Effect of Adenosine on Coronary Microvascular Function
Adenosine causes potent vasodilation primarily of the coronary microcirculation with minimal effect on epicardial conduit arteries, acting through A2 receptors to increase coronary blood flow and improve microvascular function in both patients with and without coronary artery disease. 1, 2
Mechanism of Microvascular Vasodilation
Adenosine exerts its microvascular effects through specific receptor-mediated pathways:
A2 receptor activation on vascular smooth muscle and endothelial cells stimulates adenylate cyclase, increasing cyclic adenosine monophosphate, which leads to vasodilation of the coronary microcirculation 1, 2, 3
The vasodilatory mechanism involves activation of intermediate-conductance calcium-activated potassium (K(Ca)) channels via the adenylate cyclase signaling pathway, causing smooth muscle relaxation 4
A1 receptors provide an opposing inhibitory effect on adenylate cyclase-mediated dilation, creating a balanced regulatory system 4
The vasodilation occurs through both inhibition of slow inward calcium current (reducing calcium uptake) and activation of adenylate cyclase in smooth muscle cells 2
Clinical Assessment of Microvascular Function
Adenosine serves as the gold standard agent for assessing coronary microvascular function through measurement of coronary flow reserve (CFR) and index of microvascular resistance (IMR): 1
Intravenous adenosine infusion at 140 μg/kg/min for 90 seconds allows quantification of coronary blood flow reserve and assessment of microvascular function 5
Intracoronary adenosine doses of 30-60 μg for left coronary artery and 20-30 μg for right coronary artery achieve maximal coronary hyperemia for functional assessment 1
Adenosine produces 4.4-4.6 times resting coronary blood flow velocity, similar to papaverine, representing maximal microvascular vasodilation 6
Effects in Patients With and Without Coronary Disease
The microvascular response to adenosine differs based on underlying coronary pathology:
In patients with normal coronary arteries, adenosine causes uniform maximal hyperemia across the entire coronary microcirculation 6
In patients with coronary stenoses, adenosine significantly increases blood flow in normal coronary arteries with little or no increase in stenotic arteries, creating differential perfusion that allows detection of functionally significant stenoses 2
In patients with microvascular dysfunction (coronary blood flow velocity increase <3.5 times baseline after papaverine), the dose-response characteristics to adenosine remain similar to normal patients, though the absolute hyperemic response is blunted 6
The mechanism of adenosine-induced vasodilation in coronary arterioles from patients with heart disease is endothelium-independent, relying on direct smooth muscle effects through A2 receptors and intermediate-conductance K(Ca) channels 4
Cardioprotective Effects on Microcirculation
Beyond vasodilation, adenosine provides multiple protective effects on the coronary microcirculation during ischemia:
Adenosine inhibits oxygen radical release from activated neutrophils, preventing endothelial cell damage and preserving microvascular perfusion during ischemia-reperfusion 7
It inhibits platelet aggregation, reducing microvascular thrombosis and maintaining microcirculatory patency 7
Adenosine reduces cardiomyocyte apoptosis and improves microvascular function through anti-inflammatory effects and inhibition of cytokine release 5
In the AMISTAD trial, adenosine infusion (70 μg/kg/min for 3 hours) in anterior STEMI patients significantly reduced infarct size (median 15% versus 45.5% with placebo), suggesting improved microvascular salvage, though the larger AMISTAD-2 trial did not show significant clinical benefit 5
Critical Clinical Considerations
When using adenosine for repetitive microvascular assessments, measurements should be performed on separate days because adenosine itself exerts cardioprotective effects that can interfere with subsequent measurements 5
The ultra-short half-life of less than 10 seconds in whole blood means effects are transient, with coronary hyperemia duration much shorter after adenosine than after papaverine 2, 6
Asthma represents an absolute contraindication for intravenous adenosine due to risk of bronchospasm 1
Patients taking dipyridamole or carbamazepine require dose reduction to 3 mg due to potentiation of adenosine effects 8
Patients should avoid Valsalva maneuvers during intravenous infusion as this interrupts continuous drug delivery and causes fluctuations in coronary blood flow 8, 1
Common transient side effects include chest discomfort, dyspnea, flushing, and transient bradycardia, but serious complications are rare 1