Tracey L. Bryan

The effects of dobutamine and dopamine on intrapulmonary shunt and gas exchange in healthy humans

The development of intrapulmonary shunts with increased cardiac output during exercise in healthy humans has been reported in several recent studies, but mechanisms governing their recruitment remain unclear. Dobutamine and dopamine are inotropes commonly used to augment cardiac output; however, both can increase venous admixture/shunt fraction (Qs/Qt). It is possible that, as with exercise, intrapulmonary shunts are recruited with increased cardiac output during dobutamine and/or dopamine infusion that may contribute to the observed increase in Qs/Qt. The purpose of this study was to examine how dobutamine and dopamine affect intrapulmonary shunt and gas exchange. Nine resting healthy subjects received serial infusions of dobutamine and dopamine at incremental doses under normoxic and hyperoxic (inspired O(2) fraction = 1.0) conditions. At each step, alveolar-to-arterial Po(2) difference (A-aDo(2)) and Qs/Qt were calculated from arterial blood gas samples, intrapulmonary shunt was evaluated using contrast echocardiography, and cardiac output was calculated by Doppler echocardiography. Both dobutamine and dopamine increased cardiac output and Qs/Qt. Intrapulmonary shunt developed in most subjects with both drugs and paralleled the increase in Qs/Qt. A-aDo(2) was unchanged due to a concurrent rise in mixed venous oxygen content. Hyperoxia consistently eliminated intrapulmonary shunt. These findings contribute to our present understanding of the mechanisms governing recruitment of these intrapulmonary shunts as well as their impact on gas exchange. In addition, given the deleterious effect on Qs/Qt and the risk of neurological complications with intrapulmonary shunts, these findings could have important implications for use of dobutamine and dopamine in the clinical setting.

Effect of modality on cardiopulmonary exercise testing in male and female COPD patients

The purpose of this study was to examine the physiological responses to treadmill and cycle cardiopulmonary exercise testing (CPET) in male and female COPD patients. Fifty-five patients [28 males (FEV1=58.2±19.5% predicted), and 27 females (FEV1=65.3±16.6% predicted)] completed a treadmill and a cycle CPET in random order on two separate days. Respiratory and cardiovascular data were obtained. Compared to the cycle CPET, the treadmill elicited greater peak power output and peak oxygen uptake, while arterial saturation at peak exercise was lower with the treadmill; however, there were no differences between the responses in men and women. No differences were observed in heart rate, ventilation, tidal volume/breathing frequency, inspiratory capacity, or dyspnea responses between modalities or sex. The physiological responses between treadmill and cycle CPET protocols are largely similar for both men and women with COPD, indicating that either modality can be used in mild/moderate COPD patients.

Dopamine receptor blockade improves pulmonary gas exchange but decreases exercise performance in healthy humans

At rest, dopamine induces recruitment of intrapulmonary arteriovenous anastomoses (IPAVA) and increases venous admixture (i.e. Q̇s/Q̇t ). Dopamine increases during exercise, and may be partly responsible for exercise‐induced IPAVA recruitment. In this study, we antagonized dopamine receptors with metoclopramide, and observed improved pulmonary gas exchange but no difference in IPAVA recruitment during exercise. Dopamine blockade decreased cardiac output at peak exercise, resulting in decreased exercise performance. Increasing endogenous dopamine is important for the normal healthy response to exercise.

The carotid chemoreceptor contributes to the elevated arterial stiffness and vasoconstrictor outflow in COPD

The reason(s) for the increased central arterial stiffness in chronic obstructive pulmonary disease (COPD) are not well understood. In this study, we inhibited the carotid chemoreceptor with both low‐dose dopamine and hyperoxia, and observed a decrease in central arterial stiffness and muscle sympathetic nervous activity in COPD patients, while no change was observed in age‐ and risk‐matched controls. Carotid chemoreceptor inhibition increased vascular conductance, secondary to reduced arterial blood pressure in COPD patients. Findings from the current study suggest that elevated carotid chemoreceptor activity may contribute to the increased arterial stiffness typically observed in COPD patients.

Pulmonary capillary blood volume response to exercise is diminished in mild chronic obstructive pulmonary disease

BACKGROUND Previous work suggests that mild chronic obstructive pulmonary disease (COPD) patients have greater lung dysfunction than previously appreciated from spirometry alone. There is evidence of pulmonary microvascular dysfunction in mild COPD, which may reduce diffusing capacity (DLCO) and increase ventilatory inefficiency during exercise. The purpose of this study was to determine if DLCO, pulmonary capillary blood volume (Vc), and membrane diffusing capacity (Dm) are diminished during exercise in mild COPD, and whether this is related to ventilatory inefficiency and dyspnea. METHODS Seventeen mild COPD patients (FEV1/FVC: 64 ± 4%, FEV1 = 94 ± 11%pred) and 17 age- and sex-matched controls were recruited. Ten moderate COPD patients were also tested for comparison (FEV1 = 66 ± 7%pred). DLCO, Vc, and Dm were determined using the multiple-fraction of inspired oxygen (FIO2) DLCO method at baseline and during steady-state cycle exercise at 40W, 50%, and 80% of V˙O2peak. Using expired gas data, ventilatory inefficiency was assessed by V˙E/V˙CO2. RESULTS Compared to controls, mild COPD had lower DLCO at baseline and during exercise secondary to diminished Vc (P < 0.05). No difference in Dm was observed between controls and mild COPD at rest or during exercise. Patients with high V˙E/V˙CO2 (i.e. ≥34) had lower Vc and greater dyspnea ratings compared to control at 40W. Moderate COPD patients were unable to increase Vc with increasing exercise intensity, suggesting further pulmonary vascular impairment with increased obstruction severity. CONCLUSION Despite relatively minor airflow obstruction, mild COPD patients exhibit a diminished DLCO and capillary blood volume response to exercise, which appears to contribute to ventilatory inefficiency and greater dyspnea.