Analysis Tools
cardiovascular system
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• hearts show areas of peripheral fibrosis in myocardia in 1-year-old mice
• however, sedentary mice exhibit otherwise normal heart morphology, and normal left ventricle mass-to-body weight ratio, left ventricle mass-to-tibia length ratio, left ventricle wall thickness, ejection fraction, fractional shortening, and myocardial structural organization including sarcomeric organization at 1 year of age
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• left ventricle cardiomyocytes from 1-year-old mice exhibit increased contractile magnitude measured as a change in cell shortening and increased contraction velocities
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• electrocardiography in 1-year-old female mice shows faster heart rates
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• 1-year-old females exhibit episodes of spontaneous ventricular tachycardia
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• 4 of 5 female mice exhibit one or two episodes of premature ventricular contractions, with average lasting time of an episode of approximately 290 ms and is occasionally accompanied by incidents of bigeminy and trigeminy
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• left ventricle cardiomyocytes exhibit a higher peak amplitude of electrically stimulated intracellular calcium transients and faster decay rate
• left ventricle cardiomyocytes exhibit an increase in sarcoplasmic reticulum calcium content as indicated by an increase in the amount of calcium released from the sarcoplasmic reticulum upon application of caffeine
• the faster decay rate of the intracellular calcium transients in cardiomyocytes is due to enhanced SERCA2 pumping of calcium into the sarcoplasmic reticulum
• left ventricle cardiomyocytes from 1-year-old mice exhibit increased contractile magnitude measured as a change in cell shortening and increased contraction and relaxation velocities
• however, factional calcium release from the sarcoplasmic reticulum is unchanged
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• mice exhibit increased susceptibility of heart to stress, resulting either in hypertrophy in the case of mild stress induced by sham surgery or in dilation and remodeling in the case of mechanical stress induced by transverse aortic constriction
• 2-month-old female mice subjected to transverse aortic constriction to stimulate pressure overload exhibit enlarged hearts, increased interstitial fibrosis, higher levels of hydroxyproline, more prominent calcification of myocardia, reduced relative left ventricle wall thickness, and increased left ventricle internal diameter during diastole, increased end diastolic volume, and increased isovolumetric relaxation time, indicating that females develop a dilated cardiomyopathy-like phenotype
• mutant sham mice develop an hypertrophic cardiomyocyte-like phenotype, potentially as a response to the surgical operation stress, with increased left ventricle anterior and posterior wall thickness in diastole and systole, reduced internal diameter during diastole and systole and end diastolic volume, and increased ejection fraction and fractional shortening
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homeostasis/metabolism
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• mice exhibit increased susceptibility of heart to stress, resulting either in hypertrophy in the case of mild stress induced by sham surgery or in dilation and remodeling in the case of mechanical stress induced by transverse aortic constriction
• 2-month-old female mice subjected to transverse aortic constriction to stimulate pressure overload exhibit enlarged hearts, increased interstitial fibrosis, higher levels of hydroxyproline, more prominent calcification of myocardia, reduced relative left ventricle wall thickness, and increased left ventricle internal diameter during diastole, increased end diastolic volume, and increased isovolumetric relaxation time, indicating that females develop a dilated cardiomyopathy-like phenotype
• mutant sham mice develop an hypertrophic cardiomyocyte-like phenotype, potentially as a response to the surgical operation stress, with increased left ventricle anterior and posterior wall thickness in diastole and systole, reduced internal diameter during diastole and systole and end diastolic volume, and increased ejection fraction and fractional shortening
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muscle
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• left ventricle cardiomyocytes from 1-year-old mice exhibit increased contractile magnitude measured as a change in cell shortening and increased contraction velocities
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