Mechanism of tachycardia during myocardial perfusion imaging with adenosine

Abstract

Background: Myocardial perfusion imaging using adenosine is accompanied by tachycardia for which neither the mechanism nor the receptor subtype is known. In order to understand the receptor subtype responsible for tachycardia, we determined the effects of regadenoson (REG), a selective A 2Aadenosine receptor agonist, on heart rate (HR) and blood pressure (BP) in awake rats. Methods: Male SD rats chronically instrumented to record BP through carotid artery were used in the study. Effect of REG (0.3μg/kg-50μg/kg) given as a rapid i.v. bolus on HR and BP was recorded. Results: REG caused an increase in mean BP and systolic pressure (SP) at lower doses while at higher doses there was a decrease in BP and SP. REG caused a dose-dependent increase in HR (maximal increase; 28 ± 5%). The increase in HR was evident at the lowest dose of REG at which there was no appreciable decrease in BP. The A 2Aantagonist, ZM241385 (30μg/kg, n=5), prevented the decrease in BP (REG: -14±3%, ZM: 1±1%) and attenuated the tachycardia (REG: 27±3%, ZM: 18±3%) caused by REG. Pretreatment with metoprolol (MET, 1 mg/kg, n=5), a beta-blocker, attenuated the increase in HR (REG: 27±3%, MET: 15±2%), but had no effect on hypotension caused by REG. In the presence of hexamethonium (HEX, 10 mg/kg, n=5), a ganglionic blocker, the tachycardia was prevented (REG: 27±3%, HEX: -1±2%), but BP was further reduced (REG: -11±2%, HEX: -49±5%). REG (10 mg/kg, n=6) also significantly (p<0.05) increased plasma norepinephrine levels (control:146±11, REG:269±22 ng/ml). Conclusion: The separation of HR and BP effects by dose, time and pharmacological interventions (b-blocker and ganglionic blocker) provides evidence that the increase in HR caused by REG is independent of the hypotensive effect, suggesting that REG, via activation of A 2Areceptors, may cause a direct stimulation of the sympathetic nervous system.