Hyperbaric oxygen treatment reveals spatiotemporal OXPHOS plasticity in the porcine heart.

Cardiomyocytes meet their high ATP demand almost exclusively by oxidative phosphorylation (OXPHOS). Adequate oxygen supply is an essential prerequisite to keep OXPHOS operational. At least two spatially distinct mitochondrial subpopulations facilitate OXPHOS in cardiomyocytes, i.e. subsarcolemmal (SSM) and interfibrillar mitochondria (IFM). Their intracellular localization below the sarcolemma or buried deep between the sarcomeres suggests different oxygen availability. Here, we studied SSM and IFM isolated from piglet hearts and found significantly lower activities of electron transport chain enzymes and F1FO-ATP synthase in IFM, indicative for compromised energy metabolism. To test the contribution of oxygen availability to this outcome, we ventilated piglets under hyperbaric hyperoxic (HBO) conditions for 240 min. HBO treatment raised OXPHOS enzyme activities in IFM to the level of SSM. Complexome profiling analysis revealed that a high proportion of the F1FO-ATP synthase in the IFM was in a disassembled state prior to the HBO treatment. Upon increased oxygen availability, the enzyme was found to be largely assembled, which may account for the observed increase in OXPHOS complex activities. Although HBO also induced transcription of genes involved in mitochondrial biogenesis, a full proteome analysis revealed only minimal alterations, meaning that HBO-mediated tissue remodeling is an unlikely cause for the observed differences in OXPHOS. We conclude that a previously unrecognized oxygen-regulated mechanism endows cardiac OXPHOS with spatiotemporal plasticity that may underlie the enormous metabolic and contractile adaptability of the heart.

Reliability of the microdialysis pump CMA 107 under hyperbaric conditions.

OBJECTIVE: Microdialysis measurements of extracellular substances under hyperbaric conditions were manifold used in several investigations. However, to our knowledge there is no analysis, which verified the applicability of microdialysis pumps under hyperbaric conditions. Thus, a goal of this study was to investigate the reliability of the microdialysis pump (MDP) CMA 107 in a hyperbaric environment up to 2.4bar absolute pressure. METHODS: The CMA 107 with a perfusion rate of 2microL/min was stored in a decompression chamber. The ambient pressure was increased from 1 to 2.4bar absolute within 15min, maintained for 90min and then decreased to 1bar within 15min. The vials were changed every 15min, weighed before as well as after collecting the sample volume and the absolute recovery of glutamate, pyruvate, lactate, glucose and glycerol was determined. The same setup was performed under normobaric conditions. RESULTS: The pumping capacity was 1.7% greater than expected under normobaric conditions, 36.5% less than expected in the compression phase, 10.5% less than expected in the isopression phase and 26.3% greater than expected in the decompression phase under hyperbaric conditions. The absolute recoveries under hyperbaric conditions were affected during the isopression phase with a deviation from -6 to +20% compared to normobaric environments. CONCLUSION: The study demonstrated that an absolute ambient pressure up to 2.4bar did influence the pumping capacity and the reliability of the absolute recovery. These results need to be taken into consideration when interpreting microdialysis studies performed under hyperbaric conditions.

Endothelin-1 and cerebral blood flow in a porcine model.

The purpose of the study was to investigate whether provoked changes of cerebral perfusion pressure and arterial carbon dioxide tension are able to influence the cerebral metabolism of endothelin-1 (ET-1) in a porcine model. Brain tissue oxygen tension, regional cerebral blood flow and mean arterial blood pressure were monitored in 10 healthy pigs during induced hyperventilation (HV), hypertension (HrT) and hypotension (HoT). ET-1 was determined in the arterial and cerebrovenous blood. Microdialysis samples (lactate, glucose and pyruvate) were taken from brain and subcutaneous tissue. A significant decrease (p<0.05) of the arterial ET-1 (1.46+/-0.33 fmol/mL) compared to the baseline (2.18+/-0.36 fmol/mL) was observed after the HoT-period. We detected a positive correlation between cerebrovenous ET-1 and extracellular cerebral glucose (0.68; p<0.05) after the baseline as well as a negative correlation of -0.81 (p<0.005) between the cerebrovenous ET-1 level and the extracellular cerebral lactate after the HoT-period. These data imply that with increasingly pathological changes of the cerebral metabolism endothelin becomes progressively more important in the regulation of cerebral vascular tone.

Influence of moderate and profound hyperventilation on cerebral blood flow, oxygenation and metabolism.

OBJECTIVE: The aim of the present study was to examine the impact of moderate and profound hyperventilation on regional cerebral blood flow (rCBF), oxygenation and metabolism. MATERIALS AND METHODS: Twelve anesthetized pigs were subjected to moderate (mHV) and profound (pHV) hyperventilation (target arterial pO(2): 30 and 20 mmHg, respectively) for 30 min each, after baseline normoventilation (BL) for 1 h. Local cerebral extracellular fluid (ECF) concentrations of glucose, lactate, pyruvate and glutamate as well as brain tissue oxygenation (p(ti)O(2)) were monitored using microdialysis and a Licox oxygen sensor, respectively. In nine pigs, regional cerebral blood flow (rCBF) was also continuously measured via a thermal diffusion system. RESULTS: Both moderate and profound hyperventilation resulted in a significant decrease in rCBF (BL: 37.9+/-4.3 ml/100 g/min; mHV: 29.4+/-3.6 ml/100 g/min; pHV: 23.6+/-4.7 ml/100 g/min; p<0.05) and p(ti)O(2) (BL: 22.7+/-4.1 mmHg; mHV: 18.9+/-4.9 mmHg; pHV: 13.0+/-2.2 mmHg; p<0.05). A p(ti)O(2) decrease below the critical threshold of 10 mmHg was induced in three animals by moderate hyperventilation and in five animals by profound hyperventilation. Furthermore, significant increases in lactate (BL: 1.06+/-0.18 mmol/l; mHV: 1.36+/-0.20 mmol/l; pHV: 1.67+/-0.17 mmol/l; p<0.005), pyruvate (BL: 46.4+/-7.8 micromol/l; mHV: 58.0+/-10.3 micromol/l; pHV: 66.1+/-12.7 micromol/l; p<0.05), and lactate/glucose ratio were observed during hyperventilation. (Data are presented as mean+/-S.E.M.) CONCLUSIONS: Both moderate and profound hyperventilation may result in insufficient regional oxygen supply and anaerobic metabolism, even in the uninjured brain. Therefore, the use of hyperventilation cannot be considered as a safe procedure and should either be avoided or used with extreme caution.

Reliability of the NeuroTrend sensor system under hyperbaric conditions.

OBJECTIVE: The goal of this study was to investigate the reliability of the multi-parameter sensor NeuroTrend in a hyperbaric environment for up to 3bar absolute pressure. Measurement of brain tissue oxygenation (ptiO2) under hyperbaric conditions is supposed to elucidate whether hyperbaric oxygenation therapy has the potential to improve ptiO2 to a clinically significant degree in pathological altered brain tissue after traumatic brain injury. METHODS: The NeuroTrend sensor hose, filled with equilibrated plasma samples, was stored in a decompression chamber. The plasma samples were equilibrated with three different gas mixtures. After determination of the initial values for temperature, oxygen partial pressure (pO2), carbon dioxide partial pressure (pCO2) and hydrogen ion concentration (pH) in the plasma, the ambient pressure was stepwise increased from 0.1 to 3 bar. The same set-up was performed without increasing the ambient pressure. RESULTS: No significant difference in the mean values for all 23 measurement points and for all parameters (pO2, pCO2, pH) of all 10 NeuroTrend sensors was found, under both normobaric and hyperbaric conditions. CONCLUSION: The study demonstrated that an absolute ambient pressure up to 3 bar did not influence the measuring properties and the reliability of the NeuroTrend sensor.

Experiences with continuous intra-arterial blood gas monitoring: precision and drift of a pure optode-system.

OBJECTIVE: The utility of continuous intra-arterial blood gas analysis (CBGA) with combined electrochemical and optode sensors has been demonstrated. More recently, a pure optode sensor with a changed sensing element architecture has become available. The aim was to determine the measurement accuracy and long-term stability of the new sensor. DESIGN: A prospective explorative study was performed. Simultaneous measurements of intermittent blood gas analyses (IBGA) (ABL 610, Radiometer, Copenhagen) and CBGA (Diametrics Medical, High Wycombe, Bucks., UK) were compared using Bland-Altman analysis. PATIENTS: Twenty-five patients admitted to the ICU and requiring mechanical ventilation for an expected minimum of about 96 h were included. RESULTS: Mean monitoring time was 106.1 (range 15-231) hours. Bias and precision for PO(2 )were -0.2 kPa (1%)+/-1.8 kPa (9.5%); PCO(2): 0.03 kPa (0.6%)+/-0.44 kPa (9.3%); pH: -0.001 (0.01%)+/-0.04 (0.45%). The sensor showed no change of measurement characteristics during 4 days of measurement. However, in 69 cases continuous monitoring was interrupted (reversible sudden drops of PO(2) measurement) possibly caused by thrombotic deposition and/or sensor bending and accidental sensor retraction. CONCLUSIONS: The precision and bias of the PCO(2)- and pH-sensing elements were in line with the findings of the older sensor technology. The possibility that the PO(2) optode could offer greater accuracy than the older technology is suggested by comparisons with results reported in previous studies. No sensor drift occurred during long-term measurement over more than 4 days.