The ischemic preconditioning effect of adenosine in patients with ischemic heart disease

Bita Sadigh,Miguel Quintana,Lars Åke Brodin,Christer Sylvén,Margareta Berglund

doi:10.1186/1476-7120-7-52

Abstract

IntroductionIn vivo and in vitro evidence suggests that adenosine and its agonists play key roles in the process of ischemic preconditioning. The effects of low-dose adenosine infusion on ischemic preconditioning have not been thoroughly studied in humans.AimsWe hypothesised that a low-dose adenosine infusion could reduce the ischemic burden evoked by physical exercise and improve the regional left ventricular (LV) systolic function.Materials and methodsWe studied nine severely symptomatic male patients with severe coronary artery disease. Myocardial ischemia was induced by exercise on two separate occasions and quantified by Tissue Doppler Echocardiography. Prior to the exercise test, intravenous low-dose adenosine or placebo was infused over ten minutes according to a randomized, double blind, cross-over protocol. The LV walls were defined as ischemic if a reduction, no increment, or an increment of < 15% in peak systolic velocity (PSV) was observed during maximal exercise compared to the baseline values observed prior to placebo-infusion. Otherwise, the LV walls were defined as non-ischemic.ResultsPSV increased from baseline to maximal exercise in non-ischemic walls both during placebo (P = 0.0001) and low-dose adenosine infusion (P = 0.0009). However, in the ischemic walls, PSV increased only during low-dose adenosine infusion (P = 0.001), while no changes in PSV occurred during placebo infusion (P = NS).ConclusionLow-dose adenosine infusion reduced the ischemic burden and improved LV regional systolic function in the ischemic walls of patients with exercise-induced myocardial ischemia, confirming that adenosine is a potential preconditioning agent in humans.

Highlights

In vivo and in vitro evidence suggests that adenosine and its agonists play key roles in the process of ischemic preconditioning
peak systolic velocity (PSV) increased from baseline to maximal exercise in non-ischemic walls both during placebo (P = 0.0001) and low-dose adenosine infusion (P = 0.0009)
In the ischemic walls, PSV increased only during low-dose adenosine infusion (P = 0.001), while no changes in PSV occurred during placebo infusion (P = NS)

Summary

Introduction

In vivo and in vitro evidence suggests that adenosine and its agonists play key roles in the process of ischemic preconditioning. The effects of low-dose adenosine infusion on ischemic preconditioning have not been thoroughly studied in humans. Ischemic preconditioning is triggered by the binding of several humoral factors such as adenosine, bradykinin, and opioids to their cardiac receptors[3,4], thereby initiating a series of complex and divergent signal cascades that eventually converge on protein kinase C. The cardioprotective effect of ischemic preconditioning seems to be biphasic, with an early opioid mediated phase occurring within minutes from the initial ischemic insult and lasting for two to three hours, and a late phase becoming apparent 12 to 24 hours later, lasting three to four days and requiring de novo protein synthesis[3,4]. The aim of this study was to explore whether low-dose adenosine infusion exerts an ischemic preconditioning effect in severely symptomatic patients with advanced coronary artery disease The major cellular mechanism responsible for the beneficial effects of ischemic preconditioning seems to be the opening of KATP channels either on the cardiac sarcolemmal or mitochondrial membrane [5,6,7].

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