Imaging techniques for assessing pulmonary artery hypertension and right ventricular performance with special reference to COPD

Several imaging techniques, both noninvasive and minimally invasive, have now been applied widely for determining cardiovascular performance in patients with chronic respiratory disease, particularly COPD. Moreover, some of these techniques are useful for evaluating response to therapeutic intervention in these patients. The plain chest radiograph is useful primarily for detecting the presence of pulmonary artery hypertension in patients with COPD. Radionuclide angiocardiography, using either first-pass techniques or the gated equilibrium technique, is particularly useful for determining right and left ventricular ejection fraction. Echocardiography has evolved as a technique for assessing right ventricular size and function and, in some cases, the degree of pulmonary artery hypertension.     

Increased alveolar fluid clearance following thoracotomy: Report of a case and results of an analysis

Alveolar fluid clearance was studied in the resected lung of a 58-year-old man who had undergone exploratory thoracotomy 9 days earlier. An isosmolar albumin solution was instilled into the distal air spaces, and the albumin and electrolyte concentrations were measured over 4h. Alveolar sodium and fluid clearance had increased by nearly 200% from the control values in the resected lungs of patients without prior thoracotomy (n=5), and histological examination showed that the number of alveolar type II epithelial cells was markedly elevated. These results suggest that an increase in the number of alveolar type II cells may accelerate alveolar fluid clearance under certain clinical conditions.     

Neuropeptides in pulmonary edema fluid of adult respiratory distress syndrome

A role for peptidergic nerves in the adult respiratory distress syndrome (ARDS) was examined by radioimmunochemically quantifying neuropeptides in pulmonary edema (PE) fluids from seven patients with ARDS and six patients with PE from congestive heart failure (CHF). The PE fluid mean concentrations of substance P (SP) and gastrin-releasing peptide (GRP) were significantly higher in ARDS (0.59 ±0.29SD and 0.10=0.03 nM, respectively,P < 0.001 for both) than in CHF (0.19±0.08 and 0.04±0.01), whereas no difference was detected between the mean levels of vasoacti ve intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) in the two forms of PE. Mean alveolar fluid concentration of SP was 8.7 nM (range 2.1–20.5 nM,N=4) in sheep with acute lung injury from intravenousPseudomonas aeruginosa, but was undetectable in sheep with balloon-induced high left atrial pressure simulating CHF (N=2) or control sheep (N=2). Pulmonary lymphatic clearance of SP, which reflected the rate of generation of SP in the lungs, attained a maximum of 25–95 pmol/h in sheep givenP. aeruginosa intravenously, but was detected in only one of four control sheep at a lower level. Some pulmonary neuropeptides thus are released locally by acute lung injury and may contribute to endothelial and/or epithelial abnormalities underlying the altered capillary-alveolar permeability in ARDS.     

Pelvic neuroblastoma—Implications for a new favorable subgroup: A Children's cancer group experience

Background: The survival in neuroblastoma is influenced by patient age, disease stage, tumor site, and several biologic factors. This study was undertaken to determine if primary pelvic lesions are associated with an unusually favorable outcome. Methods: Nine hundred eighty-six patients registered on Children's Cancer Group studies from 1980 to 1993 were reviewed, and 41 (4.3%) were found to have pelvic tumors. Survival was analyzed, and correlations among age, stage of disease, surgical resectability, histopathology, serum ferritin, and N-myc oncogene amplification were evaluated. Results: Age at diagnosis was comparable between patients with pelvic and nonpelvic tumors. Disease distribution was similar, with stages III and IV comprising 78% (32 of 41) of pelvic lesions compared with 73% (692 of 945) for nonpelvic tumors. There was no outcome difference in favorable stages (I, II, and IV-S), with 3-year progression-free survival rates of 88% and 82% for pelvic and nonpelvic sites, respectively. However, in stages III and IV, the 3-year progression-free survival was 70% for pelvic lesions compared with 47% for nonpelvic tumors (p=0.04). Some favorable biologic factors were more common in children with pelvic lesions. Conclusions: The pelvis is an unusual primary site for neuroblastoma but represents a more favorable prognostic subgroup, which is most evident in advanced-stage disease. Presented at the 47th Annual Cancer Symposium of The Society of Surgical Oncology, Houston, Texas, March 17–20, 1994.     

Imaging techniques for assessing cardiovascular performance in chronic obstructive pulmonary disease

A variety of imaging techniques are now available for evaluating cardiovascular function. Plain chest radiographs, radionuclide angiocardiography, 201Tl myocardial imaging, and M-mode and two-dimensional echocardiography have been used to detect pulmonary hypertension, right ventricular enlargement, and occult ventricular performance disturbances in patients with chronic obstructive pulmonary disease (COPD). Furthermore, radionuclide angiocardiography and echocardiography combined with hemodynamic measurements have been used to assess short- and long-term cardiovascular effects of such therapeutic agents as theophylline, beta-adrenergics, vasodilators, digitalis, and oxygen. This review evaluates these imaging techniques and their application to COPD patients.     

Science review: mechanisms of ventilator-induced injury

Acute respiratory distress syndrome (ARDS) and acute lung injury are among the most frequent reasons for intensive care unit admission, accounting for approximately one-third of admissions. Mortality from ARDS has been estimated as high as 70% in some studies. Until recently, however, no targeted therapy had been found to improve patient outcome, including mortality. With the completion of the National Institutes of Health-sponsored Acute Respiratory Distress Syndrome Network low tidal volume study, clinicians now have convincing evidence that ventilation with tidal volumes lower than those conventionally used in this patient population reduces the relative risk of mortality by 21%. These data confirm the long-held suspicion that the role of mechanical ventilation for acute hypoxemic respiratory failure is more than supportive, in that mechanical ventilation can also actively contribute to lung injury. The mechanisms of the protective effects of low tidal volume ventilation in conjunction with positive end expiratory pressure are incompletely understood and are the focus of ongoing studies. The objective of the present article is to review the potential cellular mechanisms of lung injury attributable to mechanical ventilation in patients with ARDS and acute lung injury.     

Effects of leukotriene B4 in the human lung. Recruitment of neutrophils into the alveolar spaces without a change in protein permeability.

Leukotriene B4 (LTB4) is a major product of human alveolar macrophages and has potent chemotactic activity for neutrophils (PMN) in vitro. To evaluate the effects of LTB4 in the normal human lung, we instilled LTB4 (5 X 10(-7)M, 10 ml) into a subsegment of the right middle lobe and 0.9% NaCl (10 ml) into a subsegment of the lingula using a fiberoptic bronchoscope in 12 healthy human volunteers. 4 h later, we performed bronchoalveolar lavage of the same subsegments. Compared with the NaCl instillation, LTB4 caused a large increase in lavage total cells (NaCl = 6.8 +/- 1.0 X 10(6) vs. LTB4 = 26.4 +/- 5.0 X 10(6), P less than 0.01), most of which were PMN (NaCl = 12.2 +/- 4.6% vs. LTB4 = 55.7 +/- 6.0%, P less than 0.001). In contrast, there was only a small increase in lavage total protein, and the lavage total protein correlated weakly with lavage total cells and PMN. The production of superoxide anion by the lavage PMN in response to phorbol myristate acetate was similar to that of peripheral blood PMN. The migration of lavage PMN was normal toward the chemotactic peptide FMLP, but reduced toward LTB4 and zymosan-activated human serum. Morphometric analysis using transmission electron microscopy indicated a selective loss of small granules in the lung neutrophils as compared with peripheral blood neutrophils. The data indicate that in the normal human lung, LTB4 can recruit active PMN into the airspaces without causing a significant change in the protein permeability of the epithelial barrier.     

Beta‐Adrenergic Receptor Polymorphisms and Cardiac Graft Function in Potential Organ Donors

Prior studies have demonstrated associations between beta‐adrenergic receptor (βAR) polymorphisms and left ventricular dysfunction—an important cause of allograft nonutilization for transplantation. We hypothesized that βAR polymorphisms predispose donor hearts to LV dysfunction after brain death. A total of 1043 organ donors managed from 2001–2006 were initially studied. The following βAR single nucleotide polymorphisms were genotyped: β1AR 1165C/G (Arg389Gly), β1AR 145A/G (Ser49Gly), β2AR 46G/A (Gly16Arg) and β2AR 79C/G (Gln27Glu). In multivariable regression analyses, the β2AR46 SNP was significantly associated with LV systolic dysfunction, with each minor allele additively decreasing the odds for LV ejection fraction <50%. The β1AR1165 and β2AR46 SNPs were associated with higher dopamine requirement during the donor management period: donors with the GG and AA genotypes had ORs of 2.64 (95% CI 1.52–4.57) and 2.70 (1.07–2.74) respectively for requiring >10 μg/kg/min of dopamine compared to those with the CC and GG genotypes. However, no significant associations were found between βAR SNPs and cardiac dysfunction in 364 donors managed from 2007–2008, perhaps due to changes in donor management, lack of power in this validation cohort, or the absence of a true association. βAR polymorphisms may be associated with cardiac dysfunction after brain death, but these relationships require further study in independent donor cohorts.     

Noninvasive radiographic assessment of cardiovascular function in acute and chronic respiratory failure

Noninvasive radiographic techniques have provided a means of studying the natural history and pathogenesis of cardiovascular performance in acute and chronic respiratory failure. Chest radiography, radionuclide angiocardiography and thallium-201 imaging, and M mode and crosssectional echocardiography have been employed. Each of these techniques has specific uses, attributes and limitations. For example, measurement of descending pulmonary arterial diameters on the plain chest radiograph allows determination of the presence or absence of pulmonary arterial hypertension. Right and left ventricular performance can be evaluated at rest and during exercise using radionuclide angiocardiography. The biventricular response to exercise and to therapeutic interventions also can be assessed with this approach. Evaluation of the pulmonary valve echogram and echocardiographic right ventricular dimensions have been shown to reflect right ventricular hemodynamics and size. Each of these noninvasive techniques has been applied to the study of patients with respiratory failure and has provided important physiologic data.