Leukocyte Adhesion to the Coronary Microvasculature During Ischemia and Reperfusion in an In Vivo Canine Model

Circulation ◽  
1996 ◽  
Vol 93 (10) ◽  
pp. 1784-1787 ◽  
Author(s):  
Frank M. Sheridan ◽  
Paul G. Cole ◽  
David Ramage
1997 ◽  
Vol 272 (2) ◽  
pp. H618-H624 ◽  
Author(s):  
L. D. Horwitz ◽  
D. Kaufman ◽  
Y. Kong

Ischemia and reperfusion cause coronary vascular and myocardial injury, which may be due to leukocyte-mediated processes. Antileukocyte measures have reduced injury after brief reperfusion periods of 1-3 h, but there has been little information on whether benefits are apparent after longer periods of reperfusion. We examined the effect of pretreatment with a monoclonal antibody (R15.7) to the CD18 family of leukocyte adhesion molecules (beta2-integrins) in dogs exposed to regional coronary ischemia for 1 h of left anterior descending coronary artery ligation and then reperfused for 48 h. Coronary microvascular permeability was assessed in vivo by measurement of protein leak index (PLI), using a double-isotope technique with autologous radiolabeled transferrin and erythrocytes. Vasorelaxation was measured in vitro with preconstricted epicardial coronary artery rings subjected to increasing concentrations of the endothelium-dependent vasodilators bradykinin (BK) and ADP and the endothelium-independent vasodilator nitroprusside. At 48 h of reperfusion in untreated dogs there were substantial increases in PLI in the previously ischemic regions, indicative of increased extravascular transferrin. These abnormalities were decreased, but not abolished, in the dogs treated with R15.7. Relaxation of rings from the ischemic/reperfused artery to BK and ADP were blunted in the untreated dogs. R15.7 resulted in improvement in some, but not all, indexes of relaxation in response to BK and ADP. Relaxation to nitroprusside was normal in ischemic/reperfused coronary rings from both treated and untreated dogs. Therefore, after 1 h of regional coronary ischemia and 48 h of reperfusion, coronary endothelial injury, which was manifested by increased coronary microvascular permeability and abnormalities in coronary endothelium-dependent relaxation, was reduced by pretreatment with the anti-CD18 integrin antibody R15.7.


2001 ◽  
Vol 120 (5) ◽  
pp. A195-A195
Author(s):  
E OLOUGHLIN ◽  
C SIM ◽  
M PERRY ◽  
E ELLIOTT ◽  
Z LI

1991 ◽  
Vol 66 (05) ◽  
pp. 609-613 ◽  
Author(s):  
I R MacGregor ◽  
J M Ferguson ◽  
L F McLaughlin ◽  
T Burnouf ◽  
C V Prowse

SummaryA non-stasis canine model of thrombogenicity has been used to evaluate batches of high purity factor IX concentrates from 4 manufacturers and a conventional prothrombin complex concentrate (PCC). Platelets, activated partial thromboplastin time (APTT), fibrinogen, fibrin(ogen) degradation products and fibrinopeptide A (FPA) were monitored before and after infusion of concentrate. Changes in FPA were found to be the most sensitive and reproducible indicator of thrombogenicity after infusion of batches of the PCC at doses of between 60 and 180 IU/kg, with a dose related delayed increase in FPA occurring. Total FPA generated after 100-120 IU/kg of 3 batches of PCC over the 3 h time course was 9-12 times that generated after albumin infusion. In contrast the amounts of FPA generated after 200 IU/kg of the 4 high purity factor IX products were in all cases similar to albumin infusion. It was noted that some batches of high purity concentrates had short NAPTTs indicating that current in vitro tests for potential thrombogenicity may be misleading in predicting the effects of these concentrates in vivo.


1993 ◽  
Vol 69 (01) ◽  
pp. 021-024 ◽  
Author(s):  
Shawn Tinlin ◽  
Sandra Webster ◽  
Alan R Giles

SummaryThe development of inhibitors to factor VIII in patients with haemophilia A remains as a serious complication of replacement therapy. An apparently analogous condition has been described in a canine model of haemophilia A (Giles et al., Blood 1984; 63:451). These animals and their relatives have now been followed for 10 years. The observation that the propensity for inhibitor development was not related to the ancestral factor VIII gene has been confirmed by the demonstration of vertical transmission through three generations of the segment of the family related to a normal (non-carrier) female that was introduced for breeding purposes. Haemophilic animals unrelated to this animal have not developed functionally significant factor VIII inhibitors despite intensive factor VIII replacement. Two animals have shown occasional laboratory evidence of factor VIII inhibition but this has not been translated into clinical significant inhibition in vivo as assessed by clinical response and F.VIII recovery and survival characteristics. Substantial heterogeneity of inhibitor expression both in vitro and in vivo has been observed between animals and in individual animals over time. Spontaneous loss of inhibitors has been observed without any therapies designed to induce tolerance, etc., being instituted. There is also phenotypic evidence of polyclonality of the immune response with variable expression over time in a given animal. These observations may have relevance to the human condition both in determining the pathogenetic factors involved in this condition and in highlighting the heterogeneity of its expression which suggests the need for caution in the interpretation of the outcome of interventions designed to modulate inhibitor activity.


Circulation ◽  
1995 ◽  
Vol 92 (12) ◽  
pp. 3549-3559 ◽  
Author(s):  
Tamás Simor ◽  
Wen-Jang Chu ◽  
Lynne Johnson ◽  
Andras Safranko ◽  
Mark Doyle ◽  
...  

2021 ◽  
pp. 088532822110309
Author(s):  
Jinhua Hu ◽  
Bin Ai ◽  
Shibo Zhu ◽  
Zhen Wang ◽  
Huimin Xia ◽  
...  

To investigate the biocompatibility of polylactic acid-glycolic acid copolymer (PLGA) and PLGA/gelatin scaffolds and their suitability for tubular urethral replacement in a canine model. PLGA and PLGA/gelatin scaffolds was constructed by electrospinning. Microstructural differences between the scaffolds was examined by Scanning electron microscopy (SEM) followed by mechanical properties testing. Biocompatibility of the material was evaluated using SEM 4, 8, 12 and 72 h after PLGA and PLGA/gelatin scaffolds co-culture with urothelial cells. And confocal analysis was also used to showed the cell adhesive and growth at 12 h. Approximately 2 cm of the anterior urethra of twelve dogs were removed and replaced with a scaffold. After the surgery for 1 month performed urethrography and for 3 month perform hematoxylin–eosin (H&E) and Masson. The results indicated that PLGA and PLGA/gelatin scaffolds had a void microfilament structure, similar to that of normal acellular matrix tissue. And the tensile strength was decreased whereas the tensile deformation and suture retention strength was increased in PLGA/gelatin scaffolds compared to that in PLGA scaffolds Urothelial cells grew well on both scaffolds. Postoperatively, animals recovered well and urinated spontaneously. However, urethrography showed varying degrees of urethral strictures in the reconstructed urethras. H&E and Masson showed that multilayer urothelial cells were formed in both the proximal and distal segments of the reconstructed urethras but without continuity. There was a small amount of smooth muscle and blood vessels under the epithelium, but regenerative urothelial cells at the midpoint of the reconstructed segment did not continue. Lots of lymphocyte infiltration was observed under the epithelium, some collagen tissue was deposited under the neo-urethral epithelium were observed. In conclusion, PLGA and PLGA/gelatin scaffolds are not suitable for tubularized urethral replacement in the canine model.


1992 ◽  
Vol 7 (4) ◽  
pp. 236-243 ◽  
Author(s):  
Michael J. Bishop ◽  
Menglung Su ◽  
Emil Y. Chi ◽  
Paul Kubilis

2007 ◽  
Vol 32 (6) ◽  
pp. 876-881 ◽  
Author(s):  
Toshikazu Tanaka ◽  
Chunfeng Zhao ◽  
Yu-Long Sun ◽  
Mark E. Zobitz ◽  
Kai-Nan An ◽  
...  

2003 ◽  
Vol 162 (3) ◽  
pp. 873-885 ◽  
Author(s):  
Scott J. Harvey ◽  
Keqin Zheng ◽  
Barbara Jefferson ◽  
Peter Moak ◽  
Yoshikazu Sado ◽  
...  

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