Attenuated purine production during subsequent ischemia in preconditioned rabbit myocardium is unrelated to the mechanism of protection

Preconditioned hearts release less purines during ischemia than virgin hearts. This study tested whether this reduced purine production is related to the mechanism of protection by ischemic preconditioning. Coronary effluent from isolated rabbit hearts was collected and purine (adenosine + inosine + hypoxanthine) levels were measured. All hearts underwent two cycles of 5 min global ischemia, each followed by 10 in reperfusion. In the first minute of renew after the first ischemic period untreated hearts released 155 +/- 14 nmol purines per g wet weight, but only 104 +/- 16 nmol/g following the second bout of ischemia (P<0.05). Thus, preconditioned hearts released less purines during ischemia. When 8-(p-sulfophenyl)theophylline (100 mu M), which prevents the infarct size-limiting effect of ischemic preconditioning by blocking adenosine receptors, was present in the perfusate, the pattern of purine release was not altered (151 +/- 13 nmol/g during the first minute after the first 5-min ischemic episode dropping to 117 +/- 6 nmol/g after the second ischemic period, P<0.05). Furthermore, pharmacological preconditioning with 5 min exposure of the heart to either adenosine (10 mu M) or phenylephrine (0.1 mu M) 15 min prior to the first ischemia did not affect purine release during early reperfusion after either the first (144 +/- 16 nmol/g and 153 +/- 12 nmol/g. respectively) or second (84 +/- 12 nmol/g and 111 +/- 9 nmol/g, respectively) bout of ischemia, Since the attenuated purine release was apparently unaffected by the presence or absence of a protected state, we conclude that this pattern is unrelated to the mechanism by which preconditioning protects the heart. (C) 1996 Academic Press Limited