Evaluation of spinal cord protective threshold of serum memantine, an NMDA receptor antagonist, in a rabbit model of paraplegia.

PURPOSE: To evaluate the threshold of serum memantine for prevention of spinal cord injury (SCI) in a rabbit paraplegic model. METHODS: Forty-two New Zealand white rabbits were divided into 7 groups. Preoperatively, oral memantine was given starting from 60 mg OD for 7 days in the initial group, then reducing the dose and/or duration to 60 mg OD for 5 days, 30 mg OD for 5 days, 30 mg OD for 3 days, 15 mg OD for 3 days, 30 mg single dose, and 60 mg single dose, in subsequent 6 groups. A paraplegic model was created by clamping both infrarenal aorta and inferior vena cava (IVC) for 45 min. Motor evoked potentials (MEPs), modified Tarlov score (0-5), serum memantine concentration, and histopathology of the spinal cord were evaluated. RESULTS: Half of all rabbits (21/42) showed spinal protection. Receiver operating characteristic (ROC) curve analysis showed serum level of 4.5 ng/ml as a cutoff value for spinal protection (sensitivity 86%, specificity 62%, area under the curve (AUC) 0.785, P = .002). Sixteen rabbits had serum level ≥ 4.5 ng/ml (group A), with 26 rabbits having < 4.5 ng/ml (group B). Further comparison was done between groups A and B. The mean modified Tarlov score at 6, 24, 48, and 72 h was 4.5 ± 0.9 and 2.4 ± 1.6, in groups A and B, respectively (P < .001). The modified Tarlov score showed positive correlation with serum memantine level (Spearman's rho = 0.618, P = .01). Results of MEP and histopathology were significantly better for group A. CONCLUSIONS: We showed that memantine is protective against SCI at serum levels ≥ 4.5 ng/ml in a rabbit model; thus, it can be a potential adjunct for spinal protection during thoracic/thoracoabdominal aortic surgeries.

Negative pressure wound therapy induces early wound healing by increased and accelerated expression of vascular endothelial growth factor receptors.

BACKGROUND: Negative pressure wound therapy (NPWT) is commonly used to accelerate wound healing, especially following thoracic surgery; however, the mechanism remains elusive. Given the important role of vasculogenesis in wound healing, we evaluated whether NPWT might accelerate vasculogenesis in the wound area. Toward this end, we investigated the temporal expression of vascular endothelial growth factor receptors (VEGFRs) in an NPWT-wound healing rabbit model. METHODS: Rabbits were divided into an NPWT group and a non-NPWT control group, and tissue samples were collected around wounds made in the skin of each rabbit at five time points: 0, 7, 14, 21, and 28 days after wound creation. Cryopreserved samples were then immunostained and subject to image analysis to evaluate the temporal changes in VEGFR1, VEGFR2, and VEGFR3 expression in the wound-healing process. RESULTS: Results of histological analysis of the temporal changes in VEGFR expression throughout the healing process showed that compared to the control group, VEGFR2 and VEGFR3 were abundantly and rapidly expressed in the NPWT group, and were expressed earlier than VEGFR1. CONCLUSIONS: NPWT promotes the expression of VEGFR2 and VEGFR3, which provides insight into the mechanism by which NPWT accelerates wound healing. Level of Evidence: Not ratable.

Novel Anastomotic Device for Distal Coronary Anastomosis: Preclinical Results From Swine Off-Pump Coronary Artery Bypass Model.

PURPOSE: We evaluated the safety and feasibility of a new anastomotic device that simplifies coronary distal anastomosis during minimally invasive and robotically assisted coronary artery bypass graft surgery (CABG). DESCRIPTION: Fourteen miniature pigs underwent off-pump CABG using bilateral internal thoracic arteries (ITA), namely, left ITA to left anterior descending artery and right ITA to right coronary artery. The device was used for distal anastomosis in a device group (n = 11), and conventional 7-0 polypropylene suture in a control group (n = 3). Graft flow was measured intraoperatively. One-month, 3-month, and 6-month postoperative angiography evaluations were done. Histopathologic examination of the anastomosis was also done. EVALUATION: Baseline and intraoperative characteristics were similar in the two groups. There was no difference of anastomotic time between groups (p = 0.59). Graft flows were also similar (p = 0.55), with good diastolic pattern in both groups. Angiography demonstrated FitzGibbon A patency in all anastomoses of both groups at each evaluation period. Histopathologic examination showed nonspecific inflammatory changes in the device group. CONCLUSIONS: The safety and feasibility of this anastomotic device for distal coronary anastomosis were shown in the swine model.

Paraplegia prevention by oral pretreatment with memantine in a rabbit model.

OBJECTIVE: To evaluate the role of memantine (N-methyl-d-aspartate receptor antagonist) pretreatment for the prevention of spinal cord ischemia after infrarenal aortic clamping in a rabbit model. METHODS: Thirty New Zealand White rabbits were divided into 5 different groups of 6 rabbits. Groups 60-7 and 60-5 received oral memantine 60 mg once a day for 7 and 5 days, respectively, and groups 30-5 and 30-3 received oral memantine 30 mg once a day for 5 and 3 days, respectively, all before surgery. Group C (control) received normal feeds without memantine. A paraplegic model was created by clamping both the aorta and the inferior vena cava infrarenally and just proximal to their bifurcations for 45 minutes. The modified Tarlov score, motor evoked potential (MEP), serum memantine concentration, and histopathology of the spinal cord were evaluated. RESULTS: The mean modified Tarlov scores were 4.2±1.3, 4.3±1.0, 4.2±1.3, 4.3±1.2, and 0.8±1.6 in groups 60-7, 60-5, 30-5, 30-3, and C, respectively at 6, 24, 48, and 72 hours (P<.009 for individual groups vs control). Percentage amplitude loss of MEP by the end of surgery was 29.5%±46.3%, 11.9%±28.0%, 30.0%±46.8%, 16.7%±40.8%, and 81.8%±40.3% for the 5 groups, respectively (P=.049). After declamping, MEP reappeared in 83%, 100%, 83%, 83%, and 33% of cases in the 5 groups, respectively (P=.073). The serum memantine level was similar in the 4 memantine groups. Spinal cords were normal in most of the rabbits in groups 60-7, 60-5, 30-5, and 30-3, but severely ischemic in most of the rabbits in group C (P=.041). CONCLUSIONS: Oral memantine pretreatment is protective against spinal cord ischemia, and can be an additional strategy for the prevention of paraplegia during thoracoabdominal aortic surgeries.

Development of a suturing device for anastomosis for small caliber arteries.

The use of minimally invasive and robotic operations has been increasing for coronary artery bypass surgery; however, no suturing devices have been universally adopted for use in these procedures. We developed a new suturing device that enables omission of manual ligation after a running suture. Twenty-two rabbits were used in this study. In 22 rabbits, the right carotid artery was bypassed using an autologous jugular vein graft. Half of the animals were operated on using the new device and the other half using conventional suturing methods. Postoperative evaluations were performed at 1, 3, and 6 months. Suturing time was 15.6 ± 2.4 min in the device group and 16.6 ± 4.4 min in the control group (p = 0.34). Graft patency and blood flow measurements were not significantly different between the two groups. Histopathological examination of the anastomotic site showed common inflammatory responses in both groups. No particular histopathological change was seen related to the device. In conclusion, the safety of the new suturing device was confirmed, and its efficacy was equal to that of the conventional suturing technique.