Adult and elderly population access to trauma centers: an ecological analysis evaluating the relationship between injury-related mortality and geographic proximity in the United States in 2010.

Background: Ongoing development and expansion of trauma centers in the United States necessitates empirical analysis of the effect of investment in such resources on population-level health outcomes. Methods: Multiple linear regressions were performed to predict state-level trauma-related mortality among adults and the elderly across 50 US states in 2010. The number of trauma centers per capita in each state and the percentage of each state's population living within 45-min of a trauma center served as the key independent variables and injury-related mortality served as the dependent variable. All analyses were stratified by age (adult versus elderly; elderly ≥ 65 years old) and were performed in SPSS. Results: The proportion of a population with geographic proximity to a trauma center demonstrates a consistent inverse linear relationship to injury-related mortality. The relationship reliably retains its significance in models including demographic covariates. Interestingly, access to Levels I and II trauma centers demonstrates a stronger correlation with mortality than was observed with Level III centers. Conclusion: Trauma center access is associated with reduced trauma-related mortality among both adults and the elderly as measured by state reported mortality rates. Ongoing efforts to designate and verify new trauma centers, particularly in poorly-served 'trauma deserts', could lead to lower mortality for large populations.

Erosion of Transplantation Tolerance After Infection.

Recent clinical studies suggest that operational allograft tolerance can be persistent, but long-term surviving allografts can be rejected in a subset of patients, sometimes after episodes of infection. In this study, we examined the impact of Listeria monocytogenes (Lm) infection on the quality of tolerance in a mouse model of heart allograft transplantation. Lm infection induced full rejection in 40% of tolerant recipients, with the remaining experiencing a rejection crisis or no palpable change in their allografts. In the surviving allografts on day 8 postinfection, graft-infiltrating cell numbers increased and exhibited a loss in the tolerance gene signature. By day 30 postinfection, the tolerance signature was broadly restored, but with a discernible reduction in the expression of a subset of 234 genes that marked tolerance and was down-regulated at day 8 post-Lm infection. We further demonstrated that the tolerant state after Lm infection was functionally eroded, as rejection of the long-term surviving graft was induced with anti-PD-L1 whereas the same treatment had no effect in noninfected tolerant mice. Collectively, these observations demonstrate that tolerance, even if initially robust, exists as a continuum that can be eroded following bystander immune responses that accompany certain infections.

Delayed Cytotoxic T Lymphocyte-Associated Protein 4-Immunoglobulin Treatment Reverses Ongoing Alloantibody Responses and Rescues Allografts From Acute Rejection.

Antibody-mediated rejection has emerged as the leading cause of late graft loss in kidney transplant recipients, and inhibition of donor-specific antibody production should lead to improved transplant outcomes. The fusion protein cytotoxic T lymphocyte-associated protein 4-immunoglobulin (CTLA4-Ig) blocks T cell activation and consequently inhibits T-dependent B cell antibody production, and the current paradigm is that CTLA4-Ig is effective with naïve T cells and less so with activated or memory T cells. In this study, we used a mouse model of allosensitization to investigate the efficacy of continuous CTLA4-Ig treatment, initiated 7 or 14 days after sensitization, for inhibiting ongoing allospecific B cell responses. Delayed treatment with CTLA4-Ig collapsed the allospecific germinal center B cell response and inhibited alloantibody production. Using adoptively transferred T cell receptor transgenic T cells and a novel approach to track endogenous graft-specific T cells, we demonstrate that delayed CTLA4-Ig minimally inhibited graft-specific CD4(+) and T follicular helper responses. Remarkably, delaying CTLA4-Ig until day 6 after transplantation in a fully mismatched heart transplant model inhibited alloantibody production and prevented acute rejection, whereas transferred hyperimmune sera reversed the effects of delayed CTLA4-Ig. Collectively, our studies revealed the unexpected efficacy of CTLA4-Ig for inhibiting ongoing B cell responses even when the graft-specific T cell response was robustly established.

Molecular biomarkers for assessing the heat-adapted phenotype: a narrative scoping review.

Heat acclimation/acclimatisation (HA) mitigates heat-related decrements in physical capacity and heat-illness risk and is a widely advocated countermeasure for individuals operating in hot environments. The efficacy of HA is typically quantified by assessing the thermo-physiological responses to a standard heat acclimation state test (i.e. physiological biomarkers), but this can be logistically challenging, time consuming, and expensive. A valid molecular biomarker of HA would enable evaluation of the heat-adapted state through the sampling and assessment of a biological medium. This narrative review examines candidate molecular biomarkers of HA, highlighting the poor sensitivity and specificity of these candidates and identifying the current lack of a single 'standout' biomarker. It concludes by considering the potential of multivariable approaches that provide information about a range of physiological systems, identifying a number of challenges that must be overcome to develop a valid molecular biomarker of the heat-adapted state, and highlighting future research opportunities.

Modulation of spontaneous activity in the overactive bladder: the role of P2Y agonists.

Spinal cord transection (SCT) leads to an increase in spontaneous contractile activity in the isolated bladder that is reminiscent of an overactive bladder syndrome in patients with similar damage to the central nervous system. An increase in interstitial cell number in the suburothelial space between the urothelium and detrusor smooth muscle layer occurs in SCT bladders, and these cells elicit excitatory responses to purines and pyrimidines such as ATP, ADP, and UTP. We have investigated the hypothesis that these agents underlie the increase in spontaneous activity. Rats underwent lower thoracic spinal cord transection, and their bladder sheets or strips, with intact mucosa except where specified, were used for experiments. Isometric tension was recorded and propagating Ca(2+) and membrane potential (E(m)) waves were recorded by fluorescence imaging using photodiode arrays. SCT bladders were associated with regular spontaneous contractions (2.9 ± 0.4/min); ADP, UTP, and UDP augmented the amplitude but not their frequency. With strips from such bladders, a P2Y(6)-selective agonist (PSB0474) exerted similar effects. Fluorescence imaging of bladder sheets showed that ADP or UTP increased the conduction velocity of Ca(2+)/E(m) waves that were confined to regions of the bladder wall with an intact mucosa. When transverse bladder sections were used, Ca(2+)/E(m) waves originated in the suburothelial space and propagated to the detrusor and urothelium. Analysis of wave propagation showed that the suburothelial space exhibited properties of an electrical syncitium. These experiments are consistent with the hypothesis that P2Y-receptor agonists increase spontaneous contractile activity by augmenting functional activity of the cellular syncitium in the suburothelial space.

Neuronal-derived nitric oxide modulates the activity of mouse detrusor smooth muscle.

AIMS: We investigated the roles of neuronal-derived nitric oxide (NO) in the modulation of spontaneous activity of mouse detrusor smooth muscle. METHODS: Detrusor smooth muscle strips were isolated from nNOS gene knock-out (nNOS(-/-) ) mice and their wild type siblings (nNOS(+/+) ). The properties of smooth muscle cells were assessed using intracellular electrophysiology and Ca(2+) imaging by laser-scanning confocal microscopy. The effects of an nNOS inhibitor, 7-nitro indazole (7-NI) on electrically evoked contractility were assessed using nNOS(+/+) mouse detrusor strips. RESULTS: In spontaneously active cells, the frequency of spontaneous action potentials (sAPs) and whole cell Ca(2+) flashes in nNOS(-/-) preparations was lower than that in the nNOS(+/+) preparations. The frequency of sAPs was enhanced by a nitric oxide donor, diethylamine NONOate sodium salt (NONOate; 100 µM), both when used alone and when the cGMP pathway was blocked by 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ, 10 µM). 7-NI (100 µM) significantly suppressed the electrically evoked contraction of mouse detrusor strips. CONCLUSIONS: We suggest that neuronal-derived NO facilitates the generation of spontaneous activity via a cGMP-independent pathway, and consequently enhances the evoked contraction of detrusor. Dysregulation of nNOS containing nerves may underlie bladder pathologies.

Changes in TRPC channel expression during postnatal development of cerebellar neurons.

In the brain, classical (canonical) transient receptor potential (TRPC) channels are thought to be involved in different aspects of neuronal development. We investigated the developmental expression profile of TRPC channels in rat cerebellum during the first 6 weeks after birth. TRPC3 expression is significantly up-regulated whereas TRPC4 and TRPC6 expression are significantly down-regulated over this period of time. TRPC3 expression is mainly found on Purkinje cells and their dendrites, suggesting that the increase in TRPC3 expression reflects development of the dendritic tree of Purkinje cells. TRPC4 expression was restricted to granule and their precursor cells. TRPC6 expression is found on Purkinje cell bodies, on mature granule cells in the internal granule cell layer (but not their precursors) and interneurons in the molecular layer. The decrease in TRPC4 expression suggests that it is required for proper granule cell development whereas the decrease in TRPC6 expression is presumably correlated with interneuron development. Moreover, we demonstrate the presence of functional TRPC channels on Purkinje cell dendrites that are activated following stimulation of metabotropic glutamate receptors. Our results reveal cell-specific expression patterns for different TRPC proteins and suggest that developmental changes in TRPC protein expression may be required for proper postnatal cerebellar development.

Structural and functional consequences of alveolar cell recognition by CD8(+) T lymphocytes in experimental lung disease.

CD8(+) T cells infiltrate the lung in many clinical conditions, particularly in interstitial lung disease. The role(s) that CD8(+) T cells might be playing in the pathogenesis of inflammatory lung disease is unclear at present, as is the direct contribution of CD8(+) T cell effector activities to lung injury. This report describes a transgenic model used to evaluate the impact, on respiratory structure and function, of CD8(+) T lymphocyte recognition of a target antigen expressed endogenously in alveolar epithelial cells. We found that adoptive transfer of cloned CD8(+) cytotoxic T lymphocytes (CTLs) specific for an alveolar neo-antigen (influenza hemagglutinin) leads to progressive lethal injury in transgenic mice, which dramatically affects lung structure and function. Transgenic recipients of CD8(+) CTLs exhibited tachypnea and progressive weight loss, becoming moribund over a period of several days. Concomitantly, the animals developed a progressive interstitial pneumonitis characterized initially by lymphocytic infiltration of alveolar walls and spaces, followed by an exuberant mononuclear cell infiltration that correlated with restrictive pulmonary mechanics and a progressive diffusion impairment. These results indicate that antigen-specific CD8(+) T cell recognition of an alveolar epithelial "autoantigen" is, in and of itself, sufficient to trigger an inflammatory cascade that results in the histological and physiological manifestations of interstitial pneumonia.

The origin of the skewed amplitude distribution of spontaneous excitatory junction potentials in poorly coupled smooth muscle cells.

The skewed amplitude distribution of spontaneous excitatory junction potentials (sEJPs) in the mouse vas deferens and other electrically-coupled smooth muscle syncytia has been attributed to electrically-attenuated depolarizations resulting from the spontaneous release of quantized packets of ATP acting on remote smooth muscle cells (SMCs). However, in the present investigation surface SMCs of the mouse isolated vas deferens were poorly electrically coupled, with input resistances (176+/-18 MOmega, range: 141-221 MOmega, n=4) similar to those of dissociated cells. Furthermore, the amplitude of evoked EJPs was more variable in surface compared with deeper SMCs (F test, F=17.4, P<0.0001). Using simultaneous electrophysiology and confocal microscopy to investigate these poorly-coupled cells, it is shown that alpha-latrotoxin-stimulated sEJPs correlate, in timing (median delay ranged from -30 to -57 ms, P<0.05 in all experiments, n=5) and amplitude (Pearson product moment correlation, rho>0.55 and P<0.001), with purinergic neuroeffector Ca2+ transients (NCTs) in SMCs. The temporal correlation between sEJPs of widely ranging amplitude with NCTs in the impaled SMC demonstrates that all sEJPs could arise from neurotransmitter action on the impaled cell and that the skewed distribution of sEJPs can be explained by the variable effect of packets of ATP on a single SMC. The amplitude correlation of sEJPs and NCTs argues against the attenuation of electrical signal amplitude along the length of a single SMC. The skewed sEJP amplitude distribution arising from neurotransmitter release on single SMCs is consistent with a broad neurotransmitter packet size distribution at sympathetic neuroeffector junctions.

Electrical and optical study of nerve impulse-evoked ATP-induced, P2X-receptor-mediated sympathetic neurotransmission at single smooth muscle cells in mouse isolated VAS deferens.

Simultaneous electrophysiology and confocal microscopy were used to investigate purinergic neurotransmission at single smooth muscle cells (SMCs) in mouse isolated vas deferens, and to explore the relationship between two high-resolution P2X-receptor-mediated measures of per pulse ATP release: transient peaks in the first time derivative of the rising phase of excitatory junction potentials (EJPs) recorded in single SMCs ('discrete events'; DEs) and neuroeffector Ca(2+) transients (NCTs) in the impaled SMCs. This study shows that discrete events represent neurotransmitter release onto the impaled cell. First, the median amplitude of the first derivative of the EJP was larger when there was a coincident NCT in the impaled cell, compared with instances when no coincident NCT occurred. Second, the time-to-peak amplitude of the first derivative was shorter if there was a coincident NCT in the impaled cell, compared with when no coincident NCT was observed within the field. Surprisingly, first derivative amplitude increased with the distance (of the corresponding NCT) from the microelectrode. The microelectrode did not locally inhibit the functional quantal size as there was no effect of distance on the normalized NCT amplitude. When the significant effect of distance (between the microelectrode and NCTs) on the first derivative amplitude was removed, there was no correlation between the unstandardized residual (of distance vs. first derivative amplitude) and NCT amplitude. The absence of a correlation between DE and NCT amplitudes suggests that the NCT amplitude is a poor measure of quantal size. The usefulness of NCTs hence lies primarily in locating neurotransmitter release and measuring changes in local release probability.

Psychophysical assessment of visual dysfunction.

Selected psychophysical techniques for nonhuman animals are described. These include operant learning methods and a new reflexive technique that may prove especially efficient. Problems of particular interest for toxicological research include control of the physical stimulus, choice of species, separation of stimulus from attentional effects, response bias, and pre- and post-training efficiency.

Photopolymers in orthopedics: characterization of novel crosslinked polyanhydrides.

Novel, high modulus, degradable polymers were prepared from methacrylated anhydride monomers of tricarballylic acid (MTCA) and pyromellitylimidoalanine (MPMA-ala). Kinetic studies indicate that the time scale of photopolymerization of MTCA (< 30 s) is suitable for in vivo applications. Additionally, the tensile modulus of copolymers of these novel monomers with methacrylic anhydride (MA) ranged from 0.8 to 2.1 GPa, which lies between the modulus of trabecular and cortical bone. Degradation studies indicate that the copolymers of MTCA and MPMA-ala with MA are initially surface degrading, which is important to maintaining polymer strength through the degradation process. Monomers such as these that can be rapidly polymerized using ultraviolet or blue light into high modulus degradable materials have great potential in orthopedics.

The "July phenomenon" and the care of the severely injured patient: fact or fiction?

BACKGROUND: The "July phenomenon," a common belief in medical academia, refers to purported errors, inefficiency, and negative outcomes during the summertime transition of the house staff. We hypothesized that care in a trauma service is consistent throughout the year and that the July phenomenon therefore is a myth. METHODS: The records of adults admitted to a trauma service between July 1994 and September 1999 were evaluated. The care of and outcomes for patients admitted in July and August were compared with those of patients admitted in April and May. RESULTS: Nine hundred seventeen patients were evaluated over 5 years. Patients were well matched by the Injury Severity Score, the Glasgow Coma Score, by mechanism, and by survival probability. Patients admitted in the spring were significantly older, by a mean of 5.1 years. Length of stay and intensive care unit stay were similar. Emergency department times were similar, as were resuscitation times, infection rates, and hospital costs. The mortality of patients was similar between the 2 times. CONCLUSIONS: There was no evidence of an increase in negative outcomes early in the academic year compared with the end of the academic year. We believe that a systematic approach to the diagnosis, resuscitation, and treatment of trauma prevented a July phenomenon.

Sodium nitroprusside mitigates oleic acid-induced acute lung injury.

BACKGROUND: Acute lung injury (ALI) is associated with pulmonary hypertension, intrapulmonary shunting, and increased microvascular permeability, leading to altered oxygenation capacity. Oleic acid (OA) creates a significant ALI that physiologically mimics human adult respiratory distress syndrome (ARDS). It has been hypothesized that pulmonary vasodilatation may improve ALI. Studies in our laboratory using this model and nitric oxide (NO) have shown that NO inhalation is detrimental and worsens the effects of OA. We studied the effect of pretreatment with a potent vasodilator, sodium nitroprusside (SNP), on ALI induced by OA in an isolated lung model. We hypothesized that pretreatment with SNP will worsen pulmonary hypertension and oxygenation in OA-induced ALI, similar to the effects seen with inhaled NO in this model. METHODS: Rabbit heart lung blocks were isolated, flushed in vivo, harvested, immediately perfused with whole blood, and ventilated with 50% oxygen. Pulmonary artery pressure was determined every 15 seconds for 90 minutes of perfusion. Oxygenation was determined by blood gas analysis of pulmonary venous effluent at 0, 20, 40, 60, and 90 minutes after initiation of OA infusion. Four groups were studied: saline control (SC), oleic acid control (OAC; 20-minute infusion of 50% OA/ethanol into pulmonary circulation), SNP control (NPC; 10 microg/ kg/min SNP infused without subsequent OA infusion), and SNP treatment (NPRx); 10 microg/kg/min SNP infused before OA/ethanol. Pulmonary artery pressure (PAP), oxygenation (arterio-venous oxygen difference [AVO2], compliance (CPL), and wet/dry lung weight were determined. RESULTS: No significant differences were found between the NPRx group and SC. Pretreatment with SNP eliminated the detrimental effects of OA infusion. CONCLUSIONS: Contrary to our hypothesis, pretreatment with SNP eliminates the decrease in oxygenation and increase in lung weight, and ameliorates pulmonary hypertension in our isolated lung model of OA-induced ALI.

Postinjury thromboxane receptor blockade ameliorates acute lung injury.

BACKGROUND: Acute lung injury is associated with pulmonary hypertension, intrapulmonary shunting, and increased microvascular permeability, leading to altered oxygenation capacity. Thromboxane A2 has been found to be a central mediator in the development of septic and oleic acid (OA)-induced acute lung injury. Our previous study demonstrated a beneficial effect of preinjury thromboxane A2 receptor blockade. The current study examines the efficacy of postinjury receptor blockade on oxygenation capacity and pulmonary hemodynamics in an isolated lung model of OA-induced acute lung injury. METHODS: Four groups of rabbit heart-lung preparations were studied for 60 minutes in an ex vivo perfusion-ventilation system. Saline control lungs received saline solution during the first 20 minutes of study. Injury control lungs received an OA-ethanol solution during the first 20 minutes. Two treatment groups were used: T10, in which the thromboxane receptor antagonist, SQ30741, was infused 10 minutes after the initiation of OA infusion; and T30, in which the thromboxane receptor antagonist was infused 30 minutes after OA infusion. RESULTS: Significant differences were found in oxygenation (oxygen tension in T10 = 62.6 +/- 11.7 mm Hg, T30 = 68.2 +/- 21.2 mm Hg; injury control = 40.2 +/- 9.0 mm Hg, saline control = 123.5 +/- 16.01 mm Hg; p < 0.001) and percentile change in pulmonary artery pressure (T10 = 1.1% +/- 19.4% increase, T30 = 11.2% +/- 7.3% increase; injury control = 47.6% +/- 20.5%, saline control = 4.2% +/- 6.81%; p < 0.001). CONCLUSIONS: This study demonstrates that blockade of the thromboxane A2 receptor, even after the initiation of acute lung injury, eliminates pulmonary hypertension and improves oxygenation.

Nitric oxide potentiates acute lung injury in an isolated rabbit lung model.

BACKGROUND: The effect of inhaled nitric oxide (NO) treatment on pulmonary function in the setting of adult respiratory distress syndrome is controversial. We examined the effect of inhaled NO on pulmonary function in an isolated rabbit lung model of oleic acid (OA)-induced acute lung injury. We hypothesized that NO would decrease pulmonary artery pressure and improve oxygenation. METHODS: Rabbit heart-lung blocks were isolated, flushed in vivo, harvested, and immediately perfused with whole blood and ventilated with 50% oxygen (O2). Pulmonary artery pressure was determined every 15 seconds for 60 minutes of perfusion. Oxygenation was determined by blood gas analysis of pulmonary venous effluent at 0, 20, 40, and 60 minutes after initiation of OA infusion. Rabbits were randomized into four study groups: saline control; OA control, which received a 20-minute infusion of 50% OA/ethanol solution; NO treatment (20 ppm NO inhaled before OA infusion); and NO control, which underwent NO (20 ppm) pretreatment, followed by saline infusion. Pulmonary artery pressure, oxygenation (arteriovenous O2 difference), compliance, and wet/dry lung weight were determined. RESULTS: Pretreatment with NO caused significant increases in pulmonary artery pressure (NO treatment versus NO control and saline control; no significant difference between NO treatment group and OA control group), and did not improve oxygenation in our model. CONCLUSIONS: Contrary to our hypothesis, pretreatment with NO potentiates acute lung injury in our isolated lung model. There was significant exacerbation of pulmonary hypertension and no improvement in oxygenation. Further investigation of the possible deleterious effects of NO in acute lung injury are needed, especially in the early acute phases of this process.

Thromboxane receptor blockade improves oxygenation in an experimental model of acute lung injury.

BACKGROUND: Adult respiratory distress syndrome remains a major cause of morbidity and mortality. We investigated the role of thromboxane receptor antagonism in an experimental model of acute lung injury that mimics adult respiratory distress syndrome. METHODS: Three groups of rabbit heart-lung preparations were studied for 30 minutes in an ex vivo blood perfusion/ventilation system. Saline control (SC) lungs received saline solution during the first 20 minutes of study. Injury control (IC) lungs received an oleic acid-ethanol solution during the first 20 minutes. Thromboxane receptor blockade (TRB) lungs received the same injury as IC lungs, but a thromboxane receptor antagonist (SQ30741) was added to the blood perfusate just prior to study. Blood gases were obtained at 10-minute intervals, and tidal volume, pulmonary artery pressure, and lung weight were continuously recorded. Oxygenation was assessed by measuring the percent change in oxygen tension over the 30-minute study period. Tissue samples were collected from all lungs for histologic evaluation. RESULTS: Significant differences were found between SC and IC lungs as well as TRB and IC lungs when comparing pulmonary artery pressure (SC = 33.1 +/- 2.2 mm Hg, TRB = 35.4 +/- 2.1 mm Hg, IC = 60.4 +/- 11.1 mm Hg; p < 0.02) and percent change in oxygenation (SC = -20.6% +/- 10.3%, TRB = -24.2% +/- 9.5%, IC = -57.1% +/- 6.2%; p < 0.03). None of the other variables demonstrated significant differences. CONCLUSIONS: Thromboxane receptor blockade prevents the pulmonary hypertension and the decline in oxygenation seen in an experimental model of acute lung injury that mimics adult respiratory distress syndrome.

HIV and medical nutrition therapy.

In those who are infected with human immunodeficiency virus, poor nutritional status can result from numerous causes, including anorexia, catabolism, chronic infection, fever, poor nutrient intake, nausea, vomiting, diarrhea, malabsorption, metabolic disturbances, lack of access to food, depression, and side effects of drug, radiation, and chemotherapy treatments. A compromised immune system may not be reversed by any medical treatments at this time, but malnutrition may be prevented and reversed by using current therapies, including medical nutrition therapy that includes nutrition assessment, the development of an individualized nutrition therapy plan, and implementation of the therapy. There is substantial evidence that medical nutrition therapy saves lives, reduces morbidity, improves health outcomes, reduces costs, and shortens hospital stays.

Potentiation of noise induced threshold shifts and hair cell loss by carbon monoxide.

Previous studies have determined that severe systemic hypoxia disrupts cochlear function acutely, but have suggested that augmentation of cochlear perfusion may successfully protect cochlear function under all but the most profound hypoxic treatments. In the current study we report on the chronic effects of simultaneous exposures to noise and carbon monoxide on pure tone thresholds and hair cell survival in rats. Following initial threshold determination, rats received acute exposure to carbon monoxide, noise, or both agents concurrently. Thresholds were evaluated 2-4 and 6-8 weeks later. The data show that carbon monoxide alone does not affect either auditory thresholds or compromise hair cells at the light microscopic level. The noise exposure alone produced variable, but quite limited permanent threshold shifts which were related to the power spectrum of the broad band noise that was employed. Hair cell loss was restricted to the basal turn of the cochlea. Simultaneous exposure to carbon monoxide and noise induced large threshold shifts at all frequencies studied, but the effect was greatest at the highest test frequency; an effect not consistent with the noise power spectrum. Widespread hair cell loss persisted over fully half of the basilar membrane in the most severely affected rat. Outer hair cells appear to be particularly vulnerable. Carbon monoxide plus noise did not appear to preferentially disrupt a particular row of outer hair cells. These data complement existing evidence that hyperoxia can mitigate against noise induced injury and reinforce the view that some types of noise induced damage may result from metabolic insufficiencies.