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Progressive troponin I loss impairs cardiac relaxation and causes heart failure in mice

¹Department of Biomedical Science and Center for Molecular Biology and Biotechnology, Florida Atlantic University, Boca Raton, Florida; and ²Department of Physiology, University of Wisconsin School of Medicine, Madison, Wisconsin

Submitted 18 December 2006 ; accepted in final form 23 May 2007

Cardiac troponin I (TnI) knockout mice exhibit a phenotype of sudden death at 17–18 days after birth due to a progressive loss of TnI. The objective of this study was to gain insight into the physiological consequences of TnI depletion and the cause of death in these mice. Cardiac function was monitored serially between 12 and 17 days of age by using high-resolution ultrasonic imaging and Doppler echocardiography. Two-dimensional B-mode and anatomical M-mode imaging and Doppler echocardiography were performed using a high-frequency (20–45 MHz) ultrasound imaging system on homozygous cardiac TnI mutant mice (cTnI^–/–) and wild-type littermates. On day 12, cTnI^–/– mice were indistinguishable from wild-type mice in terms of heart rate, atrial and LV (LV) chamber dimensions, LV posterior wall thickness, and body weight. By days 16 through 17, wild-type mice showed up to a 40% increase in chamber dimensions due to normal growth, whereas cTnI^–/– mice showed increases in atrial dimensions of up to 97% but decreases in ventricular dimensions of up to 70%. Mitral Doppler analysis revealed prolonged isovolumic relaxation time and pronounced inversion of the mitral E/A ratio (early ventricular filling wave-to-late atrial contraction filling wave) only in cTnI^–/– mice indicative of impaired LV relaxation. cTnI^–/– mouse hearts showed clear signs of failure on day 17, characterized by >50% declines in cardiac output, ejection fraction, and fractional shortening. B-mode echocardiography showed a profoundly narrowed tube-like LV and enlarged atria at this time. Our data are consistent with TnI deficiency causing impaired LV relaxation, which leads to diastolic heart failure in this model.

damaged relaxation; echocardiography; Doppler analysis

This article has been cited by other articles:

				J. Du, J. Liu, H.-Z. Feng, M. M. Hossain, N. Gobara, C. Zhang, Y. Li, P.-Y. Jean-Charles, J.-P. Jin, and X.-P. Huang Impaired relaxation is the main manifestation in transgenic mice expressing a restrictive cardiomyopathy mutation, R193H, in cardiac TnI Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2604 - H2613. [Abstract] [Full Text] [PDF]