Intramyocardial injections and protection against myocardial ischemia. An attempt to examine the cardioprotective actions of adenosine.
BACKGROUND
Although adenosine has been proposed to be a cardioprotective agent, direct examination of such protection is confounded by its short half-life and hemodynamic effects. We attempted to avoid these problems by injecting adenosine directly into cardiac muscle.


RESULTS
We gave four adenosine injections (each 0.15 mL, 5 mg.mL-1 saline) into the left ventricular wall of rat hearts before a 60-minute occlusion. Although infarcts were smaller in adenosine-treated hearts (29 +/- 6%) than in controls (52 +/- 5%; P < .05), injection of saline also reduced infarct size (29 +/- 7%). Infarcts in hearts subjected to needle insertion but no fluid injection differed neither from control nor from fluid-treated hearts (38 +/- 4%). Adenosine reduced ectopic beats and the incidence of ventricular tachycardia during occlusion. In contrast, saline injection prolonged the duration of arrhythmias. To examine the spatial relationship between protection and the injection site, we gave 18 saline injections (each 0.15 mL) into canine myocardium before a 60-minute occlusion. Infarcts were smaller in saline-treated hearts than in controls (P < .01). Because infarcts in four hearts occupied < 3% of the risk region, we concluded that fluid injection did not itself cause appreciable necrosis and speculated that muscle was protected in the vicinity of the injection site. Previous work indicated that muscle can be protected by stretch. We examined this hypothesis by adding gadolinium chloride (a stretch-activated channel blocker) to the saline (0.008 g.mL-1) injection in rat hearts. We again found small infarcts after saline injection (26 +/- 5%); however, gadolinium blocked protection (50 +/- 7%; P < .03).


CONCLUSIONS
Although we were only partially successful in documenting adenosine-mediated cardioprotection, we found evidence for myocyte protection via a stretch-activated mechanism.
Whittaker
P
P
Heart Institute, Good Samaritan Hospital, Department of Medicine, Los Angeles, CA 90017, USA.
Kloner
R A
RA
Przyklenk
K
K
D000241:Adenosine / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005260:Female; D005682:Gadolinium / Q000008:administration & dosage / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D007267:Injections; D009203:Myocardial Infarction / Q000473:pathology; D017202:Myocardial Ischemia / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000633:toxicity; D017180:Tachycardia, Ventricular / Q000517:prevention & control
D012965:Sodium Chloride; D005682:Gadolinium; D000241:Adenosine; C038958:gadolinium chloride