Ruthenium red-induced transition from ventricular fibrillation to tachycardia in isolated rat hearts:: possible involvement of changes in mitochondrial calcium uptake

Introduction cular tachycardia (VT) is considered to be the most common precursor of ventricular fibrillation (VF) and sudden cardiac death. However, the mechanisms underlying the transition from VT to VF remain unclear despite more than a century of study. Here, we investigated whether perfusion of the heart with blockers of mitochondrial Ca2+ uniporter changed the macrodynamics of the heart between VT and VF. s periments were performed using Langendorff perfused isolated rat hearts in which left ventricular pressure (LVP) and left ventricular cardiomyogram (LVCMG) were measured. Sustained VT or VF was induced by burst pacing of the left ventricular muscles. s pacing-induced sustained VF, perfusion of the heart with ruthenium red (RR) or Ru 360, blockers of mitochondrial Ca2+ uniporter, resulted in the reversible conversion of VF to VT. In contrast, during pacing-induced sustained VT, perfusion of the heart with spermine, an activator of mitochondrial Ca2+ uptake, resulted in the reversible conversion of VT to VF, and the effect was antagonized by cotreatment with RR. In addition, RR-induced conversion of VF to VT was antagonized by cotreatment with S(−)-Bay K8644 (Bay K), an activator of L-type Ca2+ channels, suggesting that the inactivation of L-type Ca2+ channels was responsible for the RR-induced effect on the macrodynamics of hearts. In fact, perfusion with verapamil, an antagonist of L-type Ca2+ channels, during pacing-induced sustained VF, resulted in the conversion of VF to VT. sion tudy demonstrated that perfusion of isolated rat hearts with blockers of Ca2+ uptake by mitochondria resulted in the reversible conversion of pacing-induced sustained VF to VT, suggesting that changes in mitochondrial Ca2+ uptake were possibly involved in the transition between VT and VF.