Combined use of hyperbaric oxygenation and antioxidants in the therapy of experimental myocardial infarct

In rabbits with experimental myocardial infarction, the combined use of hyperbaric oxygenation and ionol greatly potentiated the effect of the antioxidant on contractile function of the left ventricle, the time course of antioxidant lipid activity and superoxide dismutase activity of the myocardium.     

Action of natural and synthetic antioxidants on the electrical parameters and stability of natural and artificial membranes

The effect of antioxidants alpha-tocopherol and ionol on membranes of human red cells and bilayer lipid membrane (BLM) from azolektin has been studied. Ionol at concentration 4-10 mM induces the hemolysis of erythrocytes, the cells form changes are observed at concentration 2 mM alpha-tocopherol doesn't show the hemolytic properties at concentration 23 mM. The ionol concentration 1 mM doesn't change the form of the cells, but influence the passive electric parameters: the capacity (Cs) of erythrocytic membrane increases and the intracellular conductance (chi i) decreases. Tocopherol (3 mM) induces the decrease both Cs and chi i. The fast increase of membrane conductance is almost immediately registered on one side of BLM at addition of ionol (0,2-0,4 g/ml). Phosphatidylionol synthesized from ionol and contining the acyl chains C15H31 and C17H35 doesn't influence the electrical properties of BLM.     

Comparison of antioxidant activity between aromatic indolinonic nitroxides and natural and synthetic antioxidants

In view of the possible employment of nitroxide compounds in various fields, it is important to know how they compare with other synthetic antioxidant compounds currently used in several industries and with naturally occurring antioxidants. To address this issue, the antioxidant activity of two aromatic indolinonic nitroxides synthesized by us was compared with both commercial phenolic antioxidants (BHT and BHA) and with natural phenolic antioxidants (alpha-hydroxytyrosol, tyrosol, caffeic acid, alpha-tocopherol). DPPH radical scavenging ability and the inhibition of both lipid and protein oxidation induced by the peroxyl-radical generator, AAPH, were evaluated. The results obtained show that overall: (i) the reduced forms of the nitroxide compounds are better scavengers of DPPH radical than butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BLT) but less efficient than the natural compounds; (ii) the nitroxides inhibit both linolenic acid micelles and bovine serum albumin (BSA) oxidation to similar extents as most of the other compounds in a concentration-dependent fashion. Since the aromatic nitroxides tested in this study are less toxic than BHT, these compounds may be regarded as potential, alternative sources for several applications. The mechanisms underlying the antioxidant activity of nitroxides were further confirmed by UV-Vis absorption spectroscopy experiments and macroscale reactions in the presence of radicals generated by thermolabile azo-compounds. Distribution coefficients in octanol/buffer of the nitroxides and the other compounds were also determined as a measure of lipophilicity.     

Lipid peroxidation in experimental myocardial infarct: the action of hyperbaric oxygenation

Rats with experimental myocardial infarction demonstrated decrease in the activity of superoxide dismutase and catalase and increase in the content of lipid peroxidation (LPO) products and Schiff bases both in and outside the area of necrosis. The combined ischemic damage and hyperbaric oxygenation resulted in the over additive effect of accumulation of LPO products in and outside the area of infarction. The data suggest that it is desirable to use antioxidants during hyperbaric oxygenation.     

Innate immune response after acute myocardial infarction and pharmacomodulatory action of tacrolimus in reducing infarct size and preserving myocardial integrity

Background

This study investigated the association between innate immune reaction and myocardial damage after acute myocardial infarction (AMI) and anti-inflammatory role of tacrolimus in reducing infarct size. Male mini-pigs (n=18) were equally categorized into sham control (SC), untreated AMI (by ligation of left anterior descending coronary artery), and AMI-Tacrolimus (AMI-Tac) (0.5 mg intra-coronary injection 30 minutes post-AMI). Cardiac magnetic resonance imaging (MRI) was performed at post-AMI days 2, 5 and 21 before sacrificing the animals.

Results

By post-AMI day 21, left ventricular ejection fraction (LVEF) was lowest in untreated AMI animals, significantly higher in SC than in AMI-Tac group (all p<0.003). Infarct areas at basal, middle, and apical levels, numbers of CD14+ and iNOS+ cells in infarct area (IA) and peri-IA, and protein expression of CD14, CD68, and Ly6g from circulating inflammatory cells showed an opposite pattern compared with that of LVEF in all groups (all p<0.005). Protein expressions of MCP-1, MIP-1, TNF-α, NF-κB, iNOS, and IL-12 in IA and peri-IA exhibited an identical pattern compared to that of CD14, CD68, and Ly6g from circulating inflammatory cells (all p<0.01). Expressions of myocardial damage biomarkers in IA and peri-IA [γ-H2AX, β-myosin heavy chain (MHC), Smad3, TGF-β] were highest in AMI and higher in AMI-Tac than in SC, whereas expressions of myocardial integrity biomarkers (connexin43, mitochondrial cytochrome-C, α-MHC, BMP-2, Smad1/5) were opposite to those of damage biomarkers (all p<0.001).

Conclusion

Innate immune responses were markedly augmented and LVEF was significantly reduced after AMI but were remarkably improved after tacrolimus treatment.