BACKGROUND
Although early reperfusion is the most desirable intervention after ischemic myocardial insult, it may add to damage through oxidative stress.
OBJECTIVES
We investigated the cardioprotective effects of a single intravenous dose of heat shock protein (HSP72) coupled to a single-chain variable fragment (Fv) of monoclonal antibody 3E10 (3E10Fv) in a rabbit ischemia-reperfusion model. The Fv facilitates rapid transport of HSP72 into cells, even with intact membranes.
METHODS
A left coronary artery occlusion (40 min), reperfusion (3 h) model was employed in 31 rabbits. Of these, 12 rabbits received the fusion protein (Fv-HSP72) intravenously. The remaining 19 control rabbits received a molar equivalent of 3E10Fv alone (n = 6), HSP72 alone (n = 6), or phosphate buffered saline (n = 7). Serial echocardiographic examinations were performed to assess left ventricular (LV) function before and after reperfusion. Micro-single photon emission computed tomography imaging of 99mTc-labeled annexin-V was performed with micro-computed tomography to characterize apoptotic damage in vivo, followed by gamma counting of the excised myocardial specimens to quantify cell death. Histopathological characterization of the myocardial tissue, and sequential cardiac troponin I measurements were also undertaken.
RESULTS
Myocardial annexin-V uptake was 43% lower in the area at risk (p = 0.0003) in Fv-HSP72-treated rabbits compared to controls receiving HSP72 or 3E10Fv alone. During reperfusion, troponin I release was 42% lower and the echocardiographic LV ejection fraction 27% higher in the Fv-HSP72-treated group compared to controls. Histopathological analyses confirmed penetration of 3E10Fv-containing molecules into cardiomyocytes in vivo, and treatment with Fv-HSP72 showed fewer apoptotic nuclei compared to control rabbits.
CONCLUSIONS
A single-dose administration of Fv-HSP72 fusion protein at the time of reperfusion reduced myocardial apoptosis almost by half, and improved LV functional recovery following myocardial ischemia-reperfusion injury in rabbits. It might have a potential to serve as an adjunct to early reperfusion in the management of myocardial infarction.
Purpose: Aneurysms develop only rarely in aortocoronary saphenous vein grafts (SVGs), and the usual treatment is surgical replacement of the diseased segment. However, in patients at appreciable risk for redo surgery, alternative therapies are desirable. We report the first compassionate use of a percutaneously delivered endoluminal graft (ELG) for internal exclusion of an SVG aneurysm. Methods: A 47-year-old male with two coronary bypass procedures and SVG angioplasty presented with an 8-mm diameter aneurysm lying between 80% and 70% stenotic lesions in an SVG to the obtuse marginal branch. The risks of a third bypass operation were considerable, so the decision was made to attempt internal exclusion of the SVG aneurysm. Results: An ELG composed of 2.0-mm diameter unexpanded PTFE graft material with Palmaz stents for fixation was delivered with a low-profile system, but a second ELG was necessary for complete exclusion of the aneurysmal sac. Both ELGs were dilated after initial deployment. The patient was discharged after 9 days without sequelae, and he remains asymptomatic with arteriographically documented ELG patency 5 months after treatment. Conclusions: In this patient with limited therapeutic options, percutaneous aneurysm exclusion in an SVG was effective in restoring a viable blood conduit. It remains to be seen if ELGs have a potential in aortocoronary SVGs.
In this patient with limited therapeutic options, percutaneous aneurysm exclusion in an SVG was effective in restoring a viable blood conduit. It remains to be seen if ELGs have a potential in aortocoronary SVGs.
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