Cardioprotection by Stimulation of Mitochondrial Benzodiazepine Receptors During Reperfusion, in a Porcine Acute Ischemia-Reperfusion Model

The Mitochondrial Translocator Protein and Arrhythmogenesis in Ischemic Heart Disease

“…Initial results in large animals were also encouraging. Specifically, treatment of pigs with 4′ClDzp at the time of reperfusion following 60 minutes of left anterior descending coronary artery occlusion was associated with rapid ST segment resolution and a trend towards reduced infarct size in the absence of major hemodynamic complications [ 69 ].…”

Targeting the Translocator Protein (18 kDa) in Cardiac Diseases: State of the Art and Future Opportunities

“…76,126 In a preclinical study conducted on pigs, Ro5-4864 intracoronary administration at the onset of reperfusion, after 60 min of coronary occlusion, improved faster ST-segment elevation resolution without hemodynamic complications and reduced microvascular damage, but it did not significantly reduce infarct size. 127 As mitochondrial membrane fluidity appears to be impaired after cardiac IR, Paradis et al investigated the causes of this membrane alteration on mitochondria isolated from rat hearts subjected to a half-hour ischemia followed by a quarter-hour reperfusion; the administration of Ro5-4864 appeared to ameliorate this condition. 35 Specifically, membrane fluidity was measured by evaluating the change in steady-state fluorescence anisotropy of two fluorescent probes, namely 1,6diphenyl-1,3,5-hexatriene (DPH) and hematoporphyrin IX (HP), that bound, respectively, to hydrophobic lipid regions and protein sites in mitochondrial membranes.…”

“…Ro5-4864 can also decrease the incidence of arrhythmias and reduce calcium overload. In addition, if administered at reperfusion, it protects against postischemic arrhythmias following reperfusion in rabbit hearts; if administered before ischemia, it improves the recovery of the post-IR contractile performance. , In a preclinical study conducted on pigs, Ro5-4864 intracoronary administration at the onset of reperfusion, after 60 min of coronary occlusion, improved faster ST-segment elevation resolution without hemodynamic complications and reduced microvascular damage, but it did not significantly reduce infarct size …”

“… 76 , 126 In a preclinical study conducted on pigs, Ro5-4864 intracoronary administration at the onset of reperfusion, after 60 min of coronary occlusion, improved faster ST-segment elevation resolution without hemodynamic complications and reduced microvascular damage, but it did not significantly reduce infarct size. 127 …”