Hypoxic right ventricular cardiomyopathy. A morphological and pathogenetic study on the myocardial atrophy and fatty...

The autopsy report of an asymptomatic, non familial cardiomyopathy with widespread fatty infiltration of the right ventricular wall in two alcoholic subjects, who were also heavy smokers and suffering from a serious laryngeal obstruction, led the Authors to investigate, on the basis of a thorough review of the literature, the possibility that hypoxia, alcoholism and smoke could have caused the development of the cardiac lesion. The presence of myocardial fatty infiltration is explained, under conditions of high-flow hypoxia, by the reduced fatty acid oxidation. The higher tissue levels of fatty acyl-CoA, fatty acyl-carnitine and alpha-glycerophosphate thereby lead to the increased conversion of the FFA into tissue lipids. Under hypoxic conditions there is also an increased polyols synthesis. The reduced conversion of dyacylglycerol into phosphatidic acid causes its tissutal increase and the interaction with fatty acyl-CoA to produce triacylglycerol and CoASH. In alcoholic patients reduced oxidation and increased FFA synthesis is sustained by the altered mitochondrial respiratory control and excess of acetate, with the consequent increase in acetyl-CoA, fatty acyl-CoA and alpha-glycerophosphate concentration. In addition, fatty acid ethyl esters normally absent in the myocardium are formed. The fact that, in hypoxic or alcoholic subjects with cardiomyopathy, an impaired myocardial contractility has been noted as the most relevant haemodynamic factor may be explained by both the reduced energy production following the decrease in aerobic glycolysis and FFA oxidation, and specific genetic changes that lead to both the production of a myosin with lower Ca2 + ATPase activity and a reduced protein (and therefore myofibrillar) synthesis. This fact can result in a severe atrophy of the cardiac myocytes. The lower their contractile activity, the more evident the process of atrophy. The lesion principally affects the right ventricle for both metabolic and anatomical reasons. It has been shown how, under normal conditions, the RV metabolism is suited to a relatively reduced O2 supply situation, with a high lactate dehydrogenase and alpha-hydroxybutiratedehydrogenase activity. It is more likely to be affected therefore whenever there is a chronic state of high-flow hypoxia. While alpha-HBDH allows the RV extensive utilization of ketone bodies as an energy source, its notable increase under hypoxic conditions further increases the synthesis of fatty acids and therefore fatty infiltration of the myocardium. The relatively lower capacity for oxygen extraction and lower tissue perfusion of the RV compared with the left ventricle make an adequate oxygen supply in the case of increased O2 demand even more difficult.(ABSTRACT TRUNCATED AT 400 WORDS)