Beta-adrenergic Receptor Blockade Effects on Cardio-pulmonary Exercise Testing

Abstract Background: Beta-blockers are increasingly prescribed while the effects of beta-adrenergic receptor blockade on cardio-pulmonary exercise test (CPET) derived parameters remain under-studied. Methods: 21 young healthy adults repeated 3 CPET at an interval of 7 days at the same time of the day. The tests were performed 3 hours after a random, double blind, cross-over single dose intake of placebo, 2.5 mg bisoprolol or 5 mg bisoprolol. Gaz exchange, heart rate and blood pressure were measured at rest and during cyclo-ergometric CPET.Results: Maximal workload and VO2max were unaffected by the treatment, with maximal respiratory exchange ratio > 1.15 in all tests. A beta-blocker dose-dependent effect reduced resting and maximal blood pressure and heart rate and the chronotropic response to exercise, evaluated by the heart rate/VO2 slope (placebo: 2,9 ± 0,4 beat/ml/kg; 2,5 mg bisoprolol: 2,4 ± 0,5 beat/ml/kg; 5 mg bisoprolol: 2,3 ± 0,4 beat/ml/kg, p<0.001). Ventilation efficiency measured by the VE/VCO2 slope and the ventilatory equivalent for CO2 at the ventilatory threshold were not affected by beta1-receptor blockade. Post-exercise chronotropic recovery measured after 1 min was enhanced under beta1-blocker (placebo: 26 ± 7 bpm; 2,5 mg bisoprolol: 32 ± 6 bpm; 5 mg bisoprolol: 33 ± 6 bpm, p<0.01).Conclusion: The present results suggest that a single dose of bisoprolol does not affect metabolism, respiratory response and exercise capacity. However, beta-adrenergic blockade dose-dependently reduced exercise hemodynamic response by lowering the pressure and chronotropic responses.

Download Full-text

Neurally mediated cardiac effects of forskolin in conscious dogs

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.271.4.h1473 ◽

1996 ◽

Vol 271 (4) ◽

pp. H1473-H1482 ◽

Cited By ~ 2

Author(s):

M. Iwase ◽

Y. Ishikawa ◽

Y. T. Shen ◽

R. P. Shannon ◽

N. Sato ◽

...

Keyword(s):

Heart Rate ◽

Adenylyl Cyclase ◽

Adrenergic Receptor ◽

Left Ventricular ◽

Conscious Dogs ◽

Receptor Blockade ◽

Beta Adrenergic Receptor ◽

Beta Adrenergic ◽

Ganglionic Blockade ◽

Adrenergic Receptor Blockade

Because major cardiovascular disease states are characterized by defects in adenylyl cyclase regulation, it becomes important to understand the mechanisms by which adenylyl cyclase activators affect inotropy and chronotropy in intact conscious animals. Accordingly, we examined the inotropic and chronotropic responses to forskolin in 11 normal conscious, chronically instrumented dogs and 3 dogs with ventricular denervation (VD). Left ventricular first derivative of pressure (LV dP/dt) increased by 96 +/- 7%, P < 0.05, in response to forskolin (50 nmol.kg-1.min-1) in normal dogs and by significantly less, 52 +/- 14%, in VD dogs. Circulating norepinephrine (NE) levels increased similarly in both groups (from 226 +/- 18 to 389 +/- 33 pg/ml in normal dogs, from 177 +/- 23 to 329 +/- 71 pg/ml in VD dogs). In the presence of ganglionic blockade, the increase in LV dP/dt in response to forskolin was reduced (+62 +/- 4%) in normal dogs but was unchanged in VD dogs (+52 +/- 12%). Ganglionic blockade abolished the increase in circulating NE levels in both groups. Increases in heart rate in the presence of ganglionic blockade (+54 +/- 6 beats/min) were less than in the presence of atropine alone (+92 +/- 10 beats/min). Notably, the LV dP/dt and heart rate responses to forskolin were further attenuated by beta-adrenergic receptor blockade in the presence and absence of ganglionic blockade. Morphine also attenuated the increases in both LV dP/dt and plasma NE in response to forskolin. Increases in LV dP/dt in response to NKH-477 (30 micrograms/kg), a water-soluble forskolin derivative, were similar before and after ganglionic blockade (+63 +/- 8 and +51 +/- 10%, respectively). However, in vitro experiments in LV sarcolemmal membrane preparations demonstrated that stimulation of adenylyl cyclase by forskolin and NKH-477 was not affected by beta-adrenergic receptor blockade. These results indicate that in conscious dogs, inotropic and chronotropic effects of forskolin are not only due to direct activation of adenylyl cyclase, but the effects also are mediated by neural mechanisms and potentiated by the prevailing level of sympathetic tone.

Download Full-text