TY - JOUR
T1 - Intramyocardial injections and protection against myocardial ischemia
T2 - An attempt to examine the cardioprotective actions of adenosine
AU - Whittaker, Peter
AU - Kloner, Robert A.
AU - Przyklenk, Karin
PY - 1996/6/1
Y1 - 1996/6/1
N2 - Background: Although adenosine has ben 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. Methods and 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 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 carioprotection, we found evidence for myocyte protection via a stretch-activated mechanism.
AB - Background: Although adenosine has ben 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. Methods and 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 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 carioprotection, we found evidence for myocyte protection via a stretch-activated mechanism.
KW - Adenosine
KW - arrhythmia
KW - gadolinium
KW - myocardial infarction
KW - signal transduction
UR - http://www.scopus.com/inward/record.url?scp=0029882774&partnerID=8YFLogxK
U2 - 10.1161/01.CIR.93.11.2043
DO - 10.1161/01.CIR.93.11.2043
M3 - Article
C2 - 8640981
AN - SCOPUS:0029882774
VL - 93
SP - 2043
EP - 2051
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 11
ER -