Endothelial dysfunction in small arteries and early signs of atherosclerosis in ApoE knockout rats

Endothelial dysfunction is recognized as a major contributor to atherosclerosis and has been suggested to be evident far before plaque formation. Endothelial dysfunction in small resistance arteries has been suggested to initiate long before changes in conduit arteries. In this study, we address early changes in endothelial function of atherosclerosis prone rats. Male ApoE knockout (KO) rats (11- to 13-weeks-old) were subjected to either a Western or standard diet. The diet intervention continued for a period of 20-24 weeks. Endothelial function of pulmonary and mesenteric arteries was examined in vitro using an isometric myograph. We found that Western diet decreased the contribution of cyclooxygenase (COX) to control the vascular tone of both pulmonary and mesenteric arteries. These changes were associated with early stage atherosclerosis and elevated level of plasma total cholesterol, LDL and triglyceride in ApoE KO rats. Chondroid-transformed smooth muscle cells, calcifications, macrophages accumulation and foam cells were also observed in the aortic arch from ApoE KO rats fed Western diet. The ApoE KO rats are a new model to study endothelial dysfunction during the earlier stages of atherosclerosis and could help us improve preclinical drug development.publishedVersio

A Single Simulated Heliox Dive Modifies Endothelial Function in the Vascular Wall of ApoE Knockout Male Rats More Than Females

Introduction: The number of divers is rising every year, including an increasing number of aging persons with impaired endothelial function and concomitant atherosclerosis. While diving is an independent modulator of endothelial function, little is known about how diving affects already impaired endothelium. In this study, we questioned whether diving exposure leads to further damage of an already impaired endothelium. Methods: A total of 5 male and 5 female ApoE knockout (KO) rats were exposed to simulated diving to an absolute pressure of 600 kPa in heliox gas (80% helium, 20% oxygen) for 1 h in a dry pressure chamber. 10 ApoE KO rats (5 males, 5 females) and 8 male Sprague-Dawley rats served as controls. Endothelial function was examined in vitro by isometric myography of pulmonary and mesenteric arteries. Lipid peroxidation in blood plasma, heart and lung tissue was used as measures of oxidative stress. Expression and phosphorylation of endothelial NO synthase were quantified by Western blot. Results and Conclusion: A single simulated dive was found to induce endothelial dysfunction in the pulmonary arteries of ApoE KO rats, and this was more profound in male than female rats. Endothelial dysfunction in males was associated with changing in production or bioavailability of NO; while in female pulmonary arteries an imbalance in prostanoid signaling was observed. No effect of diving was found on mesenteric arteries from rats of either sex. Our findings suggest that changes in endothelial dysfunction were specific for pulmonary circulation. In future, human translation of these findings may suggest caution for divers who are elderly or have prior reduced endothelial function

Evaluation of Divers’ Neuropsychometric Effectiveness and High-Pressure Neurological Syndrome via Computerized Test Battery Package and Questionnaires in Operational Setting

Introduction: When divers are compressed to water depths deeper than 150 meter sea water (msw), symptoms of high-pressure neurological syndrome (HPNS) might appear due to rapid increase in pressure on the central nervous system during compression. The aim of this study was to first operate a new computerized tool, designed to monitor divers' wellbeing and cognitive function, and to record the results. The second aim was to evaluate the feasibility and validity of the Physiopad software and HPNS questionnaires as a new tool for monitoring divers wellbeing in an operational setting, including sensible visualization and presentation of results. Methods: The Physiopad was operated onboard Deep Arctic (TechnipFMC Diving Support Vessel). The diving work was performed between 180 and 207 msw. The data from 46 divers were collected from the HPNS questionnaires, Hand dynamometry test, Critical Flicker Fusion Frequency test (CFFF), Adaptive Visual Analog Scale (AVAS), Simple Math Process (MathProc test), Perceptual Vigilance Task (PVT), and Time Estimation Task (time-wall). Result: Diver's subjective evaluation revealed different symptoms, possibly also HPNS related, which lasted from 1 to 5 days in storage, with the common duration being 1 day. The results from Physiopad battery testing showed no signs of significant neurological alteration. Conclusion: The present study showed that there was no association between subjective measurements of HPNS and neuropsychometric test results. We also confirmed the feasibility of using the computerized test battery to monitor saturation divers at work. The HPNS battery and Physiopad software could be an important tool for monitoring diver's health in the future. This tool was not used during the Bahr Essalam project to operationally evaluate any HPNS effect on divers as data analysis was performed post-project.info:eu-repo/semantics/publishe

Evaluation of Divers’ Neuropsychometric Effectiveness and High-Pressure Neurological Syndrome via Computerized Test Battery Package and Questionnaires in Operational Setting

Introduction: When divers are compressed to water depths deeper than 150 meter sea water (msw), symptoms of high-pressure neurological syndrome (HPNS) might appear due to rapid increase in pressure on the central nervous system during compression. The aim of this study was to first operate a new computerized tool, designed to monitor divers’ wellbeing and cognitive function, and to record the results. The second aim was to evaluate the feasibility and validity of the Physiopad software and HPNS questionnaires as a new tool for monitoring divers wellbeing in an operational setting, including sensible visualization and presentation of results. Methods: The Physiopad was operated onboard Deep Arctic (TechnipFMC Diving Support Vessel). The diving work was performed between 180 and 207 msw. The data from 46 divers were collected from the HPNS questionnaires, Hand dynamometry test, Critical Flicker Fusion Frequency test (CFFF), Adaptive Visual Analog Scale (AVAS), Simple Math Process (MathProc test), Perceptual Vigilance Task (PVT), and Time Estimation Task (time-wall). Result: Diver’s subjective evaluation revealed different symptoms, possibly also HPNS related, which lasted from 1 to 5 days in storage, with the common duration being 1 day. The results from Physiopad battery testing showed no signs of significant neurological alteration. Conclusion: The present study showed that there was no association between subjective measurements of HPNS and neuropsychometric test results. We also confirmed the feasibility of using the computerized test battery to monitor saturation divers at work. The HPNS battery and Physiopad software could be an important tool for monitoring diver’s health in the future. This tool was not used during the Bahr Essalam project to operationally evaluate any HPNS effect on divers as data analysis was performed post-project

Endothelial dysfunction in small arteries and early signs of atherosclerosis in ApoE knockout rats

Endothelial dysfunction is recognized as a major contributor to atherosclerosis and has been suggested to be evident far before plaque formation. Endothelial dysfunction in small resistance arteries has been suggested to initiate long before changes in conduit arteries. In this study, we address early changes in endothelial function of atherosclerosis prone rats. Male ApoE knockout (KO) rats (11- to 13-weeks-old) were subjected to either a Western or standard diet. The diet intervention continued for a period of 20-24 weeks. Endothelial function of pulmonary and mesenteric arteries was examined in vitro using an isometric myograph. We found that Western diet decreased the contribution of cyclooxygenase (COX) to control the vascular tone of both pulmonary and mesenteric arteries. These changes were associated with early stage atherosclerosis and elevated level of plasma total cholesterol, LDL and triglyceride in ApoE KO rats. Chondroid-transformed smooth muscle cells, calcifications, macrophages accumulation and foam cells were also observed in the aortic arch from ApoE KO rats fed Western diet. The ApoE KO rats are a new model to study endothelial dysfunction during the earlier stages of atherosclerosis and could help us improve preclinical drug development

Endothelial dysfunction in small arteries and early signs of atherosclerosis in ApoE knockout rats

Endothelial dysfunction is recognized as a major contributor to atherosclerosis and has been suggested to be evident far before plaque formation. Endothelial dysfunction in small resistance arteries has been suggested to initiate long before changes in conduit arteries. In this study, we address early changes in endothelial function of atherosclerosis prone rats. Male ApoE knockout (KO) rats (11- to 13-weeks-old) were subjected to either a Western or standard diet. The diet intervention continued for a period of 20-24 weeks. Endothelial function of pulmonary and mesenteric arteries was examined in vitro using an isometric myograph. We found that Western diet decreased the contribution of cyclooxygenase (COX) to control the vascular tone of both pulmonary and mesenteric arteries. These changes were associated with early stage atherosclerosis and elevated level of plasma total cholesterol, LDL and triglyceride in ApoE KO rats. Chondroid-transformed smooth muscle cells, calcifications, macrophages accumulation and foam cells were also observed in the aortic arch from ApoE KO rats fed Western diet. The ApoE KO rats are a new model to study endothelial dysfunction during the earlier stages of atherosclerosis and could help us improve preclinical drug development

Extensive simulated diving aggravates endothelial dysfunction in male pro-atherosclerotic ApoE knockout rats

Introduction: The average age of the diving population is rising, and the risk of atherosclerosis and cardiovascular disease in divers are accordingly increasing. It is an open question whether this risk is altered by diving per se. In this study, we examined the effect of 7-weeks simulated diving on endothelial function and mitochondrial respiration in atherosclerosis-prone rats. Methods: Twenty-four male ApoE knockout (KO) rats (9-weeks-old) were fed a Western diet for 8 weeks before 12 rats were exposed to simulated heliox dry-diving in a pressure chamber (600 kPa for 60 min, decompression of 50 kPa/min). The rats were dived twice-weekly for 7 weeks, resulting in a total of 14 dives. The remaining 12 non-diving rats served as controls. Endothelial function of the pulmonary and mesenteric arteries was examined in vitro using an isometric myograph. Mitochondrial respiration in cardiac muscle tissues was measured using high-resolution respirometry. Results and Conclusion: Both ApoE KO diving and non-diving rats showed changes in endothelial function at the end of the intervention, but the extent of these changes was larger in the diving group. Altered nitric oxide signaling was primarily involved in these changes. Mitochondrial respiration was unaltered. In this pro-atherosclerotic rat model of cardiovascular changes, extensive diving appeared to aggravate endothelial dysfunction rather than promote adaptation to oxidative stress

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

Age, weight and decompression sickness in rats

© 2015 Taylor and Francis. 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