Protective Effects of Hydrogen Peroxide Against Ischemia/Reperfusion Injury in Perfused Rat Hearts.

Abstract

Among the several mechanisms proposed for ischemic preconditioning (IPC), generation of reactive oxygen species (ROS) is reported to be involved in the cardioprotective effects of IPC. The present study was designed to investigate whether repetitive exposure to hydrogen peroxide (H(2)O(2)) can protect the myocardium against subsequent ischemia/reperfusion injury, and whether the H(2)O(2)-induced cardioprotection is related to the preservation of energy metabolism. Langendorff-perfused rat hearts were exposed to two, 5 min episodes of IPC or to various concentrations of H(2)O(2) twice and then to 35 min global ischemia and 40 min reperfusion. Using (31)P nuclear magnetic resonance ((31)P-NMR) spectroscopy, cardiac phosphocreatine (PCr) and ATP and intracellular pH (pH(i)) were monitored. IPC and the treatment with 2 micromol/L H(2)O(2) significantly improved the post-ischemic recovery of left ventricular developed pressure (LVDP) and the PCr and ATP compared with those of the control ischemia/reperfusion (LVDP: 36.9 +/-7.4% of baseline in control hearts, 84.0+/-3.5% in IPC, 65.4+/-3.8% in H(2)O(2); PCr: 51.1+/-5.3% in control hearts, 81.4+/-5.5% in IPC, 81.7+/-5.2% in H(2)O(2); ATP: 12.3+/-1.6% in control hearts; 30.0+/-2.8% in IPC, 28.6+/-2.3% in H(2)O(2), mean +/- SE, p<0.05). However, lower (0.5 micromol/L) or higher (10 micromol/L) concentration of H(2)O (2) had no effect. There were significant linear correlations between mean LVDP and high-energy metabolites after 40 min reperfusion in H(2)O(2)-treated hearts. In IPC-treated hearts, the mean LVDP was greater than that in the 2 micromol/L H(2)O(2)-treated hearts under similar levels of high-energy metabolites. IPC also ameliorated intracellular acidification (6.38+/-0.03 in control hearts, 6.65+/-0.04 in IPC, p<0.05), but treatment with H(2)O(2) did not affect pH(i) during ischemia (6.40+/-0.05 in H(2)O(2)). In conclusion, H(2)O(2) had protective effects against ischemia/reperfusion injury and the effects were related to the preservation of energy metabolism. IPC could have additional protective mechanisms that are associated with the amelioration of intracellular acidosis during ischemia.

Heart Preservation Using Continuous Ex Vivo Perfusion Improves Viability and Functional Recovery

“…A major advantage of the Langendorff model is its ability to specifically address our study aim of directly comparing CP with CS, the current gold standard, without the wide range of confounding effects present in a transplantation model. 33 This method is well-established 19,20,[34][35][36][37] and has a track record of predicting the clinical performance of a wide range of clinical protocols in cardiac surgery, including anti-ischemic interventions 31 and methods of cardiac preservation. 38,39 Although the heart rate and preload…”

Protein Kinase A Catalytic Subunit Alters Cardiac Mitochondrial Redox State and Membrane Potential Via the Formation of Reactive Oxygen Species

“…It has been reported that ROS could act as a second messenger in response to the stimulation of intracellular signaling pathways and protect myocytes from pathological conditions such as ischemia/reprefusion injury. 44,45 Thus, it is also necessary to consider that ROS (induced by the stimulation of BAR) in adequate amounts have beneficial effects on myocardial function.…”

Myocardial Creatine Concentration in Various Nonischemic Heart Diseases Assessed by 1H Magnetic Resonance Spectroscopy

“…In animal studies, 31 P MRS was useful in examining cardioprotection against ischemia. [28][29][30] A combined study of 1 H and 31 P MRS provided more detailed information on myocardial creatine metabolism. 7 Future investigations, coupled with technical development, will demonstrate the true role of MRS in elucidating the pathological mechanisms of diseased hearts.…”