Oligomeric rods of alkyl- and hydridogallium imides.

Reaction of [RGa(NMe(2))(2)](2), where R = Me, Et, Bu, and Hx, with ammonia at 150 degrees C in an autoclave produced insoluble white powders formulated as oligomers of [RGaNH](n). The analogous reaction between NH(3) and MeGa[N(SiMe(3))(2)](2) at low temperature (<25 degrees C) formed an isolable intermediate, [MeGa(mu-NH(2))N(SiMe(3))(2)](2), that was characterized using single-crystal X-ray diffraction. Infrared spectroscopy and X-ray diffraction of the oligomers were consistent with a rodlike structure comprised of six-membered, [RGaNH](3) rings stacked perpendicular to the long axis of the rod. The method of synthesis, formula, and diffraction results suggested a structural similarity between the alkyl, [RGaNH](n)(), and the previously reported hydride, [HGaNH](n). The structural and electronic properties of rods having the general formula H(3)[(HXYH)(3)](n)H(3) (XY = GaN, GeC; n = 1-9) were investigated using density functional theory. Atomic electronegativity differences between the group 13/15 and 14/14 systems were found to play important roles in the geometrical structures of the two rods and also caused significant differences in the electronic structures. Energetically, it was found to be increasingly favorable to add additional cyclotrigallazane rings to the GaN rods, while for the GeC rods, there was a roughly constant energy cost associated with each additional ring. The electric dipole moments of the GaN rods increased substantially with length; in the GeC rods, charge separation occurred to a much smaller extent and had a polarization opposite to that found in GaN. In addition, increased dipole moments correlated with smaller electronic excitation energies, as predicted by time-dependent density functional theory. All of the powders exhibited luminescence in the visible spectrum at room temperature. Structure observed in the photoluminescence spectra of [HGaNH](n) and [MeGaNH](n) was interpreted as arising from rods of different length.

Base Effects on the Formation of Four- and Five-Coordinate Cationic Aluminum Complexes.

This work was conducted as part of our continuing effort to determine the factors that affect cation formation for organometallic aluminum complexes. In this study, the interactions of R(2)AlX (where R = Me, (i)Bu, (t)Bu; X = Cl, Br, I) with the monodentate bases thf, pyridine, NEt(3), HN(i)Pr(2), H(2)N(i)Bu, H(2)N(t)Bu, and O=PPh(3) are examined to determine the role of the base in cation formation. These reactions resulted in the neutral adducts of the general form R(2)AlX.base (1-6, 8, 10, and 12) as well as the cationic complexes [R(2)Al(base)(2)]X (7, 9, and 11). The reactions of Me(2)AlX (where X = Cl, Br) with PMDETA (N,N',N",N"'-pentamethyldiethylenetriamine) and the catalytic activity of the resulting cationic complexes (13 and 14) are also discussed. All of the compounds were characterized by mp, IR, (1)H-NMR, and elemental analyses, and in one an X-ray crystallographic study was carried out. X-ray data for 13: triclinic, P&onemacr;, a = 6.9542(6) Å, b = 12.2058(10) Å, c = 13.2417(11) Å, alpha = 106.236(2) degrees, beta = 98.885(2) degrees, gamma = 93.807(2) degrees, V = 1059.06(15) Å(3), and Z = 2 for 181 parameters refined on 4358 reflections having F > 6.0sigma(F), R = 0.0697, and R(w) = 0.0697.

Extracorporeal membrane oxygenation (ECMO) as lung or heart assist.

Extracorporeal membrane oxygenation (ECMO) may serve as extracorporeal lung assist (ECLA) in patients with acute respiratory failure (ARF) or as extracorporeal heart assist (ECHA) in patients with low output syndrome (LOS) after open heart surgery. From 1988 to 1992 seven patients underwent ECMO in our hospital; four suffered from ARF and three from LOS. Various bypass techniques were employed. Two ARF patients, aged 58 and 18 years, had veno-venous bypass; in the latter, ECMO was reinstituted as a veno-arterial bypass one week after weaning. In a three-year-old boy, the ECMO outflow tubing was primarily connected to the pulmonary artery, and shortly afterwards relocated to the common carotid artery. In a 31-year-old man with ARF, and three LOS patients, a 56-year-old woman, and two men aged 68 and 70 years, ECMO was veno-arterial with direct access to the ascending aorta. A heparin-coated system was used, and all but one patient, who was treated with warfarin, received a daily low dose of heparin, which was withdrawn after from one to nine days. Six patients were weaned off ECMO after 4.5 to 21 days. Three ARF patients recovered completely; the child died. In one LOS patient, ECMO was withdrawn due to a poor general condition. Two others were weaned off ECMO and the intra-aortic balloon pump, and the inotropic support was significantly reduced, but both died of multiple system organ failure. Although no firm conclusions can be drawn from these few case reports, the heparin-coated system used as ECLA appears promising, whereas ECHA seems to imply a poor prognosis in patients who are not candidates for cardiac transplantation.

A New Class of Aluminum Cations Based upon Tetradentate (N(2)O(2)) Chelating Ligands.

Herein are described the synthesis and characterization of the complexes of formula LAlR (where R = Cl and L = Salen (1), SalenCl (2), Acen (3) and where R = Me and L = Salen (4), SalenCl (5), Acen (6); Salen = N,N'-ethylenebis((2-hydroxyphenyl)methylimine), SalenCl = N,N'-ethylenebis((2-hydroxy-5-chlorophenyl)methylimine), Acen = N,N'-ethylenebis((2-hydroxyphenyl)-1-ethylimine)). The LAlCl derivatives dissolve in water and MeOH to yield the cationic complexes [LAl(H(2)O)(2)](+)Cl(-) (L = Salen (7), SalenCl (8), Acen (9)) and [LAl(MeOH)(2)](+)Cl(-) (L = Salen (10), SalenCl (11), Acen (12)), respectively. An alternative preparation of the cationic species involves the reaction of the LAlCl derivative with NaBPh(4). This leads to complexes of formula [LAl(MeOH)(2)](+)BPh(4)(-) (L = Salen (13), SalenCl (14), Acen (15)). Complexes 4-6 can be reacted with either MeOH or 4-chloro-3,5-dimethylphenol (Ph') to form complexes of general formula LAlOR (R = Me, L = Salen (16), SalenCl (17), Acen (18); R = Ph', L = Salen (19), SalenCl (20), Acen (21)). All of the compounds were characterized by IR, melting points, elemental analyses, and, when soluble, NMR. Additionally, the crystal structures of 7, 13, 15, and 18 were obtained.

Adenosine protects ultrastructure of isolated rat lungs against fat emulsion injury.

In isolated rat lungs subjected to fat emulsion damage, a model simulating adult respiratory distress syndrome, we have previously reported that adenosine (ADO) reduces pulmonary vascular resistance (PVR) and the fluid filtration rate (FFR). In the present study the aim was to examine morphologically this effect of ADO. Two groups of isolated rat lungs were subjected to the injury. Marked and significant differences were found between the groups; in lungs not given ADO, FFR and airway pressure were higher and, as evaluated by electron microscopy, the endothelial lining was thin and partly disrupted. The epithelial cells of the alveolar walls were also partly disrupted and the alveolar septa were split enclosing interstitial edema. In lungs receiving ADO from the onset of exposure to fat emulsion, FFR was lower and ultrastructure did not differ from non-injured non-treated controls perfused for the same length of time.

Management of a giant intracranial aneurysm using surface-heparinized extracorporeal circulation and controlled deep hypothermic low flow perfusion. A case report.

Extracorporeal circulation with controlled hypothermic low flow perfusion was introduced during the surgical treatment of a patient with a giant intracranial aneurysm of the anterior communicating artery. Heparin-coated equipment (Carmeda Bio-Active Surface; CBAS) was utilized, thus reducing the need for systemic heparinization. Direct cannulation of the right atrium and aorta was established through thoracotomy. Blood flow through the circuit was kept at 4.5 l/min during normothermia. Core cooling, in combination with external surface cooling, was performed for 30 min to a temperature of 18 degrees C (nasopharynx). During a period of 25 min, the time for surgical repair of the aneurysm, blood flow was minimized to 0.4 l.min-1, equilibrating central and peripheral blood pressures to approximately 5-10 mmHg (0.65-1.3 kPa). Reperfusion was started immediately after the low flow period concomitantly with rewarming, aiming at a temperature of 36 degrees C following 150 min. The patient could be weaned off the extracorporeal circulation with minimal inotropic support. The postoperative course was uneventful apart from a left-sided hemiparesis, probably due to an infarction in the area of the right pericallosal artery (A2). The patient was weaned off the ventilator after 6 days. He recovered and the hemiparesis regressed slowly.

Adenosine modulates vascular resistance and fluid filtration in isolated rat lungs.

In adult respiratory distress syndrome, a major concern is to reduce increments in pulmonary vascular resistance (PVR) and maintain the patency of lung microvessels. We have investigated the effects of adenosine, a potent systemic vasodilator, on PVR and fluid filtration rate (FFR) in isolated blood-perfused rat lungs. The preparations were undamaged or subjected to fat emulsion-induced injury simulating ARDS. In undamaged lungs adenosine caused a significant dose-dependent reduction of hypoxia-induced increases in PVR. Furthermore, the increase in FFR upon elevation of left atrial pressure by 0.77 kPa was significantly hampered by adenosine, 24 nmol.ml-1.min-1. Employing the same rate of infusion, adenosine, in a group of injured preparations, significantly reduced the rise in PVR towards baseline and completely abolished the further increase upon a superimposed injection of serotonin. In another series of preparations with lung injury randomly assigned to an adenosine group and a control group, adenosine significantly reduced FFR. Thus, adenosine, even when infused at low rates, reduced increments in PVR and fluid filtration, both in undamaged and in fat emulsion-injured isolated lungs.

Evidence against endogenously released adenosine as modulator of the pressor response to hypoxia in isolated rat lungs.

Unlike other vascular beds, lung vessels constrict when exposed to hypoxia. However, a marked difference has been noticed as regards the elicitability of hypoxic pulmonary vasoconstriction (HPV) in vivo as compared to in vitro models, like a preparation of isolated rat lungs; in the latter, HPV cannot be evoked from the onset of perfusion, but might be triggered gradually by repeated hypoxic challenges. The formation of adenosine, a potent dilator of most vascular beds, is enhanced during conditions of hypoxia or ischemia. Our hypothesis therefore was that pulmonary vasoconstriction was initially antagonized by tissue-adenosine accumulating during the circulatory arrest necessary for lung isolation, and then, gradually invigorated along with the elimination of adenosine during periods of perfusion with normally oxygenated blood. In a first series of isolated rat lungs, we studied release of adenosine in connection with the third and the sixth hypoxic challenges. Although the vascular responses were of significantly different size, there was no sign of increased adenosine formation during any of the two provocations, as assessed by release of its more stable metabolites hypoxanthine, xanthine and uric acid. In a series of tissue preparations taken at the height of a fully developed hypoxic pressor response and immediately frozen, we could not find significant changes in tissue level of adenosine, hypoxanthine and inosine as compared to controls that had never been exposed to hypoxic challenges. Further, we found no correlation between the size of pressor responses and concentrations of adenosine and its metabolites, in either blood or in lung tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Does PEEP facilitate the resolution of extravascular lung water after experimental hydrostatic pulmonary oedema?

The effect of mechanical ventilation with positive end-expiratory pressure on the resolution of hydrostatic pulmonary oedema created by temporary left atrial balloon inflation was studied in mechanically ventilated dogs. Immediately after the hydrostatic process was terminated, by deflating the left atrial balloon, the animals were ventilated for 4 h with zero end-expiratory pressure (ZEEP, n = 6) or with a positive end-expiratory pressure (PEEP, n = 6) of 1.0 kPa (10 cmH2O). Gas exchange and extravascular lung water content (EVLW) with the double indicator dilution technique (dye/cold) were studied and gravimetric determination of lung water was made postmortem. EVLW decreased from 31.6 +/- 7.3 mean +/- SD ml.kg.1 during maximal oedema to 14.5 +/- 2.1 ml.kg.1 (p less than 0.001) 4 h after deflation of the left atrial balloon in dogs ventilated with ZEEP. The corresponding values in dogs ventilated with PEEP were a reduction in EVLW from 28.0 +/- 4.1 to 20.7 +/- 4.0 ml.kg.1 (p less than 0.01) (mean decrease 7.3 +/- 4.0 ml.kg.1). EVLW was significantly higher after 4 h on PEEP than after ZEEP (p less than 0.01). Gravimetric values at the end of the experiment were 12.4 +/- 2.8 ml.kg.1 (ZEEP) and 14.7 +/- 4.5 ml.kg.1 (PEEP) (NS). Oxygenation improved in both groups during the resolution of oedema with a more evident and early effect in the PEEP group. It is concluded that mechanical ventilation with PEEP of 1.0 kPa (10 cmH2O) in the resolution phase after experimental hydrostatic oedema improves oxygenation but retards the resolution of oedema.

[Extracorporeal membrane oxygenation. A therapeutic alternative in acute heart and/or pulmonary failure?]. / Ekstrakorporal membranoksygenering. Et behandlingsalternativ ved akutt hjerte- og/eller lungesvikt?

Extracorporeal membrane oxygenation was introduced as a supplement ot mechanical ventilation in the treatment of two patients with severe acute respiratory failure and as heart assist in one patient with acute refractory cardiac failure after open heart surgery. The system includes a membrane oxygenator and a roller pump. The whole circuit is coated with partially degraded heparin covalently bound to the surface (Carmeda Bioactive Surface), reducing the need of systemic heparinization to a minimum. In the first case of acute respiratory failure a veno-venous bypass was employed, with cannulas in the right atrium and the femoral vein. Given a blood flow through the circuit of 2.5 l/min, ventilator settings could be favourably reduced. The patient was weaned off the bypass system after six days, off the ventilator after 120 days, and recovered completely. In two cases the system served as partial venoarterial bypass, and blood was returned to the ascending aorta. A 31 year-old male victim of a smoke inhalation lung injury was on bypass for four and a half days. He recovered completely after another 17 days of mechanical ventilation. A 68 year-old man with pump failure after cardiac surgery needed extracorporeal support as heart assist for seven days. On the eighth day he was weaned off intra-aortic balloon-pumping as well. Unfortunately, he died of septicemia, with multiple organ failure, 13 days later. The heparin-coated extracorporeal membrane oxygenation system may represent a major advancement in the treatment of critically ill patients in need of cardiopulmonary assist.

Extracorporeal carbon dioxide removal performed with surface-heparinized equipment in patients with ARDS.

To avoid the drawbacks of systemic anticoagulation during prolonged extracorporeal circulation in patients with adult respiratory distress syndrome (ARDS) a heparinization technique has been developed by which partially degraded heparin can be covalently end-point attached to the surface of the equipment constituting the extracorporeal circuit (Carmeda Bio-Active Surface, CBAS) thereby localizing the anticoagulatory effect. Since 1986 we have used extracorporeal circuits and membrane lungs coated with the CBAS for extracorporeal lung assistance (ECLA) in 14 patients suffering from ARDS. The patients were on ECLA for 3 to 55 days with a survival rate of 43%. Our experience so far is that by using equipment coated with CBAS it is possible to perform long-term extracorporeal circulation with a minimum of intravenously administered heparin, thus avoiding the risk of major coagulation defects.

Hypoxic pulmonary vasoconstriction in the adult respiratory distress syndrome.

Increased pulmonary vascular resistance (PVR) and microvascular hyperpermeability resulting in lung edema and arterial hypoxemia are mainstays in the development of adult respiratory distress syndrome (ARDS). The proposed pathophysiologic mechanisms include activation of complement and polymorphonuclear leukocytes secreting lysosomal enzymes, toxic oxygen metabolites (TOM) and eicosanoids. Platelets and coagulation factors are also involved, and in the most severe cases even monocytes are activated as reflected in release of thromboplastin. The latter may elicit disseminated intravascular coagulation (DIC). Under physiologic conditions lung blood flow is diverted from poorly to better oxygenated areas by way of hypoxic pulmonary vasoconstriction (HPV), thereby counteracting a decrease in arterial oxygenation. Many vasoactive substances have been proposed and again refuted as possible mediators of HPV. In this study we have focused on the following: histamine, catecholamines, arachidonates, calcium, phosphoinositides and TOM as well as endothelium-derived relaxing and constricting factors. Whether HPV is present in ARDS and whether it is advantageous or not seems to depend on the stage and extent of disease. We discuss possible interactions between HPV and ARDS mediators and between HPV and various vasoactive agents tested for therapeutic effects. Out of the abundance of mediators released, prostacyclin, prostaglandin E1, activated complement and platelet activating factor have been shown explicitly to inhibit HPV whereas others are suspected of doing so. In therapeutical use, prostacyclin has proved to reduce PVR and at the same time enhance cardiac output and oxygen delivery. In mild to moderate ARDS, improvement of arterial oxygenation has also been obtained employing almitrine bismesylate, a potentiator of HPV. Experimentally, adenosine effectively reduces increments in PVR and microvascular permeability with modest effects on systemic circulation. However, further investigations are warranted to decide whether adenosine or more specific blockers as, for instance, monoclonal antibodies against tumor necrosis factor should be integrated in ARDS therapy in the future.

Neuromonitoring in hypothermia and in hypothermic hypoxia.

Severe accidental hypothermia is often associated with global ischaemia due to cardiac arrest. The purpose of the present study was to evaluate whether rewarming on cardiopulmonary bypass (CPB) should be slow or as fast as possible. Pigs were cooled to 23 degrees C (rectum), subsequently followed by 1 h period of circulatory arrest, whereupon rewarming was started. Pigs were randomly allocated to 3 groups: slowly rewarmed (2 h), rapidly rewarmed (0.5 h) and a control group on CPB maintaining normothermia. EEG was continuously analyzed by means of Anesthesia-Brain-Monitor (ABM-system), which allows simultaneous monitoring of EEG, blood- and intracranial pressures, heart rate and capnogram as trend graphs. The ABM-system thus delivers a continuous on-line printout of all measured variables. Cooling resulted after about 30 min in electrocerebral inactivity (ECI) in all pigs. EEG reappeared in all animals regardless of the considerable long cardiocirculatory arrest, followed by nearly 3 hours of ECI! It would appear tempting to rewarm an accidentally cooled organism as fast as possible. The present study, however, indicate that the brain during rewarming seems to have its own speed for regeneration of the EEG. This speed showed to be slower than the steeply rising temperature during rapid rewarming. Furthermore, a too vigorous rewarming may jeopardize cerebral metabolism; 90 min after the start of rewarming the EEG had reappeared in 5 out of 8 pigs in slow group, but only in 2 out of 7 in rapidly rewarmed animals. In controls the EEG was continuously present throughout the experiments.

Hypoxic pulmonary vasoconstriction in the human lung: effect of repeated hypoxic challenges during anesthesia.

Six patients, ages 29-58 yr, were investigated during barbiturate and fentanyl anesthesia. After intubation with a double-lumen bronchial catheter, one lung was ventilated continuously with 100% O2, and the other was rendered hypoxic during three 15-min periods by ventilation with 95% N2 + 5% O2, with intervening 15-min periods of oxygen ventilation. Cardiac output was determined by thermodilution, and the distribution of blood flow between the lungs was assessed from the excretion of a continuously infused poorly soluble gas (SF6). The first hypoxic challenge resulted in a 10% increase in cardiac output (QT) and a reduction in the fractional perfusion of the test lung from 57% to 31% of QT. The pulmonary artery mean pressure increased by 54%, and the vascular resistance of the test lung increased threefold. The venous admixture increased from 19% to 40% of QT, whereas the inert gas shunt remained unaltered at 15% (inert gases also being eliminated by nitrogen-ventilated areas). The arterial oxygen tension decreased from 353 mmHg to 79 mmHg. On resumption of the control state, central hemodynamics and gas exchange returned to the initial values. The second and third hypoxic challenges resulted in reductions in the fractional perfusion of the test lung to 35% and 37% of QT. All other variables were altered to the same degree as during the first challenge. The authors conclude that hypoxic challenge of one lung in an intravenously anesthetized human subject elicits a maximum vasoconstrictor response within the first 15 min, and this response cannot be potentiated by repeated challenges.

Imagery and hallucination in schizophrenic patients.

Volitional auditory imagery and spontaneous imagery/fantasy are examined in schizophrenic vs. nonschizophrenic psychiatric inpatients. Imaginal aspects of schizophrenia are also studied with regard to concurrent presence or absence of hallucination. Comparisons of imaginal function between diagnostic groups and among hallucinatory subgroups turned up few significant differences. Findings do not support the Mintz and Alpert (Mintz, S., and Alpert, M. Imagery vividness, reality testing, and schizophrenic hallucinations. J. Abnorm. Psychol., 79: 310-316, 1972) enhanced vividness model of schizophrenic hallucination but do provide some support for an imagery deficit model.