Keith Van Meter

A phase I study of low-pressure hyperbaric oxygen therapy for blast-induced post-concussion syndrome and post-traumatic stress disorder.

This is a preliminary report on the safety and efficacy of 1.5 ATA hyperbaric oxygen therapy (HBOT) in military subjects with chronic blast-induced mild to moderate traumatic brain injury (TBI)/post-concussion syndrome (PCS) and post-traumatic stress disorder (PTSD). Sixteen military subjects received 40 1.5 ATA/60 min HBOT sessions in 30 days. Symptoms, physical and neurological exams, SPECT brain imaging, and neuropsychological and psychological testing were completed before and within 1 week after treatment. Subjects experienced reversible middle ear barotrauma (5), transient deterioration in symptoms (4), and reversible bronchospasm (1); one subject withdrew. Post-treatment testing demonstrated significant improvement in: symptoms, neurological exam, full-scale IQ (+14.8 points; p<0.001), WMS IV Delayed Memory (p=0.026), WMS-IV Working Memory (p=0.003), Stroop Test (p<0.001), TOVA Impulsivity (p=0.041), TOVA Variability (p=0.045), Grooved Pegboard (p=0.028), PCS symptoms (Rivermead PCSQ: p=0.0002), PTSD symptoms (PCL-M: p<0.001), depression (PHQ-9: p<0.001), anxiety (GAD-7: p=0.007), quality of life (MPQoL: p=0.003), and self-report of percent of normal (p<0.001), SPECT coefficient of variation in all white matter and some gray matter ROIs after the first HBOT, and in half of white matter ROIs after 40 HBOT sessions, and SPECT statistical parametric mapping analysis (diffuse improvements in regional cerebral blood flow after 1 and 40 HBOT sessions). Forty 1.5 ATA HBOT sessions in 1 month was safe in a military cohort with chronic blast-induced PCS and PTSD. Significant improvements occurred in symptoms, abnormal physical exam findings, cognitive testing, and quality-of-life measurements, with concomitant significant improvements in SPECT.

Detection of Right to Left Shunts in Decompression Sickness in Divers

The diagnostic accuracy of bubble contrast transthoracic and transesophageal echocardiography and transcranial Doppler sonography in the detection of patent foramen ovale in divers with decompression sickness was assessed. Transcranial Doppler has a better positive and negative predictive value than the other modalities.

Hyperbaric oxygen therapy improves spatial learning and memory in a rat model of chronic traumatic brain injury

In the present experiment we use a rat model of traumatic brain injury to evaluate the ability of low-pressure hyperbaric oxygen therapy (HBOT) to improve behavioral and neurobiological outcomes. The study employed an adaptation of the focal cortical contusion model. 64 Male Long-Evans rats received unilateral cortical contusion and were tested in the Morris Water Task (MWT) 31-33 days post injury. Rats were divided into three groups: an untreated control group (N=22), an HBOT treatment group (N=19) and a sham-treated normobaric air group (N=23). The HBOT group received 80 bid, 7 days/week 1.5 ATA/90-min HBOTs and the sham-treated normobaric air group the identical schedule of air treatments using a sham hyperbaric pressurization. All rats were subsequently retested in the MWT. After testing all rats were euthanized. Blood vessel density was measured bilaterally in hippocampus using a diaminobenzadine stain and was correlated with MWT performance. HBOT caused an increase in vascular density in the injured hippocampus (p<0.001) and an associated improvement in spatial learning (p<0.001) compared to the control groups. The increased vascular density and improved MWT in the HBOT group were highly correlated (p<0.001). In conclusion, a 40-day series of 80 low-pressure HBOTs caused an increase in contused hippocampus vascular density and an associated improvement in cognitive function. These findings reaffirm the clinical experience of HBOT-treated patients with chronic traumatic brain injury.

Hyperbaric Oxygen as an Adjunct in Zygomycosis: Randomized Controlled Trial in a Murine Model

ABSTRACT Zygomycosis was induced by injecting CD-1 mice with 5 mg of intraperitoneal deferoxamine and then 106 CFU of intravenous and intrasinus Rhizopus arrhizus. The addition of hyperbaric oxygen (2.0 atm absolute twice daily) to amphotericin B did not improve survival over that achieved with amphotericin B and placebo air treatments.

Low pressure hyperbaric oxygen therapy and SPECT brain imaging in the treatment of blast-induced chronic traumatic brain injury (post-concussion syndrome) and post traumatic stress disorder: a case report.

A 25-year-old male military veteran presented with diagnoses of post concussion syndrome and post traumatic stress disorder three years after loss of consciousness from an explosion in combat. The patient underwent single photon emission computed tomography brain blood flow imaging before and after a block of thirty-nine 1.5 atmospheres absolute hyperbaric oxygen treatments. The patient experienced a permanent marked improvement in his post-concussive symptoms, physical exam findings, and brain blood flow. In addition, he experienced a complete resolution of post-traumatic stress disorder symptoms. After treatment he became and has remained employed for eight consecutive months. This case suggests a novel treatment for the combined diagnoses of blast-induced post-concussion syndrome and post-traumatic stress disorder.A 25-year-old male military veteran presented with diagnoses of post concussion syndrome and post traumatic stress disorder three years after loss of consciousness from an explosion in combat. The patient underwent single photon emission computed tomography brain blood flow imaging before and after a block of thirty-nine 1.5 atmospheres absolute hyperbaric oxygen treatments. The patient experienced a permanent marked improvement in his post-concussive symptoms, physical exam findings, and brain blood flow. In addition, he experienced a complete resolution of post-traumatic stress disorder symptoms. After treatment he became and has remained employed for eight consecutive months. This case suggests a novel treatment for the combined diagnoses of blast-induced post-concussion syndrome and post-traumatic stress disorder.

Epidermal closure regulates histolysis during mammalian (Mus) digit regeneration

Abstract Mammalian digit regeneration progresses through consistent stages: histolysis, inflammation, epidermal closure, blastema formation, and finally redifferentiation. What we do not yet know is how each stage can affect others. Questions of stage timing, tissue interactions, and microenvironmental states are becoming increasingly important as we look toward solutions for whole limb regeneration. This study focuses on the timing of epidermal closure which, in mammals, is delayed compared to more regenerative animals like the axolotl. We use a standard wound closure device, Dermabond (2‐octyl cyanoacrylate), to induce earlier epidermal closure, and we evaluate the effect of fast epidermal closure on histolysis, blastema formation, and redifferentiation. We find that fast epidermal closure is reliant upon a hypoxic microenvironment. Additionally, early epidermal closure eliminates the histolysis stage and results in a regenerate that more closely replicates the amputated structure. We show that tools like Dermabond and oxygen are able to independently influence the various stages of regeneration enabling us to uncouple histolysis, wound closure, and other regenerative events. With this study, we start to understand how each stage of mammalian digit regeneration is controlled.

Endogenous bone regeneration is dependent upon a dynamic oxygen event.

Amputation of the digit tip within the terminal phalangeal bone of rodents, monkeys, and humans results in near‐perfect regeneration of bone and surrounding tissues; however, amputations at a more proximal level fail to produce the same regenerative result. Digit regeneration is a coordinated, multifaceted process that incorporates signaling from bioactive growth factors both in the tissue matrix and from several different cell populations. To elucidate the mechanisms involved in bone regeneration we developed a novel multi‐tissue slice‐culture model that regenerates bone ex vivo via direct ossification. Our study provides an integrated multi‐tissue system for bone and digit regeneration and allows us to circumvent experimental limitations that exist in vivo. We used this slice‐culture model to evaluate the influence of oxygen on regenerating bone. Micro–computed tomography (µCT) and histological analysis revealed that the regenerative response of the digit is facilitated in part by a dynamic oxygen event, in which mutually exclusive high and low oxygen microenvironments exist and vacillate in a coordinated fashion during regeneration. Areas of increased oxygen are initially seen in the marrow and then surrounding areas of vasculature in the regenerating digit. Major hypoxic events are seen at 7 days postamputation (DPA 7) in the marrow and again at DPA 12 in the blastema, and manipulation of oxygen tensions during these hypoxic phases can shift the dynamics of digit regeneration. Oxygen increased to 21% oxygen tension can either accelerate or attenuate bone mineralization in a stage‐specific manner in the regenerative timeline. These studies not only reveal a circumscribed frame of oxygen influence during bone regeneration, but also suggest that oxygen may be one of the primary signaling influences during regeneration.

The applications of hyperbaric oxygen therapy in emergency medicine

Hyperbaric oxygen therapy involves the administration of oxygen in an environment where the ambient pressure has been increased. The ensuing hyperoxia and the elevated pressure have a number of beneficial clinical effects. Many of the clinical indications for hyperbaric oxygen therapy (HBOT) involve emergent conditions. It is therefore important for emergency physicians to be familiar with the applications of HBOT. Emergency physicians have become well represented in hyperbaric medicine. Currently, emergency physicians comprise approximately 15% of the membership of the Undersea and Hyperbaric Medical Society (UHMS). Along with internal medicine and anesthesiology/critical care medicine, emergency medicine is among the most heavily represented specialities in the UHMS (UHMS personal communication, February 1991). This is not surprising, considering the variety of emergent conditions that can be treated with HBOT. and the general attributes of an emergency physician: a broad general background, the ability to resuscitate unstable patients, and 24-hour in-house availability. The UHMS recognized the important association between Emergency Medicine and Hyperbaric Medicine when they convened a symposium entitled “Hyperbaric Oxygen in Emergency Medical Care” in 1983.’ This will not be a comprehensive review of hyperbaric medicine. Outstanding reviews of diving medicine and clinical hyperbaric medicine6-9 already have been written. This review will examine the relevance of HBO therapy to emergency medicine. It is necessary, however, to preface this review with a brief discussion of the background, the basic physics, and the physiology of HBOT.

Hyperbaric oxygen improves rate of return of spontaneous circulation after prolonged normothermic porcine cardiopulmonary arrest

AIM This controlled, prospective, randomized porcine study tests the hypothesis that high-dose hyperbaric oxygen (HDHBO2) compared with normobaric oxygen (NBO2) or standard-dose hyperbaric oxygen (SDHBO2), improves return of sustained spontaneous circulation (ROSC) after a normothermic, normobaric, 25-min, non-intervened-upon cardiopulmonary arrest. The study incorporated a direct mechanical ventricular assist device (DMVAD) for open chest continuous cardiac compressions (OCCC) to assist advanced cardiac life support (ACLS). The experiment demonstrates a dose response to oxygen concentration in the breathing mix used in resuscitative ventilation. MATERIALS AND METHODS Male pigs (average 30kg weight) underwent a 25-min, normothermic, non-intervened-upon cardiopulmonary arrest. Following arrest all animals were ventilated with 100% oxygen and were subjected to OCCC, incorporating DMVAD-aided ACLS. The animals so treated were randomized to be in one of three groups, with six animals in each group. The NBO2 group remained at 1.0 atmosphere absolute (ATA), while the SDHBO2 and HDHBO2 groups were initially placed at 1.9 and 4.0ATA, respectively. Uniform, but not American Heart Association (AHA) protocol, ACLS was maintained as needed over the ensuing 2h for all animals in all groups. At the end of 2h, the animals were euthanized. RESULTS Continuously sustained ROSC (mean arterial pressure > or =50mmHg at all times), without the need of the pump assist over the 2-h resuscitation attempt that followed the 25-min arrest, occurred in four out of six animals in the HDHBO2 group, and in none of the animals in the NBO2 or SBHBO2 groups (p< or =0.001). CONCLUSIONS Our results show significantly sustained ROSC using HDHBO2 to resuscitate swine after a 25-min, non-intervened-upon, normothermic cardiopulmonary arrest. These results could not be achieved using NBO2 or SDHBO2.

Hyperbaric Oxygen Promotes Proximal Bone Regeneration and Organized Collagen Composition during Digit Regeneration

Oxygen is critical for optimal bone regeneration. While axolotls and salamanders have retained the ability to regenerate whole limbs, mammalian regeneration is restricted to the distal tip of the digit (P3) in mice, primates, and humans. Our previous study revealed the oxygen microenvironment during regeneration is dynamic and temporally influential in building and degrading bone. Given that regeneration is dependent on a dynamic and changing oxygen environment, a better understanding of the effects of oxygen during wounding, scarring, and regeneration, and better ways to artificially generate both hypoxic and oxygen replete microenvironments are essential to promote regeneration beyond wounding or scarring. To explore the influence of increased oxygen on digit regeneration in vivo daily treatments of hyperbaric oxygen were administered to mice during all phases of the entire regenerative process. Micro-Computed Tomography (μCT) and histological analysis showed that the daily application of hyperbaric oxygen elicited the same enhanced bone degradation response as two individual pulses of oxygen applied during the blastema phase. We expand past these findings to show histologically that the continuous application of hyperbaric oxygen during digit regeneration results in delayed blastema formation at a much more proximal location after amputation, and the deposition of better organized collagen fibers during bone formation. The application of sustained hyperbaric oxygen also delays wound closure and enhances bone degradation after digit amputation. Thus, hyperbaric oxygen shows the potential for positive influential control on the various phases of an epimorphic regenerative response.