Acadesine extends the window of protection afforded by ischaemic preconditioning.

OBJECTIVE: The aim was to test whether acadesine (5-amino-4-imidazolecarboxamide riboside, AICAR), an adenosine regulating agent which increases tissue adenosine during ischaemia, could prolong the window of protection from ischaemic preconditioning. METHODS: A branch of the left coronary artery of a rabbit heart was occluded for 30 min and reperfused for 180 min to induce infarction. Infarct size was determined with triphenyl tetrazolium staining. Prior to the 30 min ischaemia, rabbits were subjected to one of the following seven protocols: (1) No treatment (controls). (2) Preconditioning with 5 min of regional ischaemia followed by 2 h of reperfusion. (3) Treatment with acadesine (2.5 mg.kg-1.min-1 intravenously for 5 min starting 155 min prior to 30 min ischaemia followed by 210 min infusion of 0.5 mg.kg-1.min-1. (4) Treatment with acadesine (same schedule as in group 3) plus preconditioning as in group 2. (5) Treatment with acadesine for a shorter period (acadesine 2.5 mg.kg-1.min-1 for 5 min starting 30 min prior to preconditioning followed by 0.5 mg.kg-1.min-1 for only 60 min) plus preconditioning as in group 2. (6) Treatment with preconditioning followed by adenosine receptor blockade with 8-(p-sulphophenyl)theophylline (SPT) 10 mg.kg-1 intravenously immediately after and again 15 min after preconditioning. (7) Treatment with short infusion of acadesine plus preconditioning plus SPT. RESULTS: Preconditioning followed by 2 h of reperfusion offered little protection against infarction [28.6(SEM 2.7)% of the ischaemic zone infarcted] as compared to control [38.7(3.1)% infarction]. Treatment with acadesine alone did not modify the infarct size [37.8(3.5)%], but both of the acadesine plus preconditioning groups showed a significant limitation of infarct size with 13.9(3.1)% infarction in group 4 and 12.7(2.2)% infarction in group 5 (both p < 0.01 v control). Although SPT alone did not modify the infarct size [26.8(3.3)%], SPT blocked the protective effect of acadesine [25.3(2.9)%, p < 0.05 v group 5]. CONCLUSION: Acadesine can delay the natural decay of preconditioning. This delay appeared to be mediated by adenosine and may have therapeutic potential.

Acadesine extends the window of protection afforded by ischaemic preconditioning in conscious rabbits.

OBJECTIVE: Ischaemic preconditioning protects myocardium from infarction if the reperfusion interval between the brief and prolonged ischaemic intervals is less than 1 h. In anaesthetised rabbits acadesine (5-amino-4-imidazolecarboxamide riboside, AICAR), an adenosine enhancer which increases tissue adenosine during ischaemia, prolongs the window of protection to 2 h. The aim of this study was to try to determine the maximum extension of this window of protection, using chronically instrumented, unsedated rabbits. METHODS: Rabbits were instrumented with a balloon occluder around a major branch of the left coronary artery for reversible coronary occlusion. Five to seven days after surgery all animals underwent a 30 min coronary occlusion. Animals were randomised to one of seven groups: (1) No additional treatment (control); (2) Ischaemic preconditioning with 5 min regional ischaemia followed by 10 min reperfusion before the 30 min coronary occlusion; (3) and (4) Ischaemic preconditioning followed by 2 or 4 h of reperfusion before the 30 min occlusion, respectively; (5) Treatment with acadesine (2.5 mg.kg-1.min-1 intravenously for 5 min and then 0.5 mg.kg-1.min-1 beginning 45 min before and continuing until 30 min after release of the 30 min occlusion) without ischaemic preconditioning; (6) and (7) Treatment with the higher dose of acadesine for 5 min beginning 35 min before the 5 min ischaemic period, and then the lower dose continuing until 30 min after release of the 30 min coronary occlusion in rabbits with 4 or 6 h reperfusion intervals, respectively. RESULTS: Rabbits with ischaemic preconditioning with 10 min reperfusion preceding the 30 min coronary occlusion (group 2) had only 5.6(SEM 1.1)% infarction of the ischaemic zone. Ischaemic preconditioning followed by 2 h reperfusion (group 3) offered continued protection [18.2(2.2)% infarction] as compared to control animals [37.7(2.6)% infarction]. However, protection waned if ischaemic preconditioning was followed by 4 h reperfusion (group 4) [36.7(3.0)% infarction]. Additionally, treatment with acadesine alone did not modify infarct size (group 7) [39.5(4.0)%], but acadesine largely restored the protection of ischaemic preconditioning despite a 4 h reperfusion interval (group 5) [20.4(3.0)% infarction, P < 0.01 v control]. However, when reperfusion was extended to 6 h (group 6) acadesine could no longer restore protection [36.2(0.9)% infarction]. CONCLUSIONS: The protection afforded by a 5 min ischaemic preconditioning period lasts from 2 to 4 h in the awake, unsedated rabbit, and acadesine can extend the duration of this window of protection to at least 4 h but not to 6 h.

Coronary artery slow flow associated with angina pectoris and hypotension--a case report.

A 56-year-old woman with a history of angina pectoris developed substernal chest pressure and hypotension during coronary angiography. Her baseline coronary angiogram appeared normal. During this episode, injection of contrast medium into the left coronary artery demonstrated coronary artery slow flow in the left anterior descending artery and branches of the circumflex coronary artery, which normalized following the sublingual administration of nitroglycerin. There were no focal areas of coronary artery spasm. This phenomenon may represent a heretofore undescribed mechanism for myocardial ischemia and its sequelae.