Myocardial stunning occurs when the heart is exposed to transient ischemia followed by reperfusion. Stunning results in reversible systolic and diastolic dysfunction without histological evidence of myocardial necrosis. Pediatric patients with congenital heart disease are often exposed to transient ischemia during operative repair of their cardiac defects and experience resultant post-operative ischemia during operative repair during operative repair of their cardiac defects and experience resultant post-operative myocardial dysfunction. Proteolytic truncation of the carboxy-terminus of troponin I is linked to the stunned phenotype and recent transgenic work has established that expression of truncated troponin I is sufficient to reproduce the pathophysiology of myocardial stunning. Since neonatal heart expresses the slow skeletal isoform of troponin I for the first several months of life, the contribution of this isoform to stunning is relevant to the care of these children in the peri- operative period. To this end, we propose to elucidate how modification of slow skeletal troponin contributes to stunning using transgenesis with assessment of cardiac muscle function in isolated trabeculae and intact heart. This work should a more complete understanding of the impact of stunning in immature heart and potentially suggest rationale and pediatric-specific therapies for post-ischemic dysfunction.
| Soergel, David G; Georgakopoulos, Dimitrios; Stull, Linda B et al. (2004) Augmented systolic response to the calcium sensitizer EMD-57033 in a transgenic model with troponin I truncation. Am J Physiol Heart Circ Physiol 286:H1785-92 |
| Takimoto, Eiki; Soergel, David G; Janssen, Paul M L et al. (2004) Frequency- and afterload-dependent cardiac modulation in vivo by troponin I with constitutively active protein kinase A phosphorylation sites. Circ Res 94:496-504 |
| Kogler, H; Soergel, D G; Murphy, A M et al. (2001) Maintained contractile reserve in a transgenic mouse model of myocardial stunning. Am J Physiol Heart Circ Physiol 280:H2623-30 |
