Post-myocardial infarction arrhythmogenesis

Background: Myocardial infarction (MI), a consequence of coronary artery occlusion, results in extensive cardiac myocyte (CM) death triggering a healing response or remodeling [1] with replacement myofibroblasts and extracellular matrix/ fibrous tissue deposition within the surviving myocardium. The fibrous tissue extends within the border zone (adjacent to the infarct area) potentially insulating against electrical conduction between CMs and contributing towards the formation of localized re-entry circuits. We used a novel type of electron microscopy (serial block face scanning electron microscopy, SBF-SEM) to investigate nano-scale structural changes to the cells forming the border zone.
Methods & Results: A translationally relevant porcine model of MI, presenting mild to moderate left ventricular dysfunction (n = 3/group; control and MI) was employed [2]. We examined tissue from the border and infarct zones using SBF-SEM [3, 4] at 15 nm in the X-Y plane to investigate the t-tubular (t-t) organization of the CMs and relationship between CMs and neighbouring myofibroblasts. Border zone CMs had regions devoid of t-ts with those remaining t-ts swollen and fused to form grossly extended networks. The structural organization between the border zone CMs and myofibroblasts are consistent with (i) gap junction mediated CM-myofibroblast communication (ii) partial cell fusion and (iii) a geometric organization with an inter-cellular separation of 160 ± 38 nm (12 CM-myofibroblasts, n = 3 pigs).
Conclusion: Our data showing extensive t-t remodeling provide novel structural insights towards understanding the impaired electrical properties of the CMs. Further, post-MI there are multiple modes of CM myofibroblast at the border zone, offering a potential platform for arrhythmogenic inter-cellular cross-talk. Identification and characterisation of structural remodelling and realignments could offer
opportunities for the development of novel anti-arrhythmic strategies.
Acknowledgements: This work was funded by the British Heart
Foundation
References:
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