Remote effect of local hypoxia/ischemia in the heart during myocardial infarction

Ischemic ventricular tachycardia (VT) occurs 48-72 hours after myocardial infarction (MI; heart attack) occasionally resulting in sudden cardiac death. The cardiac specific Sarco-(endo)plasmic reticulum (SR) calcium ATPase (SERCA2) is thought to be responsible for these arrhythmias. Replacement of normal SERCA2a sub-isoform by SERCA2b, a more efficient Ca²⁺ uptake pump not expressed in healthy conditions, is hypothesized to explain increased release of Ca²⁺ by SR, initiating post-MI tachycardias. This arrhythmogenic change of SERCA2 appeared in left ventricle (LV), at the MI location, and in other healthy heart regions. This observation suggests hypoxic/ischemic cells in LV release biochemicals changing SERCA2 expression affecting all cardiac regions when released into circulation. This hypothetical remote effect was tested by developing an assay mimicking hypoxic/ischemic MI conditions using Sprague Dawley rat ventricular myocytes. A preparation of cardiac cells was exposed in culture to hypoxia/ischemia (preparation #1). A second preparation of healthy normoxic cardiomyocytes (preparation #2) were incubated with media from preparation #1. After 3 days, healthy cells from preparation #2 exhibited typical arrhythmogenic characteristics compared to hypoxic/ischemic cells of preparation #1. The remote effect of substance(s) X produced by hypoxic/ischemic cells was evident in preparation #2 by measuring spontaneous contractile and Ca²⁺ activity in cultured cardiomyocytes.