We conclude that adenosine released during the preconditioning occlusion stimulates cardiac A1 receptors, which leaves the heart protected against infarction even after the adenosine has been withdrawn.
BACKGROUND
Recent data from this laboratory indicate that pretreatment with adenosine can protect the heart against infarction via A1-receptors, but because of systemic hypotension, adenosine had to be given into the coronary circulation.
METHODS AND RESULTS
In this study, we tested whether the protection could be achieved by intravenous administration of the A1-selective adenosine agonists N6-(phenyl-2R-isopropyl)-adenosine (PIA) and 2-chloro-N6-cyclopentyladenosine (CCPA). Nine groups of open-chest anesthetized rabbits were subjected to 30 minutes of regional coronary ischemia and 3 hours of reperfusion. Infarct size was determined by tetrazolium staining. Control hearts receiving no treatment had 38 +/- 4% of the risk zone infarcted. Preconditioning with 5 minutes of ischemia and 10 minutes of reperfusion before ischemia limited the infarct to 8 +/- 4%. Intravenous PIA 15 minutes before 30-minute ischemia also limited infarct size to 6 +/- 2% at the highest dose. CCPA offered similar protection. When the PIA was given at reperfusion, infarct size was 46 +/- 6%, indicating that receptor activation must precede ischemia to protect. Pretreatment with CGS 21680, a selective A2-receptor agonist, caused identical hypotension but failed to limit infarct size (43 +/- 3%), indicating again that the A1-receptor is involved. When rabbits pretreated with PIA were paced at 220 beats per minutes, PIA still limited infarct size (16 +/- 4%), indicating that protection was not the result of bradycardia.
CONCLUSIONS
These results indicate that stimulation of adenosine A1-receptors causes the heart to become resistant to ischemia and that this protection can be achieved with intravenous administration of A1-selective agents.
BACKGROUND
The vulnerability of the myocardium of a diabetic animal to an ischemic insult is controversial. To address this issue, streptozotocin-induced non-insulin-dependent diabetes (NIDD) was induced in rats, and the effects of regional myocardial ischemia were assessed by measuring infarct size.
METHODS AND RESULTS
Open-chest rats with NIDD and age-matched control rats underwent 30 or 45 minutes of regional ischemia and 2-hour reperfusion. Infarct size was measured by tetrazolium. Control rats had 32.0 +/- 3.3% infarction of the risk zone after a 30-minute coronary occlusion, whereas NIDD rats had significantly smaller infarcts (11.5 +/- 3.1% of the risk area, P < .005). When ischemic time was extended to 45 minutes, infarct size in control animals averaged 57.9 +/- 6.2%, whereas only 37.3 +/- 5.6% of ischemic myocardium was infarcted in NIDD rats (P < .05). In a subset NIDD group, rats experienced a period of ischemic preconditioning (three cycles of 5-minute ischemia/5-minute reperfusion) before 45-minute ischemia. Infarct size in these rats averaged only 6.9 +/- 3.0% (P < .01 vs nonpreconditioned NIDD rats with 45-minute coronary occlusions). Collateral flow was measured in NIDD rat hearts with radioactive microspheres. Collateral flow was < 1% of normal myocardial blood flow.
CONCLUSIONS
We conclude that NIDD protects the heart from infarction and that this protection is not related to the development of coronary collaterals. Furthermore, preconditioning can further protect the NIDD heart.
We conclude that hyperbaric oxygen limits infarct size in the reperfused rabbit heart and that the effect can be achieved when hyperbaric oxygen is begun at reperfusion.
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