ATP-loaded immunoliposomes specific for cardiac myosin provide improved protection of the mechanical functions of myocardium from global ischemia in an isolated rat heart model.
Earlier demonstrated cardio-protection by ATP-loaded liposomes (ATP-L) was further improved by attachment of cardiac myosin-specific monoclonal 2G4 antibody onto the surface of ATP-L. ATP-IL were infused for 1 min duration before starting the global ischemia for 25 min followed by reperfusion for 30 min in an isolated rat heart. The left ventricular developed pressure at the end of reperfusion in ATP-IL group significantly recovered to above 80% of the baseline compared to ca 25% in the Kreb's-Henseleit (KH) buffer, ca 60% in the IL, and ca 70% in the ATP-L treated groups. At the end of the reperfusion, left ventricular end diastolic pressure significantly reduced to 15 +/- 2 mmHg in ATP-IL group compared to 59 +/- 6 mmHg in the KH buffer, 31 +/- 4 mmHg in the IL and 23 +/- 3 mmHg in the ATP-L controls. The extent of preservation depended on the amount of the antibody present on the surface of the ATP-IL.
Verma
Daya D
DD
Department of Pharmaceutical Sciences, Bouve College of Health Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA.
Levchenko
Tatyana S
TS
Bernstein
Eugene A
EA
Mongayt
Dmitriy
D
Torchilin
Vladimir P
VP
D000255:Adenosine Triphosphate / Q000008:administration & dosage*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D024722:Cardiac Myosins / Q000276:immunology* / Q000378:metabolism; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D066298:In Vitro Techniques; D008081:Liposomes / Q000008:administration & dosage* / Q000276:immunology; D017202:Myocardial Ischemia / Q000188:drug therapy*; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism; D010316:Particle Size; D051381:Rats; D016277:Ventricular Function, Left / Q000187:drug effects
D000911:Antibodies, Monoclonal; D002316:Cardiotonic Agents; D008081:Liposomes; D000255:Adenosine Triphosphate; D024722:Cardiac Myosins