SELECTIVE INDUCTION OF THE CREATINE KINASE-B GENE IN CHRONIC VOLUME OVERLOAD HYPERTROPHY IS NOT AFFECTED BY ACE-INHIBITOR THERAPY

Hypertrophied and failing myocardium has been shown to undergo creatin e kinase. (CK) isoform switching, resulting in increased MB and BB com ponents, We tested the hypothesis that chronic volume overload hypertr ophy due to mitral regurgitation in the dog causes CK isoenzyme switch ing and that this could be reversed by angiotensin converting enzyme i nhibitor therapy. Thirteen adult mongrel dogs had mitral regurgitation induced by mitral valvular chordal rupture: six were treated with ram ipril for 4 months and seven were untreated for 4 months. Twelve dogs were sham-operated: six received ramipril for 3 months and six were un treated. Left ventricular end-diastolic volume increased from 58 +/- 4 to 104 +/- 10 ml in untreated (P<0.001) and from 55 +/- 3 to 91 +/- 6 ml in treated dogs (P<0.01) as LV mass/volume ratio decreased in both untreated (1.60 +/- 0.07 to 1.13 +/- 0.08 g/ml, P<0.001) and treated dogs (1.44 +/- 0.06 to 1.20 +/- 0.08 g/ml, P<0.01). CK-MB isoform was 7.4 +/- 1.1% in normal shams and increased to 13.5 +/- 1.9% and 18.1 /- 3.0% in both treated and untreated mitral regurgitation dogs; respe ctively (P<0.05). Steady state CK-B mRNA increased three fold in treat ed and untreated dogs with mitral regurgitation (P<0.003) compared to normals, while CK-M mRNA expression did not differ in all groups. Thus , chronic volume overload hypertrophy of mitral regurgitation induces CK isoform switching by selective induction of the CK-B gene, and rami pril therapy does not affect this isoform switch. This may reflect a r esponse to increased diastolic stress and more efficient energy utiliz ation in the volume overloaded myocardium. (C) 1997 Academic Press Lim ited.