Hypoxic Pulmonary Vasoconstriction and Gas Exchange During Exercise: METHODS part 2
Protocol
The protocol was approved by the Hospital Clinic-Facultat de Medicina Research Committee on Human Investigations. Patients were allowed to continue taking their usual steroid regimen (if any), but treatment with all oral or inhaled bronchodilators was withdrawn 24 hours before the study. Specifically, patients were not receiving additional medication that could have either vasoactive or bron- choactive effects. After the patient had fasted overnight and without premedication, pulmonary and systemic arterial catheterization were performed. Forty-five minutes after starting the inert gas infusion, measurements of pulmonary and systemic hemodynamic variables and respiratory and inert gas exchange parameters were taken at rest. Then, exercise was begun on a cycle ergometer (E. Jaeger) at a power output (33 ±8 W) equivalent to 50 to 60 percent of their maximal tolerated work load (which had been quantified on a previous day), and a second set of hemodynamic and gas exchange measurements was obtained approximately ten minutes later. The patients were allowed to rest for 15 to 30 minutes until pulmonary and systemic hemodynamic variables and respiratory gas exchange parameters had returned to resting conditions. Nifedipine (20 mg) was then given sublingualis and resting and exercise measurements were repeated as before (at 45 minutes and 1 h after nifedipine, respectively). All measurements were taken in a semirecumbent position. A steady state condition (as defined by variations of less than ±5 percent in heart rate and minute ventilation and of less than ±0.1 percent in Fe02 and FeCO^ was monitored in each of the steps of the present protocol (rest and exercise with and without nifedipine) by continuously monitoring electrocardiogram, minute ventilation, respiratory rate, and mixed expired Oz and C02. The hemodynamic measurements were obtained before and after blood sampling for respiratory and inert gas analysis. Given that there were no significant differences between these two hemodynamic measurements, only values obtained after blood sampling are reported.
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Safety Measures
Our primary concern at all times during the study was the safety of the patient. Consequently, improvement in monitoring procedures included a continuous graphic recording of systemic and pulmonary arterial pressures as well as continuous electrocardiographic (HP-7830A) and ear oximetry (Biox II; Ohmeda-BOC, UK) monitoring. Patients were instructed to stop exercise should unusual symptoms (other than discomfort) develop, but none of them did. Three physicians were present at all times, with one directing his attention exclusively to the patient.
Statistical Analysis
An analysis of variance for repeated measures (MANOVA, SPSS) was used to compare measurements at rest and during exercise, before and after nifedipine. Interaction between exercise and nifedipine was specifically checked. Linear regression was used when appropriate. Comparison of the regression lines was done by one-way analysis of covariance. Probability values lower than 0.05 were considered significant in all cases. Results are expressed as mean ± SEM.
