| To demonstrate (1) preservation of myocardial function and integrity following targeted cytoskeleton-specific immunoliposome (CSIL) treatment of globally ischemic myocardium, (2) a dose response and (3) a time response to treatment. Cell membrane lesion sealing of hypoxic cardiocytes in culture with CSIL has been reported.; Langendorff perfused isolated rat hearts were subjected to global ischemia. CSIL or control treatments were administered at 1 min of a total of 25 min of ischemia, followed by 30 minutes of reperfusion. Various doses of CSIL were delivered also at 1 min of ischemia. For the time-response study, treatments were infused at 5, 10 and 20 min of ischemia. Hemodynamic, histochemical, biochemical, and ultrastructural assessments of myocardial preservation were undertaken.; Greater preservation of myocardial function and integrity was observed in hearts treated with CSIL relative to controls. From the initial study, the left ventricular developed pressure (LVDP) curve for hearts treated with CSIL (41.4 ± 11.2%) was greater than controls of PBS, IgG-L or PL (11.6 ± 2.7, 20.9 ± 8.3, and 7.0 ± 6.1%, respectively), p = 0.01. Histochemical mean infarct size of hearts treated with CSIL (7 ± 3%) was smaller than that of hearts treated with PBS, IgG-L or PL (38.5 ± 4.4, 28.6 ± 7.8, and 60.1 ± 9.3%, respectively), p = 0.01. The LVDP of hearts treated with CSIL with 1.0, 0.5, and 0.2 mg Ab/dose was 87.4 ± 6.9, 34.3 ± 8.7, and 25.7 ± 7.1%, respectively. A linear dose response to antibody concentration in CSILs was also observed. For the time response study, the LVDP of hearts treated with CSIL at 5, 10 and 20min of ischemia was greater than that with IgG-L at the corresponding time points (p < 0.03). Histochemical and ultrastructural myocardial integrity was consistent with the functional data.; Preservation of myocardial viability ex vivo was achieved with CSIL therapy. The extent of preservation is proportional to the dose and 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. |
