Differences in Glucose Metabolism Among Women With Spinal Cord Injury May Not Be Fully Explained by Variations in Body Composition.

OBJECTIVE: To investigate the differences in glucose metabolism among women with paraplegic, and tetraplegic spinal cord injury (SCI) in comparison to their able-bodied (AB) counterparts after adjusting for differences in body composition. DESIGN: Cross-sectional study. After an overnight fast, each participant consumed a 75-g glucose solution for oral glucose tolerance test (OGTT). Blood glucose, insulin, and C-peptide concentrations were analyzed before and 30, 60, 90, and 120 minutes after ingesting glucose solution. Insulin sensitivity index (ISI) was estimated using the Matsuda index. Percentage fat mass (%FM) and total body lean mass (TBLM) were estimated using data from dual-energy x-ray absorptiometry. Visceral fat (VF) was quantified using computed tomography. Outcome measures were compared among groups using analysis of covariance with %FM (or VF) and TBLM as covariates. SETTING: Research university. PARTICIPANTS: Women (N=42) with SCI (tetraplegia: n=8; paraplegia: n=14) and their race-, body mass index-, and age-matched AB counterparts (n=20). INTERVENTIONS: Not applicable. RESULTS: At fasting, there was no difference in glucose homeostasis (glucose, insulin, C-peptide concentrations) among 3 groups of women. In contrast, glucose, insulin, and C-peptide concentrations at minute 120 during OGTT were higher in women with tetraplegia versus women with paraplegia and AB women (P<.05, adjusted for TBLM and %FM). In addition, women with tetraplegia had lower ISI (P<.05, adjusted for TBLM and %FM) versus AB women. These differences remained after adjusting for VF and TBLM. CONCLUSION: Our study confirms that impaired glucose metabolism among women with tetraplegia may not be fully explained by changes in their body composition. Future studies exploring additional factors involved in glucose metabolism are warranted.

Normalization of disrupted clock gene expression in males with tetraplegia: a crossover randomized placebo-controlled trial of melatonin supplementation.

STUDY DESIGN: Crossover double blind, randomized placebo-controlled trial. OBJECTIVES: Circadian oscillators are located both in the brain and in peripheral organs. Melatonin, the main brain-derived hormone governing circadian variations, is highly associated with daylight patterns. However, in subjects with tetraplegia the melatonin levels are blunted. Here we studied peripheral oscillators in peripheral blood mononuclear cells (PBMCs) in males with tetraplegia by examining how exogenous melatonin may influence the expression of clock gene mRNAs. SETTING: Sunnaas Rehabilitation Hospital, Nesoddtangen, Norway. METHODS: Six males with tetraplegia received 2 mg of melatonin or placebo 4 days before the study period. We also included six able-bodied men sleeping or kept awake during the night. Plasma samples were collected four times during a 24-h period. The mRNA expression levels of the clock genes PER1, PER2, BMAL1, and REV-ERBα were quantified in PBMCs using quantitative RT-PCR. RESULTS: The mRNA expression levels of PER-1 and -2 and REV-ERBα were increased at 04:00 h compared with the able-bodied controls (p < 0.05). Melatonin supplementation changed mRNA peak-time toward the time of supplementation. CONCLUSIONS: Several peripheral clock genes displayed distorted expression levels in tetraplegia. Supplementation with melatonin changed the mRNA expression levels of these genes toward those observed among able-bodied. SPONSORSHIP: Financial support was provided from the Throne Holst Foundation, Sunnaas Rehabilitation hospital and the University of Ferrara (FAR2016).

Spinal Cord Injury Level Influences Acute Plasma Caffeine Responses.

PURPOSE: This study aimed to investigate the absorption curve and acute effects of caffeine at rest in individuals with no spinal cord injury (SCI), paraplegia (PARA), and tetraplegia (TETRA). METHODS: Twenty-four healthy males (eight able-bodied [AB], eight PARA, and eight TETRA) consumed 3 mg·kg caffeine anhydrous (CAF) in a fasted state. Plasma caffeine [CAF], glucose, lactate, free fatty acid, and catecholamine concentrations were measured during a 150-min rest period. RESULTS: Peak [CAF] was greater in TETRA (21.5 µM) compared with AB (12.2 µM) and PARA (15.1 µM), and mean peak [CAF] occurred at 70, 80, and 80 min, respectively. Moderate and large effect sizes were revealed for TETRA compared with PARA and AB (-0.55 and -1.14, respectively) for the total area under the [CAF] versus time curve. Large interindividual responses were apparent in SCI groups. The change in plasma catecholamine concentrations after CAF did not reach significance (P > 0.05); however, both adrenaline and noradrenaline concentrations were lowest in TETRA. Significant increases in free fatty acid were seen over time (P < 0.0005), but there was no significant influence of SCI level. Blood lactate concentration reduced over time (P = 0.022), whereas blood glucose concentration decreased modestly (P = 0.695), and no difference between groups was seen (P > 0.05). CONCLUSION: The level of SCI influenced the caffeine absorption curve, and there was large interindividual variation within and between groups. Individual curves should be considered when using caffeine as an ergogenic aid in athletes with an SCI. The results indicate TETRA should trial low doses in training and PARA may consider consuming caffeine greater than 60 min before exercise performance. The study also supports caffeine's direct effect on adipose tissue, which is not secondary to catecholamine release.

Rapidly Resolving Weakness Related to Hypokalemia in Patients Infected With Dengue Virus.

OBJECTIVES: Dengue is a mosquito-borne disease caused by arbovirus and well known for its typical fever with thrombocytopenia syndrome. Acute hypokalemic quadriparesis is a rare presentation of dengue with uncertain pathogenesis. We aim to describe the clinical and biochemical characteristics of rapidly resolving weakness related to hypokalemia in patients infected with dengue virus. METHODS: A retrospective review of the records of patients with diagnosis of dengue-associated hypokalemic weakness was performed. Demography, clinical, biochemical characteristics, and outcome of the patients were recorded during acute phase of illness. RESULTS: Our study cohort comprised 12 patients and all were males from urban dwelling. The median age was 34.5 years (range, 18-50). Presentation was acute onset rapidly worsening pure motor quadriparesis preceded by short lasting febrile episode. Weakness ranged from 2/5 to 4/5 on Medical Research Council (MRC) scale with generalized hyporeflexia or areflexia. The baseline serum potassium was mean ± SD (2.7 ± 0.48 mmol/L). All patients showed elevation of liver transaminases and elevated creatine phosphokinase level. Weakness improved in 24-72 hours in all patients with correction of serum potassium. CONCLUSIONS: Dengue-associated acute hypokalemic paralysis is an underrecognized entity having favorable outcome. It should be suspected in patients presenting as acute pure motor quadriparesis after febrile illness in dengue endemic areas.

Vitamin D deficiency in Swiss elite wheelchair athletes.

STUDY DESIGN: This is a retrospective analysis of total serum 25-hydroxyvitamin D (25[OH]D) in Swiss elite wheelchair athletes. OBJECTIVES: The aim was to investigate the occurrence of vitamin D deficiency in Swiss elite wheelchair athletes over the whole year and to detect differences between winter and summer months, and between indoor and outdoor athletes. SETTING: This study was conducted in Switzerland. METHODS: A total of 164 blood samples from 72 Swiss elite wheelchair athletes (mean±s.d.: age 32±13 years) were analyzed for total serum 25[OH]D. All participants were members of the national team in their discipline. The following disciplines have been included: rugby, athletics, cycling, tennis, ski alpine, curling and basketball. According to general guidelines, insufficient vitamin D status was defined between 50 and 75 nmol l-1, deficiency below 50 nmol l-1 and severe deficiency below 27.5 nmol l-1. RESULTS: In all, 73.2% of all samples showed an insufficiency/deficiency in vitamin D status. Total serum 25[OH]D was significantly higher during summer compared with winter months (69.5±21.4 nmol l-1 vs 51.5±21.9 nmol l-1; P<0.001). Indoor sports showed a higher amount of vitamin D insufficiency/deficiency (80.9%) than outdoor sports (70.1%), with a significantly higher 25[OH]D concentration in outdoor sports (P=0.042). CONCLUSION: A high percentage of vitamin D deficiency was found among Swiss elite wheelchair athletes. Conclusively, we recommend supplementation with vitamin D-especially during winter-to prevent a deficiency and an impairment of performance.

Reduced peak, but no diurnal variation, in thrombin generation upon melatonin supplementation in tetraplegia. A randomised, placebo-controlled study.

Tetraplegic patients have increased risk of venous thrombosis despite anti-thrombotic prophylaxis. Moreover, they have blunted plasma variations in melatonin and altered diurnal variation of several haemostatic markers, compared with able-bodied. However, whether healthy individuals and tetraplegic patients, with or without melatonin, display abnormalities in thrombin generation during a 24-hour (h) cycle, is unknown. We therefore used the Calibrated Automated Thrombogram (CAT) assay to examine diurnal variations and the possible role of melatonin in thrombin generation. Six men with long-standing complete tetraplegia were included in a randomised placebo-controlled cross-over study with melatonin supplementation (2 mg, 4 consecutive nights), whereas six healthy, able-bodied men served as controls. Ten plasma samples were collected frequently during a 24-h awake/sleep cycle. No significant diurnal variation of any of the measured CAT indices was detected in the three study groups. Whereas endogenous thrombin potential (ETP) was independent (p > 0.05) of whether the tetraplegic men received melatonin or placebo, melatonin decreased (p = 0.005) peak values in tetraplegia compared with those given placebo. Able-bodied men had lower (p = 0.019) ETP and Lag-Time (p = 0.018) compared with tetraplegics receiving placebo. Neither the Time-to-Peak nor the Start-Tail was affected (p > 0.05) by melatonin in tetraplegia. In conclusion, indices of thrombin generation are not subjected to diurnal variation in healthy able-bodied or tetraplegia, but peak thrombin generation is reduced in tetraplegic men receiving oral melatonin.

Brain-derived neurotrophic factor concentrations in tetraplegic athletes.

STUDY DESIGN: A prospective cohort with acute tetraplegia. OBJECTIVE: The purpose of this study was to investigate acute changes in serum brain-derived neurotrophic factor (BDNF) concentrations in tetraplegic spinal cord-injured (SCI) athletes during a typical training session of wheelchair rugby. SETTINGS: German Sport University Cologne, Cologne, Germany. METHODS: Eleven male SCI (AIS A and B) athletes completed a 90-min training session: The warm-up period included continuous pushing, submaximal increasing sprints and agility drills. The main training section comprised ball handling, passing drills, scrimmage activity and tactical practice. At the end of the training session, the athletes did moderate continuous pushing as a short cool-down. Venous blood samples were taken at rest before exercise, after the warm-up period and immediately following the first part of the main training section. Serum was pipetted after 30 min of blood sample resting and a subsequent centrifugation. BDNF concentrations were measured using an enzyme immunoassay ELISA kit. RESULTS: Heart rate (P < 0.01) and lactate (P = 0.04 and P < 0.01) concentration differed significantly in warm-up and main training part in comparison with basal values at rest. At rest, BDNF concentrations were 33.2 ± 21.6 ng ml(-1), after warm up 31.9 ± 18.9 ng ml(-1) and after the training session 29.9 ± 11 ng ml(-1), without significant differences (P > 0.05). CONCLUSIONS: A typical wheelchair rugby training session does not affect basal serum BDNF concentration in elite SCI athletes. In comparison with concentrations previously reported in healthy subjects, the current values at rest were slightly higher or rather at the upper limit.

Glucocorticoid-induced myopathy in the intensive care unit.

Glucocorticoids (GC) are used for intensive care unit (ICU) patients on several indications. We present a patient who was admitted to the ICU due to severe respiratory failure caused by bronchospasm requiring mechanical ventilation and treated with methylprednisolone 240 mg/day in addition to antibiotics and bronchiolytics. When the sedation was lifted on day 10, the patient was awake but quadriplegic. Blood samples revealed elevated muscle enzymes, electromyography showed myopathy, and a muscle biopsy was performed. Glucocorticoid-induced myopathy was suspected, GC treatment was tapered, and muscle strength gradually returned. The patient made full recovery from the quadriplegia a few months later.

Biomarkers of inflammation in persons with chronic tetraplegia.

In addition to lung volume restriction, individuals with chronic tetraplegia exhibit reduced airway caliber and bronchodilator responsiveness similar to persons with asthma. In asthma, airflow obstruction is closely linked to airway inflammation. Conversely, little is known regarding the airway inflammatory response in tetraplegia. To compare levels of biomarkers of inflammation in exhaled breath condensate (EBC) and serum in subjects with chronic tetraplegia, mild asthma, and able-bodied controls.Prospective, observational pilot study. Thirty-four subjects participated: tetraplegia (n = 12), asthma (n = 12), controls (n = 10). Biomarkers in EBC [8-isoprostane (8-IP), leukotriene B4 (LT-B4), prostaglandin E2 (PG-E2), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6)] and serum (8-IP, LT-B4, TNF-α, IL-6) were determined using commercially available EIA kits (Cayman Chemical Company, Ann Arbor, MI). Separate, one-way ANOVA with Bonferroni's post-hoc analyses were performed to determine group differences in demographic and dependent variables [EBC and serum biomarkers, fractional exhaled nitric oxide (FeNO), pulmonary function parameters, and specific airway conductance (sGaw)]. The tetraplegia group had significantly elevated 8-IP levels in EBC compared to the asthma (68 ± 38 versus 21 ± 13 pg ml(-1); p < 0.001) and control groups (22 ± 13 pg ml(-1); p < 0.01), respectively. FeNO levels were significantly elevated in the asthma compared to the control group (26 ± 18 versus 11 ± 4 ppb; p < 0.05), and trended higher than levels in the tetraplegia group (15 ± 6; p = 0.08). Levels of serum biomarkers did not differ significantly among groups. Through analysis of EBC, levels of 8-IP were significantly elevated compared to levels found in individuals with mild asthma and healthy controls. Further studies are needed to extend upon these preliminary findings that suggest the presence of airway inflammation in subjects with chronic tetraplegia, and how this relates to pulmonary dysfunction in this population.

Circadian rhythms of hemostatic factors in tetraplegia: a double-blind, randomized, placebo-controlled cross-over study of melatonin.

STUDY DESIGN: This is a double-blind, randomized, placebo-controlled cross-over study of melatonin in complete tetraplegia. OBJECTIVES: Tetraplegic patients have an increased risk of venous thrombosis despite prophylaxis, blunted variations in melatonin and altered circadian variation of several hemostatic markers. To examine whether melatonin could modify the regulation of hemostasis, we measured plasma melatonin and several markers of hemostasis in tetraplegic subjects with or without melatonin supplement. SETTING: The study was conducted in the Section for Spinal Cord Injury, Sunnaas Hospital, Nesoddtangen, Norway. METHODS: Six subjects with long-standing complete tetraplegia were included in this cross-over study with 2 mg of melatonin or placebo given 4 days before sampling. We also included six able-bodied men without any intervention. Plasma samples were then collected frequently during a 24-h awake/sleep cycle. The plasma concentrations of melatonin and the various markers were analyzed using linear mixed models. RESULTS: The 24-h profiles of prothrombin fragment 1+2 and von Willebrand factor, but not D-dimer, activated FVII, tissue factor pathway inhibitor and plasminogen activator inhibitor type 1, differed (P<0.05) between tetraplegic patients and able-bodied subjects. The absolute plasma concentration of activated FVII was higher (P<0.05) among the able-bodied compared with the tetraplegic groups. Supplementation of melatonin had no impact on these findings. CONCLUSIONS: We found differences in circadian variation of several hemostatic markers between able-bodied and tetraplegics. These differences were apparently unrelated to fluctuations in the melatonin concentrations, suggesting little or no role of melatonin in the regulation of hemostasis in tetraplegia. SPONSORSHIP: Financial support was provided from the Throne Holst Foundation.

Oxidized low-density lipoprotein, matrix-metalloproteinase-8 and carotid atherosclerosis in spinal cord injured subjects.

OBJECTIVE: Previous reports have indicated that subjects with chronic spinal cord injury (SCI) exhibit increased cardiovascular risk compared to able-bodied individuals. This study investigated the relationship between plasmatic oxidized low-density lipoprotein (OxLDL), matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) levels and vascular remodeling in SCI subjects and the role of physical activity in this regard. METHODS: We studied 42 men with chronic (≥2 years) SCI [18 sedentary (S-SCI) and 24 physically active (PA-SCI)] and 16 able-bodied men by clinical, anthropometric, laboratory, and carotid intima-media thickness (IMT) analysis. All enrolled subjects were normotensive, non-diabetics, non-smokers and normolipemic. Plasmatic OxLDL, MMP-2, MMP-8, MMP-9, TIMP-1 and TIMP-2 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Carotid IMT, IMT/diameter ratio and OxLDL levels of PA-SCI and able-bodied subjects were statistically similar. Conversely, S-SCI subjects exhibited higher IMT, IMT/diameter ratio and OxLDL levels compared to PA-SCI (p < 0.01, p < 0.001 and p = 0.01, respectively) and able-bodied (p < 0.001 for all) individuals. Results of bivariate correlation analysis including all injured subjects showed that carotid IMT and IMT/diameter ratio only correlated with OxLDL, MMP-8 and MMP-8/TIMP-1 ratio. Further stepwise regression analysis adjusted for the presence or not of physical activity and age showed that OxLDL was associated with carotid IMT and IMT/diameter ratio, while MMP-8 was associated with IMT/diameter ratio in SCI individuals. CONCLUSIONS: Plasmatic OxLDL and MMP-8 levels are associated with carotid atherosclerosis and there is an interaction among physical inactivity, atherosclerosis and OxLDL in SCI individuals.

Cardiometabolic risk factors in Iranians with spinal cord injury: analysis by injury-related variables.

Persons with spinal cord injury (SCI) have a high prevalence of abnormalities in carbohydrate and lipid metabolism. These abnormalities cause adverse coronary heart disease (CHD) in patients with SCI. In this study, we performed a detailed analysis of the level-specific cardiometabolic risk factors in individuals with SCI and analyzed the association of injury level on these risk factors. This was a cross-sectional study of 162 patients with SCI, assessing the prevalence of diabetes mellitus, dyslipidemia, hypertension, obesity, and smoking. Fasting blood sugar (>100) was diagnosed in 27 patients (16.7%). Of the total patients, 36 (22.2%) had a total cholesterol (TC) level of >200. A triglyceride level of >150 was present in 56 patients (34.6%). Hypertension was present in 2.5% of the entire patient group. Body mass index (BMI), TC, and low-density lipoprotein cholesterol (LDL-C) were significantly higher in the paraplegia group than the tetraplegia group (24.44 +/- 4.23 vs 22.65 +/- 4.27, p = 0.01; 185.71 +/- 40.69 vs 163.28 +/- 37.92, p < 0.001; and 102.51 +/- 28.20 vs 89.15 +/- 22.35, p = 0.01, respectively). Patients with paraplegia may have increased hypertension, higher BMI, and increasing levels of serum LDL-C and TC than those with tetraplegia. Conventional risk factors for CHD should be identified and treated in individuals with SCI.

Low-dose baclofen therapy raised plasma insulin-like growth factor-1 concentrations, but not into the normal range in a predictable and sustained manner in men with chronic spinal cord injury.

OBJECTIVE: To evaluate, whether once-daily oral baclofen administration increases and/or sustains plasma insulin-like growth factor-1 (IGF-1) concentration in 11 men with chronic spinal cord injury (SCI) and IGF-1 deficiency (i.e. <250 ng/ml). DESIGN: Prospective, open-label, dose titration study. Baclofen was administered at 20 mg/day for 8 weeks; then increased to 40 mg/day for another 8 weeks. Plasma IGF-1 and self-reported side effects were measured at baseline and every other week for the duration of the study. RESULTS: The subjects were 43 ± 12 years old, had duration of injury of 20 ± 12 years; eight subjects had a complete motor injury, and eight had paraplegia. Nine of 11 subjects completed the 20 mg/day treatment and 5 subjects completed the 40 mg/day treatment. Plasma IGF-1 levels improved with each baclofen dose; however, only one subject increased from baseline and remained above the targeted physiological range of 250 ng/ml throughout treatment. A significant increase in IGF-1concentration was observed between baseline and week 2 (154 ± 63 vs. 217 ± 69 ng/ml; P < 0.05), weeks 8 and 10 (188 ± 95 vs. 228 ± 93 ng/ml; P < 0.05), and weeks 8 and 16 (188 ± 95 vs. 259 ± 92 ng/ml; P < 0.05). No serious side effects were observed at 20 mg/day; the 40 mg/day dose was less well tolerated. CONCLUSION: Baclofen was not effective at sustaining plasma IGF-1 concentrations in the physiological range in men with chronic SCI.

Spinal cord injury level and the circulating cytokine response to strenuous exercise.

PURPOSE: A complete spinal cord injury (SCI) above the sixth thoracic vertebra (T6) results in the loss of sympathetic innervation of the adrenal medulla. This study examined the effect of a complete SCI above and below T6 on plasma concentrations of epinephrine, circulating interleukin 6 (IL-6) and other inflammatory cytokines in response to acute strenuous exercise. METHODS: Twenty-six elite male wheelchair athletes (8 = C6-C7 tetraplegic [TETRA], 10 = T6-L1 paraplegic [PARA], and 8 = non-spinal-cord-injured controls [NON-SCI]) performed a submaximal exercise test followed by a graded exercise to exhaustion on a motorized treadmill. Blood samples were taken preexercise, postexercise, and 30 min postexercise and analyzed for concentrations of IL-6, IL-10, IL-1 receptor antagonist (IL-1ra), tumor necrosis factor α (TNF-α), epinephrine, and cortisol. RESULTS: The circulating IL-6 concentration was significantly elevated at postexercise and 30 min postexercise (post30; approximately fivefold) in NON-SCI and PARA (P = 0.003), whereas concentrations in TETRA did not change significantly from preexercise values. IL-10, IL-1ra, and TNF-α were unaffected by exercise in all groups; however, both SCI groups presented elevated concentrations of IL-10 compared with NON-SCI (P = 0.001). At postexercise, epinephrine concentrations were significantly higher than preexercise and post30 concentrations in NON-SCI (approximately threefold) and PARA (approximately twofold) (P = 0.02). Plasma epinephrine concentrations were unchanged in TETRA throughout exercise; concentrations were significantly lower than NON-SCI and PARA at all time points. Plasma cortisol concentrations were significantly elevated in all groups at postexercise and post30 compared with preexercise (P < 0.001). Total exercise time was similar between groups (NON-SCI = 38 ± 6; PARA = 35 ± 5; TETRA = 36 ± 5 min). CONCLUSIONS: These findings suggest that the sympathetic nervous system plays an important regulatory role in the circulating IL-6 response to exercise and has implications for the metabolic and inflammatory responses to exercise in individuals with injuries above T6.

Fanconi syndrome following honeybee stings.

A 32-year-old gentleman was attacked by honey bees about 8 months and immediately afterwards his eyelids, cheeks and pinnae became swollen, red, and tender. However, the patient did not develop any renal or serum sickness symptoms and his physical examination and laboratory investigations were normal. He recovered completely. A week later, while working on his farm, he experienced a sudden loss of muscular tone in all four limbs without losing his consciousness. The medical examination subsequently revealed flaccid quadriparesis associated with a serum potassium of 2.1 mEq/L. He was also found to have hyperchloremic metabolic acidosis with normal anion gap and preserved ability to acidify urine to a pH of 5.5. These findings were suggestive of proximal renal tubular acidosis (Fanconi syndrome). Other abnormalities like hypophosphataemia, hypouricemia, renal glucosuria and high urinary excretion of calcium, phosphorus and uric acid further supported the diagnosis of proximal tubular dysfunction. The renal biopsy revealed dense lymphocytic interstitial infiltrate, a feature often seen in Sjogren's syndrome, in which at least 50% of patients fail to acidify urine. In our patient, thorough search for other causes of proximal renal tubular acidosis was negative.

Cerebrovascular reactivity and dynamic autoregulation in tetraplegia.

Humans with spinal cord injury have impaired cardiovascular function proportional to the level and completeness of the lesion. The effect on cerebrovascular function is unclear, especially for high-level lesions. The purpose of this study was to evaluate the integrity of dynamic cerebral autoregulation (CA) and the cerebrovascular reactivity in chronic tetraplegia (Tetra). After baseline, steady-state hypercapnia (5% CO(2)) and hypocapnia (controlled hyperventilation) were used to assess cerebrovascular reactivity in 6 men with Tetra (C5-C7 lesion) and 14 men without [able-bodied (AB)]. Middle cerebral artery blood flow velocity (MCAv), cerebral oxygenation, arterial blood pressure (BP), heart rate (HR), cardiac output (Q; model flow), partial pressure of end-tidal CO(2) (Pet(CO(2))), and plasma catecholamines were measured. Dynamic CA was assessed by transfer function analysis of spontaneous fluctuations in BP and MCAv. MCAv pulsatility index (MCAv PI) was calculated as (MCAv(systolic) - MCAv(diastolic))/MCAv(mean) and standardized by dividing by mean arterial pressure (MAP). Resting BP, total peripheral resistance, and catecholamines were lower in Tetra (P < 0.05), and standardized MCAv PI was approximately 36% higher in Tetra (P = 0.003). Resting MCAv, cerebral oxygenation, HR, and Pet(CO(2)) were similar between groups (P > 0.05). Although phase and transfer function gain relationships in dynamic CA were maintained with Tetra (P > 0.05), coherence in the very low-frequency range (0.02-0.07 Hz) was approximately 21% lower in Tetra (P = 0.006). Full (hypo- and hypercapnic) cerebrovascular reactivity to CO(2) was unchanged with Tetra (P > 0.05). During hypercapnia, standardized MCAv PI reactivity was enhanced by approximately 78% in Tetra (P = 0.016). Despite impaired cardiovascular function, chronic Tetra involves subtle changes in dynamic CA and cerebrovascular reactivity to CO(2). Changes are evident in coherence at baseline and MCAv PI during baseline and hypercapnic states in chronic Tetra, which may be indicative of cerebrovascular adaptation.