Cardioprotective effect of diadenosine tetraphosphate (AP4A) cardioplegia in isolated rat hearts.
Preischemic administration of diadenosine tetraphosphate (AP4A) has been shown to be cardioprotective. We evaluated the protective effect of AP4A when used as a cardioplegic adjuvant and tested contributions of the ATP-sensitive potassium channel (K ATP channel), adenosine receptor (AR), and purine 2y receptor (P2yR) to the effect of AP4A. Isolated buffer-perfused rat hearts were subjected to 23 min of ischemia (37 degrees C) followed by 20 min of reperfusion. Cardioplegia solution (St. Thomas Hospital solution) was infused during the first 3 min of ischemia. AP4A (10 microM) or AP4A with glibenclamide (K ATP channel blocker, 100 microM), 8-SPT (AR antagonist, 300 microM) or reactive blue (P2yR antagonist, 13 nM) were added to the cardioplegia solution. Compared with the cardioplegia solution alone, administration of AP4A with the solution significantly increased the recovery of rate-pressure production (75% +/- 11% vs 58% +/- 10%; P < 0.05) and dp/dt at the end of reperfusion, and reduced the leakage of creatine kinase (3.2 +/- 3.7 vs 13.2 +/- 10.1 IU/g; P < 0.05) during reperfusion. This effect was reversed by coadministration of glibenclamide or reactive blue but not 8-SPT. The addition of AP4A into the cardioplegia solution led to an added cardioprotective effect, either by opening the K ATP channel or by activating P2yR.
Ahmet
I
I
First Department of Surgery, Osaka University Medical School, Suita, Japan.
Sawa
Y
Y
Nishimura
M
M
Matsuda
H
H
D000241:Adenosine / Q000378:metabolism / Q000502:physiology; D000818:Animals; D002314:Cardioplegic Solutions / Q000008:administration & dosage*; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006324:Heart Arrest, Induced; D066298:In Vitro Techniques; D008297:Male; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011983:Receptors, Purinergic / Q000378:metabolism / Q000502:physiology; D015290:Second Messenger Systems
D002314:Cardioplegic Solutions; D015226:Dinucleoside Phosphates; D010975:Platelet Aggregation Inhibitors; D015221:Potassium Channels; D011983:Receptors, Purinergic; C020733:diadenosine tetraphosphate; D000241:Adenosine