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Load-sensitive measures may overestimate global systolic function in the presence of left ventricular hypertrophy: a
K A Connelly1, D L Prior, D J Kelly
1Dept. of Medicine, University of Melbourne, St. Vincent's Hospital, Victoria, Australia. connelly@medstv.unimelb.edu.au
Insights
Transgenic rats with left ventricular hypertrophy (LVH) show overestimated systolic function with standard measures. Load-insensitive assessments reveal normal contractility, suggesting adjusted interpretation is needed for LVH models.
Area of Science:
- Cardiovascular Research
- Animal Models
- Physiology
Background:
- Transgenic animal models are crucial for studying cardiovascular disease pathogenesis.
- Assessing cardiac function in small animal models is challenging due to high heart rates and small heart sizes.
- Concentric left ventricular hypertrophy (LVH) can complicate the interpretation of cardiac contractility.
Purpose of the Study:
- To investigate if load-sensitive measures overestimate cardiac function in a rat model of LVH.
- To compare load-sensitive and load-insensitive measures of contractility in transgenic rats with LVH.
- To determine the utility of pressure-volume (P-V) relationships in assessing cardiac function in LVH.
Main Methods:
- Utilized conductance catheter technology for pressure-volume (P-V) loop analysis in (mRen-2)27 transgenic rats and Sprague-Dawley controls.
- Performed echocardiography to assess cardiac structure and function.
- Evaluated load-sensitive (e.g., ejection fraction) and load-insensitive (e.g., preload recruitable stroke work) measures of contractility.
Main Results:
- Transgenic rats exhibited higher blood pressure, body weight, and heart rate compared to controls.
- Load-sensitive systolic function measures were elevated in transgenic rats, suggesting enhanced function.
- Load-insensitive measures of contractility, including preload recruitable stroke work and end-systolic P-V relationship, were not significantly different between groups.
Conclusions:
- Conventional, load-sensitive measures may overestimate systolic function in the presence of LVH.
- Load-insensitive P-V relationships provide a more accurate assessment of cardiac contractility in LVH models.
- Routine use of combined echocardiography and load-insensitive measures is recommended for accurate systolic function assessment in LVH.
Abstract:
Transgenic animal models have provided a vital insight into the pathogenesis of cardiovascular disease, but functional cardiac assessment is often limited by high heart rates and small heart size. We hypothesized that in the presence of concentric left ventricular (LV) hypertrophy (LVH), load-sensitive measures of contractility may be misinterpreted as overestimating global cardiac function, because the normal function of excess sarcomeres may displace a greater volume of blood during contraction. Conductance catheter technology was used to evaluate pressure-volume (P-V) relationships as a load-insensitive method of assessing cardiac function in vivo in 18-wk-old heterozygous (mRen-2)27 transgenic rats (a model of LVH), compared with age-matched Sprague-Dawley (SD) controls. Anesthetized animals underwent echocardiography followed by P-V loop analysis. Blood pressure, body weight, and heart rate were higher in the Ren-2 rats (P < 0.05). Load-sensitive measures of systolic function, including fractional area change, fractional shortening, ejection fraction, and positive peak rate of LV pressure development, were greater in the Ren-2 than control animals (P < 0.05). Load-insensitive measures of systolic function, including the preload recruitable stroke work relationship and the end-systolic P-V relationship, were not different between Ren-2 and SD rats. Regional wall motion assessed by circumferential shortening velocity suggested enhanced circumferential fiber contractility in the Ren-2 rats (P = 0.02), but tissue Doppler imaging, used to assess longitudinal function, was not different between groups. Although conventional measures suggested enhanced systolic function in the Ren-2 rat, load-insensitive measures of contractility were not different between Ren-2 and SD animals. These findings suggest that the normal range of values for load-sensitive indexes of contractility needs to be altered according to the degree of LVH. To accurately identify changes in systolic function, we suggest that a combination of echocardiography with assessment of load-insensitive measures be used routinely.
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