Related Experiment Video
Updated: Jul 28, 2026
Use of a Hanging Weight System for Coronary Artery Occlusion in Mice
Published on: April 19, 2011
Does a selective adenosine A(1) receptor agonist protect against exercise induced ischaemia in patients with coronary
A D Kelion1, T P Webb, M A Gardner
1Department of Cardiology, John Radcliffe Hospital, Oxford, UK GlaxoSmithKline Research and Development, Greenford, Middlesex, UK.
Background:
The "warm up" effect in angina may represent ischaemic preconditioning, which is mediated by adenosine A(1) receptors in most models.
Objective:
To investigate the effect of a selective A(1) agonist, GR79236 (GlaxoSmithKline), on exercise induced angina and ischaemic left ventricular dysfunction in patients with coronary artery disease.
Design:
A double blind crossover study.
Patients:
25 patients with multivessel coronary artery disease.
Interventions:
On mornings one week apart, patients received intravenous GR79236 10 microgram/kg or placebo, and then carried out two supine bicycle exercise tests separated by 30 minutes. Equilibrium radionuclide angiography was done before and during exercise.
Results:
The onset of chest pain or 1 mm ST depression was delayed and occurred at a higher rate-pressure product during the second exercise test following either placebo or GR79236. Compared with placebo, GR79236 did not affect these indices during equivalent tests. GR79236 reduced resting global ejection fraction from (mean (SD)) 63 (7)% to 61 (5)% (p < 0.05) by a selective reduction in the regional ejection fraction of "ischaemic" left ventricular sectors (those where the ejection fraction fell during the first exercise test following placebo). Ischaemic sectors showed increased function during the second test following placebo (72 (21)% v 66 (20)%; p = 0.0001), or during the first test following GR79236 (69 (21)% v 66 (20)%; p = 0.0001). Sequential exercise further increased the function of ischaemic sectors even after drug administration.
Conclusions:
GR79236 failed to mimic the warm up effect, and warm up occurred even in the presence of this agent. This suggests that ischaemic preconditioning is not an important component of this type of protection. The complex actions of the drug on regional left ventricular function at rest and during exercise suggest several competing A(1) mediated actions.
Related Concept Videos
01:30Adrenergic Agonists: Direct-Acting Agents
These agents can be classified...
01:30Adrenergic Agonists: Therapeutic Uses
Emergency and Intensive Care Unit (ICU) applications: Pressor agents increase blood pressure, heart rate, and contractility in shock and organ failure situations. Dopamine can induce vasodilation and stimulate adrenoceptors. Endogenous catecholamines are effective in treating cardiogenic shock. α2-agonists like clonidine can reverse anesthesia-induced hypertension.
Allergies and anaphylaxis:...
01:22Adrenergic Antagonists: Pharmacological Actions of ɑ-Receptor Blockers
α1-blockers: These drugs inhibit α1-adrenoceptors on smooth muscle cells, resulting in vasodilation. This vasodilation lowers blood pressure, making α1-blockers valuable in treating hypertension. Additionally, α1-blockers effectively address urinary obstruction...
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:16Antianginal Drugs: Nitrates and β-Blockers
Organic nitrates, such as nitroglycerin, play a pivotal role. Once metabolized, they liberate nitric oxide, a molecular marvel. Nitric oxide triggers guanylyl cyclase and augments cGMP production. This biochemical cascade orchestrates the relaxation of vascular smooth muscles, ushering in vasodilation and enhancing coronary blood flow. Administered...
01:20Exercise and Cardiovascular Response
Light to moderate physical activity initiates a series of interconnected responses in the body. The heart rate modestly increases in anticipation of the workout, followed by widespread vasodilation as oxygen consumption by skeletal muscles increases. This results in decreased peripheral resistance, increased capillary blood flow, and accelerated...