Dysfunction of the myocardium related to chronic insufficiency of nigro-striatal dopamine in rats and correction of these disturbances with melatonin

We studied the dependence of the maximum and final diastolic pressures in the left ventricle on the level of tension of the myocardium (the latter parameter was measured using a dosed increase in the volume of a polyethylene cartridge inserted into the cardiac ventricle) on isolated hearts of control rats and animals with chronic nigro-striatal (NS) dopamine (DA) insufficiency induced by unilateral injection of a selective neurotoxin, 6-hydroxydopamine, into the brain (model of hemiparkinsonism). In addition, we calculated the diastolic rigidity of the myocardium (the ratio between the increment of the final diastolic pressure and the enhancement of the volume of the cartridge in the left ventricle). We found that, under conditions of insufficiency of cerebral DA, the reactivity of the myocardium with respect to an increase in the volume loading, i.e., the ability of the cardiac muscle to intensify the contraction force upon expansion of the ventricle, is disturbed. The plateau of the Frank-Starling curve in rats with DA insufficiency was significantly smaller than that observed in control animals, and the rigidity of the myocardium increased. Therefore, we demonstrated that the state of the cardiac muscle becomes worse in rats with chronic NS DA insufficiency. A single injection of a powerful antioxidant and inhibitor of opening of the mitochondrial pore, melatonin, into animals with the model of hemiparkinsonism (1 h prior to the experiment) restored significantly the disturbed contractile function of the heart.