| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Ann Thorac Surg 2000;69:12-13
© 2000 The Society of Thoracic Surgeons
a Division of Cardiothoracic Surgery, University of Washington, Seattle, Washington, USA
Address reprint requests to Dr Boyle, Division of Cardiothoracic Surgery, University of Washington, 1959 Pacific Ave NE, Box 356310, Seattle, WA 98195
e-mail: boyle{at}washington.edu
In the process of harvesting an organ for transplantation, flushing the organ with various perfusates, and, ultimately, implanting the organ into the recipient, a number of abnormal hemodynamic forces have an impact on the microvasculature of the graft. First, the microvasculature can be acutely overdistended by the preservation solution infused at the time of organ harvest from the donor. Second, there is a loss of the usual pulsatile blood flow when the organs lie flaccid on ice during the transport period. At this point, the microvasculature is sensing a minimal intravascular pressure. Finally, when the graft is implanted, the conditions of reperfusion may have an impact on graft function as well. It is increasingly appreciated that extremes in perfusion pressure may ultimately affect graft function both in the short and long term. Inasmuch as these are variables that can be controlled, it is important to define the optimal hemodynamic conditions for organ preservation and reperfusion.
Recently, a great deal has been learned about how the mechanical forces of flowing blood on the vessel wall interact with other endogenous and exogenous factors to regulate microvascular behavior [1]. These forces can be in the form of pressure, tension (or stretch), and shear. Pressure is the force acting inward on the surface of the tissue elements. Tension pulls tissue along one axis, normally without constraining the tissue in the other directions. Shear stresses are small forces that cause very modest deformation of the full thickness of the arterial wall, but are the most physiologically significant in terms of cellular activation [1]. What is clear is that many of these mechanical forces are transduced to biologic activity, particularly at the endothelial cell level. Because of their location at the interface between the blood and the body’s tissues, endothelial cells are uniquely situated to respond to alterations in hemodynamic forces. Specifically, evidence suggests that endothelial cells serve as mechanoreceptors by which changes in blood flow or tissue stress and strain are recognized by the endothelial cellular membranes [2]. At the cellular level, when endothelial cells are exposed to abnormal hemodynamic forces, they undergo conformational changes, redistribution of cytoskeleton and organelles, cell proliferation, production of extracellular matrix, and transport of macromolecules [1]. In addition to alterations in the physical properties of the endothelial cell layer, when the endothelium senses different flow environments, there are marked changes in cell signaling, resulting in the activation of ion channels and G proteins and the induction of oscillations in intracellular calcium concentration [3–5]. These changes ultimately promote long-term alterations in endothelial properties through the induction of specific genes that encode new proteins [5]. Genes that are transcriptionally activated in this manner include a number of growth factors, cytokines, inflammatory adhesion molecules, and procoagulant proteins [6–11]. In this way, fluctuations in hemodynamic force sensed at the microvascular level can contribute to a dysfunctional, activated endothelial cell layer that promotes vasomotor dysfunction, neutrophil adhesion, and increased microvascular thrombogenicity on reperfusion. Coupled with the oxidative stress-induced endothelial cell activation that is inherent in the organ preservation process, one can appreciate how organ function can be drastically impaired on reperfusion [12].
Although a great deal has been learned about how abnormal hemodynamic stresses have an impact on endothelial cell activation in vitro, comparatively little is known about how this affects pathophysiology in vivo. Specifically, little is known about how these forces alter clinically significant events, such as organ preservation for transplantation. In the present study, Halldrosson and colleagues [13] have nicely illustrated that the perfusion pressure of the initial reperfusate contributes to the degree of tissue injury seen on lung reperfusion. The premise of the paper is that by controlling the conditions of reperfusion at a lower pressure, they demonstrate improved pulmonary graft preservation. This line of inquiry complements the shear stress–related endothelial biology literature, where it has been demonstrated that high, low, and fluctuating shear forces are actively involved in the well-characterized endothelial injury patterns that contribute to the development of atherosclerosis [14]. Although the role of high or low shear stress as an inciting factor in the development of atherosclerosis is still being uncovered, what is clear is that at many sites at which advanced lesions are predictably found, such as at branch and bend points in the vasculature, there are marked abnormalities in flow with wide, complex fluctuations in the degree of shear stress [1]. Comparatively little is known about the acute microvascular responses to abnormal hemodynamic forces in vivo. Because a transplant graft undergoes complex fluctuations in the degree of hemodynamic stress throughout the preservation process, it is likely vulnerable to endothelial cell injury acutely just as the vasculature is to atherosclerosis chronically.
Judging from what is known, it is a reasonable hypothesis that avoiding high, low, and fluctuating degrees of hemodynamic stress at the endothelial cell layer is important in organ preservation. In vivo, organs are known to tightly autoregulate blood flow to avoid either too high or too low a pressure. The teleologic importance of microvascular autoregulation is lost in the transplanted graft when the graft is flushed, left flaccid on ice, and then uncontrollably reperfused after implantation. Because the organ is no longer able to autoregulate, it is perhaps up to the transplant surgeon to determine these conditions. Early in the history of transplantation, surgeons used continuous organ perfusion to prevent the long period of time when the organs sat on ice. A number of studies demonstrated far superior preservation with continuous perfusion devices compared with storing organs on ice alone [15, 16]. In this study, the authors’ work demonstrates that once the organ is reperfused, the conditions of reperfusion can still affect organ function, and that a sudden uncontrolled increase in pressure may in fact be damaging. Taken together, these studies demonstrate the importance of the perfusion conditions in all phases of the preservation process. It is tempting to speculate from what is available in the literature that avoiding overdistention of the organ on the initial infusion of the perfusate, continuously perfusing the organ during transport, and, ultimately, controlling the perfusion pressure on reperfusion to allow a more gradual increase in pressure will lead to maximal recovery of a preserved organ. Simply put, avoiding too high, too low, and, perhaps, too quick a change in perfusion pressure may be maximally beneficial.
On a broader scale, it is important to recognize that abnormal forces imposed on vascular endothelial cells may have implications beyond organ preservation. This may be particularly true in the setting of myocardial protection during ischemic cardiac arrest, the role of pulseless flow on the systemic inflammatory response to cardiopulmonary bypass, and the influence of bypass conduit harvest and handling on outcomes in coronary artery surgical procedures. It is only with studies such as these, in which investigators model clinically significant events in whole-organ preparations, that we will be able to better bridge the gap between the growing basic rheology literature and the clinical acute organ dysfunction seen in the setting of cardiovascular surgery.
References
This article has been cited by other articles:
|
|
 |
|
  A. Parolari, P. Rubini, A. Cannata, L. Bonati, F. Alamanni, E. Tremoli, and P. Biglioli Endothelial damage during myocardial preservation and storage Ann. Thorac. Surg., February 1, 2002; 73(2): 682 - 690. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
