1.0 mmol/l. Functional parameters including systolic and diastolic pressure (P sys , P dias , mmHg), maximal + dP/dt/DevP (sec -1 ) and (calculated) peak systolic circumferential wall stress (σ sys , kdyn/m 2 ) were measured at 50% of the intracardiac balloon volume at which maximal developed pressure (DevP) occurred. EC 50 (μmol/l) of the force Ca 2+ relationship and maximum Ca 2+ activated force (σ sysmx , kdyn/cm 2 ) were assessed by stepwise increase of Ca 2+ in the perfusate and plotting σ sys vs. intracellular peak systolic Ca 2+ measured by the aequorin bio-Iuminescence method. Results at baseline and Ca 2+ response were as follows: P sys σ sys +dP/dt/DevP EC 50 σ sysmx Control 139 ± 5 # 68 ± 5 15.4 ± 0.1 0.67 ± 001 78 ± 5 IGF-1 169 ± 6 # * 68 ± 2 17.7 ± 0.2 # * 0.73 ± 0.02 * 103 ± 4 * GH 162 ± 5 # * 67 ± 3 16.5 ± 0.2 * 0.74 ± 0.01 * 107 ± 4 * G + I 153 ± 4 * 69 ± 3 156 ± 0.3 0.72 ± 0.02 * 106 ± 2 * Data are mean ± SEM: * p < 0.05 vs. control. # vs. G + I P dias , Ca sys , Ca dias , shape and duration of the Ca 2+ 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 P sys , suggesting a concenlric growth pattern. In addition to the increased P sys enhanced systolic performance was demonstrated by an increased σ sysmx , although this effect is not seen on σ sys at baseline due to an increased EC 50 . These data support the hypothesis, that both IGF-l and GH have a direct effect on cardiac performance by influencing geometry and maximum Ca 2+ activated force capacity.