Journal
PHARMACEUTICAL RESEARCH
Volume 22, Issue 12, Pages 2115-2120Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-005-8354-x
Keywords
ATP; experimental myocardial infarction; heart muscle; ischemia; liposomes; mechanical functions; rabbits; reperfusion
Funding
- NHLBI NIH HHS [R01 HL55519] Funding Source: Medline
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Purpose. We assessed whether the infusion of ATP-loaded liposomes (ATP-L) can limit the fraction of the irreversibly damaged myocardium in rabbits with an experimental myocardial infarction. Methods. ATP-L, empty liposomes (EL), or Krebs-Henseleit (KH) buffer were administered by intracoronary infusion, followed by 30 min of occlusion and 3 h of reperfusion. Unisperse Blue dye was used to demarcate the net size of the occlusion-induced ischemic zone (area at risk) and nitroblue tetrazolium staining was used to detect the final fraction of the irreversibly damaged myocardium within the total area at risk. Results. The total size of the area at risk in all experimental animals was approx. 20% wt. of the left ventricle. The final irreversible damage in ATP-L-treated animals was only ca. 30% of the total area at risk as compared with ca. 60% in the group treated with EL (p < 0.009) and ca. 70% in the KH buffer-treated group (p < 0.003). Conclusions. ATP-L effectively protected the ischemic heart muscle in rabbits with an experimental myocardial infarction as evidenced by a significantly decreased fraction of the irreversibly damaged heart within the total area at risk. ATP-L may provide an effective exogenous source of the ATP in vivo to protect ischemically damaged cells.
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