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Hypoxic Pulmonary Vasoconstriction and Gas Exchange During Exercise: METHODS

Pulmonary Vasoconstriction

Patients

Eight male patients (x ± SEM, 62 ±1 year) with the standard clinical criteria of COPD and with previous functional confirmation of nonreversible chronic airflow limitation (FEV„ 1.15 ±0.12 L [36 ±3 percent predicted]) were selected from the outpatient clinic of our institution. None of them had clinical evidence of overt right heart failure. Type В COPD was present in five patients whereas the three remaining patients had predominantly type A COPD. Consent was obtained after the purposes and risks of the investiga­tion were explained and understood by each patient. All were clinically stable (none had required hospitalization during the previous two months) and none had evidence of renal, liver, or intrinsic heart disease. None of them was receiving oxygen therapy at home. Pulmonary function test (PFT) evaluation included meas­urement of static and dynamic lung volumes (HF-47804A Pulmonary System Desk; Hewlett-Packard, Palo Alto, Calif), plethysmography functional residual capacity and airway resistance (Body test, E. Jaeger, WUrzburg, FRC), and single-breath carbon monoxide dif­fusing capacity (Deo) (Resparameter model A, PK Morgan Ltd, Chatham, UK). The Deo values were corrected for hemoglobin. Predicted values for PFT were from our own laboratory.

Procedures

A transvenous balloon-tipped catheter (Swan-Canz 7F, Edwards Laboratories, Santa Ana, Calif) was placed into the pulmonary artery under pressure wave monitoring (HF-78303 A), and a polyethylene catheter (Seldicath, Plastimed, France) was inserted in the radial artery. Cardiac output (Qt) was determined by the thermodilution technique (9520A, Edwards Laboratories, Santa Ana, Calif). Intravascular pressures were continuously monitored (HP-7754 B) using HF-1290 A transducers and were read at end expiration over three respiratory cycles (the external zero reference level was positioned at midchest). During exercise, the pronounced pleural pressure swings made the measurement of pulmonary capillary wedge pressure (Pw) difficult. Therefore, we elected to report Pw only at rest and to calculate total pulmonary vascular resistance fTPVR) as mean Ppa divided by Qr. Right ventricular stroke work index (RVSWI) was derived as ([Ppa-Pra].CI.0.0136)/ heart rate) (in g.m/m), where cardiac index (CI) was Qt (L.min)/ body surface area (ms).
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Minute ventilation (Ve) and respiratory rate (f) were recorded minute by minute using a calibrated Wright spirometer. Low dead space, low resistance, and nonrebreathing valves were used to collect the expired gas through a heated-mixing box, either at rest (No. 1500, Hans Rudolph, Kansas City, Mo) or during exercise (E. Jaeger, WUrzburg, FRG). Oxygen uptake (VoJ and carbon dioxide output (VcoJ were calculated from mixed expired fractions of Os and CO, (Multi-gas MS2, Medishield, Ohmeda-BOC UK), respec­tively, and the respiratory quotient (R) as VcoJVo2. Po2, Pco2, and pH were analyzed in duplicate (IL 1302 pH blood gas analyzer; Instrumentation Laboratories, Milan, Italy). Hemoglobin concentra­tion was measured (OSM-2 Hemo-oximeter, Radiometer, Copen­hagen, Denmark) and oxygen saturation was computed through Kelmans subroutines. Alveokr-arterial Os pressure difference (P[A- aJOJ venous admixture (Qs/Qt), dead space-tidal volume ratio (Vd/ Vt, and systemic O, delivery were calculated using standard formulas.

The Va/Q distributions were estimated by the multiple inert gas elimination technique. Particular features of its set-up in our laboratory have been reported elsewhere. Briefly, after infusing a 5 percent dextrose solution of six inert gases (SFe, ethane, cyclo­propane, enflurane, ether, and acetone) through a peripheral vein for about 30 minutes at a constant rate, duplicate samples of heparinized arterial and mixed venous blood and mixed expired gas were simultaneously withdrawn. Inert gas concentrations in mixed expired samples and the gas phase of equilibrated arterial and mixed venous samples were measured by gas chromatography (Hewlett-Packard 5880A). Solubilities of inert gases were measured for each patient and the Va/Q distributions were estimated from the inert gas data using a least-square fit to the data by a multicompartmental model with enforced smoothing in the usual manner. Wfe defined shunt as the percentage of Qt perfusing essentially unventilated alveoli (Va/Q <0.005), low and high Va/Q regions as those with Va/Q ratios between 0.005 and 0.1, and 10 and 100, respectively, and dead space as the percentage of Ve to lung units with Va/Q ratios higher than 100. The latter includes the anatomic dead space, unperfused alveoli, and instrument dead space. The position of the pulmonary blood flow (Q) and ventilation (V) distributions is described by the Va/Q ratio at their mean (Q, V, respectively), and their dispersion by their standard deviation on a log scale (1°&d Q> bogsD V). The inert gas results are also reported as the dispersion directly obtained from retention (R) minus excretion (E) (corrected for the acetone excretion, E*) of each inert gas (DISP R-E*), which is an index of the overall amount of Va/Q mismatching.
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