Adenosine A2A and A2B Receptor Substantially Attenuate Ischemia/Reperfusion Injury in Septic rat Hearts

Autor: Bernhard M. Graf, Hendrik Busse, Michael Gruber, York Zausig, Klaus Höcherl, Timo Seyfried, Diane Bitzinger
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
Cardiotonic Agents
Receptor
Adenosine A2A
Ischemia
Myocardial Reperfusion Injury
Ischemia/reperfusion injury
030204 cardiovascular system & hematology
Pharmacology
Receptor
Adenosine A2B
Septic heart
Ventricular Function
Left
03 medical and health sciences
0302 clinical medicine
Coronary Circulation
Sepsis
Internal medicine
Ventricular Pressure
Animals
Medicine
Pharmacology (medical)
RNA
Messenger
Rats
Wistar
Receptor
AdorA2a
AdorA2b
Cardioprotection
business.industry
Myocardium
Adenosine receptor
Heart
General Medicine
bacterial infections and mycoses
Adenosine A3 receptor
medicine.disease
Adenosine
Adenosine A2 Receptor Antagonists
030104 developmental biology
Cardiology
Original Article
Cardiology and Cardiovascular Medicine
business
Reperfusion injury
Adenosine A2B receptor
medicine.drug
Zdroj: Cardiovascular Drugs and Therapy
ISSN: 1573-7241
0920-3206
DOI: 10.1007/s10557-016-6693-y
Popis: Introduction Mechanical and morphological ischemia and reperfusion (I/R) injury is reduced in septic hearts. The mechanism behind this “cardioprotection” is less well understood. As adenosine receptors play a major role for cardioprotection in non-septic hearts, we investigated the influence of adenosine receptors in a model of I/R in septic hearts. Methods SHAM operation or cecal ligation and puncture (CLP) was performed in adult male Wistar rats (n = 60). After 24 h of incubation, hearts were isolated and randomly assigned to a group with or without adenosine receptor (Ador) antagonists (SCH 58261 and MRS 1706) administered before reperfusion. Ischemia and reperfusion lasted for 40 min each. Cardiac function of the heart was determined by measuring left ventricular pressure (LVP). Results Before I/R, CLP hearts showed a significant mechanical left ventricular impairment (CLP: 63 ± 5 mmHg vs. SHAM: 104 ± 6 mmHg. After I/R, left ventricular function was significantly reduced in SHAM (24 ± 32 mmHg), but not in CLP hearts (65 ± 13 mmHg). mRNA expression for the AdorA2a and AdorA2b was significantly increased in CLP, but not in SHAM hearts. LVP of CLP hearts deteriorated when AdorA2a and AdorA2b were blocked. Conclusions The morphological and functional I/R injury in septic animals is less pronounced compared to non-septic animals. By a combined blockade of AdorA2a and AdorA2b this “cardioprotective” effect is nearly abolished in septic hearts. This is the first study showing, that AdorA2a and AdorA2b may play an important role for a reduced functional I/R injury in the septic heart.
Databáze: OpenAIRE
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