Do leukocytes contribute to impaired microvascular tissue perfusion after arterial repair?

Abstract

Impaired capillary perfusion may result in flap failure. Platelet emboli, polymorphonuclear leukocytes (PMNs), and/or vasospasm have been identified as possible causes. This study investigates the role of PMNs in causing impaired capillary perfusion in a free flap model. PMN concentrations were depleted using antineutrophil serum. The cremaster muscles of 20 Sprague-Dawley rats were isolated on a single neurovascular pedicle and after a simulated technically poor arterial anastomosis upstream and reperfusion, capillary perfusion was measured each hour for 6 hours. Even though the number of PMNs was significantly reduced in the animals treated with antineutrophil serum, capillary perfusion was not changed compared with controls. These results demonstrate that depleting circulating PMNs does not protect capillary perfusion in our model. These findings suggest that reduced capillary perfusion downstream from an anastomotic repair is not mediated by the presence of PMNs in the microcirculation.© 1998 Wiley-Liss, Inc. MICROSURGERY 18:23-28 1998Reconstructive microsurgery involves the transfer or the replantation of tissue that has been isolated on a vascular pedicle. Following this procedure, 3-30% of these transferred/replanted tissues become ischemic and go on to fail.1,2 To study the cause of failure, we developed a free muscle flap model, the isolated rat cremaster muscle, 3 which simulates a clinical free flap. Previous work using this model involved producing a technically poor vessel repair of the pedicle artery (iliac artery) upstream from the cremaster muscle and subsequent observation of the muscle microcirculation downstream from the anastomosis. 4 These studies demonstrated showers of platelet emboli and large numbers of adherent leukocytes in the downstream cremaster microcirculation following the anastomotic repair. More importantly, subsequent studies showed that following these events, capillary perfusion in the downstream microcirculation decreased significantly.5 In yet another study using the same model, emboli were eliminated with heparin administration; the decrease in capillary perfusion still persisted. 6 These surprising findings indicated that the passage of platelet emboli into the microcirculation did not obstruct microvascular perfusion mechanically, as we had suspected. We then asked the question, what other mechanism might be responsible for the observed impaired perfusion? Since it has been shown that impairment of the downstream tissue microcirculation can cause flap failure, 7 answering this question might reveal an important underlying mechanism of failure.Activated polymorphonuclear leukocytes (PMNs) are known to be involved in disease states like shock, sepsis, and organ failure. [8][9][10][11] They also mediate reperfusion injury in a variety of different tissues. 12-18The purpose of this study was to investigate whether PMNs cause the alterations in microcirculatory perfusion seen in our free flap model following a simulated technically poor repair of the upstream pedicle artery. ...

The topical use of non-thermal dielectric barrier discharge (DBD): Nitric oxide related effects on human skin

“…Since we observed a pronounced penetration of NO through intact epidermis in Franz diffusion cell experiments and an enrichment of skin tissue with bioactive NO derivates, we hypothesize that NO penetration is the main responsible mechanism for plasmainduced enhancement of microcirculation. It is known that topically applied chemical NO donors are able to enhance dermal microcirculation [31] which may be useful in the treatment of impaired microcirculation often observed, for example, in Raynaud, diabetic foot syndrome as well as poorly perfused flaps after skin grafting [32].…”

Functional Analyses of Patient-derived IgG Monoclonal Anticardiolipin Antibodies Using In Vivo Thrombosis and In Vivo Microcirculation Models

“…Specifically, IS3 and IS4 were from patients IS, while the three "CL" antibodies were from patient CLE. In addition, we utilized a recently developed animal model to study the biological activities of monoclonal aCL in activating EC in vivo (33,34). Table 2 summarizes data that characterized the aCL preparations, including their thrombogenic potential and biological properties, as well as binding specificities from previous studies (30,31).…”

E-Selectin mediates pathogenic effects of antiphospholipid antibodies

“…(i) Analysis of EC activation in the microcirculation of the exposed cremaster muscle in mice: Activation of ECs in the pretreated mice was assessed by direct visualization and quantitation of leukocytes (WBC) adhering to ECs in the microcirculation of the exposed cremaster muscle in mice as described elsewhere [7–9,23,24]. After a stabilization period of 30 min, the number of adhering WBCs that remained stationary for a period of 30 s (sticking) within five different venules (diameter, 25 to 35 µm) was determined.…”