Arve Jørgensen

Early genetic responses in rat vascular tissue after simulated diving

Diving causes a transient reduction of vascular function, but the mechanisms behind this are largely unknown. The aim of this study was therefore to analyze genetic reactions that may be involved in acute changes of vascular function in divers. Rats were exposed to 709 kPa of hyperbaric air (149 kPa Po(2)) for 50 min followed by postdive monitoring of vascular bubble formation and full genome microarray analysis of the aorta from diving rats (n = 8) and unexposed controls (n = 9). Upregulation of 23 genes was observed 1 h after simulated diving. The differential gene expression was characteristic of cellular responses to oxidative stress, with functions of upregulated genes including activation and fine-tuning of stress-responsive transcription, cytokine/cytokine receptor signaling, molecular chaperoning, and coagulation. By qRT-PCR, we verified increased transcription of neuron-derived orphan receptor-1 (Nr4a3), plasminogen activator inhibitor 1 (Serpine1), cytokine TWEAK receptor FN14 (Tnfrsf12a), transcription factor class E basic helix-loop-helix protein 40 (Bhlhe40), and adrenomedullin (Adm). Hypoxia-inducible transcription factor HIF1 subunit HIF1-α was stabilized in the aorta 1 h after diving, and after 4 h there was a fivefold increase in total protein levels of the procoagulant plasminogen activator inhibitor 1 (PAI1) in blood plasma from diving rats. The study did not have sufficient power for individual assessment of effects of hyperoxia and decompression-induced bubbles on postdive gene expression. However, differential gene expression in rats without venous bubbles was similar to that of all the diving rats, indicating that elevated Po(2) instigated the observed genetic reactions.

Fluoroscopy-free resuscitative endovascular balloon occlusion of the aorta (REBOA) for controlling life threatening postpartum hemorrhage

Background Severe postpartum hemorrhage occurs in 1/1000 women giving birth. This condition is often dramatic and may be life threatening. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) has in recent years been introduced as a novel treatment for hemorrhagic shock. We present a series of fluoroscopy-free REBOA for controlling life threatening postpartum hemorrhage. Methods In 2008 an ‘aortic occlusion kit’ was assembled and used in three Norwegian university hospitals. The on-call interventional radiologist (IR) was to be contacted with a response time < 30 minutes in case of life threatening PPH. Demographics and characteristics were noted from the medical records. Results This retrospective study includes 36 patients treated with fluoroscopy-free REBOA for controlling severe postpartum hemorrhage in the years 2008–2015. The REBOA success rate was 100% and no patients died from REBOA related complications. Uterine artery embolization was performed in 17 (47%) patients and a hysterectomy in 16 (44%) patients. A short (11cm) introducer length was strongly associated with iliac artery thrombus formation (ρ = 0.50, P = 0.002). In addition, there was a strong negative correlation between uterine artery embolization and hysterectomy (ρ = -0.50, P = 0.002). Conclusions Our Norwegian experience indicates the clinical safety and feasibility of REBOA in life threatening PPH. Also, REBOA can be used in an emergency situation without the use of fluoroscopy with a high degree of technical success. It is important that safety implementation of REBOA is established, especially through limited aortic balloon occlusion time and a thorough balloon deflation regime.

Effects of hyperbaric oxygen preconditioning on cardiac stress markers after simulated diving

Hyperbaric oxygen preconditioning (HBO‐PC) can protect the heart from injury during subsequent ischemia. The presence of high loads of venous gas emboli (VGE) induced by a rapid ambient pressure reduction on ascent from diving may cause ischemia and acute heart failure. The aim of this study was to investigate the effect of diving‐induced VGE formation on cardiac stress marker levels and the cardioprotective effect of HBO‐PC. To induce high loads of VGE, 63 female Sprague–Dawley rats were subjected to a rapid ambient pressure reduction from a simulated saturation dive (50 min at 709 kPa) in a pressure chamber. VGE loads were measured for 60 min in anesthetized animals by the use of ultrasonography. The animals were divided into five groups. Three groups were exposed to either diving or to HBO‐PC (100% oxygen, 38 min at 303 kPa) with a 45 or 180 min interval between HBO‐PC and diving. Two additional groups were used as baseline controls for the measurements; one group was exposed to equal handling except for HBO‐PC and diving, and the other group was completely unexposed. Diving caused high loads of VGE, as well as elevated levels of the cardiac stress markers, cardiac troponin T (cTnT), natriuretic peptide precursor B (Nppb), and αB‐crystallin, in blood and cardiac tissue. There were strong positive correlations between VGE loads and stress marker levels after diving, and HBO‐PC appeared to have a cardioprotective effect, as indicated by the lower levels of stress marker expression after diving‐induced VGE formation.

Animal study assessing safety of an acoustic coupling fluid that holds the potential to avoid surgically induced artifacts in 3D ultrasound guided operations

BackgroundUse of ultrasound in brain tumor surgery is common. The difference in attenuation between brain and isotonic saline may cause artifacts that degrade the ultrasound images, potentially affecting resection grades and safety. Our research group has developed an acoustic coupling fluid that attenuates ultrasound energy like the normal brain. We aimed to test in animals if the newly developed acoustic coupling fluid may have harmful effects.MethodsEight rats were included for intraparenchymal injection into the brain, and if no adverse reactions were detected, 6 pigs were to be included with injection of the coupling fluid into the subarachnoid space. Animal behavior, EEG registrations, histopathology and immunohistochemistry were used in assessment.ResultsIn total, 14 animals were included, 8 rats and 6 pigs. We did not detect any clinical adverse effects, seizure activity on EEG or histopathological signs of tissue damage.ConclusionThe novel acoustic coupling fluid intended for brain tumor surgery appears safe in rats and pigs under the tested circumstances.

Differentiation at necropsy between in vivo gas embolism and putrefaction using a gas score

Gas bubble lesions consistent with decompression sickness in marine mammals were described for the first time in beaked whales stranded in temporal and spatial association with military exercises. Putrefaction gas is a post-mortem artifact, which hinders the interpretation of gas found at necropsy. Gas analyses have been proven to help differentiating putrefaction gases from gases formed after hyperbaric exposures. Unfortunately, chemical analysis cannot always be performed. Post-mortem computed tomography is used to study gas collections, but many different logistical obstacles and obvious challenges, like the size of the animal or the transport of the animal from the stranding location to the scanner, limit its use in stranded marine mammals. In this study, we tested the diagnostic value of an index-based method for characterizing the amount and topography of gas found grossly during necropsies. For this purpose, putrefaction gases, intravenously infused atmospheric air, and gases produced by decompression were evaluated at necropsy with increased post-mortem time in New Zealand White Rabbits using a gas score index. Statistical differences (P<0.001) were found between the three experimental models immediately after death. Differences in gas score between in vivo gas embolism and putrefaction gases were found significant (P<0.05) throughout the 67h post-mortem. The gas score-index is a new and simple method that can be used by all stranding networks, which has been shown through this study to be a valid diagnostic tool to distinguish between fatal decompression, iatrogenic air embolism and putrefaction gases at autopsies.

A reliable and valid protocol for measuring maximal oxygen uptake in pigs

Background Most knowledge about cellular and molecular adaptation in the heart after exercise training comes from rodent models, and this has substantially improved our knowledge about exercise-induced cardiac adaptations. However, in rodents, the electrophysiological properties of the heart are different from the human heart. Therefore, the need of exercise-training models in larger animal models is obvious. Physiological studies of cardio-respiratory fitness require training regimens that give robust and adequate testing procedures to quantify the outcome. Methods We developed a valid and reproducible protocol for measuring maximal oxygen uptake (VO2max) in young pigs. As previous studies have exercised pigs using horizontal treadmills, we determined whether treadmill inclination may influence the level of peak oxygen uptake (VO2peak) achieved, and whether the true VO2max was reached. Eight young pigs were used. Submaximal and VO2peak were tested at five different inclinations from 13 to 30°. Results At submaximal VO2, there was an excellent test-retest at all treadmill inclinations (r 2 = 0.99, coefficient of variation = 1.8%). The level of VO2peak was dependent upon treadmill inclination and the true VO2max, defined as a levelling-off of VO2 despite increased running speed, was only reached a treadmill inclination of 24°. For VO2peak we only observed a significant test-retest correlation when using 19 and 24° inclination of the treadmill (r 2 = 0.88, coefficient of variation = 9.7%). Conclusion The use of inappropriate treadmill inclination might hide training-induced adaptations if the true VO2max is not reached. This study shows that the present test protocol can be used in future studies of exercise on treadmill, when the aim is to measure submaximal and VO2max in pigs.