PLUG AND SEAL - PREVENTION OF HYPOXIC CARDIOCYTE DEATH BY SEALING MEMBRANE LESIONS WITH ANTIMYOSIN-LIPOSOMES

The hallmark of cell death is the development of cell membrane lesions . Such lesions in the myocardium are usually associated with acute myo cardial infarction. Minimizing myocardial necrosis by thrombolytic rep erfusion therapy constitutes the only major treatment to date. We envi sioned a method to seal these membrane lesions using immunoliposomes a s a novel adjunctive approach. An antigen to intracellular cytoskeleta l myosin in hypoxic embryonic cardiocytes is used as an anchoring site , and a specific antibody on immunoliposomes as the anchor to plug and to seal the membrane lesions. H9C2 cells were used because they are c ardiocytes and are propagated in tissue culture and their viability ma y be assessed by various methods. Viability assessed by [H-3]thymidine uptake in hypoxic cardiocyte cultures (n = 6 each) treated with antim yosin-immunoliposomes (3.26 +/- 0.483 x 10(6) c.p.m.) was similar to t hat of normoxic cells (3.68 +/- 0.328 x 10(6) c.p.m.), but was greater than those of untreated hypoxic cells (0.115 +/- 0.155 x 10(6) c.p.m. ) or hypoxic cells treated with plain liposomes (1.140 +/- 0.577 x 10( 6) c.p.m.). These results were reconfirmed by trypan blue exclusion an d by fluorescent, confocal and transmission electron microscopy. They indicated that cell death in hypoxic cardiocytes can be prevented by t argeted cell membrane sealing. This concept of cell salvage should be applicable in the prevention of cell death in different biological sys tems.