Serial Noninvasive Assessment of Apoptosis During Right Ventricular Disease Progression in Rats

Journal of Nuclear Medicine

Hein J. Verberne¹  Jan M. Ruijter¹  Berthe L.F. van Eck-Smit¹  Maurice J.B. van den Hoff¹  Jacques M.T. de Bakker¹  Kora de Bruin¹  Mariana Selwaness¹  Maxim Hardziyenka¹  Hanno L. Tan¹  Maria E. Campian¹ 

关键词: right ventricle;    heart failure;    hypertrophy;    apoptosis;    fibrosis;    annexin;   

DOI  :  10.2967/jnumed.108.061366

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Right ventricular (RV) function is the major determinant of survival in patients with pulmonary hypertension. Yet, the pathophysiologic basis of RV disease is unresolved. We aimed to study the role of apoptosis in RV disease by monitoring it serially during disease progression using in vivo 99mTc-annexin-V (99mTc-annexin) scintigraphy and study whether the reduction in apoptosis resulting from chronic treatment with valsartan can be detected by 99mTc-annexin scintigraphy. Methods: RV disease after pulmonary hypertension was induced by monocrotaline injection in rats. The following 3 groups were studied: rats treated with monocrotaline (monocrotaline rats), rats treated with monocrotaline plus valsartan (valsartan rats), and age-matched controls (control rats). Serial echocardiography and in vivo 99mTc-annexin scintigraphy were performed. Apoptosis was confirmed by 99mTc-annexin autoradiography and terminal deoxynucleotidyl-transferase–mediated dUTP nick-end labeling. Fibrosis was assessed by picrosirius red staining. Results: In monocrotaline rats, in vivo 99mTc-annexin uptake peaked early and declined thereafter but remained elevated, compared with baseline. These stage-dependent changes of in vivo 99mTc-annexin uptake were paralleled by changes in autoradiography and terminal deoxynucleotidyl-transferase–mediated dUTP nick-end labeling. Valsartan rats had longer RV failure–free survival than did monocrotaline rats and had reduced apoptosis. These changes were accompanied by commensurate delays in RV hypertrophy and RV dilation. Valsartan rats also had less fibrosis than monocrotaline rats at all disease stages. Conclusion: RV disease progression is associated with an early increase in RV apoptosis, as monitored using serial in vivo 99mTc-annexin scintigraphy. Delay in RV disease progression by valsartan is accompanied by reduction in RV apoptosis. Apoptosis plays a role in RV disease progression and may be assessed by serial in vivo 99mTc-annexin scintigraphy.

【 授权许可】

Unknown