Preservation of ischemic myocardial function and integrity with targeted cytoskeleton-specific immunoliposomes.
OBJECTIVE
We sought to demonstrate preservation of myocardial function and integrity after targeted cytoskeleton-specific immunoliposome (CSIL) treatment of globally ischemic Langendorff instrumented hearts and a time response to treatment.


BACKGROUND
Cell membrane lesion sealing of hypoxic cardiocytes in culture with CSIL has been reported.


METHODS
Langendorff-perfused isolated rat hearts were subjected to global ischemia (25 min). Either CSIL or placebo administration (1-min ischemia) was followed by 30 min of reperfusion. Immunoglobulin G liposomes (IgG-L) or CSIL was also infused at 5, 10, and 20 min of ischemia, reperfused, and then prepared for histochemical staining and electron microscopy.


RESULTS
Recovery of left ventricular developed pressure (LVDP) of ischemic hearts treated with CSIL at 1 min of ischemia, assessed at 5 min of reperfusion (98 +/- 14%), was similar to that of sham-operated hearts (100%) but was significantly greater than that of placebo-treated hearts (12 +/- 7%, p = 0.01). The LVDP of hearts treated with CSIL at 5, 10, and 20 min was significantly greater than that with IgG-L at corresponding times (p < 0.03). Histochemical integrity and ultra-structural myocardial integrity were consistent with the functional data.


CONCLUSIONS
Preservation of myocardial viability ex vivo was achieved with CSIL therapy. The extent of preservation is proportional to the time of initiation of therapy. Beneficial effects were observed even when CSIL therapy was initiated at 20 min of global ischemia. Therefore, delayed CSIL intervention after the onset of ischemia may augment preservation of myocardial viability during reperfusion therapy.
Khudairi
Tala
T
Center for Cardiovascular Targeting, Department of Pharmaceutical Sciences, Bouvé College of Health Sciences, Boston, Massachusetts 02115, USA.
Khaw
Ban-An
BA
D000818:Animals; D000918:Antibody Specificity; D003599:Cytoskeleton / Q000187:drug effects*; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000276:immunology; D008081:Liposomes / Q000008:administration & dosage* / Q000276:immunology; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000473:pathology; D008955:Models, Cardiovascular; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D010919:Placebos; D051381:Rats; D020127:Recovery of Function / Q000187:drug effects; D016037:Single-Blind Method; D013997:Time Factors; D017725:Ventricular Pressure / Q000187:drug effects
D007074:Immunoglobulin G; D008081:Liposomes; D010919:Placebos