Anamourlis, Prodromos Christopher2009-04-172009-04-172009-04-17http://hdl.handle.net/10539/6894ABSTRACT In pathological left ventricular hypertrophy (LVH) with a normal intrinsic myocardial function, eccentric chamber remodelling (cardiac dilatation) can produce a right shift in systolic pressure-volume (P-V) relations (systolic chamber dysfunction). Whether comparable degrees of cardiac dilatation in physiological (exercise-induced eccentric left ventricular remodelling) and pathological LVH produce similar effects on chamber function has not been determined. Hence, the aim of my thesis was to determine the impact of cardiac dilatation on systolic chamber function in chronically exercised rats with comparable increases in cardiac diastolic volumes as those produced by two rat models of pathological dilatation. Methods: Two models of cardiac dilatation were used, namely: (1) a model of pathological cardiac hypertrophy and dilatation (induced by chronic β-adrenoreceptor agonist administration to either Sprague-Dawley or spontaneously hypertensive rats), and (2) a model of physiological cardiac hypertrophy and dilatation (induced in Sprague-Dawley rats by 4-5 months of voluntary running activity on exercise wheels). 33 Sprague-Dawley rats were placed on spontaneous running wheels for 4-5 months (Exer group) and 24 Sprague-Dawley sedentary control rats (Con group) were placed individually in normal rat cages. To induced pathological dilatation, the β-agonist, isoproterenol (ISO) was administered daily to Sprague-Dawley rats for 7 months (SD-ISO, n=10) and to spontaneously hypertensive rats (SHR) for 4-5 months (SHR+ISO, n=22). Saline was administered daily to controls (SD, n=10; SHR, n=21) and to normotensive Wistar Kyoto rats (WKY, n=17). In isolated, perfused heart preparations, left ventricular (LV) dilatation was determined from the diastolic pressure-volume (P-V) relation and the volume intercept of the diastolic P-V relation (LV V0). Systolic chamber function was assessed by comparing LV developed pressures at specific filling volumes. Intrinsic systolic myocardial function was determined from the slope of the LV systolic developed stress-strain relation (myocardial systolic elastance). Results: ISO adminstered to SD and to SHR rats produced cardiac dilatation [LV V0 (ml): SD 0.20±0.01, SD-ISO 0.27±0.02, p<0.005; SHR 0.21±0.01, SHR-ISO 0.30±0.01, p<0.001], systolic chamber dysfunction (decrease in left ventricular developed pressures at incremental filling volumes) but normal intrinsic systolic myocardial function. Habitual exercise resulted in a right shifted LV diastolic P-V relation and an increased LV V0 (Exer 0.22±0.01, Con 0.18±0.01, p<0.005). In exercised rats (Exer-dilated, n=10) with equivalent dilatation as SD-ISO and SHR-ISO (LV V0 within 95% CI of SD-ISO and SHR-ISO), despite comparable LV diastolic P-V relations and LV V0 values (0.28±0.01); both systolic chamber function and intrinsic systolic myocardial function were normal. Conclusions: These data provide evidence to indicate that as compared to pathological dilatation, a similar extent of exercise-induced dilatation does not produce the same adverse effects on systolic chamber function.enratscardiologyexercisepathological cardiac dilationThesis