First record of Contracaecum spp. (Nematoda: Anisakidae) in fish-eating birds from Zimbabwe.

Endoparasites of fish-eating birds, Phalacrocorax africanus, P. carbo, Anhinga melanogaster and Ardea cinerea collected from Lake Chivero near Harare, Zimbabwe, were investigated. Adult Contracaecum spp. were found in the gastrointestinal tract (prevalence 100 % in P. africanus, P. carbo and A. melanogaster; 25 % in A. cinerea). Parasite intensity was 11-24 (mean 19) in P. africanus, 4-10 (mean 7) in P. carbo, 4-56 (mean 30) in A. melanogaster and 2 (mean 0.5) in A. cinerea. The cormorants fed mainly on cichlid fishes and carp; the darters and the grey herons on cichlids. All these fishes are intermediate hosts of Contracaecum spp. Scanning electron microscopy revealed that Contracaecum rudolphii infected both cormorant species and darters; C. carlislei infected only the cormorants while C. tricuspis and C. microcephalum infected only the darters. Parasites from the grey heron were not identified to species because they were still developing larvae. These parasites are recorded in Zimbabwe for the first time.

Artificial intelligence applications in the intensive care unit.

OBJECTIVE: To review the history and current applications of artificial intelligence in the intensive care unit. DATA SOURCES: The MEDLINE database, bibliographies of selected articles, and current texts on the subject. STUDY SELECTION: The studies that were selected for review used artificial intelligence tools for a variety of intensive care applications, including direct patient care and retrospective database analysis. DATA EXTRACTION: All literature relevant to the topic was reviewed. DATA SYNTHESIS: Although some of the earliest artificial intelligence (AI) applications were medically oriented, AI has not been widely accepted in medicine. Despite this, patient demographic, clinical, and billing data are increasingly available in an electronic format and therefore susceptible to analysis by intelligent software. Individual AI tools are specifically suited to different tasks, such as waveform analysis or device control. CONCLUSIONS: The intensive care environment is particularly suited to the implementation of AI tools because of the wealth of available data and the inherent opportunities for increased efficiency in inpatient care. A variety of new AI tools have become available in recent years that can function as intelligent assistants to clinicians, constantly monitoring electronic data streams for important trends, or adjusting the settings of bedside devices. The integration of these tools into the intensive care unit can be expected to reduce costs and improve patient outcomes.

Sequential V(A)/Q distributions in the normal rabbit by micropore membrane inlet mass spectrometry.

We developed micropore membrane inlet mass spectrometer (MMIMS) probes to rapidly measure inert-gas partial pressures in small blood samples. The mass spectrometer output was linearly related to inert-gas partial pressure (r(2) of 0.996-1.000) and was nearly independent of large variations in inert-gas solubility in liquid samples. We infused six inert gases into five pentobarbital-anesthetized New Zealand rabbits and used the MMIMS system to measure inert-gas partial pressures in systemic and pulmonary arterial blood and in mixed expired gas samples. The retention and excretion data were transformed into distributions of ventilation-to-perfusion ratios (V(A)/Q) with the use of linear regression techniques. Distributions of V(A)/Q were unimodal and broad, consistent with prior reports in the normal rabbit. Total blood sample volume for each VA/Q distribution was 4 ml, and analysis time was 8 min. MMIMS provides a convenient method to perform the multiple inert-gas elimination technique rapidly and with small blood sample volumes.

Collaborative prototyping approaches for ICU decision aid design.

When computer-based aids do not support the human users' decision-making strategies or anticipate the organizational impacts of technological change, advances in information technology may degrade rather than enhance decision-making performance. Such failures suggest the design of human-computer cooperation for problem solving and decision-making must be driven by human cognitive and organizational process requirements rather than computer technology. Decision- and user-centered development techniques involve domain experts and end-users in the earliest phases of design to evolve an understanding of requirements through iterative prototyping. This paper presents a collaborative approach to cognitive systems engineering applied to developing a clinical aid to assist respiratory care in the surgical ICU.

Endothelin-1 is elevated in monocrotaline pulmonary hypertension.

These studies document striking pulmonary vasoconstrictor response to nitric oxide synthase (NOS) inhibition in monocrotaline (MCT) pulmonary hypertension in rats. This constriction is caused by elevated endothelin (ET)-1 production acting on ETA receptors. Isolated, red blood cell plus buffer-perfused lungs from rats were studied 3 wk after MCT (60 mg/kg) or saline injection. MCT-injected rats developed pulmonary hypertension, right ventricular hypertrophy, and heightened pulmonary vasoconstriction to ANG II and the NOS inhibitor NG-monomethyl-L-arginine (L-NMMA). In MCT-injected lungs, the magnitude of the pulmonary pressor response to NOS inhibition correlated strongly with the extent of pulmonary hypertension. Pretreatment of isolated MCT-injected lungs with combined ETA (BQ-123) plus ETB (BQ-788) antagonists or ETA antagonist alone prevented the L-NMMA-induced constriction. Addition of ETA antagonist reversed established L-NMMA-induced constriction; ETB antagonist did not. ET-1 concentrations were elevated in MCT-injected lung perfusate compared with sham-injected lung perfusate, but ET-1 levels did not differ before and after NOS inhibition. NOS inhibition enhanced hypoxic pulmonary vasoconstriction in both sham- and MCT-injected lungs, but the enhancement was greater in MCT-injected lungs. Results suggest that in MCT pulmonary hypertension, elevated endogenous ET-1 production acting through ETA receptors causes pulmonary vasoconstriction that is normally masked by endogenous NO production.

Extraction and quantification of nicardipine in human plasma.

A novel simple method of extraction, separation, identification and quantification of nicardipine in human plasma samples was completely studied. The human plasma samples were initially purified by solid-phase extraction (SPE) using a C18 cartridge. The extracted samples were separated and nicardipine present in the samples was quantified by high-performance liquid chromatography (HPLC) on a reversed-phase C18 column employing a mobile phase consisting of 60% (v/v) acetonitrile in 0.02 M NaH2PO4 with pH of 6.3 and a variable wavelength UV detector set at 254 nm. The recovery of nicardipine from plasma samples using selective SPE was 91+/-6.0% and had less interfering compounds in the HPLC analysis compared to the use of liquid-liquid (L/L) extraction. In the HPLC analysis, examining the effect of pH values of the mobile phase on the capacity factor (k') of nicardipine revealed a method for selecting a critical k' value of nicardipine to eliminate interfering peaks near the peak specific to the analyte. This method for quantification of nicardipine in human plasma samples was suitable for studying the pharmacokinetic profile of nicardipine administered as an intravenous bolus to cardiac surgical patients.

Role of wall tension in hypoxic responses of isolated rat pulmonary arteries.

The changes in force developed during 40-min exposures to hypoxia (37 +/- 1 mmHg) were recorded in large (0.84 +/- 0.02-mm-diameter) and small (0.39 +/- 0.01-mm-diameter) intrapulmonary arteries during combinations of mechanical wall stretch tensions (passive + active myogenic components), equivalent to transmural vascular pressures of 5, 15, 30, 50, and 100 mmHg, and active (vasoconstriction) tensions, stimulated by PGF2alpha in doses of 0, 25, 50, and 75% effective concentrations. Constriction was observed in all arteries during the first minute; however, at any active tension, the pattern of the subsequent response was a function of the stretch tension. At 5, 15, and 30 mmHg, the constriction decreased slightly at 5 min and then increased again to remain constrictor throughout. At 50 and 100 mmHg, the initial constriction was followed by persistent dilation. Hypoxic constrictor responses, most resembling those observed in lungs in vivo and in vitro, were observed when the mechanical stretch wall tension was equivalent to 15 or 30 mmHg and the dose of PGF2alpha was 25 or 50% effective concentration. These observations reconcile many apparently contradictory results reported previously.

Improved oxygenation with prostaglandin F2alpha with and without inhaled nitric oxide in dogs.

Dogs of mixed breed (n = 7) were anesthetized, right lung atelectasis was established, and the cyclooxygenase pathway was blocked with ibuprofen. Measurements of pulmonary gas exchange were performed (fractional concentration of inspired O2 = 0.95) after infusions of prostaglandin F2alpha (PGF2alpha; 2 microg . kg-1 . min-1), ventilation with nitric oxide (NO; 40 ppm), or both (PGF2alpha + NO) in random order. The arterial PO2 (PaO2) under control conditions was 117 +/- 16 Torr (shunt = 33 +/- 2.5%), was unchanged with NO alone (PaO2 = 114 +/- 17 Torr; shunt = 35.7 +/- 3. 1%), but was significantly improved with PGF2alpha alone (PaO2 = 180 +/- 28 Torr; shunt = 23.2 +/- 2.8%) and with the combination of PGF2alpha + NO (PaO2 = 202 +/- 30 Torr; shunt = 20.9 +/- 2.5%). The addition of NO did not significantly enhance the effectiveness of the PGF2alpha on PaO2. Simulation of these data in a computer model, combining pulmonary gas exchange and pulmonary blood flow, reproduced the results on the basis that vasoconstriction with PGF2alpha was maximal under hypoxia in the atelectatic lung and reduced by hyperoxia in the ventilated lung, consistent with the hypothesis of O2 dependence of PGF2alpha vasoconstriction.

Improvement in oxygenation by phenylephrine and nitric oxide in patients with adult respiratory distress syndrome.

BACKGROUND: Inhaled nitric oxide (NO), a selective vasodilator, improves oxygenation in many patients with adult respiratory distress syndrome (ARDS). Vasoconstrictors may also improve oxygenation, possibly by enhancing hypoxic pulmonary vasoconstriction. This study compared the effects of phenylephrine, NO, and their combination in patients with ARDS. METHODS: Twelve patients with ARDS (PaO2/FIO2 180; Murray score 2) were studied. Each patient received three treatments in random order: intravenous phenylephrine, 50-200 micrograms/min, titrated to a 20% increase in mean arterial blood pressure; inhaled NO, 40 ppm; and the combination (phenylephrine+NO). Hemodynamics and blood gas measurements were made during each treatment and at pre- and posttreatment baselines. RESULTS: All three treatments improved PaO2 overall. Six patients were "phenylephrine-responders" (delta PaO2 > 10 mmHg), and six were "phenylephrine-nonresponders." In phenylephrine-responders, the effect of phenylephrine was comparable with that of NO (PaO2 from 105 +/- 14 to 132 +/- 14 mmHg with phenylephrine, and from 110 +/- 14 to 143 +/- 19 mmHg with NO), and the effect of phenylephrine+NO was greater than that of either treatment alone (PaO2 from 123 +/- 13 to 178 +/- 23 mmHg). In phenylephrine-nonresponders, phenylephrine did not affect PaO2, and the effect of phenylephrine+NO was not statistically different from that of NO alone (PaO2 from 82 +/- 12 to 138 +/- 28 mmHg with NO; from 84 +/- 12 to 127 +/- 23 mmHg with phenylephrine+NO). Data are mean +/- SEM. CONCLUSIONS: Phenylephrine alone can improve PaO2 in patients with ARDS. In phenylephrine-responsive patients, phenylephrine augments the improvement in PaO2 seen with inhaled NO. These results may reflect selective enhancement of hypoxic pulmonary vasoconstriction by phenylephrine, which complements selective vasodilation by NO.

Pulmonary artery NADPH-oxidase is activated in hypoxic pulmonary vasoconstriction.

An NADPH-oxidase complex containing at least two protein components (gp91-phox and p22-phox) and a unique low redox potential (-245 mV) cytochrome b-245 is the source of superoxide generated for bacterial killing in neutrophils and has been suggested as the oxygen sensor in the carotid body. In pure cultures of smooth muscle cells from calf small pulmonary arteries (300 microns diameter) the presence of the 91 kD protein specific to this cytochrome was demonstrated by Western blot analysis with monoclonal antibody 48. Low-temperature-difference spectrophotometry of homogenates of these cells demonstrated the characteristic cytochrome b-245 spectrum when titrated between redox potentials of -152 and -345 mV, consistent with the low redox potential form. When these same cells were exposed to hypoxia (approximately 40 mmHg), superoxide production increased significantly from 1.4 +/- 0.2 to 73 +/- 12 nmoles.min-1 mg-1 protein. Hypoxic generation of superoxide was inhibited by the NADPH-oxidase inhibitor diphenyleneiodonium (DPI: 10 microM) but not by the mitochondrial inhibitor myxathiazole (10 microM). The hypoxic superoxide increase was significantly greater than that observed from smooth muscle cells from large pulmonary arteries or from large or small systemic arteries. Fluorescence immunocytochemistry revealed the presence of the NADPH-oxidase protein in the walls of pulmonary arteries in rat lung slices, and confocal microscopy showed the complex to be widely distributed in the vicinity of the arterial smooth muscle walls. In hypoxia or norepinephrine (NP)-induced vasoconstriction of pulmonary artery rings from cats, the sensitivity to inhibition by DPI was observed to be significantly greater for hypoxia (ED50 = 0.8 microM) than for NP-induced (ED50 = 13.4 microM) constriction. Together these observations demonstrate that the unique cytochrome b-245 containing NADPH-oxidase is present in pulmonary artery smooth muscle and that an NADPH-oxidase or NADH-oxidoreductase complex is activated to release superoxide by hypoxic conditions. It is concluded that a trans-membrane NADPH-oxidase is the most likely and that activation of this system may be involved in the initiation of hypoxic pulmonary vasoconstriction.

Causes of hypercarbia with oxygen therapy in patients with chronic obstructive pulmonary disease.

OBJECTIVES: To compare data derived from a computer model of the pulmonary circulation with data from a case series of patients with chronic obstructive pulmonary disease (COPD). To evaluate the specific factors contributing to CO2 retention due to oxygen therapy in patients with acute exacerbations of COPD. DESIGN: Data from a computer model of the pulmonary circulation were compared with a previous case series. PATIENTS: Patient data were derived from previous case series. INTERVENTIONS: Simulated application of oxygen therapy. MEASUREMENTS AND MAIN RESULTS: The computer model of the pulmonary circulation generates data comparable with those data from a series of patients with COPD treated with supplemental oxygen and permits identification of the causes for hypercarbia. Therapy with supplemental oxygen alters hypoxic pulmonary vasoconstriction and modulates the Haldane effect, resulting in changes in physiologic deadspace. CONCLUSION: Changes in physiologic deadspace are sufficient to account for the hypercarbia developed by patients with acute exacerbations of COPD when treated with supplemental oxygen.

Fentanyl and propofol uptake by the lung: effect of time between injections.

The effect of time between the administrations of fentanyl and propofol on the first pass uptake of propofol in the cat lung was studied using double indicator dilution technique. The pulmonary first pass uptake of propofol (mean +/- s.e. mean) was 58 +/- 6% in six cats (control group) that had received no fentanyl prior to propofol (1 mg/kg) administration. The uptake was significantly reduced to 32 +/- 3% in animals pretreated with fentanyl (1 microgram/kg) 30 seconds before propofol administration (n = 6). However, when fentanyl was administered 3 minutes (n = 6) or 10 minutes (n = 6) prior to propofol, the pulmonary uptake of propofol (45 +/- 5%, 50 +/- 7% respectively) was not significantly reduced. The results demonstrate that the ability of fentanyl to inhibit pulmonary removal of propofol depends on its time of administration prior to propofol. These data may have clinical implication with respect to timing of the preinduction opiate injection.

The dose-response relationship for hypoxic pulmonary vasoconstriction.

In 12 pentobarbital anesthetized dogs the lungs were independently ventilated with a double piston ventilator. The right lung was ventilated throughout with 100% oxygen. Blood was drawn from the right atrium and pumped through a bubble oxygenator to a cannula in the ligated left main pulmonary artery. The pressures in the left main pulmonary artery and the left atrium were recorded during constant flow while the oxygen tension in the left lung alveolar gas and the perfusate were varied either to match each other (Protocol 1) or differ (Protocol 2) over the range from "zero" to "100%" oxygen. From the combined data a three dimensional response surface for hypoxic pulmonary vasoconstriction was derived. The maximum increase of pulmonary vascular resistance (r%PVRmax) was defined at a stimulus oxygen tension (PSO2) of 10 mmHg amounting to a 3.15 +/- (0.18)-fold increase of the vascular resistance on "100%" oxygen. The stimulus oxygen tension was shown to be PSO2 = PVO2(0.41) x PAO2(0.59) and the dose-response sigmoid for hypoxic pulmonary vasoconstriction in canine lungs was derived as r%PVRmax = 100 (PSO2(-2.616))/(6.683 x 10(-5) + PSO2(-2.616)) These results appear to reconcile observations from a number of laboratories and to be of quite general application.

Role of hypoxic pulmonary vasoconstriction in pulmonary gas exchange and blood flow distribution. 2. Pathophysiology.

In this review, the second of a two part series, the analytic techniques introduced in the first part are applied to a broad range of pulmonary pathophysiologic conditions. The contributions of hypoxic pulmonary vasoconstriction to both homeostasis and pathophysiology are quantitated for atelectasis, pneumonia, sepsis, pulmonary embolism, chronic obstructive pulmonary disease and adult respiratory distress syndrome. For each disease state the influence of principle variables, including inspired oxygen concentration, cardiac output and severity of pathology are explored and the actions of selected drugs including inhaled nitric oxide and infused vasodilators are illustrated. It is concluded that hypoxic pulmonary vasoconstriction is often a critical determinant of hypoxemia and/or pulmonary hypertension. Furthermore this analysis demonstrates the value of computer simulation to reveal which of the many variables are most responsible for pathophysiologic results.

Role of hypoxic pulmonary vasoconstriction in pulmonary gas exchange and blood flow distribution. 1. Physiologic concepts.

The regulation of the distribution of ventilation/perfusion ratios by hypoxic pulmonary vasoconstriction contributes to both the efficiency of gas exchange and to pulmonary hemodynamics. In this review, the first of two part series, are summarized the physiologic principles on which the analysis of ventilation/perfusion ratios and of pressure-flow relationships are based. A new combined analysis is introduced that permits the important contributions of hypoxic pulmonary vasoconstriction to overall gas exchange to be demonstrated in the circumstances of clinical complexity.

Hypoxic pulmonary vasoconstriction is not endothelium dependent.

Feline intrapulmonary arteries (mean diameter, 0.9 mm) were equilibrated in Earle's solution at constant tension in a chamber bubbled with an hyperoxic gas mixture (30% oxygen, 5% carbon dioxide, balance nitrogen). The endothelium was removed from half the vessels by gentle rubbing. The isometric response to the addition of acetylcholine (1*10(-6) M) was dilator in the vessels with endothelium and constrictor in those without endothelium. Intermittent exposure to a hypoxic gas mixture (0% oxygen, 5% carbon dioxide, balance nitrogen) for 20 min with five repetitions demonstrated sustained constrictor responses in the presence or absence of endothelium. Endothelial cells are, therefore, not required for the mediation of hypoxic pulmonary vasoconstriction.

Unilateral hypoxic pulmonary vasoconstriction in the dog, pony and miniature swine.

The hypoxic pulmonary vasoconstrictor response to unilateral hypoxia was analyzed in pentobarbital anesthetized dogs (n = 5), miniature swine (n = 5), and ponies (n = 5). The left and right lungs (LL, RL) were separately ventilated with the LL exposed to inspired oxygen concentrations (CIO2) of 100%, 12%, 8% or 4%, while the RL always received a CIO2 = 100%. Pulmonary blood flow distribution was measured using 15 microns radioactive microspheres. LL PAO2, and percent pulmonary blood flow diversion (%FD) were calculated at each CIO2. At CIO2 of 4% there were significant differences (P greater than or equal to 0.05) between the %FD responses of each species (mean +/- S.E.): the %FDswine (95.1 +/- 1.3) greater than %FDpony (76.0 +/- 4.6) greater than %FDdog (50.1 +/- 9.4). For all species, the %FD was inversely related to the level of regional hypoxia, but there were marked species differences in the magnitude and sensitivity of hypoxic pulmonary vasoconstriction with the swine being the strongest responder, the pony intermediate, and the dog the weakest responder.