Assessment of hyperbaric oxygenation treatment response in parotid glands by T2 mapping following radiotherapy for head and neck tumours.

BACKGROUND: The study was designed to evaluate the influence of hyperbaric oxygenation therapy (HBOT) on the parotid gland in patients following radiotherapy for head and neck tumours. PATIENTS AND METHODS: HBOT response was monitored by 3T magnetic resonance imaging (MRI) using T2 mapping and subsequent measurement of mean T2 and T2 variability as well as by salivary tests (salivary flow, buffer capacity, and pH). Eighteen patients previously treated with irradiation doses between 50 and 80 Gy as well as 18 healthy gender and age matched controls were enrolled. MRI was performed prior to HBOT (40.2 ± 20 months after radiotherapy) and after 20 daily HBOT at 2.5 ATA (absolute atmosphere). Each HBOT consisted of breathing 100% oxygen for 90 minutes. RESULTS: Significant differences in mean T2 prior to HBOT were observed between the ipsilateral irradiated (121 ± 20 ms), contralateral parotids (107 ± 21) and control group (96 ± 12 ms). A positive correlation in patients between T2 variability and irradiation dose was detected in contralateral parotids before HBOT (R = 0.489, p = 0.0287). In addition, negative correlations were observed between mean T2 in the ipsilateral as well as the contralateral gland and salivary flow before and after HBOT. Negative correlations between mean T2, T2 variability and pH of unstimulated saliva were also observed in the sides of parotid before and after HBOT. CONCLUSIONS: The study confirmed that T2 mapping had a potential for monitoring the differences between irradiated and normal parotid glands. It could also be useful in the assessment of the glandular tissue response to HBOT.

Thermal balance of spinal cord injured divers during cold water diving: A case control study.

INTRODUCTION: This study compared the thermal balance of spinal cord injured (SCI) divers and able-bodied (AB) divers during recreational cold-water dives. METHODS: Ten divers (5 AB, 5 SCI) in matched pairs dived in a shallow lake (temperature 6°C) for 30 to 36 min wearing 5 mm 'Long John' neoprene wetsuits. A gastrointestinal temperature radio pill recorded gastro-intestinal temperature (Tgi) prior to, immediately after and at 5, 10, 15, 30, 60, 120 min post-dive. Subjective ratings of temperature perception were recorded concomitantly using a visual analogue scale (VAS). RESULTS: No difference between SCI and AB divers in Tgi before the dive was observed (P = 0.85). After the dive, SCI divers cooled significantly more than AB at all measured time intervals (P < 0.001). Post dive, the mean maximum fall in Tgi during the recovery phase in SCI divers was 0.85°C (SD 0.20) and in the AB group was 0.48°C (0.48). In addition, there was greater individual variation in SCI divers compared to AB divers. There were no statistically significant differences in temperature perception between the groups either before or at any time after the dives. CONCLUSIONS: In contrast to AB divers, divers with SCI were unable to maintain Tgi during short shallow dives in 6°C water and their temperatures fell further post-dive. The reduction in Tgi was not reflected in the subjective ratings of temperature perception by the SCI divers. The study was too small to assess how the level of spinal injury influenced thermal balance.

Comparative effects of calcium and potassium channel modulators on ischemia/reperfusion injury in the isolated rat heart.

The aim of this study was to examine and compare the effects of the acute administration of verapamil or amlodipine as representatives of the calcium channel blockers or nicorandil as a representative of the mitochondrial ATP-dependent potassium (KATP) channel opener to cardiac contractility, coronary flow, and oxidative stress markers on ischemia/reperfusion injury in the isolated rat heart. The hearts of adult male Wistar albino rats (n = 60 total, 12 per group) were divided into five groups, two controls (preconditioning with Krebs-Henseleit solution) and three experimental depending on acute administrated pharmacological agents (0,63 µmol/L of verapamil, 0,1 µmol/L of amlodipine, and 200 µmol/L of nicorandil). After stabilization and 5 min of preconditioning in experimental groups, hearts from I/R control and all experimental groups underwent global ischemia (20 min) and reperfusion (30 min). Hearts from sham group were continuously followed for 50 min, after stabilization period. Cardiodynamic parameters and coronary flow were recorded at the end of stabilization (S), at the last minute of pharmacological preconditioning (P) and at intervals of 5 min after global ischemia, during reperfusion, or in case of sham group during 20-50 min after stabilization. At the same intervals, we collected coronary venous effluent from which we spectrophotometrically measured the parameters of oxidative stress: the index of lipid peroxidation, superoxide anion radical, hydrogen peroxide, and nitrite. In summary, our findings clearly indicate that the blocking of the calcium channel or the activation of KATP may mediate the protective effect of myocardial preconditioning. The ex vivo results showed that all examined drugs after ischemia and reperfusion have beneficial cardioprotective properties associated with lower values of major pro-oxidative molecules. Obtained effects seem to be the most convincible in case of nicorandil.

Cardiac autonomic modulation induced by doxorubicin in a rodent model of colorectal cancer and the influence of fullerenol pretreatment.

The very effective anticancer drug doxorubicin (DOX) is known to have cardiotoxic side effects, which could be accompanied by autonomic modulation. Autonomic disbalance might even be an initiating mechanism underlying DOX-induced cardiotoxicity and can be studied noninvasively by the analysis of heart rate variability (HRV). A number of strategies have been assessed to predict chemotherapy-induced cardiac dysfunction while HRV, a potential detecting tool, has not yet been tested. Thus, we aimed to determine the effect of DOX treatment on HRV in a rat model of colorectal cancer. While pretreatment with fullerenol (Frl) acts protectively on DOX-induced cardiotoxicity, we aimed to test the effect of Frl pretreatment on DOX-induced HRV alterations. After the induction of colorectal cancer, adult male Wistar rats were treated with saline (n = 7), DOX (1.5 mg/kg per week, n = 7) or DOX after pretreatment with Frl (25 mg/kg per week, n = 7) for three weeks (cumulative DOX dose 4.5 mg/kg). One week after treatment rats were anaesthetized, standard ECG was measured and HRV was analyzed in time and frequency domain. During autopsy the intestines and hearts were gathered for biochemical analysis and histopathological examination. DOX treatment significantly decreased parasympathetically mediated high-frequency component (p<0.05) and increased the low-frequency component of HRV (p<0.05), resulting in an increased LF/HF ratio (p<0.05) in cancerous rats. When pretreated with Frl, DOX-induced HRV alterations were prevented: the high-frequency component of HRV increased (p<0.01), the low-frequency decreased (p<0.01), LF/HF ratio decreased consequently (p<0.01) compared to DOX only treatment. In all DOX-treated animals, disbalance of oxidative status in heart tissue and early myocardial lesions were found and were significantly reduced in rats receiving Frl pretreatment. Autonomic modulation accompanied the development of DOX-induced cardiotoxicity in rat model of colorectal cancer and was prevented by Frl pretreatment. Our results demonstrated the positive prognostic power of HRV for the early detection of DOX-induced cardiotoxicity.

The effectiveness of oxygen therapy in carbon monoxide poisoning is pressure- and time-dependent: a study on cultured astrocytes.

Carbon monoxide (CO) poisoning causes neuronal and glial apoptosis that can result in delayed neurological symptoms. The damage of brain cells can be prevented by oxygen therapy. Based on the central role of astrocytes in maintaining neuronal function and viability we investigated the toxic effects of 3000ppm CO in air followed by 24h of normoxia and evaluated the possible protective influence of 100% normobaric oxygen or 100% oxygen at a pressure of 3bar (hyperbaric) against CO poisoning in these cells. CO/normoxia caused a progressive decline of viability, increase in reactive oxygen species and decline of mitochondrial membrane potential and intracellular ATP levels in cultured rat astrocytes. Increased caspase-9, caspase-8 and calpain activity converged in activation of caspase-3/7. 1h treatment with oxygen disclosed pressure- and time-dependent efficacy in restoring astrocytic mitochondrial function and the prevention of apoptosis. The protective effect was most evident when the astrocytes were exposed to hyperbaric oxygen, but not normobaric oxygen, 1-5h after exposure to CO.

Cold perception and cutaneous microvascular response to local cooling at different cooling temperatures.

The aim of the present study was to investigate the effect of quantitatively measured cold perception (CP) thresholds on microcirculatory response to local cooling as measured by direct and indirect response of laser-Doppler (LD) flux during local cooling at different temperatures. The CP thresholds were measured in 18 healthy males using the Marstock method (thermode placed on the thenar). The direct (at the cooling site) and indirect (on contralateral hand) LD flux responses were recorded during immersion of the hand in a water bath at 20°C, 15°C, and 10°C. The cold perception threshold correlated (linear regression analysis, Pearson correlation) with the indirect LD flux response at cooling temperatures 20°C (r=0.782, p<0.01) and 15°C (r=0.605, p<0.01). In contrast, there was no correlation between the CP threshold and the indirect LD flux response during cooling in water at 10°C. The results demonstrate that during local cooling, depending on the cooling temperature used, cold perception threshold influences indirect LD flux response.

The time-dependent protective effect of hyperbaric oxygen on neuronal cell apoptosis in carbon monoxide poisoning.

INTRODUCTION: The progressive clinical course with delayed neurological damage in carbon monoxide (CO) poisoning may be due to neuron apoptosis. The usefulness of hyperbaric oxygen (HBO) in different time periods after CO exposure in neuronal cell apoptosis reduction has not been evaluated thus far. The aim was to evaluate HBO efficacy in reducing neuronal apoptosis in different time periods after CO exposure. METHODS: Wistar rats were exposed to 3000 ppm CO in air for 60 min and 100% oxygen at a pressure of three bar for 30 min 0-12 h after CO exposure. The apoptosis was evaluated by immunohistochemical analysis with antibodies against activated caspase-3 and the percentage of caspase-3 positive hippocampal ganglionic cells was reported. RESULTS: It was shown that CO poisoning results in ganglionic cell apoptosis. The percentage of apoptotic cells in rats exposed to CO was the highest (32%), whereas the percentage of apoptotic cells in rats exposed to HBO 0 and 1 h after CO was similar with a lower percentage than rats exposed to CO. The percentage of apoptotic cells in rats exposed to HBO 3 and 5 h after CO was similar with a lower percentage than rats exposed to HBO 0 and 1 h after CO. The percentage of apoptotic cells in rats exposed to HBO 7-12 h after CO was similar with a higher percentage than rats exposed to HBO 5 h after CO. CONCLUSION: HBO has a time-dependent protective effect on CO-induced neuron apoptosis with the highest efficiency at 3 and 5 h after CO poisoning.

Effect of hypobaric hypoxia on heart rate variability during exercise: a pilot field study.

The influence of hypoxia on heart rate variability (HRV) has been studied under resting conditions with mixed results. Differences have been found in physiological responses to normobaric versus hypobaric hypoxia. Our aim was to study the influence of hypobaric hypoxia on HRV during physical exercise to determine whether HRV changes due to the exercise-induced heart rate (HR) increase or whether hypoxia itself exerts an influence. We tested nine healthy non-acclimatised white males (age = 43 +/- 7 years) at 400 and 4,200 m during exercises. At 400 m HRV was measured at 50% and 75% maximal oxygen uptake (VO(2) max). At 4,200 m HR was kept equal as during exercise at 400 m by adjusting the intensity of step testing. The Poincaré plot as a non-linear method of HRV analysis was used, where the shape of the ellipse depending on HRV is expressed by two parameters, SD1 and SD2 (correlating to parasympathetic activity and both sympathetic and parasympathetic activity, respectively). We established a decrease in SD2 and an insignificant decrease in SD1 at medium HR at 4,200 m compared to 400 m. Both parameters showed similar tendencies during high-intensity exercise. Our results indicate that hypobaric hypoxia itself exerts an influence on HRV at a moderate HR.

Linear and nonlinear assessment of heart rate variability in nonacclimatized middleaged subjects at different hypoxic levels.

Studies of autonomic cardiac nervous system activity during acute exposure to hypobaric hypoxia have suggested a depression of autonomic functions and a shift in the sympatho-vagal balance towards relatively more sympathetic and less parasympathetic activity at higher hypoxic levels . This study was performed on nine non-acclimatized middle-aged healthy men (age 43.7 +/- 7.3 years), to evaluate the linear (autoregressive spectra) and non-linear (Poincaré plot, b coefficient, fractal dimension) heart rate variability (HRV) parameters at rest in supine position at three different altitudes: 400 m, 3200 m and 4200 m. A statistically significant increase of heart rate (HR) was detected at both higher altitudes in comparison with the reference level as well as comparing the values observed at 3200 m and 4200 m, respectively. Acute exposure to both hypoxic levels (3200 m and 4200 m) induced a shift of sympatho-vagal balance towards more sympathetic and less parasympathetic activity in comparison to the basal condition at 400 m asl, as indicated by autoregressive LF and HF spectral components and in particular by LF/HF ratio. The non-linear ss coefficient values demonstrated a statistically significant decrease of the complexity of the system at both hypoxic conditions as effect of hypobaric hypoxia on ANS activity of myocardium. However this fact was not confirmed by the fractal dimension parameter.

Immediate oxygen therapy prevents brain cell injury in carbon monoxide poisoned rats without loss of consciousness.

In CO-poisoned patients without loss of consciousness no significant long-term functional differences in outcome have been shown in any hyperbaric versus normobaric oxygen studies. Since brain histology changes cannot be studied in CO-poisoned patients we evaluated the efficacy of normobaric and hyperbaric oxygen therapy in preventing brain cell injury in CO-poisoned animals without loss of consciousness. Wistar rats without loss of consciousness after exposure to 3000ppm of CO for 60min were exposed to ambient air (group 1), 100% oxygen at a pressure of 1bar (group 2) and 100% oxygen at a pressure of 3bar (group 3). The rats were sacrificed after two weeks, brain samples were stained with hematoxylin-eosin and a percentage of pyknotic cells in hippocampus was reported. Analyses of differences in percentage of pyknotic cells between different kinds of therapy showed that the percentage of pyknotic cells of the second group (2.3+/-1.2%) treated with normobaric oxygen and the third group (4.5+/-4.0%) treated with hyperbaric oxygen were similar, and both of them were significantly different, with a much lower percentage of pyknotic cells, from the first group left on ambient air (47.7+/-10.0%). In conclusion, immediate normobaric and hyperbaric oxygen therapy equally prevents hippocampal cell injury in CO-poisoned rats without loss of consciousness.

S100B protein in conscious carbon monoxide-poisoned rats treated with normobaric or hyperbaric oxygen.

OBJECTIVE: To evaluate S100B, an astroglial structural protein, during normobaric and hyperbaric oxygen therapy of conscious carbon monoxide (CO)-poisoned rats. So far, the usefulness of hyperbaric oxygen therapy in conscious CO-poisoned patients has been shown with neuropsychological testing. The S100B protein has been demonstrated as a possible biochemical marker and prognostic parameter in CO-poisoned rats. DESIGN: Randomized, controlled interventional trial. SETTING: University laboratory. SUBJECTS: : Male Wistar rats weighing 254 +/- 14 g. INTERVENTIONS: The rats were exposed to a mixture of 3,000 ppm CO in air for 60 mins. After CO exposure, the first group of eight conscious rats was exposed to ambient air for 30 mins, the second group of six conscious rats was exposed to 100% normobaric oxygen for 30 mins, and the third group of six conscious rats was exposed to 100% hyperbaric oxygen at 3 bars for 30 mins. Blood samples were taken from the jugular vein just before CO exposure and immediately after oxygen therapy. The level of consciousness was evaluated at the end of exposure, and the survival rate was monitored for 14 days. The S100B concentrations were measured with a commercial immunoluminometric assay. MEASUREMENTS AND MAIN RESULTS: Analyses of differences in S100B levels between different kinds of therapy before and after treatment showed a global significant difference (p = .002). The post hoc test results showed that S100B levels after therapy of the first group treated with ambient air (0.16 +/- 0.07 microg/L) and the second group treated with normobaric oxygen (0.19 +/- 0.05 microg/L) were similar (p = .741), and both of them were significantly different, with much higher values of S100B levels after therapy, from the third group treated with hyperbaric oxygen (0.06 +/- 0.03 microg/L; p = .018 and p = .002, respectively). All the rats survived. CONCLUSIONS: S100B is elevated in conscious CO-poisoned rats left on ambient air or treated with normobaric oxygen, but not in conscious CO-poisoned rats treated with hyperbaric oxygen.