QRS/T-wave and calcium alternans in a type I diabetic mouse model for spontaneous postmyocardial infarction ventricular tachycardia: A mechanism for the antiarrhythmic effect of statins

Abstract

Background The incidence of sudden arrhythmic death is markedly increased in diabetics. Objective Develop a mouse model for Post MI VT in the diabetic heart and determine the mechanism of an antiarrhythmic effect of statins. Methods EKG transmitters were implanted in wild type (WT), placebo and pravastatin treated Type I diabetic Akita mice, MIs induced by coronary ligation, Ca2+ transients studied by optical mapping, Ca2+ transients and sparks in left VM (VM) by the Ionoptix system and confocal microscopy. Results Burst pacing of Akita mouse hearts resulted in rate related QRS/T-Wave alternans, which was attenuated in pravastatin treated mice. Post MI Akita mice developed QRS/T-wave alternans and VT, 2,820 ± 879 beats/mouse which decreased to 343 ± 115 in pravastatin treated mice, (n=13, P<0.05). Optical mapping demonstrated pacing induced VT originating in the peri-infarction zone and Ca2+ alternans, both attenuated in hearts of statin treated mice. Akita VM displayed: Ca2+ alternans, triggered activity, increased; Ca2+ transient decay time (Tau), incidence of Ca2+ sparks and cytosolic Ca2+ and decreased SR Ca2+ stores which were in part reversed in cells from statin treated mice. Homogenates of Akita ventricles demonstrated decreased SERCA2a/PLB ratio and increased ratio of protein phosphatase (PP-1) to the PP-1 inhibitor PPI-1 reversed in homogenates of pravastatin treated Akita mice. Conclusions Pravastatin decreased the incidence of post MI VT and Ca2+ alternans in Akita mouse hearts in part via the reversal of abnormalities of Ca2+ handling via the PP-1/PPI-1 pathway.

A companion to the preclinical common data elements for physiologic data in rodent epilepsy models. A report of the TASK3 Physiology Working Group of the ILAE/AES Joint Translational Task Force

“…If the QRS complex appears of normal height and duration, then the initiating impulse originates above the A‐V node. When the QRS complex appears wide and bizarre, the impulse initiating that complex originates at an ectopic pacemaker site within the ventricles Evaluate the relationship between the P waves and QRS .…”

“…With complicated arrhythmias, it may be difficult to discern a P wave from a T wave. A T wave will always follow every QRS complex, but the same is not true for P waves, which may be buried in the complex or missing from the complex altogether Frequency (heart rate): often expressed as beats/minute (bpm) Mean R‐R interval Heart rate variability (in time domain): oSDNN: Standard deviation of R‐R intervals for given epoch of time oRMSSD: root mean squared of successive differences Heart rate variability (in frequency domain): oLow frequency (LF, 0.3–0.75 Hz): represents sympathetic activity oHigh frequency (HF, 0.75–3 Hz): represents parasympathetic activity oLF/HF ratio Cardiac intervals such as P‐R interval, QT corrected (specify correction method) Measuring heart rate variability (HRV) .…”

“…When the QRS complex appears wide and bizarre, the impulse initiating that complex originates at an ectopic pacemaker site within the ventricles. 69 • Evaluate the relationship between the P waves and QRS.…”

“…A T wave will always follow every QRS complex, but the same is not true for P waves, which may be buried in the complex or missing from the complex altogether. 69,71 Parameters that can be determined: In one series of 5 unrestrained, awake Wistar rats, the mean RMSSD was 5.18 AE 1.16 msec. 72 In a study of HRV in C57BL/6J mice, the mean RMSSD was 6.1 AE 1.5 msec.…”

Vaping Perpetuates Cardiac Electrical Instability

“…Electrograms were recorded using the PowerLab platform from Advanced Instruments. Programmed electrical stimulation for VT induction was performed at twice diastolic threshold with 1 second burst pacing from 20 to 50 Hz, in 2 Hz increments 25,27 . Tocris) was used as an excitation-contraction uncoupler.…”