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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.