Cardioprotective effect of edaravone against ischaemia-reperfusion injury in the rabbit heart before, during and after reperfusion treatment.

The free radical scavenger edaravone is able to stimulate prostacyclin release and inhibit the lipoxygenase pathway in the arachidonic acid cascade. The effect of edaravone administration on myocardial damage in rabbit hearts subjected to ischaemia-reperfusion was examined at different times relative to reperfusion. All rabbits underwent sustained coronary artery occlusion for 30 min followed by 3 h of reperfusion. Rabbits were divided into the following groups: control; early (3 mg/kg edaravone IV 10 min before reperfusion); immediate (3 mg/kg edaravone IV immediately after the start of reperfusion); and late (3, 6 or 10 mg/kg edaravone IV 5 min after the start of reperfusion). Single bolus administration of edaravone 10 min before reperfusion or immediately upon initiation of reperfusion appears to be associated with reductions in infarction size and the percentage of apoptotic cells, but treatment with edaravone 5 min after initiation of reperfusion does not appear to have this protective effect.

Life-saving effect of pyridoxalated hemoglobin-polyoxyethylene conjugate on carbon monoxide intoxication of rabbits.

We examined whether pyridoxalated hemoglobin-polyoxyethylene conjugate (PHP) could be life-relievable for carbon monoxide (CO) intoxication. Toxic gas (O2, 5.0%; CO2, 16.0%; CO, 1.8%; and N2, 77.2%) was inhaled by rabbits anesthetized with urethane and the following parameters were measured: blood pressure, arterial and venous Po2, Pco2, pH, and carboxyhemoglobin (COHb). When mean blood pressure reached 0 or 20 mm Hg as an index after inhalation of the toxic gas, the toxic gas was switched to air; intravenous infusion of physiological saline or PHP (1.2 g/20 ml/kg/30 min) was simultaneously initiated. In the experiment using 0 mm Hg blood pressure, PHP prolonged the survival time and exhibited significant temporary recovery of P02 and Pco2 in comparison with saline. In the experiment using the 20 mm Hg blood pressure, a significant difference in each parameter was observed between the saline and PHP groups. Two of 8 animals in the saline group died without any recovery of each parameter. All 6 animals in the PHP group survived and each parameter recovered. PHP accelerated recovery from high COHb concentrations, low arterial and venous Po2, reduction of arterial and venous Pco2, and elevations of pH and blood pressure. These results suggest that PHP treatment during the early stage of CO intoxication is life-saving and effective in facilitating the recovery of various functions.

[Potentiation by carbon dioxide of carbon monoxide-induced death in the hypoxic condition].

This study was aimed at clarifying the effect of carbon dioxide (CO2) on the toxicity of carbon monoxide (CO) in the hypoxic condition. In order to evaluate the coexistent toxicity of CO2 and CO under hypoxic hypoxia, we investigated the difference of CO toxicity between under the hypoxic and hypercapnic hypoxia in point of lethality in conscious male mice. Furthermore, we measured blood gases (pO2 and pCO2), pH, COHb concentration, and blood pressure (BP) and heart rate (HR) in urethane anesthetized male rabbits inhaled with 2 toxic gases: N2-toxic gas (O2 5.0%, CO 1.8%, N2 93.2%) and CO2-toxic gas (O2 5.0%, CO2 16.0%, CO 1.8%, N2 77.2%). The animals were inhaled with the 2 toxic gases until the BP reached 0 or 20 mmHg. In the latter case, when the BP reached 20 mmHg, the animals were inhaled with air and were intravenously infused with saline (20 ml/kg/30 min). Conscious mouse experiment: In the both types of hypoxia, LC50 were decreased with the decrease of O2 concentration and the LC50 of CO in hypercapnic hypoxia was significantly lower than that in nitrogen-replacement hypoxia in the range of 12% and 9% of O2 concentration in male mice. BP 0 mmHg-group experiment in rabbits: All the rabbits inhaled with N2-toxic gas or CO2-toxic gas died. The time to BP 0 mmHg in CO2-toxic gas group (7.8 +/- 0.33 min) was shorter than that in N2-toxic gas group (11.5 +/- 1.00 min). Although both toxic gases lowered pO2 level and elevated COHb% of the blood, CO2-toxic gas extremely elevated pCO2 level by 80-100 mmHg corresponding to lowering the serum pH by 0.37-0.45. BP was firstly elevated during 2-3 minutes by inhalation of these toxic gases and was finally lowered to die. HR decreased continuously after the inhalation of toxic gases until the animals died. BP 20 mmHg-group experiment in rabbits:Recoveries of COHb%, pCO2 level and pH of the blood in N2-toxic gas intoxication were significantly faster than those in CO2-toxic gas group. The times to COHb 10% were 64.2 min and 78.2 min in N2-toxic gas and CO2-toxic gas, respectively. But, there was no significant difference between N2-toxic gas and CO2-toxic gas intoxications in the recoveries of pO2 level, BP and HR. The above results suggest that CO2 potentiates the CO-intoxication under hypoxic hypoxia and our methods of coexistent gas toxicity may be useful for examining the gas toxicity in fire accident.

[Potentiation of carbon dioxide for hypoxic hypoxia-induced death].

The circumstances in the hypoxic death cases are generally classified into pure hypoxic condition as replacement of O2 gas with N2 gas and hypercapnic hypoxic condition as replacement of O2 gas with CO2 gas. Although pure hypoxia and hypercapnic hypoxia should be distinguished, there are very few reports and data on their distinctive research. In order to evaluate the toxicity of both hypoxic gases in male mice, we determined the interaction range of O2 and CO2 gas concentrations, measured the spontaneous motility of mice exposed to various gases and investigated the effect CO2 gas on the hypoxic hypoxia-induced death. Gas toxicity was evaluated by the median lethal concentration (LC50) of O2 during 10 minutes' exposure to the gases, using a self-made simple experimental apparatus for acute inhalation gas toxicity. The LC50 of pure (nitrogen-replacement) hypoxic gas was 6.0% (95% Conf. L., 5.6-6.4%) in O2 and the LC50 of hypercapnic (CO2 gas-replacement) hypoxic gas was 8.8% (7.4-10.1%) which was significantly different (p less than 0.05) from that of pure hypoxic gas. From the result described above it is suggested that CO2 potentiates the hypoxic hypoxia-induced death. The potentiation of CO2 occurred in the range of 6 to 12% of O2 concentration. While there was no dead case in the normoxic gas (O2 not equal to 21.0%) even of which nitrogen was replaced with CO2 gas by 14.9%. Not only significant difference of the lethal O2 gas concentrations, but also a little differences of signs and symptoms were observed between pure hypoxia and hypercapnic hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)