Intermittent systemic hypoxic-hyperoxic training for myocardial protection in patients undergoing coronary artery bypass surgery: first results from a single-centre, randomised controlled trial.

Background: Although remote ischaemic preconditioning (RIP) provides protection against myocardial ischaemia and reperfusion injury during cardiac surgery, it is not widely used. Systemic intermittent hypoxic-hyperoxic training (IHHT) may be a suitable alternative. Methods: This is a prospective, single-centre, randomised controlled trial. 127 patients with ischaemic heart disease and indication for coronary artery bypass graft (CABG) surgery from the Cardiology Clinic IM Sechenov First Moscow State Medical University were randomly assigned to IHHT, IHHT-control or RIP. Primary endpoint was serum concentration of troponin I and lactate 2 and 24 hours after surgery. Results: Median value for troponin I 24 hours after surgery was 1.068 (0.388-1.397) ng/mL in the IHHT group and was significantly lower compared with IHHT-controls with 1.980 (1.068-3.239) ng/mL (p=0.012) and to the RIP group with 1.762 (1.288-2.186) ng/mL (p=0.029), while there was no significant difference between RIP and the IHHT-control. Serum lactate after surgery was 1.74 (1.23-2.04) mmol/L in the IHHT group and was also significantly lower compared with IHHT-controls with 2.10 (1.80-2.29) mmol/L (p=0.045) and RIP with 2.12 (1.91-2.33) mmol/L (p=0.032). No significant complications or serious adverse events were observed during IHHT. Intraoperative and early postoperative complications did not differ significantly between groups. Conclusions: The results of this first trial using IHHT for myocardial protection against perioperative ischaemic myocardial injury in patients undergoing CABG surgery are promising and further larger trials should be done with adequate power to detect clinical rather than surrogate marker benefits.

Evaluation of redox mediators for amperometric biosensors: Ru-complex modified carbon-paste/enzyme electrodes.

The properties of reagentless amperometric biosensors are mainly governed by the interaction of the used redox enzyme and the redox mediators used to facilitate the electron-transfer reaction. Both the used redox mediators and the redox enzymes differ concerning their hydrophilicity and their properties within the matrix of a carbon-paste electrode. Since there is no general procedure which is applicable for any enzyme in combination with any redox mediator, optimisation is necessary for each possible combination. Three approaches for the development of biosensors were investigated using carbon-paste electrodes enriched with redox mediator as a base in all sensor architectures. A class of redox mediators with the common formula Ru(LL)(2)(X)(2) (where LL are 1,10-phenantroline or 2,2'-bipyridine type ligands, and X is an acido ligand) was investigated. In the first approach, enzymes were integrated into the carbon paste; in the second, the enzymes were adsorbed on the surface of the mediator-containing carbon-paste electrode and held in place by a Nafion film; and in the third approach, enzymes were entrapped in polymer films, which were electrochemically deposited onto the electrode's surface. The properties of the obtained biosensors strongly depend on the sensor architecture and the specific features of the used enzyme. Thus, our investigation using three different sensor architectures can provide valuable information about the possible interaction between a specific enzyme and a redox mediators with specific properties.

Redox mediation and photomechanical oscillations involving photosensitive cyclometalated Ru(II) complexes, glucose oxidase, and peroxidase.

Intact photosensitive cyclometalated RuII derivatives of 2-phenylpyridine or N,N-dimethylbenzylamine cis-[Ru-(C approximately N)(LL)X2]PF6 [C approximately N = o-C6H4-py or o-C6H4CH2NMe2; LL = 1,10-phenanththroline (phen), 2,2'-bipyridine (bpy), or 4,4'-Me2-2,2'-bipyridine (Me2bpy); X = MeCN or pyridine (py)] are efficient mediators of glucose oxidase (GO) from Aspergillus niger and horseradish peroxidase (HRP). Their redox potentials in an aqueous buffer are in the range 0.15-0.35 V versus SCE, and the rate constants for the oxidation GO(red) (where red indicates reduced) by the electrochemically generated RuIII species equal (1.7-2.5) x 10(6) M(-1) s(-1) at pH 7 and 25 degrees C. The redox potentials of all complexes decrease cathodically by 0.4-0.6 V upon irradiation by visible light because of the photoinduced solvolysis of acetonitrile or py ligands. These in situ generated species display an even better mediating performance with HRP, although their behavior toward GO is different. The loading of a ruthenium unit into the protein interior brings about large catalytic currents in a self-assembled system GO-Ru-D-glucose. The estimated rate constant for intramolecular electron transfer from FADH2 of the active site at RuIII, k(intra), equals 4.4 x 10(3) s(-1). This suggests that the distance between the redox partners is around 19 A. The value of 21 A was obtained through the docking analysis of a possible closest-to-FAD localization of a Ru-containing fragment derived from the irradiated complex cis-[Ru(o-C6H4-py)-(phen)(MeCN)2]PF6. The operational stability of the GO-Ru assemblies depends on the nature of complex used, the highest being observed for cis-[Ru(o-C6H4-py)(Me2-bpy)(MeCN)2]PF6 (2). UV-vis studies of interaction of 2 with GO revealed photomechanical oscillations in the system GO-Ru-D-glucose. When irradiated complex 2 is mixed with GO and D-glucose, the absorbance at 510 nm increases because of the enzymatic reduction of RuIII to RuII. The absorbance drops rapidly and then increases as in the first cycle after shaking the reaction solution. Many cycles are possible, and the rate of absorbance increase does not depend on a cycle number. A plausible mechanism of the oscillations is presented.