Abstract Body: Background: The disruption of calcium homeostasis in ischemic hearts is determinant for triggering the arrhythmic phenomena and death. Interventions that act on calcium levels in cytoplasm and mitochondria might interrupt or minimize these outcomes. Trisulfate disaccharide (TD) acts by accelerating the sodium-calcium exchanger, decreasing cytosolic calcium levels. Ruthenium red (RuR) is a mitochondrial uniporter inhibitor that blocks calcium influx into mitochondria. Both agents can be useful in calcium overload elicited by myocardial ischemia (MI), modifying electrocardiographic (EKG) parameters that predict arrhythmia, arrhythmic phenomena, and cell death.
Objectives: To compare the behavior of Tp-Te and QTc EKG intervals, arrhythmia rates, and mortality in ischemic hearts under the action of TD and RuR. Materials and Methods: Adult Wistar rats (n=24) were divided in 3 groups, i.e, Control: MI with no treatment (n=8), TD: MI treated with TD 0.2 mg/kg IV (n=8), and RuR:MI treated with RuR 1 mg/kg IV (n=8). Rats were monitored by EKG and submitted to surgical MI by ligation of anterior descending artery during 10 minutes followed by reperfusion thereafter. The Tp-Te and QT intervals were analyzed before and at 10 minutes of ischemia and 10 minutes after the onset of reperfusion. The incidence of arrhythmias and mortality were determined throughout the recording time. Results: The Tp-Te and QTc intervals increased during ischemia in all groups (Control, TD and RuR), which were normalized after 10 minutes reperfusion only in TD group. The observed arrhythmias (atrioventricular block, ventricular tachycardia, and torsade of pointes) had a higher incidence in the control group and the lower incidences, with statistically significant differences, were achieved in TD and RuR groups, whose incidence was similar in these both groups. Sustained arrhythmias led to a 50% mortality in the control group and 25% in RuR group. No mortality in TD group was observed. Conclusion: The strategy of decreasing cytosolic calcium levels by the action of TD has proved to be more effective than the blockade of mitochondrial calcium uptake by RuR, with further normalization of EKG parameters predictors of mortality, and absence of sustained arrhythmias and mortality, suggesting that the management of cytosolic calcium levels is more effective than only the management of mitochondrial calcium in MI model.