Spectral and color M-mode Doppler in genetically altered mice. Assessment of diastolic function

Doppler indices of transmitral flow are used commonly to assess noninvasively LV diastolic function in man and in large animals. This review examines echocardiographic indices of LV diastole (focusing on color M-mode) in mice with abnormal LV relaxation and hypertrophic cardiomyopathy based on genetic alterations of phospholamban and alpha-tropomyosin, respectively. Phospholamban (PLB) reversibly inhibits the sarcoplasmic reticulum Ca(2+) ATPase and is a crucial regulator of myocardial relaxation; tropomyosin is a contractile protein that plays a critical role in regulating contractile activity vis-à-vis interactions with the actin and troponin complex. Accordingly, diastolic function was assessed in PLB knockout mice (PLB/KO) and age-matched transgenic mice expressing a mutant, superinhibiting form of PLB (PLB/N27A), and in mice with cardiac-specific expression a mutant a-tropomyosin (TM-180). Transmitral Doppler flow indexes suggested impaired diastolic filling in the PLB/N27A mice, but improved LV diastolic function in the PLB/KO mice and TM-180 mutants. However, the propagation velocity of early flow into the LV cavity, measured by color M-mode Doppler, confirmed the expected direction of altered LV relaxation in each mouse model. We conclude that transmitral filling patterns and color M-mode flow propagation velocity reflect changes in myocardial relaxation in genetically engineered mice, and may be useful tools to characterize LV diastolic function in other mouse models of disease.