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Preservation of ischemic myocardial function and integrity with targeted cytoskeleton-specific immunoliposomes

Tala Khudairi, PhD^* and Ban-An Khaw, PhD^*,*

^* Center for Cardiovascular Targeting, Department of Pharmaceutical Sciences, Bouvé College of Health Sciences, Boston, Massachusetts, USA
Department of Biology, Northeastern University, Boston, Massachusetts, USA

Manuscript received May 22, 2003; revised manuscript received October 24, 2003, accepted November 2, 2003.

^* Reprint requests and correspondence: Dr. Ban-An Khaw, Center for Cardiovascular Targeting, Department of Pharmaceutical Sciences, Bouvé College of Health Sciences, Northeastern University, 360 Huntington Avenue, Mugar Building Room 205, Boston, Massachusetts 02115, USA.
b.khaw{at}nunet.neu.edu

OBJECTIVES: 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.

Abbreviations and Acronyms   AMI = acute myocardial infarction   CPP = coronary perfusion pressure   CSIL = cytoskeletal-specific immunoliposomes   IgG-L = immunoglobulin G liposomes   LV = left ventricle/ventricular   LVDP = left ventricular developed pressure   NBT = nitro blue tetrazolium   NGPE = N-glutaryl phosphatidyl ethanolamine   PBS = phosphate-buffered saline