Behaviour of energy metabolites and effect of allopurinol in the "stunned" isovolumic rat heart

J Mol Cell Cardiol. 1990 Oct;22(10):1107-16. doi: 10.1016/0022-2828(90)90074-c.


The pathogenesis of post-ischaemic depression of contractility in myocardium was examined in isovolumic rat heart. 31P-NMR was used to monitor changes in ATP, creatine phosphate (CrP), inorganic phosphate (Pi), and [H+] during brief periods of ischaemia and reperfusion with and without allopurinol treatment. During 5, 10, or 15 min of total global ischaemia, the decline in function (rate-pressure product) correlated inversely with [Pi] (r = 0.92, P less than 0.01). Cardiac function exhibited a slow progressive recovery during 20 min of reperfusion, ultimately reaching only 85%, 78%, and 69% of its pre-ischaemic value following 5, 10, and 15 min of global ischaemia respectively. Following each ischaemic period [ATP], [CrP], [Pi], and [H+] all recovered to control levels within 5-10 min of initiating reperfusion. Allopurinol (2 mM) treatment of hearts made ischaemic for 15 min significantly improved contractile recovery to 89 +/- 7%. Allopurinol also exhibited significant anti-arrhythmic activity during the reperfusion period, decreasing the incidence of premature contractions and the duration of tachy-arrhythmias. Allopurinol had no effect on the final repletion of [ATP] and [CrP], or the recovery of [Pi] and [H+], although the rate of ATP repletion was elevated in the initial 5 min of reperfusion. These results show that neither depletion of the cytosolic high-energy phosphate pool, nor sustained elevations in [Pi] or [H+] are important in the production of post-ischaemic contractile impairment. The beneficial action of allopurinol suggests that xanthine oxidase derived oxygen free-radicals may be involved in the sustained contractile dysfunction following brief ischaemic episodes.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Allopurinol / pharmacology*
  • Animals
  • Arrhythmias, Cardiac / drug therapy
  • Arrhythmias, Cardiac / physiopathology
  • Coronary Disease / drug therapy
  • Coronary Disease / metabolism*
  • Coronary Disease / physiopathology
  • Energy Metabolism / drug effects
  • In Vitro Techniques
  • Male
  • Myocardial Contraction / drug effects
  • Myocardial Contraction / physiology
  • Myocardial Reperfusion Injury / drug therapy
  • Myocardial Reperfusion Injury / physiopathology
  • Myocardium / metabolism*
  • Phosphocreatine / metabolism
  • Rats
  • Rats, Inbred Strains


  • Phosphocreatine
  • Allopurinol
  • Adenosine Triphosphate