Abstract
The adenosinergic system is essential in the mediation of intrinsic protection and myocardial resistance to insult; it may be considered a cardioprotective molecule and adenosine receptors (ARs) represent potential therapeutic targets in the setting of heart failure (HF). The aim of the study was to test whether differences exist between mRNA expression of ARs in the anterior left ventricle (LV) wall (pacing site: PS) compared to the infero septal wall (opposite region: OS) in an experimental model of dilated cardiomyopathy. Cardiac tissue was collected from LV PS and OS of adult male minipigs with pacing-induced HF (n = 10) and from a control group (C, n = 4). ARs and TNF–α mRNA expression was measured by Real Time-PCR and the results were normalized with the three most stably expressed genes (GAPDH, HPRT1, TBP). Immunohistochemistry analysis was also performed. After 3 weeks of pacing higher levels of expression for each analyzed AR were observed in PS except for A1R (A1R: C = 0.6±0.2, PS = 0.1±0.04, OS = 0.04±0.01, p<0.0001 C vs. PS and OS respectively; A2AR: C = 1.04±0.59, PS = 2.62±0.79, OS = 2.99±0.79; A2BR: C = 1.2±0.1, PS = 5.59±2.3, OS = 1.59±0.46; A3R: C = 0.76±0.18, PS = 8.40±3.38, OS = 4.40±0.83). Significant contractile impairment and myocardial hypoperfusion were observed at PS after three weeks of pacing as compared to OS. TNF-α mRNA expression resulted similar in PS (6.3±2.4) and in OS (5.9±2.7) although higher than in control group (3.4±1.5). ARs expression was mainly detected in cardiomyocytes. This study provided new information on ARs local changes in the setting of LV dysfunction and on the role of these receptors in relation to pacing-induced abnormalities of myocardial perfusion and contraction. These results suggest a possible therapeutic role of adenosine in patients with HF and dyssynchronous LV contraction.
Highlights
Adenosine derives from ATP degradation; it is considered to play an important role in adaptation to inadequate oxygen supply since it accumulates under hypoxic or ischemic conditions [1,2,3]
The aim of the study was to test in this animal model of pacinginduced heart failure (HF) whether regional differences exist in adenosine receptors (ARs) mRNA expression at pacing site (PS) as compared to the opposite wall
In all animals left ventricle (LV) end diastolic pressure was at least 20 mmHg which was considered an index of severe, not end-stage, HF
Summary
Adenosine derives from ATP degradation; it is considered to play an important role in adaptation to inadequate oxygen supply since it accumulates under hypoxic or ischemic conditions [1,2,3]. Basal adenosine levels reported in myocardial interstitial fluid range from nano- to micromolar concentrations; maximal ATP-derived adenosine production might reach 100 nmol adenosine/(h.heart) in the case of oxygen shortage [4,5]. Evidence indicates that the adenosinergic system is essential in the mediation of intrinsic protection and in determining myocardial resistance to insult; adenosine may be considered as a potential cardioprotective molecule and ARs could represent potential therapeutic targets in the setting of heart failure (HF).
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