Influence of hyperoxia on diastolic myocardial and arterial endothelial function.

OBJECTIVE: Hyperoxia is known to influence cardiovascular and endothelial function, but it is unknown if there are differences between younger and older persons. The aim of this study was to monitor changes in myocardial diastolic function and flow-mediated dilatation (FMD) in younger and elderly volunteers, before and after exposure to relevant hyperbaric hyperoxia. METHODS: 51 male patients were separated into two groups for this study. Volunteers in Group 1 (n=28, mean age 26 ±6, "juniors") and Group 2 (n=23, mean age 53 ±9, "seniors") received standard HBO2 protocol (240kPa oxygen). Directly before and after hyperoxic exposure in a hyperbaric chamber we took blood samples (BNP, hs-troponin-t), assessed the FMD and echocardiographic parameters with focus on diastolic function. RESULTS: After hyperoxia we observed a high significant decrease in heart rate and systolic/diastolic FMD. Diastolic function varied in both groups: E/A ratio showed a statistically significant increase in Group 1 and remained unchanged in Group 2. E/e' ratio showed a slight but significant increase in Group 1, whereas e'/a' ratio increased in both groups. Deceleration time increased significantly in all volunteers. Isovolumetric relaxation time remained unchanged and ejection fraction showed a decrease only in Group 2. There were no changes in levels of BNP and hs-troponin-t in either group. CONCLUSION: Hyperoxia seems to influence endothelial function differently in juniors and seniors: FMD decreases more in seniors, possibly attributable to pre-existing reduced vascular compliance. Hyperoxia-induced bradycardia induced a more pronounced improvement in diastolic function in juniors. The ability of Group 1 to cope with hyperoxia-induced effects did not work in the same manner as with Group 2.

Dose-time dependency of hyperbaric hyperoxia-induced DNA strand breaks in human immune cells visualized with the comet assay.

PURPOSE: Hyperbaric oxygen exposure may induce dose-dependent DNA damage in peripheral blood mononuclear cells (PBMCs), and repetitive exposures of man may have protective cellular effects. METHOD: PBMCs, freshly isolated from non-divers and pure oxygen divers, were exposed to ambient air (21kPa) and hyperoxia at different levels: 100kPa, 240kPa, 400kPa and 600kPa) for up to 6.5 hours in an experimental pressure chamber. DNA double-strand breaks were studied in the comet assay by calculating the "tail moment" and an alternative "Yes or No" method for damaged nuclei. Previously, the experimental procedure had been optimized for human cell experiments: Pre-tests assured that DNA damage could be considered to be oxygen-induced; and cell viability remained over 95% during exposure time. RESULTS: Visible DNA damage increased with the partial pressure of oxygen (pO2) and exposure time dose-dependently. Linear regressions revealed r2 between 0.61 and 0.98 with the Yes/No method, and significant differences in slopes from control. Tail moment showed similar results, but with less accuracy. The PBMCs of oxygen divers exposed to 400kPa pO2 (up to six hours) showed a significant lower slope in the linear regression. CONCLUSION: Oxygen induces dose-dependent DNA double-strand breaks, and the Yes/No discrimination is superior to the tail moment in linearity and accuracy. Oxygen diver PBMCs seem to be more resistant to hyperbaric oxygen.

Influence of hyperoxia and physical exercise on *OH-radical stress in humans as measured by dihydroxylated benzoates (DHB) in urine.

BACKGROUND: Hyperoxia and physical exercise are known to produce reactive oxygen species (ROS), and the *OH radical is the most aggressive among them. However, knowledge is limited about *OH stress during physical work under hyperoxic conditions. METHODS: This study monitored *OH stress in human volunteers before and after a total of 135 exposures to ambient air (control), different levels of hyperoxia at rest and challenging open-water closed-circuit dives by measurement of dihydroxylated benzoates (DHB) with HPLC by electrochemical detection in urine. RESULTS: Changes in DHB in urine after control were only 3.43 +/- 4.8% (n = 9). After exposures to 100 kPa oxygen (O2) for 110 minutes DHB revealed increases in urine of 23.14 +/- 5.12% (n = 9); exposures to 240 kPa O2 for 90 minutes increases of 22.38 +/- 8.91% (n = 8); and 280 kPa 02 for 30 minutes of 21.92 +/- 10.76% (n = 17). Closed-circuit dives in open water (45-54 minutes of 125-160 kPa O2) revealed DHB increases of 66.34 +/- 25.73% (n = 92). All results differed significantly from control (p < 0.001). The closed-circuit dives also differed significantly from all exposures to hyperoxia without exercise (p < 0.001). Standardization of "oxygen burden" during each exposure (pO2 x exposure time x VO2) allowed for comparison of different exposures vs. DHB changes and revealed goodness of linear fit of r2 = 0.432 (p < 0.0001). CONCLUSIONS: Increases in urine DHB after exposures to different levels of hyperoxia at rest and during exercise are consistent with *OH stress that is greater during exercise than at rest, although other interpretations are possible. Standardization of the individual "oxygen burden" for a given exposure may become useful in future for the estimation of *OH stress.

Physical exercise might influence the risk of oxygen-induced acute neurotoxicity.

OBJECTIVE: Hyperoxia can induce acute neurotoxicity with generalized seizures. Hyperoxia-induced reduction in cerebral blood flow velocity (CBFV) might be protective. It is unclear whether dynamic exercise during hyperoxia can overcome CBFV-reduction and thus possibly increase the risk of neurotoxicity. METHODS: We studied CBFV with both-sided transcranial Doppler with fixed transducer-position and heart rate under increasing hyperoxic conditions in nine professional military oxygen divers. The divers performed dynamic exercise on a bicycle-ergometer in a hyperbaric chamber (ergometries I-III, 21kPa, 100kPa, 150kPa pO2), with continuous blood pressure (ergometries I, II), end-tidal CO2 (PetCO2; ergometry I) being measured. RESULTS: Systolic (CBFVsyst) and diastolic CBFV (CBFVdiast) readings at rest decreased with increasing pO2. During exercise, CBFVsyst and CBFVdiast significantly increased in parallel with increasing pO2, despite reduced flow velocities at rest. ERGOMETRY I: CBFVsyst increased from 65.0 +/- 11.3 cm/second at rest to 80.2 +/- 23.4cm/s during maximum workload (n.s.), diastolic from 14.5 +/- 4.1 cm/second to 15.6 +/- 7.5 cm/s (n.s.). PetCO2 increased from 43.4 +/- 7.8mmHg to 50.0 +/- 7.5mmHg. ERGOMETRY II: CBFVsyst increased from 58.2 +/- 16.5 cm/second to 99.7 +/- 17.0 cm/s (p<0.001), diastolic from 14.0 +/- 10.7 cm/second to 29.4 +/- 11.1 cm/second (p<0.01). ERGOMETRY III: CBFVsyst increased from 54.4 +/-15.0cm/second to 109.4 +/- 22.3cm/s (p<0.001), diastolic from 14.7 +/- 10.4 cm/second to 35.5 +/- 9.3 cm/second (p<0.01). INTERPRETATION: Physical exercise overrules the decrease in CBFV during hyperoxia and leads to even higher CBFV-increases with increasing pO2. A tendency towards CO2 retainment with elevated PetCOz may be causative and thus heighten the risk of oxygen-induced neurotoxicity.

Monitoring of CBFV and time characteristics of oxygen-induced acute CNS toxicity in humans.

BACKGROUND: Hyperbaric oxygen can cause central nervous system (CNS) toxicity with seizures. We tested the hypothesis that CNS toxicity could be predictable by cerebral blood flow velocity (CBFV) monitoring. METHOD: We monitored 369 mandatory oxygen tolerance tests (30 min, 280 kPa O(2)) by video-documentation and since May 2005 by additional CBFV registration (n = 61). RESULTS: The onset of early manifestations of CNS toxicity was documented in 11 of 369 tests within 22 +/- 3 min. These included twitches and/or agitation, 6 of 11 and tonic-clonic seizures in 5 of 11 cases. In both cases with CBFV monitoring, an increase in CBFV preceded symptom onset, once followed by seizure, once without seizure after timely oxygen reduction. CONCLUSIONS: During exposure to 280 kPa oxygen at rest a constant delay of approximately 20 min precedes the onset of central nervous oxygen toxicity. An increase in CBFV may indicate the impending seizure.

[Diabetes mellitus--a free radical-associated disease. Results of adjuvant antioxidant supplementation]. / Diabetes mellitus--eine mit Freien Radikalen assoziierte Erkrankung. Resultate einer adjuvanten Antioxidantiensupplementation.

Our investigations carried out in patients with diabetes mellitus revealed oxidative stress loads. The study presented here was to clarify whether a therapy with antioxidants can contribute to an improvement of prognosis. 80 patients affected with a long term diabetic late syndrome were randomised and arranged to 4 groups of n = 20 each. In contrast to a control group these patients received 600 mg of alpha lipoic acid or 100 micrograms of selenium (sodium selenite) daily or 1200 IE of D-alpha-tocopherol respectively for a time of 3 months. In comparison with the control group all groups treated in an antioxidative way showed significantly diminished serum concentrations of thiobarbituric acid reactive substances and of urinary albumin excretion rates. The symptoms of distal symmetric neuropathy measured according to the thermo- and vibration sensitivity also improved in a highly significant manner. The results prove that oxidative stress plays a promoting role in developing of long term diabetic late complications and that a therapy with adjuvant antioxidants may lead to a regression of diabetic late complications.