Comparison of intra-articular administration of adenosine, lidocaine and magnesium solution and tranexamic acid for alleviating postoperative inflammation and joint fibrosis in an experimental model of knee arthroplasty

Abstract

Background Dysregulated inflammatory responses are implicated in the pathogenesis of joint stiffness and arthrofibrosis following total knee arthroplasty (TKA). The purpose of this study was to compare the effects of intra-articular (IA) administration of tranexamic acid (TXA), an anti-fibrinolytic commonly used in TKA, and ALM chondroprotective solution on postoperative inflammation and joint tissue healing in a rat model of knee implant surgery. Methods Male Sprague–Dawley rats (n = 24) were randomly divided into TXA or ALM treatment groups. The right knee of each rat was implanted with titanium (femur) and polyethylene (tibia) implants. An IA bolus (0.1 ml) of TXA or ALM was administered after implantation and capsule closure, and before skin closure. Postoperative coagulopathy, haematology and systemic inflammatory changes were assessed. Inflammatory and fibrotic markers were assessed in joint tissue, 28 days after surgery. Results Haemostasis was comparable in animals treated with TXA or ALM after knee implant surgery. In contrast to ALM-treated animals, systemic inflammatory markers remained elevated at day 5 (IL-6, IL-12, IL-10, platelet count) and day 28 (IL-1β, IL-10) following surgery in TXA-treated animals. At day 28 following surgery, the extension range of motion of operated knees was 1.7-fold higher for ALM-treated animals compared to the TXA group. Key inflammatory mediators (NF-κB, IL-12, IL-2), immune cell infiltration (CD68+ cells) and markers of fibrosis (α-SMA, TGF-β) were also lower in capsular tissue of ALM-treated knees at day 28. Conclusion Data suggest that IA administration of ALM is superior to TXA for reducing postoperative systemic and joint inflammation and promoting restoration of healthy joint tissue architecture in a rat model of TKA. Further studies are warranted to assess the clinical translational potential of ALM IA solution to improve patient outcomes following arthroplasty.

Acute postoperative pain and dorsal root ganglia transcriptomic signatures following total knee arthroplasty (TKA) in rats: An experimental study

“…Our model reflects these clinical observations as TKA was accompanied by elevated IL-6 and TNFα levels and functional deficits consistent with acute postoperative pain. Morris et al reported a similar pattern of elevated IL-6, though not to a significant degree, following knee surgery in rats [ 17 ]. The animals were observed initially limping and then gradually recovered normal gait, confirming that rats subjected to TKA regained normal knee loading and function.…”

“…Elucidation of such pathways necessitates a preclinical TKA model that closely mimics the clinical procedure as well as outcomes including acute postoperative pain and recovery of function. While several TKA models have been reported in rats [14][15][16][17], none of these have demonstrated responsiveness to analgesia and complete restoration of knee function as reported in clinical studies. Herein, we describe a new preclinical model of TKA in rats that is accompanied by behaviors indicative of acute postoperative pain responsive to clinically employed analgesics, and exhibits functional recovery and pain resolution as observed in TKA patients.…”

ALM Therapy Promotes Functional and Histologic Regeneration of Traumatized Peripheral Skeletal Muscle

“…From previous studies on ALM solution, it is known that small-volume ALM therapy has multiple protective effects on the whole organism, such as the improvement of the cardiac and hemodynamic function, correction of coagulopathy, reduction of inflammation, endothelial injury, and infection, as well as improvement of oxygenation [ 21 , 23 , 27 , 43 , 44 ]. Additionally, the antifibrotic and antiapoptotic effect of ALM therapy may explain the significantly higher strength on days 4 and 7 compared with the control groups [ 26 , 45 ].…”

“…ALM solution demonstrated increased survival in hemorrhagic shock, cardioprotective effects, improved microvascular perfusion with concomitant improved oxygenation, and pulmoprotective and nephroprotective properties in small and large animal studies conducted to date [ 22 , 23 , 24 , 25 ]. Furthermore, Morris et al demonstrated less arthrofibrosis with ALM therapy in an animal model with total knee arthroplasty [ 26 ]. ALM therapy has also demonstrated reduced systemic inflammation, thrombocyte dysfunction, and coagulopathy after different trauma states [ 27 , 28 ].…”

Adenosine, lidocaine, and magnesium therapy augments joint tissue healing following experimental anterior cruciate ligament rupture and reconstruction

“… 14 Interestingly, perioperative adenosine, lidocaine, and Mg 2+ (ALM) therapy was shown to dampen early systemic and local inflammation in both sexes following ACL rupture and surgical repair. 14 ALM therapy was chosen because of its ability to blunt inflammation and reduce immune dysfunction in experimental models of total knee arthroplasty, 20 , 21 hemorrhagic shock, traumatic brain injury, and sepsis. 22 The aim of the present study was to investigate the effects of perioperative ALM therapy on knee function, inflammation, and joint tissue repair in males and females at 28 days postoperatively.…”