Rapid Lipid Modification of Endothelial Cell Membranes in Cardiac Ischemia/Reperfusion Injury: a Novel Therapeutic Strategy to Reduce Infarct Size.

PURPOSE: Plasma membranes constitute a gathering point for lipids and signaling proteins. Lipids are known to regulate the location and activity of signaling proteins under physiological and pathophysiological conditions. Membrane lipid therapies (MLTs) that gradually modify lipid content of plasma membranes have been developed to treat chronic disease; however, no MLTs have been developed to treat acute conditions such as reperfusion injury following myocardial infarction (MI) and percutaneous coronary intervention (PCI). A fusogenic nanoliposome (FNL) that rapidly incorporates exogenous unsaturated lipids into endothelial cell (EC) membranes was developed to attenuate reperfusion-induced protein signaling. We hypothesized that administration of intracoronary (IC) FNL-MLT interferes with EC membrane protein signaling, leading to reduced microvascular dysfunction and infarct size (IS). METHODS: Using a myocardial ischemia/reperfusion swine model, the efficacy of FNL-MLT in reducing IS following a 60-min coronary artery occlusion was tested. Animals were randomized to receive IC Ringer's lactate solution with or without 10 mg/mL/min of FNLs for 10 min prior to reperfusion (n = 6 per group). RESULTS: The IC FNL-MLT reduced IS (25.45 ± 16.4% vs. 49.7 ± 14.1%, P < 0.02) and enhanced regional myocardial blood flow (RMBF) in the ischemic zone at 15 min of reperfusion (2.13 ± 1.48 mL/min/g vs. 0.70 ± 0.43 mL/min/g, P < 0.001). The total cumulative plasma levels of the cardiac injury biomarker cardiac troponin I (cTnI) were trending downward but were not significant (999.3 ± 38.7 ng/mL vs. 1456.5 ± 64.8 ng/mL, P = 0.1867). However, plasma levels of heart-specific fatty acid binding protein (hFABP), another injury biomarker, were reduced at 2 h of reperfusion (70.3 ± 38.0 ng/mL vs. 137.3 ± 58.2 ng/mL, P = 0.0115).  CONCLUSION: The IC FNL-MLT reduced IS compared to vehicle in this swine model. The FNL-MLT maybe a promising adjuvant to PCI in the treatment of acute MI.

[Experimental study of laparoscopical lumbar interbody fusion with polyporus composite phosphate calcium and rhBMP-2 compounds in sheep].

OBJECTIVE: To study the efficacy of polyporus composite phosphate calcium and rhBMP-2 compounds with laparoscopical lumbar interbody fusion in sheep. METHODS: Fourteen uniform-weight adult sheep were randomly divided into three groups for LA-5 interbody fusion with titanium mesh. Autogenous bone and titanium mesh was applied with open anterior technique in group 1 (n=4). In group 2, 4 sheep were operated with laparoscope technique for LA-5 interbody fusion with composite phosphate calcium (CPC) and titanium mesh. In group 3, 6 sheep underwent laparoscopical L4-5 interbody fusion with titanium mesh as well as polyporus composite phosphate calcium and rhBMP-2 compounds. At Weeks 6 and 12 post-operation, the sheep were sacrificed for imaging, biomechanic and morphological examinations. RESULTS: Although there was no statistical difference between open and laparoscopical interbody fusion group when comparing the remaining disc and endplate decorticated, bone fusion occurred in 3 groups after 3 months. A much larger amount of bony callus was observed earlier in laparoscopical L4-5 interbody fusion group with titanium mesh as well as polyporus composite phosphate calcium and rhBMP-2 compounds than two other groups. CONCLUSION: Polyporus composite phosphate calcium and rhBMP-2 compounds are suitable prosthetic materials for clinical trials. When these materials are utilized with a laparoscopical technique, satisfactory interbody fusion may be achieved.