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Biomedical subjects

C Ince

Publications and source records attributed to C Ince.

At least 19 recordsLinked to original sources

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

Inhibition of nitric oxide synthesis causes myocardial ischemia in endotoxemic rats.

Inhibitors of nitric oxide (NO) synthesis have been used in the treatment of septic and endotoxic shock. However, several studies question the beneficial effect of inhibiting NO production in sepsis and endotoxemia. We have investigated the effect of inhibition of NO synthesis after endotoxemia in the isolated perfused rat heart. In hearts from endotoxin-treated animals, coronary flow was elevated 64% and oxygen consumption was elevated 20% compared with control hearts. NADH fluorescence imaging was used as an indicator of regional hypoperfusion. A homogeneous low-surface NADH fluorescence, indicative of adequate tissue perfusion, was observed in both control and endotoxin-treated hearts. The increase in coronary flow and oxygen consumption could only partially be prevented by pretreatment of the animals with dexamethasone. Addition of N omega-nitro-L-arginine (NNLA), an inhibitor of NO synthesis, to the perfusion medium eliminated differences in coronary flow and oxygen consumption between normal and endotoxin-treated hearts. However, NADH surface fluorescence images of endotoxin-treated hearts after NNLA revealed areas of high fluorescence, indicating local ischemia, whereas the control hearts remained without signs of ischemia. The ischemic areas were present at various perfusion pressures and disappeared after the infusion of L-arginine, the natural precursor of NO, or the exogenous NO donor sodium nitroprusside. Methylene blue (MB), an inhibitor of soluble guanylate cyclase, the effector enzyme of NO, also eliminated differences in coronary flow and produced similar areas of local myocardial ischemia in endotoxin-treated hearts but not in control hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases

The hippocampus in aging and Alzheimer's disease.

The role of imaging in the evaluation of neurodegenerative disorders is summarized. The primary role of imaging is to exclude potentially treatable disorders such as meningioma, extracerebral hematoma, Wernicke's disease, and hypothyroidism. Atrophic changes dominate in the hippocampal region on Alzheimer's disease versus the anterior, frontal, and temporal lobes in Pick's disease. Signal hypointensity in the putamen on T2-weighted spin-echo images favors poorly drug-responsive Parkinson's disease whereas putaminal hyperintensity is observed with Creutzfeldt-Jacob, Wilson's, and Leigh's diseases. As our population ages, a thorough understanding of imaging findings in a geriatric population assumes an increasing importance.

Aged

A novel two-compartment culture dish allows microscopic evaluation of two different treatments in one cell culture simultaneously. Influence of external pH on Na+/Ca2+ exchanger activity in cultured rat cardiomyocytes.

A new type of culture dish containing two separate compartments is described, that can be used in high-magnification microscopy. Using the dish, two halves of a single-cell culture, grown on a standard coverslip, can be exposed to different treatments simultaneously, allowing the effect of one treatment to be compared with that of the other treatment in the same culture. This way, the natural variability that might exist between different individual cultures is circumvented. In addition, by simultaneously conducting two experiments per dish, the number of experiments needed can be decreased. This both reduces the time to complete a series of experiments and allows the optimal use of specimens that are difficult to obtain, such as human material. We found there is an excellent barrier between the two compartments for lipophilic and hydrophilic compounds, and for low-molecular-mass cations. To illustrate the use of the dish we describe the influence of external pH on the activity of the Na+/Ca2+ exchanger in intact cultured neonatal rat ventricular cardiomyocytes. The intracellular free calcium concentration ([Ca2+]i) in the cardiomyocytes, measured using fura-2 and imaging fluorescence microscopy, was studied during sodium-free incubation. The resulting rise in [Ca2+]i at pH 7.4 in one compartment was compared with that in the other compartment in which the pH was either 6.0, 7.0, 7.4 or 8.0. It was found that below pH 7.4, Na+/Ca2+ exchanger activity was diminished, whereas at pH higher than 7.4 the Na+/Ca2+ exchanger activity was increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Tonometry to assess the adequacy of splanchnic oxygenation in the critically ill patient.

Tonometry, a relatively non-invasive technique for indirectly measuring the intramucosal pH (pHi) of the gastrointestinal tract, has recently been developed for use in critically ill patients. Reports in the literature suggest that the technique is of greatest benefit to patients at risk of developing reductions in splanchnic oxygenation (decreased O2 delivery) in whom early detection of the ischemic episode could possibly guide treatment. Tonometry, although still at a relatively early stage in its clinical development, could be of value for selected patient groups although further evaluation of the technique is necessary.

Clinical Trials as Topic

Imminent ischemia in normal and hypertrophic Langendorff rat hearts; effects of fatty acids and superoxide dismutase monitored by NADH surface fluorescence.

Hypertrophic hearts contain areas of hypoperfusion which can be visualized by increased NADH surface fluorescence during in vitro perfusion without oxygen-carrying particles under constant pressure and pacing. By contrast, fluorescence remained low when non-hypertrophic hearts were used instead. When during perfusion of normal hearts the pH of the medium was lowered from 7.5 to 7.0, areas of high fluorescence appeared in a few minutes. The high fluorescent areas under conditions of cardiac hypertrophy or pH 7.0 perfusion could be reduced by addition of superoxide dismutase. It indicates that oxygen free radicals interfere with proper flow regulation in areas of low pH. Fluorescence in hypertrophic hearts also diminished during addition of albumin-bound oleate to the standard, glucose-containing, medium. This is in agreement with our earlier finding of fatty acid protection from acidosis-initiated loss of capillary flow (Biochim. Biophys. Acta, 1033 (1990) 214-218). In contrast to low concentrations of free fatty acids, high concentrations interfere with tissue oxygenation. This has been illustrated by the use of 1 mM octanoate, which after a few min caused the appearance of high fluorescent areas. We conclude that decompensation of flow in hypoperfused areas of heart, as occurs in hypertrophy, may be stimulated by acidosis and oxygen free radicals.

Acidosis

A new ventilation inhomogeneity index from multiple breath indicator gas washout tests in mechanically ventilated patients.

OBJECTIVES: a) To determine the validity of a new method to analyze indicator gas washout tests on mechanically ventilated patients. This method takes into account the difference between the end-expiratory gas fraction and the mean gas fraction in the lung and provides the end-expiratory lung volume and a new index of ventilation inhomogeneity called volumes regression index. b) To determine the validity of this index as a predictor of chronic obstructive pulmonary disease. c) To compare this index with the moment ratio index and Becklake index. DESIGN: Prospective study of diagnostic test. Criterium standards: Closed-circuit indicator gas dilution technique and Tiffeneau index. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: A total of 38 mechanically ventilated postoperative patients, divided into two groups: the obstructive group (n = 21) and the nonobstructive group (n = 17), based on their preoperative lung function. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: a) The mean coefficient of variation of all lung volume measurements in a group of nine healthy volunteers was 5%, and the difference between this technique and the closed-circuit helium dilution measurements was -2 +/- 5%. In patients, the mean coefficient of variation of the lung volume measurements was 3.5%. The volumes regression index was measured as 0.02 +/- 0.04 in a dummy lung, 0.37 +/- 0.08 in the healthy volunteers, 0.64 +/- 0.23 in the nonobstructive patients, and 1.1 +/- 0.3 in the obstructive patients. The volumes regression index provided a better correlation (r2 = .46) with preoperatively determined Tiffeneau index than the Becklake index (r2 = .11) or the moment ratio index (r2 = .18). CONCLUSION: The proposed technique provides a means for accurate measurement of the end-expiratory lung volume and the amount of ventilation inhomogeneity in mechanically ventilated intensive care unit patients.

Adult

Decreased mortality rate and length of hospital stay in surgical intensive care unit patients with successful selective decontamination of the gut.

OBJECTIVE: Current studies concerning selective decontamination of the digestive tract have failed to demonstrate a decrease in the length of hospital stay and mortality rate, despite the finding of a significantly lower number of infections. To evaluate this issue in more detail, the relationship between the mortality rate and length of stay with respect to colonization and infections was studied within a group of patients receiving selective decontamination. Special attention was given to the efficacy of decontamination within each patient. The main question addressed was whether an effect on mortality rate was present, and if so, why this effect was not apparent until now. DESIGN: Prospective observational cohort study. SETTING: Surgical intensive care unit (ICU) in a university hospital. PATIENTS: Ninety-seven patients primarily admitted into the surgical ICU who received selective decontamination. Transferred patients were excluded. The majority of the surgeries were elective, and all patients completed the follow-up. INTERVENTIONS: All patients received polymyxin E, amphotericin B, and norfloxacin four times a day in a 2% solution of Orabase orally and enterally as suspensions of 200, 500, and 50 mg, respectively. Assessment of the efficacy of selective decontamination was done by identification of Gram-negative microorganisms in surveillance cultures from the oropharynx and rectum. Predicted mortality rates for each patient were calculated with a logistic regression formula. MEASUREMENTS AND MAIN RESULTS: A possible benefit of selective decontamination of the digestive tract would be expressed by lower actual mortality rates compared to predicted mortality rates. Since we expected the efficacy of decontamination to have an influence on infection and mortality rates, we evaluated these rates in terms of successful or unsuccessful decontamination. Most patients (n = 72) were successfully decontaminated. Actual death rates in these patients were significantly lower than the expected rates (as calculated by the Acute Physiology and Chronic Health Evaluation [APACHE] II scoring system) (18% vs. 40%, p = .006), whereas no difference was found in those patients with failed decontamination (n = 25, death rate 44%). The patients with unsuccessful selective decontamination had significantly longer hospital (52 vs. 34 days) and ICU lengths of stays (23 vs. 9 days; p = .002) and higher mortality rates (44% vs. 18%, p = .020) when compared with those patients who were successfully decontaminated. CONCLUSIONS: These results indicate that selective decontamination is beneficial in terms of mortality rate and length of stay in surgical patients only when successful decontamination has been achieved. The subgroup of patients for whom decontamination is not successful might be responsible for the obscurity in mortality effects of selective decontamination in studies until now. It is expected that identification and subsequent elimination of possible risk factors that cause a failure of selective decontamination can result in lower morbidity and mortality rates in critically ill, surgical patients admitted to the ICU.

Anti-Bacterial Agents

Heterogeneity of the hypoxic state in rat heart is determined at capillary level.

Heterogeneity in the hypoxic state of Tyrode-perfused rat hearts was studied using NADH and Pd-porphine videofluorometry. Ischemic as well as high-flow anoxia resulted in a homogeneous rise of tissue NADH fluorescence, whereas normoxic recovery from both types of anoxia caused transiently persisting patchy fluorescent areas. Patterns were always the same for a given heart. PO2 distribution in the vasculature measured by Pd-porphine phosphorescence showed patterns similar to the NADH fluorescence patterns. Microsphere embolization of the capillaries, but not of arterioles, elicited identical NADH fluorescence patterns as seen during recovery from anoxia without microspheres. High heartbeat rates also caused patchy fluorescent areas but not in the presence of adenosine. Patterns corresponded to those seen during normoxic recovery from anoxia under low beat rates. It is concluded that there are circulatory units in the rat heart at the capillary level that result in the temporary persistence of anoxic areas during recovery from anoxia. These vulnerable areas are the first to be compromised during high heartbeat rates.

Animals

A simple device to inject indicator gas for wash-out tests during mechanical ventilation.

OBJECTIVE: To evaluate a simple device which injects a constant fraction of indicator gas to the inspiratory mixture for performing multi-breath wash-out tests during controlled ventilation. DESIGN: the technique in which the indicator gas is injected at the mouth of the patient (post-mix) is compared with the technique where the indicator gas is administered in the bellows of the ventilator (pre-mix). SETTING: Surgical Intensive Care Unit of a University Hospital. PATIENTS: 10 post-operative mechanically ventilated patients. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: 3 wash-out tests with the post-mix and 3 wash-out tests with the pre-mix method were performed within an hour on every patient. The calculated mean end expiratory lung volume (EEV) was 1.91 +/- 0.871 with the post-mix technique and 1.89 +/- 0.881 with the pre-mix technique. There was a good agreement with a mean difference of -1.9 +/- 6.5% in the calculated EEV values by the two different techniques. CONCLUSION: The described injector is an affordable device, is easy to assemble and can be incorporated in most electronically regulated ventilators to perform multi-breath indicator gas wash-out tests for pulmonary monitoring at the bed side of ICU patients.

Aged

ATP-sensitive potassium channel is essential to maintain basal coronary vascular tone in vivo.

Glibenclamide, a known selective inhibitor of ATP-sensitive potassium channels, was infused into the coronary vasculature of anesthetized dogs and of isolated perfused rabbit hearts to assess the role of this channel in the maintenance of basal coronary resistance. Infusion of glibenclamide at a concentration of 55-80 microM in the dogs resulted in a twofold steady-state increase in coronary resistance with resultant tissue ischemia. Infusion of 1 microM glibenclamide in the isolated hearts resulted in a 67% increase in coronary resistance with resultant tissue ischemia. The ischemic changes were reversible upon removal of the drug. These findings indicate that the ATP-sensitive K+ channel plays a significant role in the maintenance of basal coronary resistance in vivo. Higher concentrations of glibenclamide (80-100 microM) in the in vivo dog heart consistently gave rise to an oscillating pattern of coronary flow. These oscillations were either eliminated or decreased in amplitude and frequency by the infusion of 8-phenyltheophylline, a specific competitive inhibitor of adenosine receptors. 31P-nuclear magnetic resonance spectroscopy performed at the peaks and troughs of these oscillations revealed oscillation of the phosphorylation potential at the same frequency. Thus adenosine release caused by tissue ischemia appears to play a major role in creating the oscillating pattern of coronary blood flow, that occurs during the inhibition of ATP-sensitive K+ channels by glibenclamide.

Adenosine Triphosphate