The Role of Free Fatty Acids in the Production of Ventricular Arrhythmias after Acute Coronary Artery Occlusion

Mechanical stretch has been demonstrated to have electrophysiological effects on cardiac muscle, including alteration of the probability of excitation, alteration of the action potential waveform, and stretch-induced arrhythmia (SIA). We demonstrate that regional ventricular ischemia due to coronary artery occlusion increases arrhythmogenic effects of transient diastolic stretch, whereas globally ischemic hearts showed no such increase. We tested our hypothesis that, during phase Ia ischemia, regionally ischemic hearts may be more susceptible to triggered arrhythmogenesis due to transient diastolic stretch. During the first 20 min of regional ischemia, the probability of eliciting a ventricular SIA ( PSIA) by transient diastolic stretch increased significantly. However, after 30 min, PSIA decreased to a value comparable with baseline measurements, as expected during phase Ib, where most ventricular arrhythmias are of reentrant mechanisms. We also suggest that mechanoelectrical coupling may contribute to the nonreentrant mechanisms underlying reperfusion-induced arrhythmia. When coronary artery occlusion was relieved after 30 min of ischemia, we observed an increase in PSIA and the maintenance of this elevated level throughout 20 min of reperfusion. We conclude that mechanoelectrical coupling may underlie triggered arrhythmogenesis during phase 1a ischemia and reperfusion.

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Effect of methylprednisolone on ventricular arrhythmias, mortality and infarct size following experimental coronary artery occlusion

The American Journal of Cardiology ◽

10.1016/s0002-9149(79)80150-2 ◽

1979 ◽

Vol 43 (2) ◽

pp. 372 ◽

Cited By ~ 2

Keyword(s):

Coronary Artery ◽

Infarct Size ◽

Ventricular Arrhythmias ◽

Coronary Artery Occlusion ◽

Artery Occlusion

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CD36 overexpression predisposes to arrhythmias but reduces infarct size in spontaneously hypertensive rats: gene expression profile analysis

Physiological Genomics ◽

10.1152/physiolgenomics.00083.2011 ◽

2012 ◽

Vol 44 (2) ◽

pp. 173-182 ◽

Cited By ~ 12

Author(s):

Jan Neckář ◽

Jan Šilhavý ◽

Václav Zídek ◽

Vladimír Landa ◽

Petr Mlejnek ◽

...

Keyword(s):

Gene Expression ◽

Coronary Artery ◽

Circadian Rhythms ◽

Infarct Size ◽

Ventricular Arrhythmias ◽

Coronary Artery Occlusion ◽

Artery Occlusion ◽

Transgenic Rats ◽

Spontaneously Hypertensive ◽

Long Chain

CD36 fatty acid translocase plays a key role in supplying heart with its major energy substrate, long-chain fatty acids (FA). Previously, we found that the spontaneously hypertensive rat (SHR) harbors a deletion variant of Cd36 gene that results in reduced transport of long-chain FA into cardiomyocytes and predisposes the SHR to cardiac hypertrophy. In the current study, we analyzed the effects of mutant Cd36 on susceptibility to ischemic ventricular arrhythmias and myocardial infarction in adult SHR- Cd36 transgenic rats with wild-type Cd36 compared with age-matched SHR controls. Using an open-chest model of coronary artery occlusion, we found that SHR- Cd36 transgenic rats showed profound arrhythmogenesis resulting in significantly increased duration of tachyarrhythmias (207 ± 48 s vs. 55 ± 21 s, P < 0.05), total number of premature ventricular complexes (2,623 ± 517 vs. 849 ± 250, P < 0.05) and arrhythmia score (3.86 ± 0.18 vs. 3.13 ± 0.13, P < 0.001). On the other hand, transgenic SHR compared with SHR controls showed significantly reduced infarct size (52.6 ± 4.3% vs. 72.4 ± 2.9% of area at risk, P < 0.001). Similar differences were observed in isolated perfused hearts, and the increased susceptibility of transgenic SHR to arrhythmias was abolished by reserpine, suggesting the involvement of catecholamines. To further search for possible molecular mechanisms of altered ischemic tolerance, we compared gene expression profiles in left ventricles dissected from 6-wk-old transgenic SHR vs. age-matched controls using Illumina-based sequencing. Circadian rhythms and oxidative phosphorylation were identified as the top KEGG pathways, while circadian rhythms, VDR/RXR activation, IGF1 signaling, and HMGB1 signaling were the top IPA canonical pathways potentially important for Cd36-mediated effects on ischemic tolerance. It can be concluded that transgenic expression of Cd36 plays an important role in modulating the incidence and severity of ischemic and reperfusion ventricular arrhythmias and myocardial infarct size induced by coronary artery occlusion. The proarrhythmic effect of Cd36 transgene appears to be dependent on adrenergic stimulation.

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