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Published on: June 14, 2015
Preservation of ischemic myocardial function and integrity with targeted cytoskeleton-specific immunoliposomes
1Center for Cardiovascular Targeting, Department of Pharmaceutical Sciences, Bouvé College of Health Sciences, Boston, Massachusetts 02115, USA.
Insights
Targeted cytoskeleton-specific immunoliposome (CSIL) treatment preserved heart function after ischemia. Beneficial effects were seen even with delayed CSIL therapy, showing its potential in reperfusion injury treatment.
Area of Science:
- Cardiovascular Research
- Ischemia-Reperfusion Injury
- Nanomedicine
Background:
- Cytoskeleton-specific immunoliposomes (CSIL) have shown potential in sealing cell membrane lesions in hypoxic cardiocytes.
- Previous studies reported CSIL's ability to protect cardiac cells in vitro.
Purpose of the Study:
- To demonstrate the preservation of myocardial function and integrity using CSIL in globally ischemic hearts.
- To investigate the time-response relationship of CSIL treatment efficacy.
Main Methods:
- Isolated rat hearts underwent global ischemia followed by reperfusion.
- CSIL or placebo was administered at different time points during ischemia (1, 5, 10, 20 min).
- Functional recovery (LVDP), histochemical staining, and electron microscopy were used for assessment.
Main Results:
- CSIL treatment at 1 min of ischemia resulted in near-complete recovery of left ventricular developed pressure (LVDP), similar to sham-operated hearts.
- CSIL treatment at later time points (5, 10, 20 min) showed significantly better functional recovery compared to control liposomes (IgG-L).
- Histological and ultrastructural analyses supported the functional findings, indicating preserved myocardial integrity.
Conclusions:
- CSIL therapy effectively preserves myocardial viability ex vivo following global ischemia.
- The therapeutic benefit of CSIL is time-dependent, with significant preservation observed even when initiated 20 minutes after ischemia onset.
- Delayed CSIL intervention may be a viable strategy to mitigate myocardial damage during reperfusion therapy.
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.
