Biomedical subjects

J Woodrow Weiss

Publications and source records attributed to J Woodrow Weiss.

11 recordsLinked to original sources

PubMed2006

Physiological basis for a causal relationship of obstructive sleep apnoea to hypertension.

Obstructive sleep apnoea (OSA) is causally related to systemic hypertension through sustained sympathoexcitation. The causes of this sympathoexcitation remain uncertain; however, substantial animal and human data suggest that cyclic intermittent hypoxia (CIH), as is experienced at night by patients with OSA, provides the causal link between upper airway obstruction during sleep and sympathetic activation during waking. Direct and indirect evidence indicates that CIH leads to sympathoexcitation by two mechanisms: (1) augmentation of peripheral chemoreflex sensitivity (hypoxic acclimatization); and (2) direct effects on sites of central sympathetic regulation, such as the subfornical organ and the paraventricular nucleus of the hypothalamus. Initial reports suggest that the molecular mechanisms influencing peripheral chemoreflex sensitivity and central sympathetic activity may be the same, involving such neuromodulators as angiotensin II, endothelin and nitric oxide.

Animals↗

PubMed2006

Evidence of impaired hypoxic vasodilation after intermediate-duration hypoxic exposure in humans.

Systemic hemodynamics, including forearm blood flow and ventilatory parameters, were evaluated in 21 subjects before and after exposure to 8 h of poikilocapnic hypoxia. To evaluate the role of sympathetic nervous system activation in the changes, in 10 of these subjects, we measured muscle sympathetic nerve activity (MSNA) before and after exposure, and the remaining 11 subjects received intra-arterial phentolamine infusion in the brachial artery to define vascular tone in the absence of sympathetically mediated vasoconstriction. Short-term ventilatory acclimatization occurred as evidenced by a decrease in resting Pco(2) (from 42 +/- 1.4 to 37 +/- 0.96 mmHg) and by an increase in the slope of the ventilatory response to acute hypoxia [from 0.7 +/- 0.1 to 1.2 +/- 0.2 l.min(-1).%Sp(O(2)) (blood O(2) saturation from pulse oximetry)] after exposure. Subjects demonstrated a significant increase in resting heart rate (from 61 +/- 2 to 65 +/- 2 beats/min) and diastolic blood pressure (from 64.8 +/- 2.7 to 70.4 +/- 2.0 mmHg). MSNA did not change significantly after exposure, although there was a trend toward a decrease in burst frequency (from 19.8 +/- 4.1 to 14.3 +/- 1.2 bursts/min). Forearm vascular resistance showed a significant decrease after termination of exposure (from 37.7 +/- 3.6 to 27.6 +/- 2.7 mmHg.ml(-1).min.100 g tissue, P < 0.05). Initially, progressive isocapnic hypoxia elicited significant vasodilation, but after 8 h of poikilocapnic hypoxic exposure, the acute challenge failed to change forearm vascular resistance. Local alpha-blockade with phentolamine restored the vasodilatory response to acute hypoxia in the postexposure setting.

Acclimatization↗

PubMed2006

Implementation and outcomes of the Multiple Urgent Sepsis Therapies (MUST) protocol.

OBJECTIVES: To describe the effectiveness of a comprehensive, interdisciplinary sepsis treatment protocol with regard to both implementation and outcomes and to compare the mortality rates and therapies of patients with septic shock with similar historical controls. DESIGN: Prospective, interventional cohort study with a historical control comparison group. SETTING: Urban, tertiary care, university hospital with 46,000 emergency department visits and 4,100 intensive care unit admissions annually. PATIENTS: Inclusion criteria were a) emergency department patients aged > or =18 yrs, b) suspected infection, and c) lactate of >4 mmol/L or septic shock. Exclusion criteria were a) emergent operation, b) prehospital cardiac arrest, and c) comfort measures only. Time period: protocol, November 10, 2003, through November 9, 2004; historical controls, February 1, 2000, through January 31, 2001. INTERVENTION: A sepsis treatment pathway incorporating empirical antibiotics, early goal-directed therapy, drotrecogin alfa, steroids, intensive insulin therapy, and lung-protective ventilation. MEASUREMENTS AND MAIN RESULTS: There were 116 protocol patients, with a mortality rate of 18% (11-25%), of which 79 patients had septic shock. Comparing these patients with 51 historical controls, protocol patients received more fluid (4.0 vs. 2.5 L crystalloid, p < .001), earlier antibiotics (90 vs. 120 mins, p < .013), more appropriate empirical coverage (97% vs. 88%, p < .05), more vasopressors in the first 6 hrs (80% vs. 45%, p < .001), tighter glucose control (mean morning glucose, 123 vs. 140, p < .001), and more frequent assessment of adrenal function (82% vs. 10%, p < .001), with a nonstatistically significant increase in dobutamine use (14% vs. 4%, p = .06) and red blood cell transfusions (30% vs. 18%, p = .07) in the first 24 hrs. For protocol patients with septic shock, 28-day in-hospital mortality was 20.3% compared with 29.4% for historical controls (p = .3). CONCLUSIONS: Clinical implementation of a comprehensive sepsis treatment protocol is feasible and is associated with changes in therapies such as time to antibiotics, intravenous fluid delivery, and vasopressor use in the first 6 hrs. No statistically significant decrease in mortality was demonstrated, as this trial was not sufficiently powered to assess mortality benefits.

Aged↗

PubMed2005

Functional imaging of working memory in obstructive sleep-disordered breathing.

Functional magnetic resonance imaging was used to map cerebral activation in 16 patients with obstructive sleep-disordered breathing (OSDB) and 16 healthy subjects, during the performance of a 2-back verbal working memory task. Six patients with OSDB were reimaged after a minimum period of 8 wk of treatment with positive airway pressure. Working memory speed in OSDB was significantly slower than in healthy subjects, and a group average map showed absence of dorsolateral prefrontal activation, regardless of nocturnal hypoxia. After treatment, resolution of subjective sleepiness contrasted with no significant change in behavioral performance, persistent lack of prefrontal activation, and partial recovery of posterior parietal activation. These findings suggest that working memory may be impaired in OSDB and that this impairment is associated with disproportionate impairment of function in the dorsolateral prefrontal cortex. Nocturnal hypoxia may not be a necessary determinant of cognitive dysfunction, and sleep fragmentation may be sufficient. There may be dissociations between respiratory vs. cortical recovery and objective vs. subjective recovery. Hypofrontality may provide a plausible biological mechanism for a clinical overlap with disorders of mood and attention.

Adult↗

PubMed2005

Serum lactate as a predictor of mortality in emergency department patients with infection.

STUDY OBJECTIVE: Little is known about risk-stratification biomarkers in emergency department (ED) patients with suspected infection, and lactate is a biologically plausible candidate. We determine whether a serum venous lactate is associated with an increased risk of death in ED patients with infection. METHODS: This was a prospective cohort study in an urban, academic medical center with 50,000 annual ED visits. A total of 1,278 consecutive patient visits met enrollment criteria between July 24, 2003, and March 24, 2004, and all patients were enrolled. Inclusion criteria were age 18 years or older, serum lactate level obtained, and admission to the hospital with an infection-related diagnosis. The main outcome measure was all-cause 28-day inhospital mortality and death within 3 days of presentation. RESULTS: Among 1,278 patient visits, there were 105 (8.2%) deaths during hospitalization, with 55 (4.3%) of 1,278 deaths occurring in the first 3 days. Mortality rates increased as lactate increased: 43 (4.9%) of 877 of patients with a lactate level between 0 and 2.5 mmol/L died, 24 (9.0%) of 267 patients with a lactate level between 2.5 and 4.0 mmol/L died, and 38 (28.4%) of 134 patients with a lactate level greater than or equal to 4.0 mmol/L died. Lactate level greater than or equal to 4.0 mmol/L was 36% (95% confidence interval [CI] 27% to 45%) sensitive and 92% (95% CI 90% to 93%) specific for any death; it was 55% (95% CI 41% to 68%) sensitive and 91% (95% CI 90% to 93%) specific for death within 3 days. CONCLUSION: In this cohort of ED patients with signs and symptoms suggestive of infection, our results support serum venous lactate level as a promising risk-stratification tool. Multicenter validation, as well as comparison of the lactate level with clinical predictors, needs to be done before widespread implementation.

Adult↗

PubMed2005

Low-concentration carbon dioxide is an effective adjunct to positive airway pressure in the treatment of refractory mixed central and obstructive sleep-disordered breathing.

OBJECTIVES: To assess the efficacy of added carbon dioxide as adjunctive therapy to positive airway pressure-refractory mixed obstructive and central sleep-disordered breathing, using a prototype device-the positive airway pressure gas modulator. DESIGN: Open-label evaluation of low concentrations of carbon dioxide added to a positive airway pressure circuit. SETTING: Physician-attended polysomnographic titration in a free-standing sleep laboratory with end-tidal and transcutaneous carbon-dioxide monitoring. PATIENTS: Six adult men (age 54 +/- 5.7 years) with severe poorly controlled mixed sleep-disordered breathing in the absence of renal or heart failure. INTERVENTIONS: Flow-independent addition of incremental concentrations of carbon dioxide during sleep. MEASUREMENTS AND RESULTS: The respiratory disturbance index before treatment was 66 +/- 14.5 events per hour of sleep, with a nocturnal desaturation low of 84.6% +/- 10.1%. Residual respiratory disturbance index on best treatment was 43 +/- 9 events per hour of sleep. There was an immediate (<1 minute) response to the addition of 0.5% to 1% carbon dioxide, and minimal changes were required to be made across the night. There was no discomfort, shortness of breath, palpitations, headache, or significant increase in respiratory or heart rate. The residual respiratory disturbance index on carbon dioxide, scored irrespective of desaturations, was in the normal range (< 5 / hour of sleep). Two subjects had a second night at the concentration of carbon dioxide determined to be efficacious, with no required concentration change. No adverse effects on overall sleep architecture were noted. CONCLUSIONS: Low concentrations of carbon dioxide added to conventional positive airway pressure effectively control severe treatment-resistant mixed obstructive and central sleep-disordered breathing.

Blood Gas Monitoring, Transcutaneous↗

PubMed2004

Arterial pressure and muscle sympathetic nerve activity are increased after two hours of sustained but not cyclic hypoxia in healthy humans.

Sustained and episodic hypoxic exposures lead, by two different mechanisms, to an increase in ventilation after the exposure is terminated. Our aim was to investigate whether the pattern of hypoxia, cyclic or sustained, influences sympathetic activity and hemodynamics in the postexposure period. We measured sympathetic activity (peroneal microneurography), hemodynamics [plethysmographic forearm blood flow (FBF), arterial pressure, heart rate], and peripheral chemosensitivity in normal volunteers on two occasions during and after 2 h of either exposure. By design, mean arterial oxygen saturation was lower during sustained relative to cyclic hypoxia. Baseline to recovery muscle sympathetic nerve activity and blood pressure went from 15.7 +/- 1.2 to 22.6 +/- 1.9 bursts/min (P < 0.01) and from 85.6 +/- 3.2 to 96.1 +/- 3.3 mmHg (P < 0.05) after sustained hypoxia, respectively, but did not exhibit significant change from 13.6 +/- 1.5 to 17.3 +/- 2.5 bursts/min and 84.9 +/- 2.8 to 89.8 +/- 2.5 mmHg after cyclic hypoxia. A significant increase in FBF occurred after sustained, but not cyclic, hypoxia, from 2.3 +/- 0.2 to 3.29 +/- 0.4 and from 2.2 +/- 0.1 to 3.1 +/- 0.5 ml.min(-1).100 g of tissue(-1), respectively. Neither exposure altered the ventilatory response to progressive isocapnic hypoxia. Two hours of sustained hypoxia increased not only muscle sympathetic nerve activity but also arterial blood pressure. In contrast, cyclic hypoxia produced slight but not significant changes in hemodynamics and sympathetic activity. These findings suggest the cardiovascular response to acute hypoxia may depend on the intensity, rather than the pattern, of the hypoxic exposure.

Adult↗

PubMed2004

Sustained muscle sympathetic activity after hypercapnic but not hypocapnic hypoxia in normal humans.

Exposure to hypercapnic hypoxia (asphyxia), but not hyperoxic hypercapnia, results in increased sympathetic activity that persists after exposure. To determine the contribution of CO2 to the post-hypoxia sympathoexcitation, we exposed 12 normal volunteers to hypocapnic and hypercapnic hypoxia (SaO2 approximately 85%) for 20 min each on different days. We measured plethysmographic forearm blood flow, muscle sympathetic nerve activity (MSNA), mean arterial pressure (MAP), and heart rate. MSNA increased during both exposures but remained elevated for 15 min only after asphyxia. Following asphyxia, MAP returned to pre-exposure values, but after hypocapnic hypoxia MAP decreased below baseline for 15 min. There were sustained decreases in heart rate after hypocapnic, but not hypercapnic hypoxia. Forearm vascular resistance (FVR) decreased below baseline during both exposures, reached its highest value above baseline after asphyxia and then declined. After hypocapnic hypoxia FVR rose to baseline after exposure. Hemodynamics are differently altered by hypercapnic relative to hypocapnic 20 min hypoxia, while only hypercapnic hypoxia produces sustained elevation of MSNA during recovery.

Adult↗

PubMed2004

Obstructive sleep-disordered breathing with a dominant cyclic alternating pattern--a recognizable polysomnographic variant with practical clinical implications.

OBJECTIVES: To define the clinical and polysomnographic features of a distinct variant of obstructive sleep-disordered breathing that is remarkably mild during rapid eye movement (REM) sleep. DESIGN: Observational study and evaluation of polysomnographic and clinical records. SETTING: American Academy of Sleep Medicine-accredited multidisciplinary sleep disorders center and laboratory. PATIENTS: 35 medication-free subjects with clinical and polysomnographic severe obstructive sleep-disordered breathing selected for dominance of 1 of 2 disordered breathing patterns. INTERVENTIONS: Positive airway pressure titration. MEASUREMENTS AND RESULTS: Nasal pressure was used to score respiratory events. Sleep was scored by both the standard criteria and cyclic alternating pattern (CAP), and the distribution of respiratory events was tabulated and analyzed. A distinct clinical and polysomnographic syndrome emerged, CAP-dominant sleep-disordered breathing, characterized by severe relatively short cycle obstructive events during non-REM sleep that were mild in REM sleep. Characteristics include lower body mass index, fewer apneas, and a lower hypoxic burden as reflected by frequency and severity of nocturnal oxygen saturation. During positive pressure titration, a remarkable respiratory instability emerged selectively during CAP, in contrast to stability during REM sleep. This partial treatment failure was associated with persistent clinical symptoms. CONCLUSIONS: This variant of sleep apnea may reflect a dominant component of respiratory instability and periodic breathing coupled with upper-airway obstruction. Its existence questions the conventional practice of calculating global respiratory indexes. Besides positive airway pressure, measures to treat periodic breathing may be required.

Electroencephalography↗

PubMed2004

Evidence of sustained forearm vasodilatation after brief isocapnic hypoxia.

Healthy subjects exposed to 20 min of hypoxia increase ventilation and muscle sympathetic nerve activity (MSNA). After return to normoxia, although ventilation returns to baseline, MSNA remains elevated for up to an hour. Because forearm vascular resistance is not elevated after hypoxic exposure, we speculated that the increased MSNA might be a compensatory response to sustained release of endogenous vasodilators. We studied the effect of isocapnic hypoxia (mean arterial oxygen saturation 81.6 +/- 4.1%, end-tidal Pco2 44.7 +/- 6.3 Torr) on plethysmographic forearm blood flow (FBF) in eight healthy volunteers while infusing intra-arterial phentolamine to block local alpha-receptors. The dominant arm served as control. Forearm arterial vascular resistance (FVR) was calculated as the mean arterial pressure (MAP)-to-FBF ratio. MAP, heart rate (HR), and FVR were reported at 5-min intervals at baseline, then while infusing phentolamine during room air, isocapnic hypoxia, and recovery. Despite increases in HR during hypoxia, there was no change in MAP throughout the study. By design, FVR decreased during phentolamine infusion. Hypoxia further decreased FVR in both forearms. With continued phentolamine infusion, FVR after termination of the exposure (17.47 +/- 6.3 mmHg x min x ml(-1) x 100 ml of tissue) remained lower than preexposure baseline value (23.05 +/- 8.51 mmHg x min x ml(-1) x 100 ml of tissue; P < 0.05). We conclude that, unmasked by phentolamine, the vasodilation occurring during hypoxia persists for at least 30 min after the stimulus. This vasodilation may contribute to the sustained MSNA rise observed after hypoxia.

Adult↗

PubMed2000

Quality of dyspnea in bronchoconstriction differs from external resistive loads.

To test the hypothesis that patients perceive the same quality of dyspnea during mild bronchoconstriction and external resistive loads, we studied subjects with asthma under two conditions: (1) during methacholine bronchoprovocation to mimic the bronchospasm of mild asthma and (2) while breathing on a circuit to which was added a range of external resistors to mimic the mechanical load of mild asthma. During each of these stimuli, respiratory variables, overall dyspnea intensity on a modified Borg scale, and the qualitative descriptors of breathlessness from a 19-item questionnaire were assessed. The "chest tightness" and "constriction" responses were significantly more frequent in the methacholine trials as compared with the external load trials (p < 0.0001). The "chest tightness" or "constriction" response was chosen during 92% of the 26 trials of methacholine bronchoconstriction compared with 3% of the 72 trials of breathing against the external resistors. Changes in functional residual capacity were not significantly different between the two conditions. We conclude that in mild asthma, the sensation of chest tightness is distinct from the sensation of work and effort and is not attributable to the mechanical load imposed on the respiratory system.

Adult↗