In vivo assessment of coronary flow and cardiac function after bolus adenosine injection in adenosine receptor knockout mice

Bolus injections of adenosine and the A(2A) adenosine receptor (AR) selective agonist (regadenoson) are used clinically as a substitute for a stress test in people who cannot exercise. Using isolated tissue preparations, our lab has shown that coronary flow and cardiac effects of adenosine are mostly regulated by the AR subtypes A(1), A(2A), and A(2B). In this study, we used ultrasound imaging to measure the in vivo effects of adenosine on coronary blood flow (left coronary artery) and cardiac function in anesthetized wild‐type, A(1) knockout (KO), A(2A)KO, A(2B)KO, A(3)KO, A(1), and A(3) double KO (A(1/3) DKO) and A(2A) and A(2B) double KO (A(2A/2B) DKO) mice in real time. Echocardiographic and Doppler studies were performed using a Visualsonic Vevo 2100 ultrasound system. Coronary blood flow (CBF) baseline data were obtained when animals were anesthetized with 1% isoflourane. Diameter (D) and velocity time integral (VTI) were measured on the left coronary arteries (CBF = ((π/4) × D(2) × VTI × HR)/1000). CBF changes were the highest within 2 min of injection (about 10 mg/kg). Heart rate, cardiac output, and stroke volume were measured by tracing the left ventricle long axis. Our data support a role for the A(2) AR in CBF and further support our conclusions of previous studies from isolated tissues. Adenosine‐mediated decreases in cardiac output and stroke volume may be A(2B) and/or A(3) AR‐mediated; however, the A(1) and A(2) ARs also play roles in overall cardiac function. These data further provide a powerful translational tool in studying the cardiovascular effects of adenosine in disease states.