Different Expression of Endothelin in the Bronchoalveolar Lavage in Patients with Pulmonary Diseases

Endothelin (ET) is a broncho- and vasoconstrictive cytokine, but it also possesses proinflammatory and mitogenic activity. It is suggested to be involved in the pathogenesis of fibrotic lung diseases. We analyzed the concentration of ET 1 in the bronchoalveolar lavage (BAL) fluid in 95 patients with different lung diseases, among them 41 patients with interstitial lung diseases (13 fibrosing alveolitis in systemic sclerosis (FASS), 9 idiopathic pulmonary fibrosis (IFP), 8 sarcoidosis (S), 6 occupational lung disease (OLD), 5 other alveolitidies A), 27 patients with pneumonia, and 8 patients with chronic obstructive pulmonary disease (COPD). A heterogeneous group of 19 patients served as controls. The median ET concentration was 3.3 pg/ml. Significantly higher concentration was found in patients with FASS (5.8 pg/ml), IPF (5.0 pg/ml), and S (5.1 pg/ml) compared with OLD (2.8 pg/ml), A (1.9 pg/ml), COPD (1.5 pg/ml), and the control group (2.5 pg/ml). In pneumonia, the elevated ET concentration (4.1 pg/ml) was accompanied by a high alveolocapillary leakage. When normalized to BAL albumin concentration, only FASS presented with significantly elevated ET/albumin in the BAL compared with the control group (134.5 vs. 56.l pg/mg, p < 0.05). There were no correlations between ET and BAL differential cell count or pulmonary function tests. In current smokers, ET in BALF was significantly higher compared with non- or ex-smokers (3.9 vs. 2.0 pg/ml, p < 0.01), but not so the ET/albumin ratio (65.0 vs. 62.5 pg/mg). In summary, ET in the BAL is differentially expressed in distinct inflammatory and interstitial lung disease. Consistently high concentrations are found in FASS and elevated ET concentration could be discussed in IPF, sarcoidosis, and pneumonia. ET concentration in BAL is influenced by current smoking habits.     

Influence of collateral blood flow and of variations in MVO2 on tissue-ATP content in ischemic and infarcted myocardium

The left anterior descending coronary artery was occluded for 22.5, 45, 90, 180, and 360 mins in anesthesized open-chest dogs and pigs and thereafter reperfused for 30 min. Myocardial oxygen consumption was varied in dogs by cholinergic stimulation (bradycardia) and by cutting of the right and left vagus nerve (tachycardia). Regional myocardial blood flow was measured with radioactive tracer microspheres at the end of the occlusion period and 5 and 30 min after reflow. Tissue content of adenine nucleotides and of phosphocreatine were determined in the subendo- and subepicardium of transmural biopsies at the end of reflow. Infarct size was determined with nitrobluetetrazolium and compared with risk region size. Porcine hearts developed infarcts sooner. Those canines with a high MVO2 due to tachycardia had larger infarcts than those with bradycardia and resembled infarct development in the pig. The evolution of infarcts with time depended strongly on collateral flow which was significantly higher in canine hearts. Higher collateral flow and lower MVO2 in one group of canine hearts also resulted in better preserved tissue ATP. The fall in tissue ATP with time after coronary occlusion was compared with the O2-supply via collateral flow during occlusion. Assuming that the oxygen entering ischemic myocardium was used for ADP phosphorylation, we could estimate the degree of ATP-"overspending". Overspending was highest in low-flow ischemia and it correlated well with the speed of infarction. The ATP-data are best explained by the phosphocreatine energy shuttle model and by assuming slow access of cytosolic ATP to the ATP-splitting sites at the myofibrils. In conclusion, we postulate that both collateral flow as well as myocardial oxygen consumption before and during occlusion determine infarct size.