Project description:INTRODUCTION:Near-infrared spectroscopy (NIRS) non-invasively detects changes in the concentration of the chromophores oxygenated (?O2Hb) and deoxygenated hemoglobin (?HHb) as the bladder detrusor muscle contracts during voiding. Such data provide novel information on bladder oxygenation and hemodynamics. We evaluated the feasibility of monitoring ambulant subjects using a wireless NIRS device. METHODS:The wireless device uses paired light-emitting diodes (wavelengths 760 and 850 nm) and a silicon photodiode detector. We monitored 14 asymptomatic subjects (10 adults, 4 children) and 6 symptomatic children with non-neurogenic lower urinary tract dysfunction (NLUTD) during spontaneous voiding after natural filling. The device was taped to the abdominal skin 2 cm above the symphysis pubis across the midline. The wireless NIRS data (patterns of change in chromophore concentration) were compared between subjects and to the data obtained using a laser-powered instrument. RESULTS:Graphs of ?O2Hb, ?HHb and total hemoglobin (?tHb) were obtained from all 20 patients. Data during uroflow showed reproducible patterns of bladder chromophore change between asymptomatic subjects (rise in ?tHb/?O2Hb), consistent with laser instrument data. In contrast, all 6 symptomatic children had a negative trend in ?tHb, with falls in ?O2Hb. One adult experienced "shy" bladder and changes in hemodynamics/oxygenation occurred while bladder volume was unchanged. CONCLUSIONS:Wireless NIRS bladder monitoring is feasible in ambulant adults and children; wireless and laser-derived data in asymptomatic subjects are comparable. Pilot data suggest that subjects with symptomatic NLUTD have impaired bladder oxygenation/hemodynamics. The fact that chromophore changes occur when bladder volume remains constant supports the concept that NIRS data are a physiologic measure.
Project description:Adequate oxygenation of the kidney is of critical importance in the neonate. Non-invasive monitoring of renal tissue oxygenation using near-infrared spectroscopy (NIRS) is a promising bedside strategy for early detection of circulatory impairment as well as recognition of specific renal injury. As a diagnostic tool, renal NIRS monitoring may allow for earlier interventions to prevent or reduce injury in various clinical scenarios in the neonatal intensive care unit. Multiple studies utilizing NIRS monitoring in preterm and term infants have provided renal tissue oxygenation values at different time points during neonatal hospitalization, and have correlated measures with ultrasound and Doppler flow data. With the establishment of normal values, studies have utilized renal tissue oxygenation monitoring in preterm neonates to predict a hemodynamically significant patent ductus arteriosus, to assess response to potentially nephrotoxic medications, to identify infants with sepsis, and to describe changes after red blood cell transfusions. Other neonatal populations being investigated with renal NIRS monitoring include growth restricted infants, those requiring delivery room resuscitation, infants with congenital heart disease, and neonates undergoing extracorporeal membrane oxygenation. Furthermore, as the recognition of acute kidney injury (AKI) and its associated morbidity and mortality in neonates has increased over the last decade, alternative methods are being investigated to diagnose AKI before changes in serum creatinine or urine output occur. Studies have utilized renal NIRS monitoring to diagnose AKI in specific populations, including neonates with hypoxic ischemic encephalopathy after birth asphyxia and in infants after cardiac bypass surgery. The use of renal tissue oxygenation monitoring to improve renal outcomes has yet to be established, but results of studies published to date suggest that it holds significant promise to function as a real time, early indicator of poor renal perfusion that may help with development of specific treatment protocols to prevent or decrease the severity of AKI.
Project description:We reviewed existing methods for analyzing, in the time domain, physical mechanisms underlying the patterns of blood pressure and flow waveforms in the arterial system. These are wave intensity analysis and separations into several types of waveforms: (i) forward- and backward-traveling, (ii) peripheral and conduit, or (iii) reservoir and excess. We assessed the physical information provided by each method and showed how to combine existing methods in order to quantify contributions to numerically generated waveforms from previous cardiac cycles and from specific regions and properties of the numerical domain: the aortic root, arterial bifurcations and tapered vessels, peripheral reflection sites, and the Windkessel function of the aorta. We illustrated our results with numerical examples involving generalized arterial stiffening in a distributed one-dimensional model or localized changes in the model parameters due to a femoral stenosis, carotid stent or abdominal aortic aneurysm.
Project description:Resonance Raman spectroscopy offers a mechanism for the noninvasive measurement of in vivo and in situ hemoglobin oxygen saturation (HbO(2)Sat) in living tissue. Clinically informative signals can be provided by resonance enhancement with deep violet excitation. It is notable that fluorescence does not significantly degrade the quality of the signals. During the controlled hemorrhage and resuscitation of rats, signal intensity ratios of oxy- vs. deoxyhemoglobin from sublingual mucosa correlated with co-oximetry values of blood withdrawn from a central venous catheter. The spectroscopic application described here has potential as a noninvasive method for the diagnosis of clinical shock and guidance of its therapy.
Project description:Disruption of microvascular blood flow is a common cause of tissue hypoxia in disease, yet no therapies are available that directly target the microvasculature to improve tissue oxygenation. Red blood cells (RBCs) autoregulate blood flow through S-nitroso-hemoglobin (SNO-Hb)-mediated export of nitric oxide (NO) bioactivity. We therefore tested the idea that pharmacological enhancement of RBCs using the S-nitrosylating agent ethyl nitrite (ENO) may provide a novel approach to improve tissue oxygenation. Serial ENO dosing was carried out in sheep (1-400 ppm) and humans (1-100 ppm) at normoxia and at reduced fraction of inspired oxygen (FiO2 ). ENO increased RBC SNO-Hb levels, corrected hypoxia-induced deficits in tissue oxygenation, and improved measures of oxygen utilization in both species. No adverse effects or safety concerns were identified. Inasmuch as impaired oxygenation is a major cause of morbidity and mortality, ENO may have widespread therapeutic utility, providing a first-in-class agent targeting the microvasculature.
Project description:Respiration can positively influence cerebrospinal fluid (CSF) flow in the brain, yet its effects on central nervous system (CNS) fluid homeostasis, including waste clearance function via glymphatic and meningeal lymphatic systems, remain unclear. Here, we investigated the effect of supporting respiratory function via continuous positive airway pressure (CPAP) on glymphatic-lymphatic function in spontaneously breathing anesthetized rodents. To do this, we used a systems approach combining engineering, MRI, computational fluid dynamics analysis, and physiological testing. We first designed a nasal CPAP device for use in the rat and demonstrated that it functioned similarly to clinical devices, as evidenced by its ability to open the upper airway, augment end-expiratory lung volume, and improve arterial oxygenation. We further showed that CPAP increased CSF flow speed at the skull base and augmented glymphatic transport regionally. The CPAP-induced augmented CSF flow speed was associated with an increase in intracranial pressure (ICP), including the ICP waveform pulse amplitude. We suggest that the augmented pulse amplitude with CPAP underlies the increase in CSF bulk flow and glymphatic transport. Our results provide insights into the functional crosstalk at the pulmonary-CSF interface and suggest that CPAP might have therapeutic benefit for sustaining glymphatic-lymphatic function.
Project description:ObjectivePulmonary hypertension is a characteristic feature of acute respiratory distress syndrome (ARDS) and contributes to mortality. Administration of sildenafil in ambulatory patients with pulmonary hypertension improves oxygenation and ameliorates pulmonary hypertension. Our aim was to determine whether sildenafil is beneficial for patients with ARDS.DesignProspective, open-label, multicenter, interventional cohort study.SettingMedical-surgical ICU of two university hospitals.PatientsTen consecutive patients meeting the NAECC criteria for ARDS.InterventionsA single dose of 50 mg sildenafil citrate administered via a nasogastric tube.Main resultsAdministration of sildenafil in patients with ARDS decreased mean pulmonary arterial pressure from 25 to 22 mmHg (P = 0.022) and pulmonary artery occlusion pressure from 16 to 13 mmHg (P = 0.049). Systemic mean arterial pressures were markedly decreased from 81 to 75 mmHg (P = 0.005). Sildenafil did not improve pulmonary arterial oxygen tension, but resulted in a further increase in the shunt fraction.ConclusionAlthough sildenafil reduced pulmonary arterial pressures during ARDS, the increased shunt fraction and decreased arterial oxygenation render it unsuitable for the treatment of patients with ARDS.
Project description:Muco-ciliary transport in the human airway is a crucial defense mechanism for removing inhaled pathogens. Optical coherence tomography (OCT) is well-suited to monitor functional dynamics of cilia and mucus on the airway epithelium. Here we demonstrate several OCT-based methods upon an actively transporting in vitro bronchial epithelial model and ex vivo mouse trachea. We show quantitative flow imaging of optically turbid mucus, semi-quantitative analysis of the ciliary beat frequency, and functional imaging of the periciliary layer. These may translate to clinical methods for endoscopic monitoring of muco-ciliary transport in diseases such as cystic fibrosis and chronic obstructive pulmonary disease (COPD).