Analysis Tools
cardiovascular system
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• slower heart rate correlates with proportionally longer RR intervals
• however, corrected QT (QTc) interval and QRS duration are normal at baseline and after epinephrine and caffeine coadministration
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• electrocardiogram shows that mice exhibit sinus rhythm with significantly slower beat rates in both males and females
• 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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• coadministration of epinephrine and caffeine induces a variety of arrhythmic events that are rarely seen in wild-type mice
• 100% of males exhibit some form of arrhythmia, while 30% of females show no arrhythmic events
• 63% of males exhibit sustained arrhythmic events
• acute treatment with flecainide does not prevent epinephrine/caffeine-induced arrhythmias
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• nearly 50% of male and female mice exhibit premature ventricular contractions (PVCs) after epinephrine and caffeine coadministration
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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
• the calcium transient decay time (90%-10% of peak) is not different in cardiomyocytes from males or females, however decay times after exposure to epinephrine and caffeine are greater than in wild-type mice
• the transient duration at 50% recovery is longer in males and females after epinephrine/caffeine when paced at either frequency
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