Analysis Tools
mortality/aging
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• fewer than the expected number of mice are born, with only 30% of male offspring born
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• fewer than the expected number of embryos are seen between E8 and E20, indicating early embryonic lethality
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growth/size/body
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• males, but not females, are smaller at 8-10 weeks of age
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cardiovascular system
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• 100% of males exhibit premature ventricular contractions (PVCs), bidirectional ventricular tachycardia (BVT), or polymorphic ventricular tachycardia (PVT)
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• males and females exhibit greater heart rate variability after epinephrine and caffeine coadministration
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• slower heart rate correlates with proportionally longer RR intervals
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• electrocardiogram shows that mice exhibit sinus rhythm with significantly slower beat rates in both males and females
• telemetric ECG of nonanesthetized mice shows sinus bradycardia in both light and dark cycles
• however, spontaneous ventricular arrhythmia is not seen and echocardiography shows no differences in left ventricular internal diameter, posterior wall thickness, ejection fraction, or fractional shortening, indicating structurally normal hearts with normal contractile function
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• males exhibit bidirectional ventricular tachycardia (BVT) or polymorphic ventricular tachycardia (PVT)
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• coadministration of epinephrine and caffeine induces a variety of arrhythmic events that are rarely seen in wild-type mice; most prevalent arrhythmias are bigeminy and bidirectional ventricular tachycardia
• 100% of males exhibit some form of arrhythmia, while 22% of females show no arrhythmic events
• acute treatment with flecainide does not prevent epinephrine/caffeine-induced arrhythmias
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• males exhibit premature ventricular contractions (PVCs) at baseline
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• QRS duration is prolonged after epinephrine and caffeine coadministration in males, but not females
• however, QRS duration is normal at baseline
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• corrected QT (QTc) interval is prolonged after epinephrine and caffeine coadministration in males, but not females
• however, QTc interval is normal at baseline
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• intracellular calcium transients in isolated ventricular cardiomyocytes from males, but not females, have lower peak amplitudes following in vitro exposure to epinephrine and caffeine compared to wild-type cells
• the calcium transient rise time (10% to 90% of peak) is longer in cardiomyocytes from males at baseline compared with wild-type male cardiomyocytes when paced at 1 Hz but not at 3.3 Hz and this difference is absent after epinephrine/caffeine treatment
• while transient duration at 50% recovery after epinephrine/caffeine is similar to wild-type mice, at a faster pacing rate of 3.3 Hz, the transient duration at 80% recovery is longer in males compared to wild-type mice
• however, the calcium transient decay time (90%-10% of peak) is not different in cardiomyocytes from males or females and exposure to epinephrine and caffeine shortens decay times similarly as in wild-type cells
• however, the percent of cells exhibiting spontaneous calcium waves is not different and the calcium wave frequencies are identical to wild-type
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• males and females coadministered epinephrine and caffeine often exhibit bidirectional ventricular tachycardia
• males and females coadministered epinephrine and caffeine infrequently exhibit polymorphic ventricular tachycardia (PVT) with sudden cardiac death
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homeostasis/metabolism
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• males and females coadministered epinephrine and caffeine often exhibit bidirectional ventricular tachycardia
• males and females coadministered epinephrine and caffeine infrequently exhibit polymorphic ventricular tachycardia (PVT) with sudden cardiac death
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