Physiotherapy and Physical Activity as Factors Improving the Psychological State of Patients With Cancer.

Physiotherapy in oncology is a process closely related to cancer treatment methods. Rehabilitation is based on physical activity in various forms involving the musculoskeletal system but also affects the emotional state. Physical activity influences physical and psychological well-being of people undergoing oncological treatment, in the course of which the most common psychiatric disorders are depression, substance use disorder, sleep disorders, fatigue syndrome, resulting in worsening of the quality of life. Difficulties in implementing physical exercise in cancer patients pose a challenge to treatment teams.

Endothelial function may be enhanced in the cutaneous microcirculation after a single air dive.

INTRODUCTION: The effects of scuba diving on the vessel wall have been studied mainly at the level of large conduit arteries. Data regarding the microcirculation are scarce and indicate that these two vascular beds are affected differently by diving. METHODS: We assessed the changes in cutaneous microcirculation before an air scuba dive, then 30 min and 24 h after surfacing. Endothelium-dependent and independent vasomotion were successively elicited by iontophoretic administration of acetylcholine and sodium nitroprusside respectively, and cutaneous blood flux was monitored by laser Doppler flowmetry. RESULTS: The response to sodium nitroprusside was significantly lower 30 min after surfacing than before diving (50 (SEM 6)% of the pre-dive values, P = 0.0003) and returned to normal values 24 h post-dive (102 (29)% of the pre-dive values, P = 0.113). When compared to pre-dive values, acetylcholine elicited a hyperaemia which was not statistically different 30 min after surfacing (123 (17)% of the pre-dive values, P = 0.230), but significantly increased 24 h post-dive (148 (10)% of the pre-dive values, P = 0.005). CONCLUSION: Microvascular smooth muscle function is transiently impaired after diving. On the contrary, microvascular endothelial function is enhanced for up to 24 h after diving. This further suggests that the microcirculation reacts differently than large conduit arteries to scuba diving. The impact of modifications occurring in the microvascular bed on the physiological effects of diving merits further study.

Metabolic Syndrome and Cognitive Functions in Schizophrenia-Implementation of Dietary Intervention.

INTRODUCTION: The co-existence of schizophrenia and metabolic syndrome is a widely described phenomenon that contributes to the worse functioning of patients in everyday life. A relatively new area of research is the relationship between metabolic syndrome (MS) and cognitive function in patients with schizophrenia. The aim of the study was to verify the relationship between the presence of metabolic syndrome and cognitive function of patients with schizophrenia and to assess the possibility of changing cognitive function by introducing appropriate dietary intervention. MATERIALS AND METHODS: The study involved 87 individuals diagnosed with schizophrenia according to ICD-10 criteria, aged 19 to 67 years (M = 41.67; SD = 11.87). Patients were in the remission phase of schizophrenia, all using antipsychotics for pharmacological treatment. From a group of 83 patients with schizophrenia and diagnosed metabolic syndrome (according to IDF criteria) 30 patients were randomly assigned to an experimental group-with dietary intervention, 29 patients-to group without dietary intervention, 24 patients with schizophrenia without metabolic syndrome was a comparison group. All groups were evaluated for cognitive function using Stroop Test, Trail Making Test (TMT), Verbal Fluency Test, Digit Span Backwards Test. In the experimental group a dietary intervention was applied, which was to provide the examined person with a 7-day dietary plan with reduced calorie content, in compliance with the Mediterranean diet. RESULTS: After the dietary intervention there was a significant improvement in the number of errors made in the third Stroop Test (p <0.001), the time taken to complete the Point Linking Test was shortened (Test B; p = 0.005), there was an improvement in Verbal Fluency Test in "animals" category (p = 0.006) "sharp objects" category (p = 0.009), the number of repeated digits has increased in Digit Span Test in "forward" category (p = 0.001) and overall completion of the test (p = 0.021). In the group of patients with MS without dietary intervention, the results of cognitive tests remained mostly unchanged. CONCLUSIONS: Change of eating habits may be a significant element of a holistic approach to the problems of treatment of schizophrenia.

Simulated air dives induce superoxide, nitric oxide, peroxynitrite, and Ca2+ alterations in endothelial cells.

Human diving is known to induce endothelial dysfunction. The aim of this study was to decipher the mechanism of ROS production during diving through the measure of mitochondrial calcium concentration, peroxynitrite, NO°, and superoxide towards better understanding of dive-induced endothelial dysfunction. Air diving simulation using bovine arterial endothelial cells (compression rate 101 kPa/min to 808 kPa, time at depth 45 min) was performed in a system allowing real-time fluorescent measurement. During compression, the cells showed increased mitochondrial superoxide, peroxynitrite, and mitochondrial calcium, and decreased NO° concentration. MnTBAP (peroxynitrite scavenger) suppressed superoxide, recovered NO° production and promoted stronger calcium influx. Superoxide and peroxynitrite were inhibited by L-NIO (eNOS inhibitor), but were further increased by spermine-NONOate (NO° donor). L-NIO induced stronger calcium influx than spermine-NONOate or simple diving. The superoxide and peroxynitrite were also inhibited by ruthenium red (blocker of mitochondrial Ca2+ uniporter), but were increased by CGP (an inhibitor of mitochondrial Na+-Ca2+ exchange). Reactive oxygen and nitrogen species changes are associated, together with calcium mitochondrial storage, with endothelial cell dysfunction during simulated diving. Peroxynitrite is involved in NO° loss, possibly through the attenuation of eNOS and by increasing superoxide which combines with NO° and forms more peroxynitrite. In the field of diving physiology, this study is the first to unveil a part of the cellular mechanisms of ROS production during diving and confirms that diving-induced loss of NO° is linked to superoxide and peroxynitrite.

Perivascular Adipose Tissue Contributes to the Modulation of Vascular Tone in vivo.

BACKGROUND: Perivascular adipose tissue (PVAT) reduces vascular tone in isolated arteries in vitro, however there are no studies of PVAT effects on vascular tone in vivo. In vitro adipocyte ß3-adrenoceptors play a role in PVAT function via secretion of the vasodilator adiponectin. OBJECTIVE: We have investigated the effects of PVAT on vessel diameter in vivo, and the contributions of ß3-adrenoceptors and adiponectin. METHOD: In anaesthetised rats, sections of the intact mesenteric bed were visualised and the diameter of arteries was recorded. Arteries were stimulated with electrical field stimulation (EFS), noradrenaline (NA), arginine-vasopressin (AVP), and acetylcholine (Ach). RESULTS: We report that in vivo, stimulation of PVAT with EFS, NA, and AVP evokes a local anti-constrictive effect on the artery, whilst PVAT exerts a pro-contractile effect on arteries subjected to Ach. The anti-constrictive effect of PVAT stimulated with EFS and NA was significantly reduced using ß3-adrenoceptor inhibition, and activation of ß3-adrenoceptors potentiated the anti-constrictive effect of vessels stimulated with EFS, NA, and AVP. The ß3-adrenoceptor agonist had no effect on mesenteric arteries with PVAT removed. A blocking peptide for adiponectin receptor 1 polyclonal antibody reduced the PVAT anti-constrictive effect in arteries stimulated with EFS and NA, indicating that adiponectin may be the anti-constrictive factor released upon ß3-adrenoceptor activation. CONCLUSIONS: These results clearly demonstrate that PVAT plays a paracrine role in regulating local vascular tone in vivo, and therefore may contribute to the modulation of blood pressure. This effect is mediated via adipocyte ß3-adrenoceptors, which may trigger release of the vasodilator adiponectin.

Rat mesenteric small artery neurogenic dilatation is predominantly mediated by ß1 -adrenoceptors in vivo.

KEY POINTS: The prevailing dogma about neurogenic regulation of vascular tone consists of major vasodilatation caused by CGRP (and possibly substance P) released from sensory-motor nerves and vasoconstriction caused by noradrenaline, ATP and neuropeptode Y release from sympathetic nerves. Most studies on perivascular nerve-mediated vasodilatation are made in vitro. In the present study, we provide evidence indicating that in vivo electrical perivascular nerve stimulation in rat mesenteric small arteries causes a large ß1-adrenoceptor-mediated vasodilatation, which contrasts with a smaller vasodilatation caused by endogenous CGRP that is only visible after inhibition of Y1 NPY receptors. ABSTRACT: Mesenteric arteries are densely innervated and the nerves are important regulators of vascular tone and hence blood pressure and blood flow. Perivascular sensory-motor nerves have been shown to cause vasodilatation in vitro. However, less is known about their function in vivo. Male Wistar rats (10-12 weeks old; n = 72) were anaesthetized with ketamine (3 mg kg-1 ) and xylazine (0.75 mg kg-1 ) or pentobarbital (60 mg kg-1 ). After a laparotomy, a section of second-order mesenteric artery was visualized in an organ bath after minimal removal of perivascular adipose tissue. The effects of electrical field stimulation (EFS) and drugs on artery diameter and blood flow were recorded with intravital microscopy and laser speckle imaging. EFS caused vasodilatation in arteries constricted with 1 µm U46619 in the presence of 140 µm suramin and 1 µm prazosin. The vasodilatation was inhibited by 1 µm tetrodotoxin and 5 µm guanethidine, although not by the 1 µm of the CGRP receptor antagonist BIBN4096bs. In the presence of 0.3 µm Y1 receptor antagonist BIBP3226, BIBN4096bs partly inhibited the vasodilatation. Atenolol at a concentration 1 µm inhibited the vasodilatation, whereas 0.1 µm of the ß2 -adrenoceptor selective antagonist ICI-118,551 had no effect. Increasing the extracellular [K+ ] to 20 mm caused vasodilatation but was converted to vasoconstriction in the presence of 1 µm BIBN4096bs, and constriction to 30 mm potassium was potentiated by BIBN4096bs. Atenolol but not BIBN4096bs increased contraction to EFS in the absence of suramin and prazosin. In mesenteric small arteries of anaesthetized rats, EFS failed to stimulate major dilatation via sensory-motor nerves but induced sympathetic ß1 -adrenoceptor-mediated dilatation.

Angiotensin Converting Enzyme Inhibitor Has a Protective Effect on Decompression Sickness in Rats.

Introduction: Commercial divers, high altitude pilots, and astronauts are exposed to some inherent risk of decompression sickness (DCS), though the mechanisms that trigger are still unclear. It has been previously showed that diving may induce increased levels of serum angiotensin converting enzyme. The renin angiotensin aldosterone system (RAAS) is one of the most important regulators of blood pressure and fluid volume. The purpose of the present study was to control the influence of angiotensin II on the appearance of DCS. Methods: Sprague Dawley rats have been pre-treated with inhibitor of angiotensin II receptor type 1 (losartan; 10 mg/kg), angiotensin-converting enzyme (ACE) inhibitor (enalapril; 10 mg/kg), and calcium-entry blocker (nifedipine; 20 mg/kg). The experimental groups were treated for 4 weeks before exposure to hyperbaric pressure while controls were not treated. Seventy-five rats were subjected to a simulated dive at 1000 kPa absolute pressure for 45 min before starting decompression. Clinical assessment took place over a period of 60 min after surfacing. Blood samples were collected for measurements of TBARS, interleukin 6 (IL-6), angiotensin II (ANG II) and ACE. Results: The diving protocol induced 60% DCS in non-treated animals. This ratio was significantly decreased after treatment with enalapril, but not other vasoactive drugs. Enalapril did not change ANG II or ACE concentration, while losartant decreased post dive level of ACE but not ANG II. None of the treatment modified the effect of diving on TBARS and IL-6 values. Conclusion: Results suggests that the rennin angiotensin system is involved in a process of triggering DCS but this has to be further investigated. However, a vasorelaxation mediated process, which potentially could increase the load of inert gas during hyperbaric exposure, and antioxidant properties were excluded by our results.

Intravital investigation of rat mesenteric small artery tone and blood flow.

KEY POINTS: Substantial information on rat mesenteric small artery physiology and pharmacology based on in vitro experiments is available. Little is known about the relevance of this for artery function in vivo. We here present an intravital model where rat mesenteric small artery diameters are studied under isolated and controlled conditions in situ with simultaneous measurement of blood flow. The responses of the isolated arteries vary with the anaesthetic used, and they are quantitatively but not qualitatively different from the responses seen in vitro. ABSTRACT: Functional characteristics of rat mesenteric small arteries (internal diameter ∼150-200 µm) have been extensively studied in vitro using isometric and isobaric myographs. In vivo, precapillary arterioles (internal diameter < 50 µm) have been studied, but only a few studies have investigated the function of mesenteric small arteries. We here present a novel approach for intravital studies of rat mesenteric small artery segments (∼5 mm long) isolated in a chamber. The agonist-induced changes in arterial diameter and blood flow were studied using video imaging and laser speckle analysis in rats anaesthetized by isoflurane, pentobarbital, ketamine-xylazine, or by a combination of fentanyl, fluanison and midazolam (rodent mixture). The arteries had spontaneous tone. Noradrenaline added to the chamber constricted the artery in the chamber but not the downstream arteries in the intestinal wall. The constriction was smaller when rats were anaesthetized by rodent mixture in comparison with other anaesthetics, where responses were qualitatively similar to those reported in vitro. The contraction was associated with reduction of blood flow, but no flow reduction was seen in the downstream arteries in the intestinal wall. The magnitude of different endothelium-dependent relaxation pathways was dependent on the anaesthesia. Vasomotion was present under all forms of anaesthesia with characteristics similar to in vitro. We have established an intravital method for studying the tone and flow in rat mesenteric arteries. The reactivity of the arteries was qualitatively similar to the responses previously obtained under in vitro conditions, but the choice of anaesthetic affects the magnitude of responses.

GLP-1 inhibits VEGFA-mediated signaling in isolated human endothelial cells and VEGFA-induced dilation of rat mesenteric arteries.

We investigated the acute effects of glucagon-like peptide-1 (GLP-1), GLP-1(1-36), and GLP-1(7-36) on vascular endothelial growth factor-A (VEGFA)-induced endothelium-dependent signaling and vasodilation. Our hypothesis was that GLP-1 released from intestinal l-cells modulates processes related to PLCγ activation, Src, and endothelial NOS (eNOS) signaling, thereby controlling endothelial vessel tone. By using RT-PCR analysis, we found mRNA for the GLP-1 receptor (GLP-1R) in human dermal microvascular endothelial cells (HDMEC), human retinal microvascular endothelial cells, and rat arteries. In isolated rat mesenteric resistance arteries precontracted with the thromboxane analog U46619 to 80-90% of maximum contraction, VEGFA (25 ng/ml) caused a small and gradual relaxation (28.9 ± 3.9%). Pretreatment of arteries with either GLP-1(1-36) (500 nM) or GLP-1(7-36) (1 nM) abolished the VEGFA-induced relaxation. VEGFA-induced relaxations were also inhibited in endothelial-denuded arteries and in arteries pretreated with the nitric oxide synthase (NOS) inhibitor, Nω-nitro-l-arginine methyl ester (100 µM). In vivo studies on male Wistar rats also revealed that GLP-1(7-36) inhibited VEGFA-induced vasodilation of the same arteries. In isolated endothelial cells, GLP-1(1-36) and GLP-1(7-36) caused a reduction in VEGFA-induced phosphorylation of PLCγ. Ca2+ imaging of endothelial cells and rat mesenteric resistance arteries using fura-2, revealed that both GLP-1 analogs caused a reduction in VEGFA-induced Ca2+ signaling. GLP-1(1-36) also reduced VEGFA-induced eNOS phosphorylation in HDMEC. In conclusion, GLP-1 reduced relaxation induced by VEGFA in resistance arteries by inhibiting VEGFR2-mediated Ca2+ signaling and endothelial NO synthesis. GLP-1, on its own, also induced phosphorylation of Src and ERK1/2 that can lead to proliferation and is implicated in vessel permeability.

Effect of simulated air dive and decompression sickness on the plasma proteome of rats.

PURPOSE: Decompression sickness (DCS) is a poorly understood systemic disease caused by inadequate desaturation following a reduction in ambient pressure. Although recent studies highlight the importance of circulating factors, the available data are still puzzling. In this study, we aimed to identify proteins and biological pathways involved in the development of DCS in rats. EXPERIMENTAL DESIGN: Eighteen male Sprague-Dawley rats were subjected to a same simulated air dive to 1000 kPa absolute pressure and divided into two groups: no DCS or DCS. A third control group remained at atmospheric pressure. Venous blood was collected after hyperbaric exposure and the plasma proteomes from four individuals per group were analyzed by using a two-dimensional electrophoresis-based proteomic strategy. RESULTS: Quantitative analysis identified nine protein spots with abundances significantly changed (false discovery rate < 0.1) between the tested conditions. Three protein spots, identified as Apolipoprotein A1, Serine Protease Inhibitor A3K (Serpin A3K), and Alpha-1-antiproteinase, appeared increased in DCS animals but displayed only weak changes. By contrast, one protein spot identified as Transthyretin (TTR) dramatically decreased (i.e. quite disappeared) in animals displaying DCS symptoms. Before diving, TTR level was not different in DCS than nondiving group. CONCLUSION: These results may lead to the use of TTR as an early biomarker of DCS.

Influence of decompression sickness on vasocontraction of isolated rat vessels.

Studies conducted in divers indicate that endothelium function is impaired following a dive even without decompression sickness (DCS). Our previous experiment conducted on rat isolated vessels showed no differences in endothelium-dependent vasodilation after a simulated dive even in the presence of DCS, while contractile response to phenylephrine was progressively impaired with increased decompression stress. This study aimed to further investigate the effect of DCS on vascular smooth muscle. Thirty-two male Sprague-Dawley rats were submitted to the same hyperbaric protocol and classified according to the severity of DCS: no-DCS (without clinical symptoms), mild-DCS, or severe-DCS (dead within 1 h). A control group remained at atmospheric pressure. Isometric tension was measured in rings of abdominal aorta and mesenteric arteries. Single dose contraction was assessed with KCl solution. Dose-response curves were obtained with phenylephrine and endothelin-1. Phenylephrine-induced contraction was observed in the presence of antioxidant tempol. Additionally, plasma concentrations of angiotensin II, angiotensin-converting enzyme, and thiobarbituric acid reactive substances (TBARS) were assessed. Response to phenylephrine was impaired only among mild-DCS in both vessels. Dose-response curves to endothelin-1 were impaired after mild-DCS in mesenteric and severe-DCS in aorta. KCl-induced contraction was affected after hyperbaric exposure regardless of DCS status in aorta only. These results confirm postdive vascular dysfunction is dependent on the type of vessel. It further evidenced that vascular dysfunction is triggered by DCS rather than by diving itself and suggest the influence of circulating factor/s. Diving-induced impairment of the L-type voltage-dependent Ca(2+) channels and/or influence of renin-angiotensin system is proposed.

Age, weight and decompression sickness in rats.

OBJECTIVE: The aim of this study was to determine if, after controlling for weight, age is associated with decompression sickness (DCS) in rats. METHODS: Following compression-decompression, male rats aged 11 weeks were observed for DCS. After two weeks recovery, surviving rats were re-dived using the same compression-decompression profile. RESULTS: In this experiment, there was a clear difference between DCS outcome at ages 11 or 13 weeks in matched rats (p = 0.002). DISCUSSION: Even with weight included in the model, age was significantly associated with DCS (p = 0.01), yet after removal of weight the association was much stronger (p = 0.002). CONCLUSION: We believe that age is likely to be found associated with the probability of DCS in a larger dataset with a wider range of parameters, after accounting for the effect of weight.

Antioxidants, endothelial dysfunction, and DCS: in vitro and in vivo study.

Reactive oxygen species (ROS) production is a well-known effect in individuals after an undersea dive. This study aimed to delineate the links between ROS, endothelial dysfunction, and decompression sickness (DCS) through the use of antioxidants in vitro and in vivo. The effect of N-acetylcysteine (NAC) on superoxide and peroxynitrite, nitric oxide (NO) generation, and cell viability during in vitro diving simulation were analyzed. Also analyzed was the effect of vitamin C and NAC on plasma glutathione thiol and thiobarbituric acid reactive substances (TBARS), plasma angiotensin-converting enzyme (ACE) activity, and angiotensin-II and DCS morbidity during in vivo diving simulation. During an in vitro diving simulation, vascular endothelial cells showed overproduction of superoxide and peroxynitrite, obvious attenuation of NO generation, and promotion of cell death, all of which were reversed by NAC treatment. After in vivo diving simulation, plasma ACE activity and angiotensin-II level were not affected. The plasma level of glutathione thiol was downregulated after the dive, which was attenuated partially by NAC treatment. Plasma TBARS level was upregulated; however, either NAC or vitamin C treatment failed to prevent DCS morbidity. During in vitro simulation, endothelial superoxide and peroxynitrite-mediated oxidative stress were involved in the attenuation of NO availability and cell death. This study is the first attempt to link oxidative stress and DCS occurrence, and the link could not be confirmed in vivo. Even in the presence of antioxidants, ROS and bubbles generated during diving and/or decompression might lead to embolic or biochemical stress and DCS. Diving-induced oxidative stress might not be the only trigger of DCS morbidity.

A rat model of chronic moderate alcohol consumption and risk of decompression sickness.

INTRODUCTION: This study aimed to establish if chronic, moderate, pre-dive alcohol consumption had any affect upon susceptibility to decompression sickness (DCS) in rats. METHODS: A treatment group of 15 rats were given water containing 12 mL ·L ⁻¹ of ethanol for four weeks. Controls (n = 15) were given water. Both groups were compressed with air to 1,000 kPa, followed by staged decompression. An additional 30 control rats from a similar previous experiment were added, raising the control-treatment ratio to 3:1. RESULTS: Rats in the treatment group consumed the equivalent of an 80 kg man drinking 2 L of 5 % alcohol by volume beer per day, which is three times the recommended daily limit for men. Overall, comparing the treatment group with the combined control groups neither weight (P = 0.23) nor alcohol consumption (P = 0.69) were associated with DCS. DISCUSSION: We observed that chronic, moderate alcohol consumption prior to compression was neither prophylactic nor deleterious for DCS in young, male rats.

Mechanism of action of antiplatelet drugs on decompression sickness in rats: a protective effect of anti-GPIIbIIIa therapy.

Literature highlights the involvement of disseminated thrombosis in the pathophysiology of decompression sickness (DCS). We examined the effect of several antithrombotic treatments targeting various pathways on DCS outcome: acetyl salicylate, prasugrel, abciximab, and enoxaparin. Rats were randomly assigned to six groups. Groups 1 and 2 were a control nondiving group (C; n = 10) and a control diving group (CD; n = 30). Animals in Groups 3 to 6 were treated before hyperbaric exposure (HBE) with either prasugrel (n = 10), acetyl salicylate (n = 10), enoxaparin (n = 10), or abciximab (n = 10). Blood samples were taken for platelet factor 4 (PF4), thiobarbituric acid reactive substances (TBARS), and von Willebrand factor analysis. Onset of DCS symptoms and death were recorded during a 60-min observation period after HBE. Although we observed fewer outcomes of DCS in all treated groups compared with the CD, statistical significance was reached in abciximab only (20% vs. 73%, respectively, P = 0.007). We also observed significantly higher levels of plasmatic PF4 in abciximab (8.14 ± 1.40 ng/ml; P = 0.004) and enoxaparin groups (8.01 ± 0.80 ng/ml; P = 0.021) compared with the C group (6.45 ± 1.90 ng/ml) but not CD group (8.14 ± 1.40 ng/ml). Plasmatic levels of TBARS were significantly higher in the CD group than the C group (49.04 ± 11.20 µM vs. 34.44 ± 5.70 µM, P = 0.002). This effect was prevented by all treatments. Our results suggest that abciximab pretreatment, a powerful glycoprotein IIb/IIIa receptor antagonist, has a strong protective effect on decompression risk by significantly improving DCS outcome. Besides its powerful inhibitory action on platelet aggregation, we suggest that abciximab could also act through its effects on vascular function, oxidative stress, and/or inflammation.

Reactive Oxygen Species, Mitochondria, and Endothelial Cell Death during In Vitro Simulated Dives.

PURPOSE: Excessive reactive oxygen species (ROS) is considered a consequence of hyperoxia and a major contributor to diving-derived vascular endothelial damage and decompression sickness. The aims of this work were: 1) to directly observe endothelial ROS production during simulated air dives as well as its relation with both mitochondrial activity and cell survival; and 2) to determine which ambient factor during air diving (hydrostatic pressure or oxygen and/or nitrogen partial pressure) is responsible for the observed modifications. METHODS: In vitro diving simulation was performed with bovine arterial endothelial cells under real-time observation. The effects of air diving, hydrostatic, oxygen and nitrogen pressures, and N-acetylcysteine (NAC) treatment on mitochondrial ROS generation, mitochondrial membrane potential and cellular survival during simulation were investigated. RESULTS: Vascular endothelial cells performing air diving simulation suffered excessive mitochondrial ROS, mitochondrial depolarization, and cell death. These effects were prevented by NAC: after NAC treatment, the cells presented no difference in damage from nondiving cells. Oxygen diving showed a higher effect on ROS generation but lower impacts on mitochondrial depolarization and cell death than hydrostatic or nitrogen diving. Nitrogen diving had no effect on the inductions of ROS, mito-depolarization, or cell death. CONCLUSION: This study is the first direct observation of mitochondrial ROS production, mitochondrial membrane potential and cell survival during diving. Simulated air SCUBA diving induces excessive ROS production, which leads to mitochondrial depolarization and endothelial cell death. Oxygen partial pressure plays a crucial role in the production of ROS. Deleterious effects of hyperoxia-induced ROS are potentiated by hydrostatic pressure. These findings hold new implications for the pathogenesis of diving-derived endothelial dysfunction.

A ternary model of decompression sickness in rats.

BACKGROUND: Decompression sickness (DCS) in rats is commonly modelled as a binary outcome. The present study aimed to develop a ternary model of predicting probability of DCS in rats, (as no-DCS, survivable-DCS or death), based upon the compression/decompression profile and physiological characteristics of each rat. METHODS: A literature search identified dive profiles with outcomes no-DCS, survivable-DCS or death by DCS. Inclusion criteria were that at least one rat was represented in each DCS status, not treated with drugs or simulated ascent to altitude, that strain, sex, breathing gases and compression/decompression profile were described and that weight was reported. A dataset was compiled (n=1602 rats) from 15 studies using 22 dive profiles and two strains of both sexes. Inert gas pressures in five compartments were estimated. Using ordinal logistic regression, model-fit of the calibration dataset was optimised by maximum log likelihood. Two validation datasets assessed model robustness. RESULTS: In the interpolation dataset the model predicted 10/15 cases of nDCS, 3/3 sDCS and 2/2 dDCS, totalling 15/20 (75% accuracy) and 18.5/20 (92.5%) were within 95% confidence intervals. Mean weight in the extrapolation dataset was more than 2SD outside of the calibration dataset and the probability of each outcome was not predictable. DISCUSSION: This model is reliable for the prediction of DCS status providing the dive profile and rat characteristics are within the range of parameters used to optimise the model. The addition of data with a wider range of parameters should improve the applicability of the model.

Effect of splenectomy on platelet activation and decompression sickness outcome in a rat model of decompression.

INTRODUCTION: Splenic platelets have been recognized to have a greater prothrombotic potential than others platelets. We studied whether platelets released by splenic contraction could influence the severity and outcome of decompression sickness (DCS) and bubble-induced platelet activation. METHODS: Sixteen, male Sprague-Dawley rats were randomly assigned to either a control or a splenectomized group. Both groups were compressed to 1,000 kPa (90 metres' sea water) for 45 min while breathing air before staged decompression (5 min at 200 kPa, 5 min at 160 kPa and 10 min at 130 kPa). The onset time of DCS symptoms and of death were recorded during a 60-min observation period post dive. Parameters measured were platelet factor 4 (PF4) for platelet activation, thiobarbituric acid reactive substances (TBARS) for oxidative stress status and Von Willebrand factor (VWf) for endothelial activation. RESULTS: There were no differences between the groups in DCS outcome or in PF4, TBARS and VWf concentrations. CONCLUSION: These results do not support that the spleen and its exchangeable platelet pool is involved in DCS pathogenesis in a rat model, invalidating the hypothesis that increased decompression-induced platelet aggregation could be influenced by splenic contraction and then play a role in DCS outcome.

Different effect of l-NAME treatment on susceptibility to decompression sickness in male and female rats.

Vascular bubble formation results from supersaturation during inadequate decompression contributes to endothelial injuries, which form the basis for the development of decompression sickness (DCS). Risk factors for DCS include increased age, weight-fat mass, decreased maximal oxygen uptake, chronic diseases, dehydration, and nitric oxide (NO) bioavailability. Production of NO is often affected by diving and its expression-activity varies between the genders. Little is known about the influence of sex on the risk of DCS. To study this relationship we used an animal model of Nω-nitro-l-arginine methyl ester (l-NAME) to induce decreased NO production. Male and female rats with diverse ages and weights were divided into 2 groups: treated with l-NAME (in tap water; 0.05 mg·mL(-1) for 7 days) and a control group. To control the distribution of nitrogen among tissues, 2 different compression-decompression protocols were used. Results showed that l-NAME was significantly associated with increased DCS in female rats (p = 0.039) only. Weight was significant for both sexes (p = 0.01). The protocol with the highest estimated tissue pressures in the slower compartments was 2.6 times more likely to produce DCS than the protocol with the highest estimated tissue pressures in faster compartments. The outcome of this study had significantly different susceptibility to DCS after l-NAME treatment between the sexes, while l-NAME per se had no effect on the likelihood of DCS. The analysis also showed that for the appearance of DCS, the most significant factors were type of protocol and weight.

A new measure of decompression sickness in the rat.

In this study we assessed the reliability of a tilting-board grip score as a measure of decompression sickness in rats. In experiments using a hyperbaric compression/decompression protocol, rats were observed for signs of decompression sickness and their grip strength measured on a tilting particle board hinged to a metal frame. Angles at which rats lost grip were converted to gravitational vectors. Decreased mean grip scores following decompression were fitted to a logistic regression model with strain, age, and weight. Decrease in grip score was significantly associated with observed decompression sickness (P = 0.0036). The log odds ratio for decompression sickness = 1.40 (decrease in grip score). In rats with no decrease in mean grip score there was a 50% probability of decompression sickness (pDCS). This increased steadily with decreases in mean grip score. A decrease of 0.3 had a 60% pDCS, a decrease of 0.6 had a 70% pDCS, and a decrease of 2.1 had a 95% pDCS. The tilting board grip score is a reliable measure of the probability of decompression sickness.