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Structural Substrates Involved in the Development of Severe Arrhythmias in Hypertensive Rat and Aged Guinea Pig Hearts

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Cardiac Remodeling and Failure

Abstract

We hypothesize that age- as well as hypertension-related myocardial remodeling can deteriorate cell-to-cell junctions and communication, thus consequently facilitate re-entry arrhythmias. The aim of the study was to characterize structural substrate that precede appearance of atrial fibrillation in aged guinea pig heart and occurrence of ventricular fibrillation in hypertensive rat heart. The experiments were performed on Langendorff-perfused heart. To induce atrial fibrillation the left atrium of old or young guinea pig was stimulated by 1 sec burst of 0.1 msec rectangular pulses at 50–70 pps. As soon as sinus rhythm was detected the stimuli burst was delivered again. To induce ventricular fibrillation the heart of hypertensive or normotensive rats was subjected to hypokalemia for 60 min unless fibrillation occurred earlier. Myocardial tissue taken during control, burst pacing and hypokalemia conditions were examined for ultrastructural and gap junction protein, connexin-43, alterations. The results showed that old guinea pig heart is prone, while young resistant to atrial fibrillation and that hypertensive rat heart is more vulnerable than normotensive rat heart to ventricular fibrillation. In correlation with these findings it was revealed that age- as well as hypertension-related myocardial remodeling is accompanied by decreased intercellular coupling and down-regulation of conexin-43. Further deterioration of cell-to-cell coupling was observed most likely due to burst pacing and hypokalemia induced calcium overload. We suggest that structural substrate for arrhythmogenesis includes impairment of intercellular junctions. Thus, age- and hypertension-related maladaptation of the heart may account for its increased susceptibility to cardiac fibrillation.

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Tribulová, N. et al. (2003). Structural Substrates Involved in the Development of Severe Arrhythmias in Hypertensive Rat and Aged Guinea Pig Hearts. In: Singal, P.K., Dixon, I.M.C., Kirshenbaum, L.A., Dhalla, N.S. (eds) Cardiac Remodeling and Failure. Progress in Experimental Cardiology, vol 5. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9262-8_27

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  • DOI: https://doi.org/10.1007/978-1-4419-9262-8_27

  • Publisher Name: Springer, Boston, MA

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