Premium
Adenosine provides contractile support in the low‐flow ischemic heart
Author(s) -
Shea Lynne M.,
Fenton Richard A.,
Dobson James G.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a863-b
Subject(s) - adenosine , medicine , adenosine receptor , adenosine a1 receptor , cardiology , inotrope , antagonist , perfusion , ischemia , adenosine receptor antagonist , heart rate , endocrinology , chemistry , anesthesia , receptor , blood pressure , agonist
Low‐flow ischemia decreases heart contractile performance. Adenosine A 2A receptor (A2AR) activation elicits an increased contractile performance in normoxic hearts. The myocardial level of adenosine increases when the supply of oxygen is restricted. The effect of adenosine to increase contractile performance (+dP/dt max ) was investigated in the low‐flow ischemic (LFI) heart and compared to the adenosine effect in the non‐ischemic fully oxygenated (NFO) heart. Perfused rat hearts were rendered LFI by reducing perfusion from 18 to 6 ml/min and paced to contract at 320 beats/min. The maximum rate of left ventricular pressure development (+dP/dt max ) was used as an index of contractile performance. Adenosine (10 μM) increased +dP/dt max with LFI and NFO hearts by 3.2 ± 1.6% and 9.6 ± 2.1%, respectively. However, adenosine in the presence of the adenosine A 1 receptor (A1R) antagonist DPCPX (0.1 μM; dipropylcyclopentylxanthine) caused a greater increase in +dP/dt max in LFI (26.6 ± 4.1%) compared to NFO (15.8 ± 3.3%) hearts. This is a significant improvement in contractile function in the LFI heart. The A2AR antagonist ZM‐241385 (0.1 μM) prevented the increase in +dP/dt max caused by adenosine in the presence of DPCPX in both LFI and NFO hearts. The results suggest that A2AR stimulation in the low‐flow ischemic heart provides important inotropic support in the absence of A1R activation. (PHS Grants: HL‐66045 & AG‐11481)