Relation between ventricular and myocyte remodeling with the development and regression of supraventricular tachycardia-induced cardiomyopathy

Abstract

Chronic supraventricular tachycardia (SVT) causes left ventricular (LV) dilatation and dysfunction. Termination of SVT appears to reduce LV size and improve function. However, changes in myocyte structure and morphology that accompany the development and regression of SVT-induced cardiomyopathy have not been studied. Accordingly, we measured LV function using echocardiography and catheterization in three groups of six pigs each: 3 weeks of atrial pacing (SVT; 240 beats/min), 4-week recovery from SVT (PST), and sham-operated controls. At each of these three end points, isolated myocyte dimensions and nuclear number were measured using fluorescence, and the volume percent of myocytes and myofibrils was computed from tissue sections using stereological techniques. SVT resulted in reduced LV fractional shortening (15±3% versus 31±2%, p<0.05), increased end-diastolic dimension (5.6±0.8 versus 3.8±0.2 cm, p<0.05), and no change in mass (2.6±0.1 versus 2.6±0.2 g/kg, p=NS) compared with controls. Myocyte length significantly increased with SVT (171±9 versus 109±11 μm, p<0.05), without significant changes in cell width (28±2 versus 26±2 μm). Nuclear number did not change with SVT; however, nuclear area/myocyte area significantly increased compared with controls (9.5±0.8 versus 8.7±0.8X10-2, p<0.05). The volume percent of myocytes within the ventricular wall and the volume percent of myofibrils within myocytes decreased with SVT compared with controls (72±3% versus 80±3% and 45±5% versus 63±4%, respectively, p<0.05), with no change in total myocyte volume (54.2±2.7 versus 54.3±1.8 μm3X1012). In the PST group, LV fractional shortening returned to control values; however, there was persistent dilatation (end-diastolic dimension: 4.2±0.1 cm, p<0.05), and LV hypertrophy developed (3.3±0.3 g/kg, p<0.05). Increased myocyte length (158±5 μm, p<0.05) and width (33±2 μm, p<0.05) were observed in the PST group. The volume percent of myocytes and myofibrils returned to control values, with total myocyte volume significantly increased in the PST group compared with the control and SVT groups (74.5±2.6 μm3X1012, p<0.05). In addition, the number of nuclei per myocyte in the PST group significantly increased from control values (5.1±0.1 versus 4.0±0.1, p<0.05). In summary, significant myocyte remodeling occurred concomitant with changes in LV morphology and function. Despite significant LV dilatation and increased myocyte size with chronic SVT, a reduction in total myocyte volume and myofibril content resulted in no LV hypertrophy. Recovery from SVT-induced cardiomyopathy resulted in LV and myocyte hypertrophy and nuclear hyperplasia.