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Biomedical subjects

C Ince

Publications and source records attributed to C Ince.

At least 19 recordsLinked to original sources

Microvascular oxygen pressure in the pig intestine during haemorrhagic shock and resuscitation.

1. The aim of this study was to investigate the relation between microvascular and venous oxygen pressures during haemorrhagic shock and resuscitation in the pig intestine. To this end microvascular PO2 (microPO2) was measured by quenching of Pd-porphyrin phosphorescence by oxygen and validated for the intestines. In addition, mesenteric venous blood gasses, blood flow, ilial CO2 production and global haemodynamics were also measured. 2. In one group (n = 11), moderate shock was induced by withdrawal of 40% of the circulating blood volume. Seven of these animals were resuscitated with a crystalloid solution and four with the withdrawn blood. In a second group of three animals, a more severe shock was induced by withdrawal of 50% of the circulating blood volume; these animals were not resuscitated. 3. Baseline mesenteric venous PO2 and microPO2 values were similar (60 +/- 9 and 60 +/- 11 mmHg, respectively). During moderate shock, microPO2 dropped significantly below mesenteric venous PO2 (26 +/- 10 versus 35 +/- 8 mmHg). After resuscitation with crystalloid solution, microPO2 and mesenteric venous PO2 rose to 44 +/- 9 and 44 +/- 6 mmHg, respectively. In the group that received the withdrawn blood, values were 41 +/- 9 and 53 +/- 12 mmHg, respectively. Severe shock resulted in a drop in the mesenteric venous PO2 (n = 3) to a value similar to that seen in the moderate shock group, but the gut microPO2 dropped to a much lower value than that of the moderate shock group (15 +/- 5 versus 26 +/- 10 mmHg). 4. The results indicate that the oxygenation of the microcirculation of the gut can become lower than the venous PO2 under conditions of haemorrhagic shock.

Animals

NADH videofluorimetry to monitor the energy state of skeletal muscle in vivo.

BACKGROUND: Reduction of the cellular energy state during ischemia of the limbs is an important determinant for development of necrosis. Since energy conversion in the mitochondria is based on electron transport from NADH to molecular O2, the NADH/NAD+ redox couple reflects the mitochondrial redox state and cellular O2 requirement. The applicability of NADH videofluorimetry to monitor noninvasively changes in the energy state of intact resting skeletal muscle as a function of oxygenation was investigated in a rat model. MATERIALS AND METHODS: In mechanically ventilated rats (n = 6), NADH fluorescence images of the gracilis muscle were recorded under different oxygenation conditions. Induction of anoxic and ischemic hypoxia were verified by simultaneous measurement of tissue oxygen pressure and afferent blood flow. RESULTS: Anoxic hypoxia and ischemic hypoxia increased the NADH fluorescence intensity by 46.0 +/- 15.0 and 30.8 +/- 26.4%, respectively. The response time of NADH fluorescence intensity, tissue oxygen pressure, and afferent blood flow was similar during development of anoxic and ischemic hypoxia. Upon reperfusion and reoxygenation, however, NADH fluorescence intensity changed significantly earlier than tissue oxygen pressure as measured by an oxygen needle electrode. CONCLUSION: These results demonstrate that changes in NADH fluorescence intensity reflect oxygenation changes in intact skeletal muscle in vivo. Since NADH videofluorimetry, in contrast to oxygen needle electrode measurements, noninvasively visualizes temporal and regional changes in the energy state of skeletal muscle, this technique has the potential to improve clinical evaluation of ischemia/reperfusion injury and tissue viability.

Animals

A novel method of evaluation of three heat-moisture exchangers in six different ventilator settings.

OBJECTIVE: The purpose of this study was to assess and compare the humidification, heating, and resistance properties of three commercially available heat-moisture exchangers (HMEs). To mimic clinical conditions, a previously validated, new, realistic experimental set-up and measurement protocol was used. DESIGN: Prospective, comparative experimental study. SETTING: Surgical Intensive Care Unit, University Hospital of Rotterdam. MATERIALS: An experimental set-up consisting of a patient model, measurement systems, and ventilator and three different HME types. INTERVENTIONS: The air flow, pressure in the ventilation circuit, pressure difference over the HME, and partial water vapour pressure and temperature at each side of the HMEs were measured. Measurements were repeated every 30 min during the first 2 h and every hour up to 24 h for each HME at six different ventilator settings. The mean inspiratory and maximum expiratory resistance, flow-weighted mean absolute humidity and temperature outputs, and humidification and heating efficiencies of HMEs were calculated. MEASUREMENTS AND RESULTS: The Dar Hygroster had the highest humidity output, temperature output, humidification efficiency, and heating efficiency values throughout the study (32.8 +/- 21. mg/l, 32.2 +/- 0.8 degrees C, 86.3 +/- 2.3%, and 0.9 +/- 0.01%, respectively) in comparison to the Humid-Vent Filter (25.3 +/- 3.2 mg/l, 31.9 +/- 0.8 degrees C, 72.2 +/- 5.3%, 0.9 +/- 0.02%, respectively) and the Pall Ultipor BB100 breathing circuit filter (23.4 +/- 3 mg/l, 28.3 +/- 0.7 degrees C, 68.8 +/- 5.9%, 0.8 +/- 0.02%, respectively). The inspiratory and expiratory resistance of the HMEs remained below clinically acceptable maximum values (2.60 +/- 0.04 and 2.45 +/- 0.05 cmH2O/l per s, respectively). CONCLUSION: The Dar Hygroster filter was found to have the highest humidity and temperature output of all three HMEs, the Humid-Vent filter had a satisfactory humidity output only at low tidal volume flow rate and minute volume settings, whereas the Pall Ultipore BB 100 never achieved a sufficient humidity and temperature output.

Hot Temperature

Low-volume resuscitation with a hemoglobin-based oxygen carrier after hemorrhage improves gut microvascular oxygenation in swine.

Using palladium-porphyrin quenching of phosphorescence, we investigated the influence of diaspirin cross-linked hemoglobin (DCLHb) on gut microvascular oxygen pressure (microPO2) in anesthetized pigs. Values of gut microPO2 were studied in correlation with regional intestinal as well as global metabolic and circulatory parameters. A controlled hemorrhagic shock (blood withdrawal of 40 mL/kg) was followed by resuscitation with either a combination of lactated Ringer's solution (75 mL/kg) and modified gelatin (15 mL/kg)(lactR/Gel) or 10% DCLHb (5 mL/kg). After resuscitation, gut microPO2 was similarly improved in the lactR/Gel group (from 25 +/- 10 mm Hg to 53 +/- 8 mm Hg) and the DCLHb group (from 23 +/- 9 mm Hg to 46 +/- 6 mm Hg), which was associated with increased gut oxygen delivery. However, the improvement after resuscitation with DCLHb was sustained for longer periods of time (75 vs 30 min). Mesenteric venous PO2 was increased after resuscitation with lactated Ringer's solution and modified gelatin but not with DCLHb, which was associated with an increased gut oxygen consumption in the latter group. We conclude that measurement of microPO2 by the palladium-porphyrin phosphorescence technique revealed DCLHb to be an effective carrier of oxygen to the microcirculation of the gut. Also, this effect can be achieved with a lower volume than is currently used in resuscitation procedures.

Animals

(Semi-)quantitative analysis of reduced nicotinamide adenine dinucleotide fluorescence images of blood-perfused rat heart.

In vivo analysis of the metabolic state of tissue by means of reduced nicotinamide adenine dinucleotide (NADH) fluorimetry is disturbed by tissue movements and by hemodynamic and oximetric effects. These factors cause changes in the absorption of ultraviolet (UV) excitation light by the tissue. Many different methods have been used in the literature to compensate measured NADH fluorescence intensities for these effects. In this paper we show on theoretical grounds that the ratio of NADH fluorescence intensity and UV diffuse reflectance intensity provides a (semi-)quantitative measure of tissue NADH concentrations. This result is corroborated by experiments with tissue phantoms in which absorption and back-scattering properties were varied. Furthermore, we have verified the validity of this compensation method in isolated Langendorff-perfused rat heart preparations. In this preparation oximetric effects (of blood and tissue) are the major determinants of the metabolism-dependent UV diffuse reflectance change. Hemodynamic effects accompanying compensatory vasodilation are negligible. Movement artifacts were eliminated by simultaneously recording fluorescence and reflectance images, using a CCD camera with a biprism configuration. The results show that the NADH fluorescence/UV reflectance ratio can be used to monitor the mitochondrial redox state of the surface of intact blood-perfused myocardium.

Animals

Nitric oxide causes dysfunction of coronary autoregulation in endotoxemic rats.

OBJECTIVE: This study tested the hypothesis that overproduction of endogenous nitric oxide (NO) during endotoxemia may modulate coronary autoregulation and myocardial reactive hyperemia. METHODS: Hearts of endotoxin-pretreated rats and controls were isolated and arranged for perfusion in a Langendorff preparation. Autoregulation was studied by examining flow-pressure relations during stepwise changes in perfusion pressure. The contribution of nitric oxide was examined by perfusion with N omega-nitro-L-arginine (NNLA), an inhibitor of nitric oxide synthesis and methylene blue (MB), an inhibitor of soluble guanylate-cyclase. RESULTS: Endotoxin-treated hearts showed massive coronary vasodilatation and autoregulatory function was impaired at perfusion pressures from 20 to 60 mmHg. Both NNLA and MB reduced coronary flow, improved autoregulation and eliminated differences in coronary flow and autoregulation between the control and endotoxin-treated group. Vasoconstriction with vasopressin, a direct smooth muscle constrictor, could not eliminate differences in autoregulation between groups. Reactive hyperemia following coronary occlusion in endotoxin-treated hearts showed decreased duration, flow repayment and repayment ratio. In the presence of NNLA or MB, however, no significant differences in reactive hyperemic flow patterns were present. CONCLUSIONS: These observations suggest that massive coronary vasodilatation due to increased myocardial NO synthesis can result in autoregulatory dysfunction and altered myocardial reactive hyperemia during endotoxemia.

Animals

In vivo structural studies of the hippocampus in normal aging and in incipient Alzheimer's disease.

Population trends indicate that in the near future the size of the elderly population will increase. This will result in a large increment in the numbers of persons suffering mild to severe levels of cognitive impairment. While considerable efforts continue to be made to explain brain changes associated with Alzheimer disease (AD), little is known of the brain changes in aging without dementia or so-called normal aging. Pathologic studies suggest that the medial temporal lobe is informative in the examination of the early brain changes related to AD. However, pathologic studies only offer a single observation and considerable uncertainty exists regarding the likelihood of progression of disease and the development of dementia. Several structural neuroimaging studies have recently investigated this anatomy and recent reports are encouraging for a medial temporal lobe based diagnosis for age-related cognitive impairments. We will present our findings on the MRI anatomy of the hippocampal formation as well as data bearing on the use of hippocampal formation imaging in the diagnosis of AD and as a predictive marker for future dementia. Our findings suggest an anatomically specific relationship between hippocampal volume and secondary memory performance. Because these observations apply to nondemented and normal elderly subjects, we are encouraged that the anatomy of age-related cognitive impairments can be reliably recognized and possibly put to use in therapeutic studies.

Aged

Clinical evaluation of diminished early expiratory flow (DEEF) ventilation in mechanically ventilated COPD patients.

OBJECTIVE: To evaluate the cardiopulmonary effects, especially the end-expiratory lung volume (EEV) and ventilation inhomogeneity during diminished early expiratory flow ventilation (DEEF), which resembles pursed-lips breathing, with the conventional intermittent positive pressure ventilation (IPPV) in postoperative mechanically ventilated patients with chronic obstructive pulmonary disease (COPD). DESIGN: A prospective study measuring cardiopulmonary parameters during IPPV, DEEF, and positive end-expiratory pressure (PEEP) as a control mode. In the PEEP mode, PEEP values were chosen such that the mean airway pressure during a breath cycle was equal to that during the DEEF mode, which was higher than the conventional IPPV mode. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: 20 postoperative mechanically ventilated COPD patients who were optimally pretreated and had normal blood oxygenation. INTERVENTIONS: Measurements were started in the IPPV (IPPV1) mode, continued in a randomized order with DEEF or PEEP, and completed with a second IPPV (IPPV2) mode, with 1 h equilibration time in each mode before each measurement. MEASUREMENTS AND RESULTS: A multi-breath indicator gas wash-out test was used to calculate the EEV and ventilation inhomogeneity. There was a 9% increase (p < 0.05) in the mean EEV during both the DEEF and PEEP mode compared to IPPV. No significant changes in the ventilation inhomogeneity and deadspace fractions or the hemodynamic parameters were found during the different ventilatory modes. CONCLUSIONS: There was no improvement in pulmonary and hemodynamic parameters during the DEEF mode in comparison to the IPPV mode. The small increase in EEV during DEEF was probably caused by the slightly higher mean expiratory pressures as in the PEEP mode. However, this had no effect on the hemodynamic parameters. As we could not observe any improvement with the DEEF ventilation in our optimally pretreated postoperative COPD patients, we do not advise applying this therapy in this group of patients, since this mode of ventilation may cause barotrauma if not monitored adequately.

Aged

Calibration of Pd-porphyrin phosphorescence for oxygen concentration measurements in vivo.

Quantitative measurement of oxygen concentrations in the microvasculature is of prime importance in issues related to oxygen transport to tissue. The introduction of the quenching of the Pd-porphyrin phosphorescence as oxygen sensor in vivo by Wilson et al. (J. Appl. Physiol. 74: 580-589, 1993) has provided in this context a major advance in this area of research. For in vivo application, the dye is coupled to albumin to restrict the dye to the circulation and to measure oxygen in the physiological range. In this study a phosphorimeter with a gated photomultiplier is presented and validated. Furthermore, a nonlinear-fit method using the Marquardt-Levenberg algorithm is used to calculate the decay time. With this new phosphorimeter, calibration measurements were performed to investigate the effects of pH, temperature, and diffusivity. The results present a preparation method for albumin coupling of the dye that eliminates the pH dependency of the quenching kinetics. Furthermore, the decreased oxygen diffusivity of serum was compared with that of water, and it was shown that calibration constants measured in water can be extrapolated to serum.

Algorithms

An experimental set-up to test heat-moisture exchangers.

OBJECTIVES: The purpose of this study was to build an experimental set-up to assess continuously the humidification, heating and resistance properties of heat-moisture exchangers (HMEs) under clinical conditions. DESIGN: The experimental set-up consists of a patient model, measurement systems and a ventilator. SETTING: Surgical ICU, University Hospital of Rotterdam. MATERIALS: A clinically used HME. MEASUREMENTS AND RESULTS: The air flow, pressure in the ventilation circuit, pressure difference over the HME, and partial water vapour pressure and temperature at each side of the HME were measured. The resistance, absolute humidity, humidification efficiency and temperature difference at the patient side of the HME were calculated. Measurements were performed during 24 h. The temperature output, humidity output and lung mechanics of the patient model were similar to values found in mechanically ventilated patients. The measurement system was in agreement with the ISO draft standard and was capable of measuring dynamic variation of water and heat exchange over the range of a clinically used ventilator setting. CONCLUSION: The experimental set-up described is reliable for evaluating HMEs and can also be used for future clinical evaluation of HMEs. The main advantages of this set-up over those described previously are: (i) measurements of dynamic variations of water and heat exchange; (ii) on-line measurements of expiratory, as well as inspiratory resistance.

Analysis of Variance

Increase of cardiac work is associated with decrease of mitochondrial NADH.

In this study we investigated the effect of work and substrate supply on mitochondrial NADH/NAD+ using epicardial autofluorescence in rat hearts perfused according to Langendorff. To avoid vasoconstrictor effects during high work output, nitroprusside-containing Tyrode solution was used. Photobleaching was avoided by using discontinuous ultraviolet excitation for NADH fluorescence measurements. To increase work, heartbeat rate was raised from 5 to 7 Hz, and concomitantly left ventricular pressure was raised stepwise from 0 to +/- 90 mmHg. During substrate-limited (5.5 mM glucose) perfusions, increase in O2 consumption (3.5 +/- 0.4 mumol.min-1.g-1, mean +/- SE, n = 6) caused by increase of heartbeat rate was associated with a significant decrease of NADH fluorescence (-31 +/- 2.5%, mean +/- SE, n = 6). During perfusions with 10 mM pyruvate increase of O2 consumption (3.6 +/- 0.7 mumol.min-1.g-1, mean +/- SE, n = 6) was associated with significant decrease of NADH fluorescence (-20 +/- 2.6%, mean +/- SE, n = 6). These results suggest that a rise in mitochondrial NADH/NAD+ is not the primary stimulus for increase in respiration and that changes of mitochondrial NADH/NAD+ are secondary to changes in O2 consumption.

Animals