The pulmonary and systemic distribution and elimination of perflubron from adult patients treated with partial liquid ventilation.

OBJECTIVE: To assess the pulmonary and systemic distribution and elimination of perflubron (C(8)F(17)Br(1); LiquiVent; Alliance Pharmaceutical; San Diego, CA) during and following the period of partial liquid ventilation. DESIGN: Prospective phase I and II clinical trial. SETTING: Adult surgical ICU. PATIENTS: Eighteen adult patients (mean +/- SEM age, 37.9 +/- 3.4 years) with severe respiratory failure, some of whom required extracorporeal life support (72%), and who were managed with partial liquid ventilation with perflubron. INTERVENTIONS: Perflubron was administered into the trachea, and gas ventilation of the perfluorocarbon-filled lung (partial liquid ventilation) was then performed. Additional doses were administered daily for from 1 to 7 days, with a median cumulative dose of 31 mL/kg (range, 3 to 60 mL/kg). MEASUREMENTS AND MAIN RESULTS: Patient blood samples were evaluated by gas chromatography for serum perflubron levels. Sequential lateral and anteroposterior radiographs were assessed, using a 5-point rating scale, for the degree of perflubron fill following the final dose. Samples of expired gas were collected, and the rate of loss of perflubron in the expired gas was measured by gas chromatography. Mean serum perflubron levels increased to 0.16 +/- 0.05 mg/dL at 24 h following administration of the initial dose. A mean maximum level of 0.26 +/- 0.05 mg/dL of perflubron was present in the serum 24 h following the administration of the last dose. This level slowly trended downward to 0.18 +/- 0.06 mg/dL over the ensuing 7 days (p = 0.281). Perflubron elimination via expired gas occurred at a mean rate of 9.4 +/- 3.0 mL/h at 1 h, and 1.0 +/- 0.4 mL/h at 48 h after the last dose (p = 0.012). By radiologic evaluation, perflubron was eliminated from the lungs progressively from 4.2 +/- 0.2 at the time of administration of the last dose, to 2.8 +/- 0.3 at 4 days later (p < 0.001). Perflubron tended to distribute and remain for longer periods in the dependent regions of the lung when compared to the nondependent regions (96-h perflubron fill score: posterior, 3.8 +/- 0.5; anterior, 1.9 +/- 0.4; p = 0.004). CONCLUSIONS: Perflubron is eliminated at a maximum rate of 9.4 +/- 3.0 mL/h by evaporative loss from the airways and is retained in greater amounts in the dependent lung regions when compared to the nondependent lung regions. There is a low but measurable maximum blood concentration of 0.26 +/- 0.05 mg/dL in patients after perflubron administration, which did not decrease significantly after cessation of partial liquid ventilation.

Serum cardiac troponin T as a prognostic marker in early sepsis.

STUDY OBJECTIVE: Sepsis is the leading cause of death in the noncardiologic ICU. Maldistributed nutritive blood flow and altered convective and diffusive oxygen transport during sepsis can lead to organ dysfunction and multiple organ failure. One of the causes of myocardial dysfunction is thought to be myocardial ischemia in sepsis; however, conventional biochemical parameters to detect myocardial ischemia lack sensitivity and specificity. Serum cardiac troponin T (S-TnT) was reported to have higher sensitivity and specificity in diagnosing minor myocardial injury. The aim of this study was to investigate if and how often S-TnT is pathologically elevated in patients with sepsis and to evaluate whether S-TnT might be a prognostic marker in early sepsis. DESIGN: Prospective study. SETTING: Surgical ICU. PATIENTS: Twenty-six patients with sepsis were included in this study within 24 h of the onset of sepsis. The patients were allocated a priori to a high S-TnT group (S-TnT > or = 0.2 microg/L) and a low S-TnT group (S-TnT<0.2 microg/L). MEASUREMENT: Blood samples for the determination of S-TnT and conventional myocardial ischemia markers as well as for adhesion molecules were drawn. Hemodynamic measurements were performed every 4 h during the first 24 h and then once per day over 7 days. S-TnT was determined by enzyme-linked immunosorbent sandwich assay. RESULTS: Eighteen patients had pathologically high S-TnT values. High S-TnT values were associated with an increased mortality rate (15/18 in the high S-TnT group vs 3/8 in the low S-TnT group; p=0.02). Significant differences between the two groups were found in the norepinephrine dosages at maximum values of S-TnT. Soluble intercellular adhesion molecule-1 was significantly elevated in the high S-TnT group. CONCLUSIONS: As high S-TnT values were associated with an increased mortality rate, it seems reasonable to further evaluate S-TnT as a prognostic marker of myocardial ischemia in patients with sepsis under different therapeutic regimens.

Regional pre- and postsynaptic sympathetic system in the failing human heart--regulation of beta ARK-1.

OBJECTIVES: Regional presynaptic sympathetic innervation varies considerably in the cardiomyopathic human heart, as shown in previous studies in vivo and in vitro. The goal of the present study was to correlate markers of presynaptic sympathetic innervation with local measurement of the postsynaptic beta-adrenergic system in failing human hearts. METHODS AND RESULTS: In nine left ventricular regions of hearts explanted from patients suffering from dilated cardiomyopathy, we measured the density of uptake(1) carriers ([3H]mazindol binding) as a marker of presynaptic function as well as beta-receptor density ([3H]CGP 12177 binding) and beta ARK-1 levels as the pivotal compounds of postsynaptic adrenergic signal transduction. Additionally, a subgroup of the patients was examined in vivo by HED-PET prior to heart transplantation. The density of uptake(1) was related to local hydroxyephedrine (HED) retention (as determined by pre-operative PET, r=0.65), whereas it was inversely correlated to regional beta ARK-1 levels (r=-0.61, P=0.04). In contrast, beta-adrenergic receptor density was not significantly correlated either to uptake(1) density or to local HED retention (r=0.15 and r=0.21). CONCLUSIONS: Regional beta ARK-1 levels rather than beta-adrenergic receptor density were correlated with presynaptic alterations in cardiomyopathic human left ventricles. It can be assumed that in the cardiomyopathic human heart, regional beta-adrenergic desensitization might be determined by differences in local beta ARK levels rather than by changes in beta-receptor density.

Oxygen dynamics during partial liquid ventilation in a sheep model of severe respiratory failure.

BACKGROUND: We evaluated the relationship of dose of perflubron and gas tidal volume to oxygen dynamics during partial liquid ventilation in the setting of respiratory failure. METHODS: Lung injury was induced in 16 sheep by using right atrial injection of 0.15 ml/kg oleic acid. Animals were ventilated with 15 ml/kg gas tidal volume and stabilized. Animals were then divided into three groups: (1) gas ventilation with a tidal volume of 15 ml/kg (control, GV, n = 5); (2) partial liquid ventilation at a gas tidal volume of 15 ml/kg with 10 ml/kg incremental pulmonary dosage of perflubron from 10 to 50 ml/kg (best fill, BF, n = 6); (3) administration of 35 ml/kg perflubron pulmonary dose with 5 ml/kg incremental increase in gas tidal volume from 10 to 30 ml/kg (best tidal volume, BTV, n = 5). RESULTS: Arterial oxygen saturation increased with increasing dose of perflubron and gas tidal volume (BF, p = 0.01; BTV, p = 0.001). A simultaneous trend toward a reduction in cardiac index was observed with increasing dose of perflubron (BF, p = 0.01). Maximal increase in mixed venous oxygen saturation was observed in the BF and BTV groups at a cumulative perflubron dose of 40 ml/kg and a gas tidal volume of 20 ml/kg, respectively. CONCLUSIONS: In this sheep lung injury model oxygenation improves with incremental increases in perflubron dose or gas tidal volume, and the mixed venous oxygen saturation appears to be optimal at a cumulative perflubron dose of 40 ml/kg and a gas tidal volume of 20 ml/kg.

Liquid ventilation provides uniform distribution of perfluorocarbon in the setting of respiratory failure.

BACKGROUND: We evaluated the effect of perfluorocarbon liquid ventilation (LV) on gas exchange and pulmonary function in the setting of respiratory failure and the distribution of the ventilating medium during LV when compared to gas ventilation (GV). METHODS: Ten sheep, 17.3 +/- 4.2 kg in weight, underwent oleic acid induction of lung injury followed by either GV (n = 5) or perfluorocarbon LV (n = 5). After 1 hour animals were killed, and chest computed tomographic (CT) imaging was performed. Average CT attenuation number was assessed as an indicator of the distribution of gas or perfluorocarbon in the dependent (posterior) and nondependent (anterior) zones of the lung (air = -1000; soft tissue = 0; perfluorocarbon = +2300 Hounsfield units [H]). RESULTS: Significant increases in PaO2 (LV = 298 +/- 76 mm Hg, GV = 43 +/- 18 mm Hg, p < 0.001), SvO2 (LV = 74% +/- 6%, GV = 32% +/- 18%, p < 0.01), and lung compliance (LV = 1.65 +/- 0.50 ml/cm H2O/kg, GV = 0.58 +/- 0.06 ml/cm H2O/kg, p < 0.01) were observed. Significant decreases in physiologic shunt (LV = 24% +/- 6%, GV = 62% +/- 14%, p < 0.01) were noted. CT attenuation data showed the presence of minimal gas ventilation in the dependent regions during GV although the nondependent regions remained well aerated (CT attention number during GV: ND = -654 +/- 160 H; D = -92 +/- 160 H, p < 0.0001). During LV, there was a fairly homogenous distribution of perfluorocarbon in the lungs (CT attenuation number during LV: D = 1071 +/- 330 Hounsfield units; ND = 1112 +/- 287 Hounsfield units; p = 0.240). Lung biopsy analysis in the LV animals was consistent with a reduction in intraalveolar hemorrhage, intraalveolar edema, and the inflammatory infiltrate. CONCLUSIONS: On the basis of the data, we conclude that in this lung injury model, (1) the distribution of the ventilating medium is uniform during LV when compared to GV, (2) LV improves gas exchange and pulmonary function, and (3) histologic evidence of lung injury is reduced after LV when compared to GV.

Distribution of pulmonary blood flow and total lung water during partial liquid ventilation in acute lung injury.

BACKGROUND: Gas exchange is improved during partial liquid ventilation (PLV) with perfluorocarbon in animal models of acute lung injury. The mechanisms are not fully defined. We hypothesize that redistribution of pulmonary blood flow (PBF) along with redistribution of, and decrease in, total lung water (TLW) during PLV may improve oxygenation. METHODS: We characterized PBF and TLW in anesthetized adult dogs by using positron emission tomography with H2(15)O. Measurements of gas exchange, PBF, and TLW were made before and after acute lung injury was induced with intravenous oleic acid. The same measurements were made during PLV (with 30 ml/kg perfluorocarbon) and compared with gas ventilated (GV) controls. RESULTS: Oxygenation was significantly improved during PLV. PBF redistributed from the dependent zone of the lung to the nondependent zones, thus potentially improving ventilation/perfusion relationships. However, a similar pattern of PBF redistribution was observed during GV such that there was no significant difference between groups. TLW redistributed in a similar pattern during PLV. By quantitative measurements, PLV ameliorated the continued accumulation of TLW compared with GV animals. CONCLUSIONS: We conclude that PBF and TLW redistribution and attenuation of increases in TLW may contribute to the improvement in gas exchange during PLV in the setting of acute lung injury.

Traumatic rupture of a cervical parathyroid adenoma.

BACKGROUND: Spontaneous rupture of a hyperplastic parathyroid gland or adenoma resulting in extracapsular hemorrhage is extremely rare. METHODS: We report a case of traumatic rupture of a cervical parathyroid gland adenoma. RESULTS: The patient had progressive stridor, neck swelling, and chest and back pain with evidence of ongoing blood loss resulting in airway compromise. Exploration of the neck and superior mediastinum revealed hypercellular parathyroid tissue consistent with adenoma or hyperplasia. CONCLUSIONS: Traumatic rupture of an enlarged parathyroid gland is a distinct and potentially lethal cause of unexplained cervical or mediastinal hemorrhage after blunt neck trauma. Failure to consider the diagnosis may result in delayed operative intervention with persistent hemorrhage resulting in airway compromise.

Partial liquid ventilation improves gas exchange and increases EELV in acute lung injury.

Gas exchange is improved during partial liquid ventilation with perfluorocarbon in animal models of acute lung injury. The specific mechanisms are unproved. We measured end-expiratory lung volume (EELV) by null-point body plethysmography in anesthetized sheep. Measurements of gas exchange and EELV were made before and after acute lung injury was induced with intravenous oleic acid to decrease EELV and worsen gas exchange. Measurements of gas exchange and EELV were again performed after partial liquid ventilation with 30 ml/kg of perfluorocarbon and compared with gas-ventilated controls. Oxygenation was significantly improved during partial liquid ventilation, and EELV (composite of gas and liquid) was significantly increased, compared with preliquid ventilation values and gas-ventilated controls. We conclude that partial liquid ventilation may directly recruit consolidated alveoli in the lung-injured sheep and that this may be one mechanism whereby gas exchange is improved.

Partial liquid ventilation provides effective gas exchange in a large animal model.

PURPOSE: The purpose of this study was to show the ability of partial liquid ventilation (PLV) to sustain gas exchange in normal large (50 to 70 kg) adult animals. METHODS: Ten adult sheep (53.7 +/- 2.8 kg) were anesthetized and mechanically ventilated. Sequential dosing of perflubron (LiquiVent, Alliance Pharmaceutical Corp, San Diego, CA) was performed to cumulative doses of 10 mL/kg, 20 mL/kg, 40 mL/kg, and 60 mL/kg. Physiological data were assessed at baseline and after each dose. Five animals were rotated through the left decubitus, right decubitus, supine, and prone positions while five animals remained prone throughout the experiment. RESULTS: PaO2 and PaCO2 did not change significantly from baseline during administration of perflubron except for the PaO2 in rotated animals when supine (rotated-supine PaO2: baseline = 519 +/- 64 mm Hg; 60 mL/kg = 380 +/- 109 mm Hg, P = .0131). In both groups, static lung compliance (CT) decreased steadily with each successive perflubron instillation (nonrotated CT: baseline = 1.55 +/- 0.22 mL/cm H2O/kg; 60 mL/kg = 0.52 +/- 0.10 ml/cmH2O/kg, P = .0003). CONCLUSIONS: These data show that during PLV in this normal animal model, effective gas exchange is sustained and CT decreases with increasing perflubron dose.

The effect of vanadium-contaminated commercially available albumin solutions on renal tubular function.

We report our findings in a patient with coronary heart disease who received an intravenous albumin solution that contained a significant level of vanadium on the first day after elective primary coronary revascularization. Six patients who underwent similar surgical procedures without albumin infusion were taken as a control group. After administration of the V-contaminated albumin solution, the urinary excretion rates of alpha-glutathione S-transferase, a marker of proximal tubular damage, showed a several-fold elevation above the reference value, and the mean excretion rate was significantly different from that of the control group (p < 0.05). pi-Glutathione S-transferase, a marker of distal tubular damage, only marginally exceeded the upper reference limit in two urine samples from this patient. In all urine samples from the control group the excretion rates of pi-GST were below the detection limit. No significant differences in the excretion rates of alpha1-microglobulin and N-acetyl-beta-D-glucosaminidase were found between the patient treated with the albumin infusion and the patients of the control group. The biological half-life of intravenously administered V was approximately 125 h. All commercially available albumin solutions contain traces of vanadium with the concentration varying between 1.1 and 677 microg/l. The free V fraction in the albumin solutions increased with total V concentration, the highest concentration of free V found being 299 microg/l. The data suggest that the use of albumin solutions containing high levels of vanadium can lead to renal injuries, especially in patients with existing impaired renal function, as is the case with extracorporal circulation. The contamination is believed to be a result of the commercial isolation process.

The 'Entlastungsgang'. A hip unloading gait as a new conservative therapy for hip pain in the adult.

'Entlastungsgang' is a gait modification aiming to unload the hip joint by producing a modified Duchenne-limp (straight spinal column, additional lifting of the pelvis on the side of the swinging leg and a consecutive side shift of the pelvis) and a wide stance gait. Sixteen patients suffering from hip pain caused mainly by hip dysplasia were investigated. They received daily gait training for 12 h combined with intensive physical therapy as in-patients for 3-4 weeks. The external muscle torque acting on the hip joint was determined by 3D-gait analysis before, during and after the gait training. We found a reduction of the muscle torque after gait training to 77.2% of the initial value. At an average follow up of 12 months we found a persisting reduction of the muscle torque to 87. 0% at spontaneous gait that was further reduced to 81.3% of the initial value. The hip score for two components of the Merle d'Aubigne and Postel score for pain and walking was significantly improved from 7.4 to 10.8 points.

[Prehospital care of acute coronary syndrome by anaesthetists. Prospective comparison with the care standards of cardiologists]. / Prähospitale Versorgung des akuten Koronarsyndroms durch Anästhesisten. Prospektiver Vergleich mit dem Versorgungsstandard durch Kardiologen.

BACKGROUND: Prehospital treatment of acute coronary syndrome (ACS) by anaesthetists acting in physician staffed emergency medical service (EMS) was compared with that of the gold standard of cardiologists. METHODS: Prospectively 599 patients with assumed ACS were traced. Prehospital diagnosis and therapy were compared with re-evaluation of ECGs and diagnosis on hospital discharge. RESULTS: In the case of ST-segment elevating myocardial infarction (STEMI) anaesthetists diagnosed 84% of cases correctly and cardiologists in 94% (p=0.048). False positive diagnoses were given in 11% by anaesthetists versus 5% by cardiologists (p=0.31). Anaesthetists accompanied all patients with instable angina versus 94% by cardiologists (p=0.06). Anaesthetists achieved 82% of patients to be pain-free versus 73% of cardiologists (p=0.01). Mortality until discharge was identical for the two groups (8.2%). CONCLUSION: In prehospital management of ACS cardiologists showed higher diagnostic competence, whereas anaesthetists revealed a greater degree of therapeutic caution. Patient mortality was not influenced.

Diastolic unloading and improved LV pump efficiency early after repair of the insufficient mitral valve.

BACKGROUND: This study aimed to evaluate the acute effect of mitral valve repair (MVR) on LV hemodynamics and geometry in patients with normal ventricular function. METHODS: In 10 patients with severe mitral regurgitation undergoing MVR, pressure-volume relationships were recorded before annuloplasty prior to and after hemodilution and after MVR during stable circulatory condition, using the conductance catheter technique (CC). Analyses were done off-line; volume calibration was based on data obtained after completion of valve repair (mean +/- s.d.). RESULTS: CC showed that only 61 +/- 15 % of left ventricular output was ejected into the systemic circulation, regurgitation volume being 39 +/- 15 %. MVR led to a reduction in LV stroke work index from 4.7 +/- 1.8 mm Hg x l x m (-2) at before valve repair to 2.2 +/- 1.0 mm Hg x l x m (-2) after surgery at unchanged cardiac index. LV diastolic filling parameters improved: LV relaxation time constant tau decreased from 52 +/- 15 to 37 +/- 11 ms and dP/dt (min) increased from - 873 +/- 231 to - 1286 +/- 283 mm Hg x s (-1). CONCLUSIONS: Despite cardioplegic arrest, MVR leads to acute improvement of diastolic LV function early after the operation. This may explain why valve repair has an acute positive effect in patients with impaired LV function.

Altered transient outward current in human atrial myocytes of patients with reduced left ventricular function.

INTRODUCTION: Electrophysiologic remodeling is involved in the self-perpetuation of atrial fibrillation. To define whether differences in atrial electrophysiology already are present in patients with increased susceptibility for atrial fibrillation, we compared patients in sinus rhythm with and without heart failure. METHODS AND RESULTS: Atrial specimens were obtained from patients with reduced left ventricular ejection fraction (LVEF; n = 10) and normal LVEF (n = 16) who were undergoing aortocoronary bypass surgery and from donor hearts (n = 4). Enzymatically isolated atrial myocytes were investigated by whole cell, patch clamp techniques. Total outward current was significantly larger in myocytes of hearts with low LVEF than normal LVEF (19.4 +/- 1.3 vs 15.1 +/- 1.2 pA/pF at pulses to +60 mV, respectively). Analysis of inactivation time courses of different outward current components revealed that the observed current difference is due to the transient calcium-independent outward current I(to1) which is twice as large in the low LVEF group than in the normal LVEF group (9.4 +/- 0.9 vs 4.7 +/- 0.4 pA/pF at pulses to +60 mV, respectively). I(to1) recovery from inactivation was significantly more rapid in myocytes of hearts with low LVEF, and action potential plateau in these cells was significantly shorter. The results of I(to1) and action potential measurements in atrial myocytes of donor hearts were very similar to the results of patients with preserved heart function. CONCLUSION: I(to1) in human atrial myocytes of patients with reduced LVEF has an increased density and altered kinetics in sinus rhythm. These differences in outward current may explain the reduced plateau phase of action potentials.

Efficacy of perfluorocarbon partial liquid ventilation in a large animal model of acute respiratory failure.

OBJECTIVE: To demonstrate the efficacy of partial perfluorocarbon liquid ventilation in large animal model of acute respiratory failure. DESIGN: Prospective, randomized, controlled trial. SETTING: Animal laboratory at a university medical center. SUBJECTS: Ten adult sheep, weighing 53.0 +/- 2.8 kg. INTERVENTIONS: After assessment of baseline physiologic data, acute respiratory failure was induced by right atrial injection of oleic acid (0.2 mL/kg). Five animals (partial liquid ventilation group) underwent sequential intratracheal dosing of 10 mL/kg of perflubron at 30-min intervals to the following cumulative doses: 10, 20, 30, 40, and 50 mL/kg. The remaining five animals were gas ventilated (control group). Physiologic data were assessed at 30-min intervals in both groups for the 2.5-hr experimental period or until death. MEASUREMENTS AND MAIN RESULTS: When compared with control animals, intratracheal perfluorocarbon instillation resulted in significant improvements in arterial oxygen saturation (arterial oxygen saturation after 50 mL/kg: partial liquid ventilation, 96 +/- 3%; control, 55 +/- 8%; p = .001) and physiologic shunt (physiologic shunt after 50 mL/kg dose: partial liquid ventilation, 2 +/- 8%; control, 64 +/- 5%; p = .004). Oxygen delivery improved with perfluorocarbon instillation, but this improvement was not significant. No significant difference in pulmonary compliance was observed during partial liquid ventilation when compared with controls (pulmonary compliance: partial liquid ventilation, 0.43 +/- 0.04 mL/ cm H2O/kg; control, 0.53 +/- 0.03 mL/cm H2O/kg; p = .102). CONCLUSIONS: Partial liquid ventilation with perflubron provides effective improvement in gas exchange in an adult animal model of respiratory failure.

[Chronic bacterial prostatitis--prostatodynia. Differentiation from the psychosomatic viewpoint]. / Chronisch-bakterielle Prostatitis--Prostatodynie. Die Differenzierung aus psychosomatischer Sicht.

56 patients with the symptoms of a chronic prostatitis could not be differentiated into the diagnostic subgroups prostate inflammation and prostatodynie by their somatic and urologic complaints. Only a semistandardized psychodiagnostic interview was able to differentiate between those two groups.

Effect of independent changes in mixed-venous PCO2 or PO2 on cardiac output in anesthetized sheep.

To determine whether changes mixed-venous PCO2 or PO2 affect cardiac output independent of changes in arterial blood gases, we used extracorporeal gas exchange to increase mixed-venous PCO2 or decrease mixed-venous PO2 in adult sheep. Sheep were anesthetized, mechanically ventilated, and connected to a veno-venous extracorporeal circuit. The circuit included a gas exchanger which was used to increase mixed-venous PCO2 or decrease mixed-venous PO2; the native lungs were ventilated to maintain arterial PCO2 and PO2 at control levels. When mixed-venous PCO2 was increased by 32% above control levels for a period of 60 min, cardiac output increased significantly to 28% above control levels. Cervical vagotomy abolished this response. In contrast, decreasing mixed-venous PO2 by 29% did not increase cardiac output. These results demonstrate that increasing mixed-venous PCO2 can increase cardiac output independent of changes in arterial blood gases and that intact vagus nerves are necessary for this response to occur.

Rate-independent effects of the new class III antiarrhythmic agent ambasilide on transmembrane action potentials in human ventricular endomyocardium.

The electrophysiologic effects of ambasilide, a new class III antiarrhythmic drug reported to be a nonselective blocker of both components (I(Kr) and I(Ks)) of the delayed-rectifier potassium current (I(K)) and other repolarizing potassium currents (I(tol), I(so)), were studied in specimens of left ventricular endomyocardium of human hearts obtained from 10 patients undergoing either heart transplantation (n = 4) or mitral valve replacement (n = 6). We recorded transmembrane action potential (TAP) characteristics at different stimulation frequencies (0.5, 1, 1.5, and 2 Hz) and with different dosages of ambasilide (1, 10, and 50 microM) by using conventional microelectrode techniques. Beginning at a concentration of 10 microM ambasilide, the TAP duration at 90% repolarization (TAPD90) was significantly prolonged and independent of stimulation frequency with a mean percentage prolongation of 18% at 10 microM and 30% at 50 microM ambasilide. TAP duration at 50% repolarization was not significantly prolonged except for 10 microM ambasilide at 0.5 Hz (17%; p < 0.05). The frequency-independent action potential (AP) prolongation by ambasilide in human ventricular endomyocardium indicates that a nonselective block of repolarizing potassium currents seems to be more favorable than a selective block of I(Kr).

Measuring functional residual capacity in normal and oleic acid-injured lungs.

Functional residual capacity (FRC) is an important oxygen reserve that is often depleted in acute respiratory failure. Recent interest in the mechanisms of liquid ventilation and limited experience in measuring FRC in paralyzed, mechanically ventilated, normal and lung-injured animal models have mandated development of accurate laboratory techniques. Eight sheep, from 17 to 27 kg, were anesthetized and instrumented to provide a tracheostomy, a pulmonary artery catheter, and carotid arterial line. They were randomized to two groups, one of which received 0.07 ml/kg of intravenous oleic acid to induce lung injury. Gas ventilation of both groups was identical except for respiratory rate, which was adjusted to normalize PaCO2. FRC was measured in duplicate by both helium dilution (HD) and body plethysmography (BP). When measurements were completed, the animals were euthanized and their endotracheal tubes clamped at end expiration. The lungs were then removed and their water displacement (WD) FRC values were measured. FRC was the difference between WD and tissue weight assuming 1 ml = 1g. Pearson's correlation coefficient (R(2)) was calculated. During in vitro measurement of test lungs, HD had an R(2) value of 0.99 and BP had an R(2) value of 0.98. When compared to WD, in vivo measurement of FRC by HD had an R(2) value of 0.94 while the value for BP was 0.97. In conclusion, both HD and BP are accurate methods of determining FRC in an uninjured and injured lung model when compared to postmortem WD. Documenting changes in FRC will aid in elucidating the mechanisms of alternative ventilatory techniques.

Extracorporeal life support for neonatal respiratory failure. A 20-year experience.

OBJECTIVE: The authors reviewed their experience with extracorporeal life support (ECLS) in neonatal respiratory failure; they define changes in patient population, technique, and outcomes. SUMMARY BACKGROUND DATA: Extracorporeal life support has progressed from laboratory research to initial clinical trials in 1972. Following a decade of clinical research, ECLS is now standard treatment for neonatal respiratory failure refractory to conventional pulmonary support techniques. Our group has the longest and largest experience with this technique. METHODS: Between 1973 and 1993, 460 neonates with severe respiratory failure were treated using ECLS. The records of all patients were reviewed. RESULTS: Overall survival was 87%. Primary diagnoses were meconium aspiration syndrome (MAS; 169 cases [96% survival]), respiratory distress syndrome/hyaline membrane disease (91 cases [88% survival]), persistent pulmonary hypertension of the newborn (37 cases [92%]), pneumonia/sepsis (75 cases [84% survival]), congenital diaphragmatic hernia (CDH; 67 cases [67% survival]), and other diagnoses (21 cases [71% survival]). Common mechanical complications included clots in the circuit (136; 85% survival); air in the circuit (67; 82% survival); cannula problems (65; 83% survival) and oxygenator failure (34; 65% survival). Patient-related complications included intracranial infarct or bleed (54 cases; 61% survival), major bleeding (48 cases; 81% survival), seizures (88 cases; 76% survival), metabolic abnormalities (158 cases; 71% survival) and infection (21 cases; 48% survival). Since 1989, treatment groups have been expanded to include premature infants (13 cases; 62% survival), infants with grade I intracranial hemorrhage (28 cases; 54% survival) and "non-honeymoon" CDH patients (15 cases; 27% survival). Since 1990, single-catheter venovenous access has been used in 131 patients (97% survival) and currently is the preferred mode of access. Follow-up ranges from 1 to 19 years; 80% of patients are growing and developing normally. CONCLUSIONS: Extracorporeal life support has become standard treatment for severe neonatal respiratory failure in our center (460 cases; 87% survival), and worldwide (8913 cases; 81% survival). The availability of ECLS makes the evaluation of other innovative methods of treatment, such as late elective repair of diaphragmatic hernia and new pulmonary vasodilators, possible. The application of ECLS is now being extended to premature and low-birth weight infants as well as older children and adults.