Zhong-Jin Yang

Introduction: Ischemia/reperfusion (I/R) injury, such as myocardial infarction, stroke, and peripheral vascular disease, has been recognized as the most frequent causes of devastating disorders and death currently. Protective effect of various preconditioning stimuli, including hyperbaric oxygen (HBO), has been proposed in the management of I/R.Methods: In this study, we searched and reviewed up‐to‐date published papers to explore the pathophysiology of I/R injury and to understand the mechanisms underlying the protective effect of HBO as conditioning strategy.Results: Animal study and clinic observation support the notion that HBO therapy and conditioning provide beneficial effect against the deleterious effects of postischemic reperfusion. Several explanations have been proposed. The first likely mechanism may be that HBO counteracts hypoxia and reduces I/R injury by improving oxygen delivery to an area with diminished blood flow. Secondly, by reducing hypoxia–ischemia, HBO reduces all the pathological events as a consequence of hypoxia, including tissue edema, increased affective area permeability, postischemia derangement of tissue metabolism, and inflammation. Thirdly, HBO may directly affect cell apoptosis, signal transduction, and gene expression in those that are sensitive to oxygen or hypoxia. HBO provides a reservoir of oxygen at cellular level not only carried by blood, but also by diffusion from the interstitial tissue where it reaches high concentration that may last for several hours, improves endothelial function and rheology, and decreases local inflammation and edema.Conclusion: Evidence suggests the benefits of HBO when used as a preconditioning stimulus in the setting of I/R injury. Translating the beneficial effects of HBO into current practice requires, as for the “conditioning strategies”, a thorough consideration of risk factors, comorbidities, and comedications that could interfere with HBO‐related protection.

Background and aims: Dysfunction of GABAergic inhibitory controls contributes to the development of neuropathic pain. We examined our hypotheses that (1) chronic constriction injury (CCI)-induced neuropathic pain is associated with increased spinal GABAergic neuron apoptosis, and (2) hyperbaric oxygen therapy (HBO) alleviates CCI-induced neuropathic pain by inhibiting GABAergic neuron apoptosis. Methods: Male rats were randomized into 3 groups: CCI, CCI+HBO and the control group (SHAM). Mechanical allodynia was tested daily following CCI procedure. HBO rats were treated at 2.4 atmospheres absolute (ATA) for 60 min once per day. The rats were euthanized and the spinal cord harvested on day 8 and 14 post-CCI. Detection of GABAergic cells and apoptosis was performed. The percentages of double positive stained cells (NeuN/GABA), cleaved caspase-3 or Cytochrome C in total GABAergic cells or in total NeuN positive cells were calculated. Results: HBO significantly alleviated mechanical allodynia. CCI-induced neuropathic pain was associated with significantly increased spinal apoptotic GABA-positive neurons. HBO considerably decreased these spinal apoptotic cells. Cytochrome-C-positive neurons and cleaved caspase-3-positive neurons were also significantly higher in CCI rats. HBO significantly decreased these positive cells. Caspase-3 mRNA was also significantly higher in CCI rats. HBO reduced mRNA expression of caspase-3. Conclusions: CCI-induced neuropathic pain was associated with increased apoptotic GABAergic neurons induced by activation of key proteins of mitochondrial apoptotic pathways in the dorsal horn of the spinal cord. HBO alleviated CCI-induced neuropathic pain and reduced GABAergic neuron apoptosis. The beneficial effect of HBO may be via its inhibitory role in CCI-induced GABAergic neuron apoptosis by suppressing mitochondrial apoptotic pathways in the spinal cord. Implications: Increased apoptotic GABAergic neurons induced by activation of key proteins of mitochondrial apoptotic pathways in the dorsal horn of the spinal cord is critical in CCI-induced neuropathic pain. The inhibitory role of HBO in GABAergic neuron apoptosis suppresses ongoing neuropathic pain.

The effects of the ketogenic diet (KD) on weight loss, metabolic, and respiratory parameters were investigated in healthy subjects. Thirty-two healthy subjects were randomized into two groups. The KD group followed a ketogenic diet for 20 days (KD t ₀–t ₂₀), then switched to a low-carbohydrate, no-ketogenic diet for 20 days (KD t ₂₀–t ₄₀), and finally was on a Mediterranean diet (MD) for 2 more months (KD t ₄₀–t _2m). The MD group followed a MD for 20 days (MD t ₀–t ₂₀), then followed a MD of 1400 kcal over the next 20 days (MD t ₂₀–t ₄₀), and completed the study with the MD for 2 months (MD t ₄₀–t _2m). Body weight, body fat, respiratory rate, and respiratory gas parameters (including respiratory exchange ratio (RER) and carbon dioxide end-tidal partial pressure (PETCO₂), oxygen uptake (VO₂), carbon dioxide production (VCO₂), and resting energy expenditure (REE)) were measured at each point. A significant decrease (p < 0.05) in RER was observed after 20 and 40 days in the KD group, but not in the MD group. In the KD group, significant reductions were observed for both carbon dioxide output and PETCO₂, however, there was no significant change in VO₂, VCO₂, and REE. While both diets significantly decreased body fat mass, the KD diet overall proved to have a higher percentage of fat loss versus the MD diet. The KD may significantly decrease carbon dioxide body stores, which may theoretically be beneficial for patients with increased carbon dioxide arterial partial pressure due to respiratory insufficiency or failure.

Organisms are known to be equipped with an adaptive plasticity as the phenotype of traits in response to the imposed environmental challenges as they grow and develop. In this study, the effects of extreme changes in oxygen availability and atmospheric pressure on physiological phenotypes ofDrosophila melanogasterwere investigated to explore adaptation mechanisms. The changes in citrate synthase activity (CSA), lifespan, and behavioral function in different atmospheric conditions were evaluated. In the CAS test, hyperoxia significantly increased CSA; both hypoxia and hyperbaric conditions caused a significant decrease in CSA. In the survivorship test, all changed atmospheric conditions caused a significant reduction in lifespan. The lifespan reduced more after hypoxia exposure than after hyperbaria exposure. In behavioral function test, when mechanical agitation was conducted, bang‐sensitive flies showed a stereotypical sequence of initial muscle spasm, paralysis, and recovery. The percentage of individuals that displayed paralysis or seizure was measured on the following day and after 2 weeks from each exposure. The majority of flies showed seizure behavior 15 days after exposure, especially after 3 h of exposure. The percentage of individuals that did not undergo paralysis or seizure and was able to move in the vial, was also tested. The number of flies that moved and raised the higher level of the vial decreased after exposure. Animal's speed decreased significantly 15 days after exposure to extreme environmental conditions. In summary, the alteration of oxygen availability and atmospheric pressure may lead to significant changes in mitochondria mass, lifespan, and behavioral function inD. melanogaster.

Background: Increased apoptotic changes in the spinal cord may be responsible for the development of chronic constriction injury (CCI)‐induced neuropathic pain. We previously reported the beneficial effect of hyperbaric oxygen (HBO) in the treatment of CCI‐induced neuropathic pain. In this study, we tested our hypotheses that HBO may achieve its beneficial effect by inhibiting CCI‐induced proapoptosis gene expression and apoptosis in the spinal cord.Methods: Male rats were randomized into: SHAM, CCI and CCI + HBO groups. Mechanical hyperalgesia was tested daily following surgery. CCI + HBO rats were treated with HBO for 1 h daily. At 3 days post‐CCI, the expression of tumour necrosis factor (TNF)‐α and caspase‐3 genes was detected. At 7 days post‐CCI, apoptotic cells in the spinal cord were detected.Results: Three days post‐CCI, mechanical allodynia had developed in the ipsilateral paw compared with SHAM animals. HBO significantly alleviated CCI‐induced mechanical allodynia. In comparison with SHAM, CCI‐induced neuropathic pain was associated with higher mRNA levels of TNF‐α and caspase‐3. HBO significantly decreased CCI‐induced mRNA levels of TNF‐α and caspase‐3. CCI‐induced neuropathic pain was also associated with more apoptotic cells in the spinal cord 7 days post‐CCI. HBO significantly reduced CCI‐induced apoptosis to the level of SHAM animals.Conclusions: Overly expressed proapoptosis genes, and subsequent increase in spinal apoptotic cells, seem to contribute to the development of CCI‐induced neuropathic pain. The inhibitory role of HBO on spinal proapoptosis genes and apoptotic changes may contribute to its beneficial effect on CCI‐induced neuropathic pain.

Gemcitabine is first-line therapy for advanced pancreatic ductal adenocarcinoma (PDAC) with a poor survival and response rate. Hyperbaric oxygenation (HBO) enhances delivery of oxygen to hypoxic tumor cells and increases their susceptibility to cytotoxic effects of chemotherapy. We hypothesized that the anticancer activity of gemcitabine (GEM) may be enhanced if tumor cells are placed in an oxygen-rich environment. The present study evaluated the effects of gemcitabine, HBO and their combination on apoptosis of tumor cells. PANC-1 and AsPc-1 PDAC tumor cell lines were used. Cultured tumor cells were treated with GEM at its growth-inhibitory concentration (IC50) and HBO at 2.5 ATA for 90 min or a combination of both (HBO then GEM and GEM then HBO). Twenty-four hours later, apoptotic cells in each group were analyzed and the apoptotic index (AI) was calculated. PANC-1 cell line: HBO alone had no effect on AI: 6.5 ± 0.1 vs. 5.9 ± 0.1. HBO before and after gemcitabine did not further increase AI: 8.2 ± 0.1 (HBO-GEM), 8.5 ± 0.1 (GEM-HBO) vs. 8.1 ± 0.1 (GEM). The combination of HBO and gemcitabine significantly increased AI: 10.7 ± 0.02 (p<0.001 vs. all groups). AsPc-1 cell line: HBO-alone had no effect on AI: 5.9 ± 0.1 vs. 5.9 ± 0.1. HBO before and after gemcitabine did not further increase AI: 8.2 ± 0.1 (HBO-GEM), 8.4 ± 0.1 (GEM-HBO) vs. 8.0 ± 0.1 (GEM). The combination of HBO and gemcitabine significantly increased AI: 9.7 ± 0.1 (p<0.001 vs. all groups). HBO-alone, whether administered before and after gemcitabine has no effect on apoptosis of PDAC cells in vitro. HBO significantly enhanced gemcitabine-induced apoptosis when administered during gemcitabine. Our findings suggest that the time window would be critical for using HBO as adjuvant to chemotherapy.

Purpose Extubation may be delayed after spine surgery mainly for the concerns of airway safety. Risk factors for delayed extubation in cervical spine surgery have been described to include prolonged surgery time and amount of crystalloids or blood transfused. To date, risk factors for delayed extubation in thoracic or lumbar spine surgery have not been investigated. We retrospectively reviewed 135 consecutive patients from 2006 to 2009 who underwent thoracic or lumbar spine surgery by one particular surgeon to identify risk factors for delayed extubation. Methods Data including patient factors, surgical time, anesthetic technique, blood loss, crystalloid and colloid administration, transfusion requirements, time to transfusion, and time to extubation were collected and analyzed. Delayed extubation was defined as the patient was not extubated in the operating room at completion of the surgery. Results One hundred and eight patients were extubated in the OR. Delayed extubation occurred in 27 patients. Delayed extubation was significantly related to total operative time (6.6 ± 0.4 vs. 5.2 ± 0.1 h), volume of crystalloid replacement (6,018 ± 408 vs. 4,186 ± 130 cm³), volume of total colloids infused (787 ± 93 vs. 442 ± 36 cm³), intraoperative blood transfused (3.7 ± 0.5 vs. 0.7 ± 0.1 units); blood loss (2,137 ± 286 vs. 832 ± 50 cm³), and time to starting blood transfusion (106 ± 12 vs. 199 ± 9 min). Conclusions Our study suggests that intraoperative factors including prolonged surgical time, significant blood loss, larger volume of crystalloid and colloid infusion, and blood transfusion may be risk factors for delayed extubation following thoracic or lumbar spine surgery. Early blood transfusion may also increase the risk of delayed extubation. Patient factors did not affect extubation time.

The usefulness of intraoperative neurophysiological monitoring (IONM), including somatosensory-evoked potential (SSEP) and transcranial electrical motor-evoked potentials (TcMEPs) in cervical spine surgery still needs to be evaluated. We retrospectively reviewed 200 cervical spine surgery patients from 2008 to 2009 to determine the role of IONM in cervical spine surgery. Total intravenous anesthesia was used for all patients. IONM alerts were defined as a 50% decrease in amplitude, a 10% increase in latency, or a unilateral change for SSEP and an increase in stimulation threshold of more than 100 V for TcMEP. Three patients had SSEP alerts that were related to arm malposition (2 patients) and hypotension (1 patient). Five patients had TcMEP alerts: 4 alerts were caused by hypotension and 1 by bone graft compression of the spinal cord. All alerts were resolved when causative reasons were corrected. There was no postoperative iatrogenic neurological injury. The sensitivities of SSEP and TcMEP alerts for detecting impending neurological injury were 37.5% and 62.5%, respectively. The sensitivity of both SSEP and TcMEP used in combination was 100%. No false-positive and false-negative alerts were identified in either SSEP or TcMEP (100% specificity). The total intravenous anesthesia technique optimizes the detection of SSEP and TcMEP and therefore improves the sensitivity and specificity of IONM. SSEP is sensitive in detecting alerts in possible malposition-induced ischemia or brachial plexus nerve injury. TcMEP specifically detects hypotension-induced spinal functional compromises. Combination use of TcMEP and SSEP enhances the early detection of impeding neurological damage during cervical spine surgery.