Gennady G. Rogatsky

Effect of Hyperbaric Oxygen Therapy on Survival After Global Cerebral Ischemia in Rats

BACKGROUND Hyperbaric oxygenation (HBO) has been considered for many years for the treatment of severe brain ischemia. However, its efficacy has not been proven. The aim of this study was to shed light on this question. METHODS Acute global cerebral ischemia was induced in 18 rats using the four-vessel occlusion model. Regional cerebral blood flow (CBF) was determined by laser-Doppler flowmetry using a flexible 1 mm fiberoptic probe. Two stainless steel screws were used to measure the spontaneous electrical activity from the contralateral hemisphere. After ischemia monitored by laser-Doppler flowmetry and ECoG, the animals were divided into two groups: (1) control animals that breathed air at atmospheric pressure and (2) rats exposed to HBO at three atmospheres absolute pressure (ATA) for 1 hour. Survival time and rate were recorded for both groups of animals for 14 days. RESULTS The survival rate in the study group was significantly higher (45%) than in the control group (0%). In the animals that did not survive the 14-day period, those exposed to HBO survived longer than the control animals (59.8+/-9.1 hour versus 17.9+/-2.7 hours, p < 0.05). CONCLUSION This investigation demonstrates that HBO administered after global cerebral ischemia can increase survival in a rat stroke model.

Relationship between Intracranial Pressure and Cortical Spreading Depression following Fluid Percussion Brain Injury in Rats

Traumatic brain injury (TBI) is known to be accompanied by an increase in intracranial pressure (ICP) and in some cases, by spontaneous generation of cortical spreading depression (CSD) cycles. However, the role of CSD in the pathophysiology of cerebral contusion is still unknown. A multiparametric monitoring assembly was placed on the right hemisphere of the rat brain to evaluate ICP, DC potential, extracellular K(+), cerebral blood flow (CBF), and electrocorticogram in 27 rats during 5 h. Fluid percussion brain injury (FPBI) with the magnitude of the impact 2.9, 3.3, 4.1, and 5.0 atmospheres was induced to the left parietal cortex in animal groups A, B, C, and D, respectively. A slow increase in ICP was evident, and was pronounced in group C and especially in group D, where four of nine animals died during the monitoring. At the end of the 5 h experiment, the mean ICP levels were 6.75 +/- 2.87, 8.40 +/- 2.70, 12.75 +/- 4.03, 29.56 +/- 9.25, and the mean total number of CSD cycles was 2.00 +/- 1.41, 4.29 +/- 4.23, 11.71 +/- 13.29, and 20.11 +/- 19.26 in groups A, B, C, and D, respectively. The maximal level of intensity of CSD cycle generation after FPBI was obtained in group D, where almost constant activity was maintained until the end of the experiment. A significant coefficient of correlation between ICP level and total number of CSD cycles was found for all ICP measurements (r = 0.47-0.63, p < 0.05, n = 27), however more significant (p < 0.001) was the coefficient during the period of monitoring between 2 and 4 h after FPBI. Our results suggest that numerous repeating CSD cycles are typical phenomena in moderate and especially severe forms of FPBI. The rising number of CSD cycles under condition of an ICP level >/=20 mm Hg may demonstrate, with high probability, the unfavorable development of TBI, caused by growing secondary hypoxic insult.

Effect of hyperbaric oxygenation on intracranial pressure elevation rate in rats during the early phase of severe traumatic brain injury

Intracranial pressure (ICP) was monitored to evaluate the therapeutic effect of hyperbaric oxygen (HBO(2)) treatment following traumatic brain injury (TBI). This subject is controversial. The aim of our study was to determine whether HBO(2) treatment has a therapeutic effect on ICP dynamics and survival following severe fluid percussion brain injury (FPBI) in rats. Changes in ICP level were analyzed every 30 min during an 8-h monitoring period following trauma and at the end of experiment (20 h). The control (A) and experimental (B) groups consisted of 7 and 4 rats, respectively. Group B was subjected to 1.5 atmospheres absolute (ATA) 100% oxygen for 60 min beginning 2 h after FPBI. No significant differences in ICP were noted between groups A and B before and after HBO(2) treatment until 3.5 h after trauma. At 4 h, for the first time, the difference became significant (P = 0.025; n = 11) and remained significant (P < 0.05) for all measurement points until end of monitoring, when mean ICP values reached 37.17 +/- 14.25 and 20.25 +/- 2.63 mm Hg in groups A and B, respectively. Linear approximation models showed different trends (b1 = 3.80 +/- 0.23; r(2) = 0.65, P < 0.001 and b1 = 1.56 +/- 0.25; r(2) = 0.77, P < 0.001) for groups A and B, respectively. Covariance analysis confirmed significant differences between slopes for groups A and B (F = 148.04, P < 0.001; df = 2,177), i.e., a significant difference in mean rate of ICP elevation. By the end of the experiment, 3 out of 7 rats from group A had died, but none from group B. We conclude that the application of HBO(2) during the early phase of severe FPBI significantly diminished ICP elevation rate and decreased mortality level.

Optimal dosing as a necessary condition for the efficacy of hyperbaric oxygen therapy in acute ischemic stroke: A critical review

Abstract The effectiveness of hyperbaric oxygen therapy (HBOT) in clinical and experimental acute ischemic stroke (AIS) has been controversial for many years. However, in the literature, no data was found on the dose/effect of HBOT in patients with AIS. We analyzed retrospectively the published data of clinical studies performed in different hyperbaric centers (a total of 265 patients). The dose of HBOT (DHBOT) was calculated considering the product intrabarochamber pO2 (ATA), the duration of a single HBOT exposure (hours), and the number of HBOT treatments. Efficacy of HBOT (EfHBOT) data regarding the number of patients who showed significant clinical improvement of their neurologic status in the course of the treatment HBOT (the percentage of the total number of patients). The level of EfHBOT in each study was compared with a corresponding value of D HBOT. A comparison of the data shows a pronounced tendency H for higher values of EfHBOT as the level of the average values of the total DHBOT increases. The coefficient of correlation between these parameters appears to be fairly high (r = 0.92). The maximum possible value of EfHBOT is 100%, which corresponded to the average values of DHBOT at a level of no less than 30 agreed units. The examined data suggest that applying optimal total DHBOT may provide a maximum possible EfHBOT in treating patients with AIS.

Responses of rat brain to induced spreading depression following exposure to carbon monoxide

Until recently carbon monoxide (CO) was known only for its noxious effects. Exposure to CO results in an autoregulatory increase in cerebral blood flow (CBF). Little information is available on brain energy metabolism under low CO concentrations and on the effect of CO on the stimulated brain. In this study cortical spreading depression (SD) was induced in order to cause transient brain depolarization and increased energy demand. The multisite assembly (MSA), which contains four bundles of optical fibers for monitoring the intramitochondrial NADH redox state and tissue reflectance as well as four DC electrodes enabling measurement from four consecutive points on the cerebral cortex, was used to measure energy metabolism and the propagation of SD waves during exposure to CO. CBF in the contralateral hemisphere was measured using the laser Doppler technique. Three experimental groups of animals were examined: SD was induced during exposure to 1000 ppm CO, immediately after exposure to CO and 90 min after cessation of exposure to CO. Three control groups were also examined, in which the animals underwent the same procedures but were not exposed to CO. In all animals exposure to CO was followed by a significant increase in CBF. The greatest effect was found when SD was induced immediately after cessation of exposure to CO. SD wave frequency decreased when induced immediately after exposure to CO, whereas it increased when SD was induced 90 min after exposure. The amplitude of the NADH oxidation waves and their integral were smaller during SD induced immediately after exposure to CO. The DC potential did not change, suggesting that CO did not affect the SD initiation mechanism but rather resulted in energy depletion during recovery from SD. This study demonstrates that even at a concentration of 1000 ppm CO interferes with the metabolic activity of the brain during repolarization of the SD-induced negativity.

New multiparametric monitoring approach for real-time evaluation of drug tissue interaction in vivo

Drug–tissue interactions can be evaluated at various levels of biological organization. The effects of different drugs are widely tested in various sliced tissues or intact organs under in vitro conditions. Very few techniques have been applied to monitor functional state of organs under in vivo conditions. In this overview, a new multiparametric monitoring approach (MPA) is presented that could be applied to various organs (brain, heart, kidney) in vivo exposed to compound effects. Tissue blood flow is evaluated by laser Doppler flowmetry, mitochondrial function by surface fluorometry reflectometry of NADH, and membrane integrity by extracellular level of K+, Ca2+, H+, or Na+. Other parameters, e.g., EEG, ECG, ICP, or temperature represent the functional state of the organ. The construction of the multiprobe assembly was adopted to various experimental as well as clinical situations to monitor various organs. Typical examples of the application of the MPA to test the effects of alcohol on the rat brain or antiischemic compounds in the gerbil brain are shown. The results collected using the MPA methodology allowed the differentiation between the various effects of a tested compound at the biochemical and physiological levels and provided suggestions as to a possible mode of action under in vivo conditions. Drug Dev. Res. 50:457–470, 2000.

Effects of Fluid Percussion Injury on Rat Brain Hemodynamics, Ionic, Electrical Activity, and Energy Metabolism in Vivo

The most commonly used evaluation method for severity of brain injury in patients is the level of consciousness, which is measured by the Glasgow Coma Scale (GCS). The majority of cases admitted to hospitals alive are classified as “mild” (GCS 13-15), 10% as moderate (GCS 9-12) and 10% are classified as severe (GCS<_8)

Acute Respiratory Distress Syndrome in Patients after Blunt Thoracic Trauma: The Influence of Hyperbaric Oxygen Therapy

The rate of mortality from acute respiratory distress syndrome (ARDS) has reportedly reached as high as 50–75%.1−3 The risk of ARDS development increases after severe blunt thoracic trauma (BTT) because of a higher likelihood for lung contusion4 and acute depression of cardiac function.5, 6 Monitoring of oxygen transport in patients with ARDS has shown that oxygen delivery and consumption were significantly higher in the survivors compared to nonsurvivors.7 This suggests that maintenance of oxygen delivery at optimal levels can potentially enable the reversal of ARDS.8 In cases of severe BTT, these oxygen transport variables may be induced by early cardiorespiratory dysfunction6, 9 which requires inotropic support.6, 8, 10 On the strength of these data, it is reasonable to conclude that the prevention and correction of oxygen deficiency are basic to intensive care during ARDS.