THE EFFECT OF HYPERCAPNIA AND HYPOXEMIA ON THE CARDIOVASCULAR-RESPONSES TO ISOPROTERENOL

Background: The reason for the increased risk of death with fenoterol and isoproterenol in asthma is unknown but may relate to their cardiovascular effects. Deaths from asthma usually occur outside hospital where hypoxemia, with or without hypercapnia, may exist. Both of these states can influence the cardiovascular system. We investigated whether different gas mixtures modified the cardiovascular effects of isoproterenol. Method: Nine healthy men were randomly assigned to receive each of three gas mixtures to achieve (1) nornoxia-normocapnia, (2) hypercapnia (end-tidal Paco(2), 50 mm Hg), (3) hypoxemia-hypercapnia (arterial oxygen saturation, 90%; Paco(2), 50 mm Hg). Isoproterenol was administered with each of the gas mixtures. Cardiovascular measurements of heart rate, blood pressure, cardiac index, ejection fraction, fractional shortening, electromechanical systole, and the QT(c) interval were made before administration of the gases, as well as before and 5 minutes after isoproterenol administration. Results: The changes after hypercapnia were not significantly different from those after nomoxia-normocapnia. Hypoxemia-hypercapnia increased heart rate, systolic and diastolic blood pressure, QT(c) interval, cardiac index, ejection fraction, and fractional shortening. Isoproterenol increased heart rate, systolic blood pressure, QT(c) interval, cardiac index, ejection fraction, and fractional shortening while the subjects breathed the normoxia-normocapnia gas mixture. It caused similar changes with the other gas mixtures. The changes were additive. Conclusion: Isoproterenol and hypoxemia-hypercapnia will increase myocardial oxygen demand and could prove to be detrimental in severe asthma.