Original article
Regadenoson, a selective A2A adenosine receptor agonist, causes dose-dependent increases in coronary blood flow velocity in humans

https://doi.org/10.1016/j.nuclcard.2007.02.016Get rights and content

Background

Regadenoson is a selective A2A adenosine receptor agonist and vasodilator used to increase the heterogeneity of distribution of coronary blood flow during myocardial perfusion imaging. This study characterized the dose dependence of regadenoson-induced coronary hyperemia.

Methods and Results

An open-label, dose-escalation study of regadenoson (10-500 μg, rapid intravenous bolus) was performed in 34 subjects; in 4 additional subjects, the effect of aminophylline to reverse the response to regadenoson was determined. Intracoronary peak blood flow velocity in either the left anterior descending or left circumflex artery was measured by continuous Doppler signal recording, heart rate, central aortic blood pressure, and adverse effects were recorded. Regadenoson increased peak blood flow velocity by up to 3.4-fold in a dose-dependent manner. The mean duration of the increase in flow velocity of 2.5-fold or greater caused by 400 to 500 μg of regadenoson was 2.3 to 2.4 minutes. Regadenoson (400-500 μg) increased heart rate by up to 21 ± 6 beats/min and decreased systolic blood pressure (−5 ± 8 mm Hg to −24 ± 16 mm Hg) and diastolic blood pressure (−8 ± 4 mm Hg to −15 ± 14 mm Hg). Aminophylline (100 mg) attenuated the increase in peak flow velocity but not tachycardia caused by 400 μg of regadenoson.

Conclusion

The results of this study demonstrate the utility of regadenoson as a coronary vasodilator for myocardial perfusion imaging.

Section snippets

Study Population

Thirty-eight subjects were enrolled at four sites from September 2001 through January 2005 into an open-label, phase 2 study of the dose dependency, duration, and reversibility of regadenoson’s coronary hyperemic effect (Table 1). Thirty-four patients were enrolled in a dose-escalation substudy, wherein each subject received a single injection of drug. Four additional patients were enrolled in a substudy to demonstrate the action of aminophylline to reverse the hyperemic effect of 400 μg of

Coronary Vasodilator Effects of Adenosine and Regadenoson

Intracoronary administration of adenosine (18 μg) resulted in a transient peak increase in coronary blood flow velocity of 3.1 ± 0.44–fold (n = 30; range, 2.4- to 3.9-fold) above baseline. The time to a near-peak (ie, ≥85% of maximum observed peak) flow velocity response to adenosine was approximately 30 seconds. Regadenoson, administered as an intravenous bolus in each patient after the response to adenosine had returned to baseline, increased coronary blood flow velocity in a dose-dependent

Discussion

A rapid intravenous bolus injection of regadenoson (400-500 μg) induced an increase in coronary blood flow by 2.5-fold or greater for a duration of 2 to 3 minutes, with side effects that were brief and well tolerated in subjects undergoing cardiac catheterization for evaluation or treatment of suspected ischemic heart disease. The results indicate that regadenoson can induce coronary hyperemia with a magnitude and duration that are suitable for myocardial perfusion imaging. The maximal coronary

Acknowledgment

We thank Drs Michael Ragosta III, Louis I. Heller, and Kenneth M. Kent for their contributions in enrolling subjects for this trial. Drs Shryock, Olmsted, Blackburn, and Belardinelli are current employees of CV Therapeutics, which provided funding for the study, and therefore have a potential conflict of interest. The other authors have indicated they have no financial conflicts of interest.

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Cited by (113)

  • Cardiovascular magnetic resonance stress and rest T1-mapping using regadenoson for detection of ischemic heart disease compared to healthy controls

    2021, International Journal of Cardiology
    Citation Excerpt :

    Other possible confounds may be due to partial-volume effects during stress, as the basal slice may be subject to changes in the extent of longitudinal atrioventricular plane descent with regadenoson through heart rate and ventricular filling. Further work is required to fully ascertain the true relationship of these effects over time, particularly given the known rapid rise and slow decay pharmacokinetic profile of regadenoson [26], as opposed to the more steady-state adenosine infusion. Our findings are consistent with previous adenosine and exercise stress T1-mapping studies in patients with CAD [9,11–13,27].

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This research was supported by a grant from CV Therapeutics, Palo Alto, Calif.

1

Drs Lieu and Shryock contributed equally to the manuscript

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