mortality/aging
• 25% of mice die by 3 months and over 50% by 12 months of age
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cardiovascular system
N |
• despite premature death and abnormal myocardial fiber physiology, mice do not exhibit any cardiac morphological alterations or structural abnormalities
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• fractional shortening is increased 19% compared to in wild-type mice and the rate corrected velocity of circumferential fiber shortening is increased 30% compared to in wild-type mice
• mice exhibit decreased ejection time compared to in wild-type mice
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• long term exposure to isoproterenol induces premature ventricular contractions, sinus asystole and atrioventricular block
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• mice treated with isoproterenol exhibit ventricular tachycardia associated with premature ventricular contractions and atrioventricular heart blocks unlike similarly treated wild-type mice
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• mice treated with isoproterenol exhibit ventricular tachycardia associated with premature ventricular contractions and atrioventricular heart blocks unlike similarly treated wild-type mice
• long term exposure to isoproterenol induces premature ventricular contractions, sinus asystole and atrioventricular block
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• sodium calcium ion exchanged current is increased by 67% compared to in wild-type cardiomyocytes
• peak calcium is increased 54% and constant calcium decay is shorter compared to in wild-type cardiomyocytes
• the amplitude of caffeine-induced calcium release is increased 30% and subsequent constant calcium decay is decreased compared to in wild-type cardiomyocytes
• cardiomyocytes exhibit a blunted response to beta-adrenergic stimulus compared to wild-type cardiomyocytes
• however, maximal beta-adrenergic stimulated parameter are similar to in wild-type cardiomyocytes
• myocytes exhibit increased calcium spark frequency and amplitude compared to in wild type cardiomyocytes
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• following 2 to 3 trains of 5 Hz field stimulation, 16% of cardiomyocytes exhibit aftercontractions unlike wild-type cells and treatment with isoproterenol increased aftercontraction frequency to 54% compared to 8% in similarly treated wild-type cells
• following 2 to 3 trains of 5 Hz field stimulation and isoproterenol treatment, 60% of cardiomyocytes exhibit abnormal calcium transients compared to 9% of similarly treated wild type cells
• under increased frequency of stimulation (5 Hz), 32% of cardiomyocytes exhibit delayed afterdepolarizations (DADs) compared to 6% of similarly treated wild-type cells
• under increased frequency of stimulation (5 Hz) and following treatment with isoproterenol, 90% of cardiomyocytes exhibit DADs with 72% suprathreshold compared to 21% of wild-type cells with 43% suprathreshold
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muscle
• fractional shortening is increased 19% compared to in wild-type mice and the rate corrected velocity of circumferential fiber shortening is increased 30% compared to in wild-type mice
• mice exhibit decreased ejection time compared to in wild-type mice
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homeostasis/metabolism
• following 2 to 3 trains of 5 Hz field stimulation, 16% of cardiomyocytes exhibit aftercontractions unlike wild-type cells and treatment with isoproterenol increased aftercontraction frequency to 54% compared to 8% in similarly treated wild-type cells
• following 2 to 3 trains of 5 Hz field stimulation and isoproterenol treatment, 60% of cardiomyocytes exhibit abnormal calcium transients compared to 9% of similarly treated wild type cells
• under increased frequency of stimulation (5 Hz), 32% of cardiomyocytes exhibit delayed afterdepolarizations (DADs) compared to 6% of similarly treated wild-type cells
• under increased frequency of stimulation (5 Hz) and following treatment with isoproterenol, 90% of cardiomyocytes exhibit DADs with 72% suprathreshold compared to 21% of wild-type cells with 43% suprathreshold
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