The aims of this study were to evaluate whether the delayed application of low-pressure reperfusion could reduce lethal reperfusion injury and whether the inhibition of the opening of the mitochondrial permeability transition pore is involved in this protection.Methods:
Isolated rat hearts (n = 120) underwent 40 minutes of global ischemia followed by 60 minutes of reperfusion. Hearts were randomly assigned to the following groups: control, postconditioning (comprising 2 episodes of 30 seconds of ischemia and 30 seconds of reperfusion), and low-pressure reperfusion (using a reduction of perfusion pressure at 70 cm H2O for 10 minutes). In additional groups, postconditioning and low-pressure reperfusion were applied after a delay of 3, 10, and 20 minutes after the initial 40-minute ischemic insult.Results:
As expected, infarct size (triphenyltetrazolium chloride staining) and lactate dehydrogenase release were significantly reduced in low-pressure reperfusion and postconditioning versus controls (P < .01), whereas functional parameters (coronary flow, rate pressure product) were improved (P < .01). Although delaying postconditioning by more than 3 minutes resulted in a loss of protection, low-pressure reperfusion still significantly reduced infarct size when applied as late as 20 minutes after reperfusion. This delayed low-pressure reperfusion protection was associated with an improved mitochondrial respiration, lower reactive oxygen species production, and enhanced calcium retention capacity, related to inhibition of permeability transition pore opening.Conclusions:
We demonstrated for the first time that low-pressure reperfusion can reduce lethal myocardial reperfusion injury even when performed 10 to 20 minutes after the initiation of reperfusion.