Medial Collateral Ligament Transection Research Articles

Effect of ultrasound on acute inflammation of transected medial collateral ligaments

Leung MC, Ng GY, Yip KK. Effect of ultrasound on acute inflammation of transected medial collateral ligaments. Arch Phys Med Rehabil 2004;85:963–6. Objective To evaluate the effect of therapeutic ultrasound on the acute inflammation of soft-tissue injuries by measuring the levels of prostaglandin E 2 (PGE 2) and leukotriene B 4 (LTB 4). Design Randomized, case-control study. Setting Laboratory animal facility. Animals Thirty 3-month-old male Sprague-Dawley rats. Intervention Rats with medial collateral ligament transection were given 5 minutes of pulsed ultrasound therapy (1:4) daily, with different durations (1, 5, 10d) and intensities (0, 0.5, 1.5, 2.3W/cm 2). Main outcome measures Levels of PGE 2 and LTB 4. Results The levels of PGE 2 and LTB 4 were higher in all intensity subgroups that received 2.3W/cm 2 intensity on postinjury day 2. On postinjury day 11, LTB 4 was significantly decreased, but PGE 2 was significantly increased. Conclusions Pulsed ultrasound therapy may stimulate inflammation of acute ligament injury.

Medial collateral ligament and partial anterior cruciate ligament transection: mRNA changes in uninjured ligaments of the sheep knee

Following knee ligament injury, clinical and experimental investigations usually focus on the injured ligament, and uninjured ligaments of the same joint are largely ignored and presumed to remain unchanged. The purpose of this study was to characterize changes in mRNA levels for a relevant subset of molecules in the uninjured knee ligaments following combined unilateral medial collateral ligament (MCL) and partial anterior cruciate ligament (ACL) transection in sheep. Semiquantitative reverse transcription-polymerase chain reaction was performed for collagen types I, III, and V; matrix metalloproteinase-13 (MMP-13); and tissue inhibitor of metalloproteinase-1 for both injured and uninjured knee ligaments at 6 and 12 weeks after injury. Collagen type I, III, and V mRNA levels were significantly increased in MCL scars at 6 weeks as well as in the uninjured lateral collateral ligament and the anteromedial band of the ACL (AM-ACL). MMP-13 mRNA levels were also elevated in the MCL at 6 and 12 weeks and in the AM-ACL 6 weeks after injury. In contrast, significant changes in the posterior cruciate ligament were not detected at either time point, indicating specificity in the transient alterations. These results suggest that following injury, responses occur in uninjured ligaments that are specific although transient in nature. These responses may be an adaptive attempt to preserve function until the scar tissue can stabilize the mechanical environment following injury.

Effect of hemorrhage on medial collateral ligament healing in a mouse model.

Medial collateral ligament injuries heal by a scar response. Increased hemorrhage at the site of medial collateral ligament injury improves healing. Controlled laboratory study. Ninety-six mice were divided into two groups. Group 1 mice underwent knee medial collateral ligament transection with the opposite knee as a sham-operated control and group 2 animals additionally had 0.25 ml of tail cut blood pipetted to the medial collateral ligament transection site and sham-operated opposite knee. Ligament specimens were harvested at 3, 7, 21, and 28 days. Immunohistochemical analysis demonstrated peak macrophage counts at day 7 in all transected specimens. Macrophage counts were higher in group 2 than in group 1 at all time points, with a statistically significant increase of macrophages noted at day 7. In situ hybridization demonstrated increased collagen gene expression, with peaks at 7 and 28 days after transection. Group 2 animals showed increased gene expression at all time points as compared with group 1, with a statistically significant increase noted at 7 and 28 days. Biomechanical testing demonstrated progressive healing at each time point. At 28 days, the load to failure was 67% that of the sham-operated knee. This study suggests there is an increased healing response with bleeding at the ligament injury site. Identification of the factors involved with increased healing may allow manipulation of the healing response in the clinical setting.

Mechanical effects of the intraarticular administration of high molecular weight hyaluronic acid plus phospholipid on synovial joint lubrication and prevention of articular cartilage degeneration in experimental osteoarthritis.

To examine in vivo the effects of a mixture of high molecular weight hyaluronic acid (HA) plus phospholipids on joint lubrication and articular cartilage degeneration. Experimental osteoarthritis (OA) of the right knee was induced by anterior cruciate and medial collateral ligament transection in 40 rabbits. The animals were subjected to 8 consecutive weekly intraarticular administrations of high molecular weight HA (the HA200 group), conventional molecular weight HA (the HA80 group), or high molecular weight HA plus L-delta dipalmitoyl phosphatidylcholine liposomes (the PHA group) and were killed 1 week after the final injection. The remaining transected right knees (the OA group) and randomly selected nontransected contralateral left knees (the control group) were collected simultaneously. Each group (n = 10) was divided into 2 equal subgroups, one of which was evaluated histologically while the other was subjected to a lubricating ability test using a pendulum friction tester. The injected knees had a tendency to demonstrate less damage to the articular cartilage compared with the OA group, and the histologic findings in all groups except for the PHA group differed significantly from the control group. There was a significant difference in the mean +/- SD friction coefficient between the control group (0.0100 +/- 0.00300) and the OA (0.0206 +/- 0.00649), HA200 (0.0190 +/- 0.00427), and HA80 (0.0177 +/- 0.00712) groups (P < 0.05 for each comparison), but not between the control group and the PHA group (0.0150 +/- 0.00330) (P = 0.15). To our knowledge, this is the first in vivo study to examine whether intraarticular injections of phospholipids influence joint lubrication by acting as a boundary lubricant, thus protecting articular cartilage from degenerative changes.

The role of IL-4 in the control of mechanical stress-induced inflammatory mediators by rat chondrocytes

A complex environment controls the metabolism of chondrocytes in the inflammatory joint. Although mechanical stimuli are essential for the chondrocyte metabolism, excessive mechanical force contributes to the release of inflammatory mediators leading the cartilage destruction under the arthritic condition. IL-4 is a chondroprotective cytokine, which is also involved in the integrin-mediated chondrocyte mechano-transduction. We examined the effects of cyclic mechanical stress on the gene expression profile of rat chondrocytes, and tested the in vitro effects of recombinant IL-4. Chondrocytes were obtained from the knee joints of 7-day-old Wister rats. Cyclic mechanical stress was applied on the cultured chondrocytes for 24 hours using Flexercell strain unit (Flexcell International Co., Hillsboro, NC, USA) with 0.5 Hz, 7% elongation, with or without treatment by recombinant IL-4. The cDNA microarray analysis revealed that, of 1080 genes, 37 genes were upregulated and 46 genes were downregulated after mechanical stress. RT-PCR and real-time PCR analysis confirmed that treatment by IL-4 resulted in the significant downregulation of mRNA expression of cysteine proteinase cathepsin B, and the inducible form of nitric oxide synthase. Next, an osteoarthritis model was created in the knee joints of Wistar rats (200 g) with anterior cruciate ligament and medial collateral ligament transection. The rats were killed 2, 4, or 6 weeks after the surgery, and the gross morphology and histology of the knee joint cartilage were examined. The preliminary results showed that intra-articular administration of IL-4 exerted a protective effect on the development of osteophytes, and cartilage lesions in this model of osteoarthritis. These results suggested the possible role of IL-4 in the control of mechanical stress-induced inflammatory mediators in vitro and in vivo.

Denervation impairs healing of the rabbit medial collateral ligament

Little is known about the contribution of innervation to ligament healing after traumatic disruption, although there is good evidence of an important role for the peripheral nervous system in the healing of fractures and skin injuries. Tissues such as ligament, with a low resting blood supply, are dependent on substantial increases in blood flow and vascular volume during the initial stages of repair. We hypothesized that this initial healing response would be strongly promoted by neurogenic inflammation. Since the saphenous nerve (a major sensory branch of the femoral nerve) supplies the medial half of the knee joint, we elected to use femoral nerve transection as a model to determine the role of sensory and autonomic innervation in the initial outcome of repair of the injured medial collateral ligament. Twelve adult, female NZW rabbits underwent right medial collateral ligament transection. Of these, six rabbits underwent right femoral nerve transection to disrupt the somatic sensory and autonomic nerve supply to the knee joint and six were kept neurologically intact (controls). At six weeks post-injury, the animals were assessed by laser Doppler perfusion imaging (LDI) to determine the local blood flow, at both the injury site and at the uninjured contralateral ligament. The animals were then killed, the knee joints were removed and the biomechanical characteristics of the healing bone–median collateral ligament (MCL)–bone complexes assessed. In a separate cohort of 16 rabbits, vascular volumes of the injured ligaments were measured by infusion of a carmine red/gelatin solution. At six weeks post-injury, in vivo measurement of perfusion with LDI revealed that normally innervated ligaments had an almost three-fold higher average blood flow. Carmine red/gelatin infusion revealed a 50% higher density of blood vessels as compared to denervated ligaments. The force required for ultimate failure was found to be 50% higher in normally innnervated MCL's as compared to denervated MCL's: 153.14±20.71 N versus 101.29±17.88 N ( p<0.05). Static creep was increased by 66% in denervated MCL's: 2.83±0.45% versus 1.70±0.12% ( p<0.05). Total creep was increased by 45% in denervated MCL's: 5.29±0.62% compared to 3.64±0.31% in innervated MCL's ( p<0.05). We conclude that intact innervation makes a critical contribution to the early healing responses of the MCL of adult rabbits.

Vascular physiology and long-term healing of partial ligament tears

Functional outcomes of anterior cruciate ligament (ACL) injury are generally poorer than those of medial collateral ligament (MCL) tears. Following ligament damage, all phases of ligament healing require an adequate blood supply. We hypothesized that the differences in healing properties of the ACL and MCL would reflect their vascular responses to joint injury. This paper examines the long-term changes in blood flow and vascular volume of rabbit knee ligaments after direct injury, and under conditions of chronic joint instability induced by section of the posterior cruciate ligament (PCL). Standardized injuries were surgically induced in adult rabbit knee ligaments: partial MCL transection, partial ACL transection, or complete PCL transection (joint instability). Sixteen weeks later the blood flow and vascular volume of the ACL and MCL were measured and compared to control and sham-operated animals. Direct ligament injury induced significant increases in standardized blood flow and vascular volume of both ACL and MCL after 16 weeks; however, the vascular volume of the ACL was not higher than the control levels in the MCL. We conclude that direct injury to both the anterior cruciate and MCLs induces long-term physiological responses. Joint laxity is a common sequel to PCL injury. Chronic joint laxity failed to induce adaptive vascular responses in the ACL, while the MCL shows significant amplification of blood supply. Although both MCL and ACL showed increased weight after PCL transection, the lack of a long-term vascular response in the ACL may be a major factor in its the diminished healing potential.

Metallic Radial Head Arthroplasty Improves Valgus Stability of the Elbow

The stabilizing influence of radial head arthroplasty was studied in eight medial collateral ligament deficient anatomic specimen elbows. An elbow testing apparatus, which used computer controlled pneumatic actuators to apply tendon loading, was used to simulate active elbow flexion. The motion pathways of the elbow were measured using an electromagnetic tracking device, with the forearm in supination and pronation. As a measure of stability, the maximum varus to valgus laxity over the range of elbow flexion was determined from the difference between varus and valgus gravity loaded motion pathways. After transection of the medial collateral ligament, the radial head was excised and replaced with either a silicone or one of three metallic radial head prostheses. Medial collateral ligament transection caused a significant increase in the maximum varus to valgus laxity to 18.0 degrees +/- 3.2 degrees. After radial head excision, this laxity increased to 35.6 degrees +/- 10.3 degrees. The silicone implant conferred no increase in elbow stability, with a maximum varus to valgus laxity of 32.5 degrees +/- 15.5 degrees. All three metallic implants improved the valgus stability of the medial collateral ligament deficient elbow, providing stability similar to the intact radial head. The use of silicone arthroplasty to replace the radial head in the medial collateral ligament deficient elbow must be questioned. Metallic radial head arthroplasty provides improved valgus stability, approaching that of an intact radial head.