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

E. Zima, V. Kékesi, Andrea Nagy, László Losonczi, Ildikó Toma, P. Soós, E. Barát, E. Huszár, B. Merkely, F. Horkay, A. Juhász-Nagy

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Abstract

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 μM (P <0.05); inosine, 18.3±2.8 compared with 0.9±0.2 μM (P <0.001); hypoxanthine, 38.1±8.0 compared with 13.4±2.6 μM (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 (STmax 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.

Original languageEnglish
JournalClinical Science
Volume103
Issue numberSUPPL. 48
Publication statusPublished - Aug 2002

Fingerprint

Pericardium
Endothelin-1
Canidae
Action Potentials
Inosine
Hypoxanthine
Dogs
Adenosine
Ischemia
Vasoconstrictor Agents
Ventricular Pressure
purine
Electrocardiography
High Pressure Liquid Chromatography
Blood Pressure

Keywords

  • Adenosine
  • Autoregulation
  • Endothelin-1
  • Inosine
  • Ischaemia
  • Pericardium

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{8cca148e3f4b4ac2b29e9b617dbc254f,
title = "Endothelin-1-induced elevations in purine metabolite concentrations - Autoregulatory protection in the canine pericardium?",
abstract = "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 μM (P <0.05); inosine, 18.3±2.8 compared with 0.9±0.2 μM (P <0.001); hypoxanthine, 38.1±8.0 compared with 13.4±2.6 μM (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 (STmax 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.",
keywords = "Adenosine, Autoregulation, Endothelin-1, Inosine, Ischaemia, Pericardium",
author = "E. Zima and V. K{\'e}kesi and Andrea Nagy and L{\'a}szl{\'o} Losonczi and Ildik{\'o} Toma and P. So{\'o}s and E. Bar{\'a}t and E. Husz{\'a}r and B. Merkely and F. Horkay and A. Juh{\'a}sz-Nagy",
year = "2002",
month = "8",
language = "English",
volume = "103",
journal = "Clinical Science",
issn = "0143-5221",
publisher = "Portland Press Ltd.",
number = "SUPPL. 48",

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TY - JOUR

T1 - Endothelin-1-induced elevations in purine metabolite concentrations - Autoregulatory protection in the canine pericardium?

AU - Zima, E.

AU - Kékesi, V.

AU - Nagy, Andrea

AU - Losonczi, László

AU - Toma, Ildikó

AU - Soós, P.

AU - Barát, E.

AU - Huszár, E.

AU - Merkely, B.

AU - Horkay, F.

AU - Juhász-Nagy, A.

PY - 2002/8

Y1 - 2002/8

N2 - 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 μM (P <0.05); inosine, 18.3±2.8 compared with 0.9±0.2 μM (P <0.001); hypoxanthine, 38.1±8.0 compared with 13.4±2.6 μM (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 (STmax 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.

AB - 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 μM (P <0.05); inosine, 18.3±2.8 compared with 0.9±0.2 μM (P <0.001); hypoxanthine, 38.1±8.0 compared with 13.4±2.6 μM (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 (STmax 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.

KW - Adenosine

KW - Autoregulation

KW - Endothelin-1

KW - Inosine

KW - Ischaemia

KW - Pericardium

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M3 - Article

VL - 103

JO - Clinical Science

JF - Clinical Science

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