Hydrogen peroxide as a protective agent during reperfusion A study in the isolated perfused rabbit heart subjected to regional ischemia

Abstract

In spite of extensive research during the last decade it has not been possible to prove that endogenously generated hydrogen peroxide or any reduced oxygen species reaches sufficient concentration during reperfusion after myocardial ischemia to contribute significantly to irreversible cell injury. In an attempt to further test this hypothesis we subjected isolated perfused rabbit hearts to 30 min regional ischemia followed by reperfusion and supplied hydrogen peroxide in low levels with or without catalase during the first 30 min of reperfusion and thereafter continued the reperfusion for a total of 120 min. Five different groups were studied: controls, and hearts supplied with 2 microM H2O2, 1 microM H2O2, 1 microM H2O2 + catalase (IU/l) or catalase alone in the initial part of the reperfusion. At the end of 120 min reperfusion, area at risk was measured with fluorescent particles and infarct zone size with tetrazolium staining. The results were: in the control group 32 +/- 5.0% of the risk zone infarcted, in the 2 microM H2O2 group 16.3 +/- 5.6% and in the 1 microM H2O2 group 6.9 +/- 0.8% (P < 0.05 compared to control). The reduction in infarct size was not present when catalase was added to the hydrogen peroxide-containing solution (26.4 +/- 4.5) or if catalase was present alone (22.9 +/- 1.8% infarction). In conclusion, hydrogen peroxide, 1 microM, protected the heart during reperfusion and reduced the amount of cell death after 120 min of reperfusion. The study demonstrated reduction or delay in infarction based only on treatment in the reperfusion period. The mechanism behind this protection remains to be determined.

Intermittent hypobaric hypoxia improves postischemic recovery of myocardial contractile function via redox signaling during early reperfusion

“…Otherwise, an aggravated injury should be observed if ROS are already excessively produced during this phase. This is further supported by the observations of Ytrehus et al (50) showing that treatment with H 2 O 2 during the first 30 min of reperfusion reduces myocardial infarct size after I/R injury in a coronary artery occlusion model. Although a lower concentration (1 mol/l) of H 2 O 2 was used in their study, the much longer treatment time (30 min) makes it explicable as the activation of protective signaling pathways by ROS accumulates with time (44).…”

The paradigm of postconditioning to protect the heart

“…Intriguingly, and in contrast to the above-described theory of ROS as an obligatory part of reperfusion induced damage, some studies suggest the possibility that some ROS species at low concentrations could protect ischaemic hearts [148][149][150][151][152][153][154]. Yet, from the above reported mechanisms of PostC, it appears that also ischaemic PostC is a cardioprotective phenomenon that requires the intervention of redox signalling to be protective [33,76,125,126].…”

Mitochondrial Reactive Oxygen Species (ROS): Which ROS is Responsible for Cardioprotective Signaling?

“…Reactive oxygen species (ROS) are second messengers of preconditioning (50) and have long been known to be required for cardioprotective signaling (6,15,40,103,135,153 mitochondria. The objective of these studies was to identify the point in the reaction sequence of ROS transformations at which the ROS signal is formed and, ultimately, to determine the identity of the ROS signal itself.…”