View source for Brown 2014 J Cardiovasc Pharmacol Ther

{{Publication
|title=Brown DA, Hale SL, Baines CP, del Rio CL, Hamlin RL, Yueyama Y, Kijtawornrat A, Yeh ST, Frasier CR, Stewart LM, Moukdar F, Shaikh SR, Fisher-Wellman KH, Neufer PD, Kloner RA (2014) Reduction of early reperfusion injury with the mitochondria-targeting peptide bendavia. J Cardiovasc Pharmacol Ther 19:121-32.
|info=[http://www.ncbi.nlm.nih.gov/pubmed/24288396 PMID: 24288396 Open Access]
|authors=Brown DA, Hale SL, Baines CP, del Rio CL, Hamlin RL, Yueyama Y, Kijtawornrat A, Yeh ST, Frasier CR, Stewart LM, Moukdar F, Shaikh SR, Fisher-Wellman KH, Neufer PD, Kloner RA
|year=2014
|journal=J Cardiovasc Pharmacol Ther
|abstract=We recently showed that [[Bendavia]], a novel mitochondria-targeting peptide, reduced infarction and no-reflow across several experimental models. The purpose of this study was to determine the therapeutic timing and mechanism of action that underlie Bendavia's cytoprotective property. In rabbits exposed to ''in vivo'' ischemia/reperfusion (30/180 min), Bendavia administered 20 minutes prior to reperfusion (0.05 mg/kg/h, intravenously) reduced myocardial infarct size by ∼50% when administered for either 1 or 3 hours of reperfusion. However, when Bendavia perfusion began just 10 minutes after the onset of reperfusion, the protection against infarction and no-reflow was completely lost, indicating that the mechanism of protection is occurring early in reperfusion. Experiments in isolated mouse liver mitochondria found no discernible effect of Bendavia on blocking the permeability transition pore, and studies in isolated heart mitochondria showed no effect of Bendavia on respiratory rates. As Bendavia significantly lowered reactive oxygen species (ROS) levels in isolated heart mitochondria, the ROS-scavenging capacity of Bendavia was compared to well-known ROS scavengers using ''in vitro'' (cell-free) systems that enzymatically generate ROS. Across doses ranging from 1 nmol/L to 1 mmol/L, Bendavia showed no discernible ROS-scavenging properties, clearly differentiating itself from prototypical scavengers. In conclusion, Bendavia is a promising candidate to reduce cardiac injury when present at the onset of reperfusion but not after reperfusion has already commenced. Given that both infarction and no-reflow are related to increased cellular ROS, Bendavia's protective mechanism of action likely involves reduced ROS generation (as opposed to augmented scavenging) by endothelial and myocyte mitochondria.
|keywords=Amplex Red
|mipnetlab=US NC Greenville Brown DA, US NC Greenville Neufer PD, US VA Blacksburg Brown DA
}}
{{Labeling
|area=Respiration, Pharmacology;toxicology
|injuries=Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS
|organism=Rat
|tissues=Heart
|preparations=Intact organ, Isolated mitochondria
|couplingstates=LEAK, OXPHOS
|pathways=S
|instruments=Oxygraph-2k
|additional=Elamipretide, Bendavia,
}}
== Terminology ==
* Figure 6: 'State 2' does not correspond to the original definition of the respiratory [[State 2]] (presence of ADP, absence of ssubstrates; equivalent to [[ROX]]), but is a [[LEAK]] state (absence of ADP, presence of substrate).