Microvascular permeability of the non-heart-beating rabbit lung after warm ischemia and reperfusion: role of neutrophil elastase

STUDY OBJECTIVES: Criteria used to define the respective roles of pulmonary mechanics and cardiovascular disease in limiting exercise performance are usually obtained at peak exercise, but are dependent on maximal patient effort. To differentiate heart from lung disease during a less effort-dependent domain of exercise, the predictive value of the breathing reserve index (BRI=minute ventilation VE]/maximal voluntary ventilation MVV]) at the lactate threshold (LT) was evaluated. DESIGN: Thirty-two patients with COPD and a pulmonary mechanical limit (PML) to exercise defined by classic criteria at maximum oxygen uptake (VO2max) were compared with 29 patients with a cardiovascular limit (CVL) and 12 normal control subjects. Expired gases and VE were measured breath by breath using a commercially available metabolic cart (Model 2001; MedGraphics Corp; St. Paul, Minn). Arterial blood gases, pH, and lactate were sampled each minute during exercise, and cardiac output (Q) was measured by first-pass radionuclide ventriculography (System 77; Baird Corp; Bedford, Mass) at rest and peak exercise. RESULTS: For all patients, the BRI at lactate threshold (BRILT) correlated with the BRI at VO2max (BRIMAX) (r=0.85, p<0.0001). The BRILT was higher for PML (0.73+/-0.03, mean+/-SEM) vs CVL (0.27+/-0.02, p<0.0001), and vs control subjects (0.24+/-0.03, p<0.0001). A BRILT > or = 0.42 predicted a PML at maximum exercise, with a sensitivity of 96.9%, a specificity of 95.1%, a positive predictive value of 93.9%, and a negative predictive value of 97.5%. CONCLUSIONS: The BRILT, a variable measured during the submaximal realm of exercise, can distinguish a PML from CVL.