Charles R. Hamm

Reduction in alveolar macrophages attenuates acute ventilator induced lung injury in rats

ObjectiveAlveolar macrophages are the sentinel cell for activation of the inflammatory cascade when the lung is exposed to noxious stimuli. We investigated the role of macrophages in mechanical lung injury by comparing the effect of high-volume mechanical ventilation with or without prior depletion of macrophages.Design and settingRandomized sham-controlled animal study in anesthetized rats.MethodsLung injury was induced by 15 min of mechanical ventilation (intermittent positive pressure ventilation) using high peak pressures and zero end-expiratory pressure. The mean tidal volume was 40 ± 0.7 ml/kg. One group of animals was killed immediately after this period of volutrauma (HV), while in a second group normoventilation was continued for 2 h at a tidal volume less than 10 ml/kg (HV-LV). One-half of the animals were depleted of alveolar macrophages by pretreatment with intratracheal liposomal clodronate (CL2MDP).MeasurementsArterial blood gas, blood pressure. After kill: lung static pressure volume curves, bronchoalveolar fluid concentration for protein, macrophage inflammatory protein 2, tumor necrosis factor α, and wet/dry lung weight ratio (W/D).ResultsDuring HV and HV+LV oxygenation, lung compliance, and alveolar stability were better preserved in animals pretreated with CL2MDP. In both groups W/D ratio was significantly greater in ventilated than in nonventilated animals (4.5 ± 0.6), but the increase in W/D was significantly less in CL2MDP treated HV and HV-LV groups (6.1 ± 0.4, 6.6 ± 0.6) than in the similarly ventilated nontreated groups (8.7 ± 0.2 and 9.2 ± 0.5).ConclusionsAlveolar macrophages participate in the early phase of ventilator-induced lung injury.

Acquired Left-Sided Pulmonary Vein Stenosis in an Extremely Premature Infant: A New Entity?

t c F p p p a ( large patent ductus arteriosus (PDA) was surgically ligated in a 22-week preterm infant after failed attempts at pharmacological closure with ibuprofen. The results of multile echocardiograms performed early were negative for other cardiac bnormalities. By 3 months of age, the child was off all respiratory upport. At 6 months, he had a respiratory deterioration requiring e-intubation and mechanical ventilation. With echocardiography, evere pulmonary hypertension and left lower pulmonary vein steosis were demonstrated. Inhaled nitric oxide (iNO) and sildenafil herapy was initiated. Although the child was extubated in 3 days, e had continued pulmonary hypertension for the next 16 months, equiring near continuous nasal cannula iNO therapy. During his ospital stay, a pulmonary perfusion scan was performed, which emonstrated decreased perfusion of the left lung (Figure 1). At 23 onths, the child had an acute respiratory decompensation and ied. At autopsy, stenosis of the left lower pulmonary vein was onfirmed (Figure 2A). Histological sectioning at the stenotic site howed narrowing of the pulmonary vein lumen and medial thickning (Figure 2B). Acquired pulmonary vein stenosis resulted in late onset pulonary hypertension in this child. Although pulmonary vein steosis after cardiovascular surgery in children is described, less is now about acquired pulmonary vein stenosis in extremely premaure infants. The long-term prognosis for children with acquired ulmonary vein stenosis is poor, with most having relentless proression of pulmonary hypertension. The unilateral left-sided steosis in our patient is intriguing. In preterm infants with a hemoynamically significant PDA such as this patient, left-to-right shunt ow may preferentially stream into the left pulmonary artery, thus ncreasing blood flow through the left pulmonary veins. This uniigure 1. Quantitative radionucleotide lung perfusion scan shows ecreased perfusion of the left lung.

Factors predicting coronary artery disease in patients with giant negative T waves.

Seventy-four patients with giant negative T waves were studied to determine which electrocardiographic variables predicted the presence of coronary artery disease. The absence of left ventricular hypertrophy and the presence of symmetric T-wave inversion predicted coronary artery disease.

Respiratory Failure Secondary to Barotrauma Is Effectively Treated by Exogenous Surfactant or Bronchoalveolar Lavage with Dilute Surfactant

Respiratory Failure Secondary to Barotrauma Is Effectively Treated by Exogenous Surfactant or Bronchoalveolar Lavage with Dilute Surfactant

The Role of Neonatal Thyroxin In Neurodevelopmental Disabilities |[dagger]| 1257

Recently, the concept that neonatal hypothyroxinemia (↓T4) is benign has been challenged and a link with cerebral palsy (CP) has been suggested. This study investigates a link between easily treatable ↓T4 and subsequent neurodevelopmental disorders. In this retrospective, case-control study data were collected in a regional university neonatal intensive care unit and its associated developmental high-risk follow-up clinic. Inclusion criteria for participation included: birth weight ≤1000 grams, born between January 1, 1992, and December 31, 1995, and survival-to-discharge. Eligible participants were selected based on availability of Thyroxin (T4) and accompanying developmental outcome data. Newborn screening procedures provided T4 and Thyroid Stimulating Hormone (TSH) data for the study. Neurodevelopmental assessments were performed at adjusted ages of 4, 12, and 24 months, by an interdisciplinary developmental team utilizing the Bayley Scales of Infant Development (BSID), the INFANIB assessment of neuromotor status and clinical assessment. Possession of T4 and developmental data provided inclusion of 60 subjects at 4 months, 82 at 12 months, and 53 at 24 months adjusted age. Analysis of data was done using Chi-square, contingency and stratified, and One-way Anova. Comparison of INFANIB results with thyroid function showed no significant association when controlling for the presence of Periventricular Leukomalacia (PVL) and Interventricular Hemorrhage (IVH). A similar conclusion was drawn for 12 month BSID results. Twenty-four month evaluations also suggested no significant relationship between T4 and developmental outcome as measured by BSID, however an association between the diagnosis of CP and Thyroid status was suggested (P≤.05). This study confirms the previously reported association between hypothyroxinemia and cerebral palsy, and fails to demonstrate an association with other abnormal neurological outcomes in this high risk population. A prospective interventional study will be needed to determine whether hypothyroxinemia is a contibuting factor in the development of CP or merely an early marker of cerebral injury.

Dopamine May Not Improve Cerebral Blood Flow after Cardiac Depression Secondary to Intestinal Ischemia-Reperfusion Injury

Dopamine May Not Improve Cerebral Blood Flow after Cardiac Depression Secondary to Intestinal Ischemia-Reperfusion Injury

Pulmonary Administration of Prostacyclin (PGI2) during Partial Liquid Ventilation (PLV) in an Animal Model of Pulmonary Hypertension (PHT) |[dagger]| 1662

Pulmonary Administration of Prostacyclin (PGI 2 ) during Partial Liquid Ventilation (PLV) in an Animal Model of Pulmonary Hypertension (PHT) † 1662

Perfluorocarbon Vapor Ventilation Prevents Seconday Lung Injury due to Intestinal Ischemia/Reperfusion • 200

Perfluorocarbon Vapor Ventilation Prevents Seconday Lung Injury due to Intestinal Ischemia/Reperfusion • 200

Inhaled Nitric Oxide (iNO) and Inhaled Prostacyclin (iPGI 2 ) in an Animal Model of Pulmonary Hypertension (PHT) : Compared Efficacy and Synergy † 1661

Inhaled Nitric Oxide (iNO) and Inhaled Prostacyclin (iPGI 2 ) in an Animal Model of Pulmonary Hypertension (PHT) : Compared Efficacy and Synergy † 1661

EFFICACY OF INHALED NITRIC OXIDE (iNO) AND ALKALOSIS DURING PARTIAL LIQUID VENTILATION IN PULMONARY HYPERTENSION. |[dagger]| 1495

We investigated the efficacy of the prevailing therapies for pulmonary hypertension when combined with partial liquid ventilation (PLV). 36 piglets(age: 7-24 days) were randomly allocated to conventional ventilation (IPPV) or PLV (initial perfluorocarbon volume: 30ml/kg; Rimar 101™) at an Fi02of 0.4. Pulmonary vascular resistance (PVR) was then increased from 51 ± 4 to 189 ± 10 mm Hg/L/ min/kg by infusion of a thromboxane(TX) mimetic (U46,619: 0.09 ± 0.01 μg/kg/min). Animals were sequentially tested under: eucapnea (EU) iNO 5ppm iNO 40 ppmeucapnea respiratory alkalosis (ALK) (pH=7.59 ± 0.01) ALK with iNO(40 ppm). Results: Table below compares changes between PLV and IPPV for each sequence (mean ± s.e.m). The changes in PVR and oxygenation (Aa02: alveolar-arterial 02 gradient) are shown as% change from the previous eucapneic state. Cardiac output (C.O.) is in ml/min/kg and lung compliance (Cdyn) in ml/cm H2O/kg. Conclusions: prior to TX, the perfluorocarbon caused a density associated cardiovascular depression of moderate degree. However this did not prevent iNO and ALK to be at least as efficient as during IPPV. For both modes of ventilation, iNO and ALK had an additive effect. PLV preserved lung compliance more efficiently than IPPV and could therefore be a more effective mode of treatment in pulmonary hypertension associated with lung injury.