Enhanced accumulation of pericardial fluid adenosine and inosine in patients with coronary artery disease

Fazekas, Levente; Horkay, Ferenc; Kékesi, Violetta; Huszár, Éva; Barát, Erzsébet; Fazekas, Réka; Szabó, Tamás; Juhász‐Nagy, Alexander; Naszlady, A

doi:10.1016/s0024-3205(99)00331-8

Cited by 21 publications

(13 citation statements)

References 26 publications

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“…Hypoxanthine is further metabolized to xanthine and urate by xanthine dehydrogenase or xanthine oxidase and it can be converted to inosine [27]. It has been considered that xanthine oxidase generated excess oxygen-free radicals, then caused ischemia injury in the pathway [28][29][30], and the enhanced release of inosine in plasma was a marker of ischemic myocardium [31]. Moreover, superoxide reacts at diffusion limited rates with other free radicals, particularly with NO to form the potent oxidant peroxynitrite, which has been shown to activate metalloproteinases and degrade troponin I, contributing to depressed myocardial function [32][33][34].…”

Section: Cdt Protectionmentioning

confidence: 99%

Metabolomic study of myocardial ischemia and intervention effects of Compound Danshen Tablets in rats using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry

Liu

Yan

et al. 2010

Journal of Pharmaceutical and Biomedical Analysis

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Section: Cdt Protectionmentioning

confidence: 99%

Metabolomic study of myocardial ischemia and intervention effects of Compound Danshen Tablets in rats using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry

Liu

Yan

et al. 2010

Journal of Pharmaceutical and Biomedical Analysis

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“…All samples were collected into syringes containing ice-cold stop solution prepared with 400 µmol\l dipyridamole and 100 µmol\l EHNA [erythro-4-(2-hydroxy-3-nonil)adenine hydrochloride] to prevent further degradation of the purine metabolites, since a high degree of degradation of adenosine is expected on the basis of earlier studies [4,6,15,16].…”

Section: Experimental Protocolmentioning

confidence: 99%

“…Human and experimental animal studies have demonstrated that the pericardial fluid (PF), which is present in the intrapericardial space, not only serves a mechanical function but also accumulates several endogenous regulatory agents of cardiac origin [1][2][3][4][5][6]. The purine metabolites, such as adenosine and its degradative products inosine and hypoxanthine, play an important cardioprotective role as a part of an endogenous metabolic coronary adaptative mechanism.…”

Section: Introductionmentioning

confidence: 99%

“…The levels of these agents are coupled to the cardiac energy state, whereby coronary flow and myocardial oxygen consumption are kept in balance [7][8][9]. The intrapericardial concentrations of these nucleosides are several-fold higher than those measured in systemic and coronary sinus blood samples under normal physiological conditions [4,6]. Interestingly, the most potent endogenous vasoconstrictor peptide produced by the endothelial cells, endothelin-1 (ET-1) [10], also has a high intrapericardial concentration [3,5,9,[11][12][13].…”

Section: Introductionmentioning

confidence: 99%

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Endothelin-1-induced elevations in purine metabolite concentrations — autoregulatory protection in the canine pericardium?

et al. 2002

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Pericardial fluid accumulates the cardioprotective purine metabolites, as well as the endogenous vasoconstrictor agent endothelin-1 (ET-1). The aim of the present study was to characterize the pericardial concentrations of the purine metabolites adenosine, inosine and hypoxanthine before and after intrapericardial administration of ET-1 to the in situ heart. The closed pericardial sac of anaesthetized dogs (n=9) was cannulated for ET-1 administration and for obtaining native pericardial fluid and control pericardial infusate samples (C1 and C2), as well as consecutive pericardial infusate samples (samples I, II and III) obtained 15 min after intrapericardial administration of 150 pmol/kg ET-1. In an additional five dogs, using the same protocol, ventricular epicardial and endocardial monophasic action potential recordings were performed to assess local ischaemic electrophysiological changes. Significant elevations of pericardial purine metabolite concentrations (measured by HPLC) were found in sample II compared with sample C2: adenosine, 4.5+/-1.7 compared with 0.5+/-0.1 microM (P<0.05); inosine, 18.3+/-2.8 compared with 0.9+/-0.2 microM (P<0.001); hypoxanthine, 38.1+/-8.0 compared with 13.4+/-2.6 microM (P<0.01). Systemic blood pressure, left ventricular pressure and contractility, and systemic plasma levels of the purine metabolites remained unchanged during the ET-1 effect, while significant ECG ST elevations (ST(max) 0.68+/-0.01 mV; P<0.001) were observed. In the five dogs analysed electrophysiologically, the left ventricular epicardial monophasic action potential duration and upstroke velocity decreased significantly at time point II compared with C2, while the endocardial monophasic action potential duration and upstroke velocity did not show ischaemia-related changes. The results suggest that intrapericardial administration of ET-1 induces subepicardial ischaemia, with parallel activation of coronary metabolic adaptive and cardiac self-protective mechanisms in the epimyocardial layer of the heart.

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“…The pericardial levels of the potent vasoconstrictor ET-1 and the cardioprotective and vasodilator adenine nucleosides are also found to exceed their plasma concentrations and may be substantially elevated in different cardiovascular diseases, such as ischemic heart disease [15,16].…”

Section: Introductionmentioning

confidence: 99%

Potential influence of the pericardial space on myocardial function: Cardiac interactions of adenosine and endothelin-1

Nagy

2011

IMAS

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Adenosine (ADO) and endothelin-1 (ET-1) play an important role in the regulation of myocardial functions. The pericardial fluid accumulates these regulatory agents and reflects well their levels in the myocardial interstitium. The aim was to investigate the interaction and cardiovascular effects of ADO and ET-1 evoked from the pericardial space, determine the pericardial elimination of intrapericardially applied adenosine and its first metabolite, inosine (INO) and observe their effects on the cardiovascular function compared to their intravenous administration. The present studies were performed on in situ dog heart using the closed pericardium model. Significant increase of the pericardial concentrations of adenine nucleosides (adenosine and inosine) after intrapericardial administration of ET-1 has been found. Regarding the adenine nucleosides-ET-1 interaction, we have demonstrated ET-1 liberation after intrapericardial administration of adenine nucleosides. The present study confirmed significantly slower elimination of adenine nucleosides in the pericardial space than in the systemic circulation. In conclusion, characteristic cardiovascular effect and bidirectional interaction of adenine nucleosides and ET-1 could be provoked by and detected in the pericardial space, reflecting parallel changes in the myocardial interstitium. The low pericardial turnover rate of adenine nucleosides may offer the opportunity of utilizing their multiple beneficial effects for local pharmaco-therapeutic interventions.

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Enhanced accumulation of pericardial fluid adenosine and inosine in patients with coronary artery disease

Cited by 21 publications

References 26 publications

Metabolomic study of myocardial ischemia and intervention effects of Compound Danshen Tablets in rats using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry

Metabolomic study of myocardial ischemia and intervention effects of Compound Danshen Tablets in rats using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry

Endothelin-1-induced elevations in purine metabolite concentrations — autoregulatory protection in the canine pericardium?

Potential influence of the pericardial space on myocardial function: Cardiac interactions of adenosine and endothelin-1

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