Hyperhomocysteinaemia-induced atrial remodelling in hypertensive rats

Studies from our laboratory and others indicate that, in addition to its purported atherothrombotic effects, hyperhomocysteinaemia (Hhe) is a powerful stimulus for ventricular remodelling, dysfunction and clinical heart failure. Because changes in atrial structure and function can impact on cardiac function in progressive ventricular remodelling and dysfunction, we conducted experiments to examine structural and functional remodelling of the atria in the hyperhomocysteinaemic hypertensive rat, a previously described model of ventricular diastolic dysfunction. Atrial muscle preparations were isolated from hearts of spontaneously hypertensive rats that were fed control, intermediate Hhe-inducing or severe Hhe-inducing diet for 10 weeks. Atrial developed tension, +dT/dt(max) and -dT/dt(max) were found to increase in parallel with levels of Hhe and ventricular diastolic dysfunction. Post-rest developed tension and the maximum developed tension observed in the presence of isoproterenol were also increased significantly in both Hhe groups compared with control. These results indicate that Hhe increases both basal and maximal contractile function in atrial muscle. Atrial structural remodelling was characterized by increased interstitial fibrosis in both Hhe groups. These data suggest that Hhe-associated changes in atrial structure and function may act to maintain ventricular filling in Hhe-induced diastolic dysfunction.