Adenosine-induced increase in myocardinal ATP: Are there beneficial effects for the ischaemic myocardium?

Abstract

The adenosine triphosphate (ATP) content of isolated Langendorff-perfused rat hearts may be increased by more than 40% above the normal value by a 2-h perfusion with adenosine (15 mumol/l). This metabolic manipulation was used to investigate the hypothetical relationship between total tissue ATP content and ischaemia-induced contractile failure, ischaemic contracture and post-ischaemic functional recovery. Adenosine perfused hearts were submitted to 20 min of normothermic ischaemia and reperfused for 45 min with or without adenosine. Control experiments were performed with adenosine-free preischaemic perfusion. In identically designed experiments the tissue-protective effect of diltiazem (0.5 mumol/l) was determined and compared with the experiments with adenosine. At the end of 120 min of preischaemic perfusion, the ATP content of the adenosine treated hearts was 34.3 +/- 1.8 mumol/g dry weight (control = 23.6 +/- 1.9 mumol/g, p less than 0.01). After a period of 20 min of normothermic ischaemia, the ATP content of the adenosine hearts decreased to 13.3 +/- .4 mumol/g, whereas ATP fell to 8.3 +/- 1.6 mumol/g in the control hearts. The creatine phosphate (CP) levels of adenosine hearts were significantly lower than those of the control group before ischaemia, but did not show major differences following ischaemia. During ischaemia, the contractile activity measured via an intraventricular balloon catheter, as well as ischaemic contracture did not differ between the adenosine and control hearts. The inclusion of diltiazem into the perfusate significantly delayed the onset of contracture. After 45 min of reperfusion, ATP contents of adenosine and control hearts reached similar values (8.4 +/- 2.3 and 8.3 +/- 2.9 mumol/g, respectively). Inclusion of adenosine (15 mumol/l in the reperfusion perfusate of the adenosine experiments prevented a further decrease, but did not increase tissue ATP content. CP values of all groups showed a partial recovery upon reperfusion, they did not differ significantly. Contractile recovery was equal in all experimental groups except for the diltiazem treated hearts, which showed during the first 10 min of reperfusion an improved mechanical performance. It is concluded that total tissue ATP is not necessarily a good indicator of functional capabilities under conditions of normothermic ischaemia and reperfusion in the isolated rat heart.

Cardiospecific Overexpression of the Prostaglandin EP 3 Receptor Attenuates Ischemia-Induced Myocardial Injury

“…25,26 It is noteworthy that some protective interventions such as ischemic preconditioning augment ischemia-induced contracture, 27,28 whereas others such as activation of A 1 adenosine receptors or inhibition of L-type calcium channels reduce contracture. 29,30 The antiischemic action of EP 3 overexpression became also evident during reperfusion, in which the release of CK and LDH into the coronary effluate was significantly reduced in the tg hearts to Ͻ25% of wt.…”

31P-NMR study of cardiac preservation: St. Thomas' Hospital cardioplegic solution versus UW preservation solution

“…To prevent expansion of the extracellular space hydroxyethyl starch is added (50 g/l) and the presence of precursors for ATP resynthesis (adenosine) might have had additional benefits in maintaining the ATP level during preservation. Indeed, it has been shown recently that the presence of increased amounts of adenosine in the perfusate (15-30 pmoYI) during normothermic ischemic conditions, results in increased tissue ATP levels [18]. Additional benefit may be expected from albumin, since this component also reduces the permeability of myocardial capillaries to hydrophilic solutes of varying molecular sizes [9, 23,311.…”