Analysis Tools
mortality/aging
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• untreated mice exhibit increased mortality (8/15) starting at 4 weeks of age, however, in survivors reaching 22 weeks of age only 1 mouse out of 20 dies
• most deaths occur between 4 to 6 weeks of age
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cardiovascular system
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• increased left ventricular mass as compared to controls
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• reduced cardiac output at 4 weeks, however, by 22 weeks CO is similar to controls
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• mice exhibit a blunted response to beta-adrenergic agonists
• although resting +dP/dt and - dP/dt are similar to wild-type, maximal +dP/dt and -dP/dt at 18-22 weeks are reduced following isoproterenol infusion
• maximal contraction amplitude is lower than wild-type at 5 mM [Ca2+]
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• increased ejection fraction
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• heart rate is less than 50% of controls at 4 weeks
• reduced heart rate at 18-22 weeks before and after isoproterenol (beta-adrenergic agonist) infusion
• 11/ 12 mice exhibit severe bradycardia
• bradycardia persists at 22 weeks in 6/7 survivors
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• multifocal ventricular tachycardia
• tachycardia persists at 22 weeks in 1/7 survivors
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• 4/ 12 mice exhibit ventricular flutter/fibrillation
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• Ipump is lower by 41.7% as compared to wild-type
• peak density of ICa is decreased by 29.2%
• Peak amplitudes of depolarization-activated K+ currents are lower as compared to wild-type
• diastolic intracellular Ca2+ is increased
• systolic intracellular Ca2+ is similar to wild-type at baseline, but lower after stimulation with isoproterenol
• decreased sarcoplasmic reticulum Ca2+ uptake
• decreased Na+ K+-ATPase activity
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growth/size/body
muscle
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• mice exhibit a blunted response to beta-adrenergic agonists
• although resting +dP/dt and - dP/dt are similar to wild-type, maximal +dP/dt and -dP/dt at 18-22 weeks are reduced following isoproterenol infusion
• maximal contraction amplitude is lower than wild-type at 5 mM [Ca2+]
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• increased ejection fraction
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nervous system
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• action potential duration is doubled, however, resting Em and action potential amplitude are similar to controls
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