CardiothoracicPostoperative Pericardial Adhesion Prevention Using Carbylan-SX in a Rabbit Model
Introduction
The development of postoperative adhesions within the pericardial space complicates reoperative cardiac surgery by obscuring anatomy and prolonging dissection. This prolonged adhesiolysis may result in potential catastrophic injury to mediastinal structures. These injuries have been shown to significantly increase morbidity and mortality [1, 2, 3, 4, 5, 6, 7, 8, 9]. Duncan et al. reported the incidence of a major vascular injury occurring at resternotomy to be 2% to 6% [1, 2, 3, 4, 5, 6, 7, 8, 9, 10]. Dobell and Jain reported the mortality rate associated with a resternotomy hemorrhage to be 39%. If the aortocoronary bypass graft is injured, the mortality rate increases to 56% [11]. While adhesion formation is a natural physiological part of wound healing, dense adhesions within the mediastinum and particularly within the pericardial space are associated with a significantly increased morbidity and mortality. Adhesion formation has been shown to result from trauma, ischemia, foreign-body reaction, infection, and hemorrhage [12].
Several attempts have been made to reduce or prevent development of postoperative adhesions in the retrosternal space [2, 3, 4, 5, 6, 7, 8, 9, 10, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22], as well as numerous products developed for adhesion prevention in the abdomen and pelvis [23]. Fibrinolytic agents, anticoagulants, anti-inflammatory agents, and antibiotics have been tried with variable success [24]. Several natural and synthetic physical barriers have been tried as well. Peritoneum, omentum, amnion, fibrin, gelatin, collagen, and hyaluronic acid (HA) were all tried, but never proved satisfactory [25, 26, 27, 28]. Physical barriers, including silicone, polytetrafluoroethylene, cellulose, polyvinyl alcohol, and polyester derivatives have also been developed [12, 29, 30, 31, 32].
Most recently, investigational focus has turned to developing bioabsorbable antiadhesion barriers. Two commonly used such materials are Interceed (Johnson and Johnson, New Brunswick, NJ) and Seprafilm (Genzyme Corp., Cambridge, MA) These have been shown in several studies to reduce the formation of postoperative adhesions [33, 34, 35].
A new, chemically modified, in situ crosslinkable derivative of hyaluronan has shown considerable promise in a variety of in vivo models of wound repair and adhesion prevention [36]. Known as CMHA-SX or Carbylan-SX (Carbylan Biosurgery Inc., Palo Alto, CA), this material restores vocal cord viscoelasticity [37], promotes sinus [38] and middle ear [39] healing with minimal scarring or ossification, and permits damaged airways to repair with minimal stenosis [40]. In two abdominal adhesion rat models, Carbylan-SX was demonstrably superior to Seprafilm in preventing abdominal-cecal adhesions and uterine horn adhesions [41]. Carbylan-SX can be formulated either as a premade film or sprayable gel, and has been shown to work by inhibiting murine fibroblast proliferation and attachment [41, 42]. Herein we describe a study designed to compare the effectiveness of Carbylan-SX film and Carbylan-SX hydrogel compared to the commercially available and clinically used Seprafilm in minimizing pericardial adhesions.
Section snippets
Animals
Forty male New Zealand white rabbits (Oryctolagus cuniculus) weighing 2.5 to 3.0 kg ordered from Western Oregon Rabbit Co. (Philomath, OR) were the subjects of this study. All rabbits were quarantined at least seven days at the Animal Resource Center (ARC) of the University of Utah. Each animal was housed individually and fed Teklad Global High Fiber Rabbit Diet (Wilmington, DE).
Materials
Carbylan-S (CMHA-S), a thiol-containing derivative of HA (950 kDa, from Novozymes Biopolymers, Inc., Bagsvaerd,
Results
A total of 38 rabbits survived the surgery and two week postoperative course. Rabbits were sacrificed at an average of 15 days ± 1 day postoperatively. Results of the subjective analysis are shown in Table 1, with the mean for the group depicted in Fig. 2. No significant findings were seen with subjective analysis.
Results of the histological evaluation, including the mean and standard deviation, for all four groups are shown in Table 2. The control group, with an epicardial abrasion only, had
Discussion
Our study included 38 animals divided into four different groups to evaluate the efficacy of Carbylan-SX film and hydrogel compared with no treatment or the commonly used Seprafilm. The heart was approached through a left thoracotomy, rather that a median sternotomy, to remain consistent with the model we have used in other rabbit cardiac studies where we have had excellent rabbit survival with minimal morbidity. We closed the pericardium around the treatment to maintain a controlled space
Acknowledgments
The authors, and in particular Dr. Prestwich, thank the Centers of Excellence Program of the State of Utah.
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