ABSTRACT
BACKGROUND: Chronic pulmonary regurgitation often leads to myocardial dysfunction and heart failure. It is not fully known why secondary hypertrophy cannot fully protect against the increase in wall stress brought about by the increased end-diastolic volume in ventricular dilation. It has been assumed that mural architecture is not deranged in this situation, but we hypothesised that there might be a change in the pattern of orientation of the aggregations of cardiomyocytes, which would contribute to contractile impairment. METHODS: We created pulmonary valvular regurgitation by open chest, surgical suturing of its leaflets in seven piglets, performing sham operations in seven control animals. Using cardiovascular magnetic resonance imaging after 12 weeks of recovery, we demonstrated significantly increased right ventricular volumes in the test group. After sacrifice, diffusion tensor imaging of their hearts permitted measurement of the orientation of the cardiomyocytes. RESULTS: The helical angles in the right ventricle approached a more circumferential orientation in the setting of right ventricular RV dilation (p = 0.007), with an increased proportion of surface-parallel cardiomyocytes. In contrast, this proportion decreased in the left ventricle. Also in the left ventricle a higher proportion of E3 angles with a value around zero was found, and conversely a lower proportion of angles was found with a numerical higher value. In the dilated right ventricle the proportion of E3 angles around -90° is increased, while the proportion around 90° is decreased. CONCLUSION: Contrary to traditional views, there is a change in the orientation of both the left ventricular and right ventricular cardiomyocytes subsequent to right ventricular dilation. This will change their direction of contraction and hinder the achievement of normalisation of cardiomyocytic strain, affecting overall contractility. We suggest that the aetiology of the cardiac failure induced by right vetricular dilation may be partly explained by morphological changes in the myocardium itself.
Subject(s)
Hypertrophy, Right Ventricular/physiopathology , Myocytes, Cardiac/pathology , Ventricular Function, Left , Ventricular Function, Right , Ventricular Remodeling , Animals , Diffusion Tensor Imaging , Disease Models, Animal , Female , Hypertrophy, Right Ventricular/diagnostic imaging , Hypertrophy, Right Ventricular/etiology , Hypertrophy, Right Ventricular/pathology , Magnetic Resonance Imaging , Myocardial Contraction , Pulmonary Valve Insufficiency/complications , Pulmonary Valve Insufficiency/physiopathology , Sus scrofa , Time FactorsABSTRACT
BACKGROUND: Persistent pulmonary hypertension in the newborn remains a syndrome with high mortality. Knowledge of changes in myocardial architecture in the setting of heart failure in persistent pulmonary hypertension is lacking, and could aid in the explanation of the prevailing high mortality. METHODS: Persistent pulmonary hypertension was induced by antenatal ligation of the arterial duct in six ovine fetuses. The hearts were compared ex vivo with five matched control hearts, using diffusion tensor imaging to provide the overall anatomical arrangement, and assessment of the angulations and course of the cardiomyocytes. Fibrosis was assessed with histology. RESULTS: We found an overall increase in heart size in pulmonary hypertension, with myocardial thickening confined to the interventricular septum. An increase of 3.5° in angulation of myocyte aggregations was found in hypertensive hearts. In addition, we observed a 2.2% increase in collagen content in the right ventricular free wall. Finally, we found a previously undescribed subepicardial layer of strictly longitudinally oriented cardiomyocytes confined to the right ventricle in all hearts. CONCLUSION: Myocardial fibrosis and possibly changes in angulations of myocytes seem to play a part in the etiology of persistent pulmonary hypertension. Moreover, a new anatomical arrangement of right ventricular mural architecture is described.
