Assessment of the efficacy of intra-articular platelet rich plasma treatment in an ACLT experimental model by dynamic contrast enhancement MRI of knee subchondral bone marrow and MRI T2∗ measurement of articular cartilage.

OBJECTIVE: The vascularization of subchondral bone plays a significant role in the progression of knee osteoarthritis (OA). Treatment with platelet-rich plasma (PRP) has positive effects on cartilage lesions. However, PRP's efficacy for subchondral bone marrow lesions and the relationship of these lesions to cartilage are still undiscovered. Therefore, our aims were first to longitudinally investigate the change in subchondral flow by dynamic contrast enhanced MRI and degeneration of cartilage by MRI T2∗ in an anterior cruciate transection rodent (ACLT) model, and second to examine changes in parameters after intra-articular PRP injection. DESIGN: A 32-week investigation in 18 rats allocated to sham-control, ACLT with normal saline injection (ACLT + NS), and ACLT with PRP injection groups ended with histological evaluation. Another rat was used as a donor of allogenic PRP. RESULTS: Compared to the sham-control group, the ACLT + NS group had higher subchondral blood volume A (0.051, 95% confidence interval: 0.009, 0.092) and lower venous washout kel (-0.030: -0.055, -0.005) from week 4; lower permeability kep from week 18 (-0.954: -1.339, -0.569); higher cartilage T2∗ values (1.803: 1.504, 2.102) reflecting collagen loss beginning at week 10. For the PRP treatment group, subchondral bone marrow A and cartilage T2∗ decreased from week 10. Histological results confirmed and were correlated with the MRI findings. CONCLUSION: Subchondral hyper-perfusion plays a vital role in the pathogenesis of OA and was associated with cartilage degeneration. The efficacy of PRP can be observed from reduced perfusion and MRI T2∗ values.

Inflammation and Hypervascularization in a Large Animal Model of Knee Osteoarthritis: Imaging with Pathohistologic Correlation.

PURPOSE: To evaluate if synovial inflammation and hypervascularization are present in a dog model of knee osteoarthritis and can be detected on conventional magnetic resonance imaging (MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), contrast-enhanced magnetic resonance imaging (CE-MRI), and quantitative digital subtraction angiography (Q-DSA) imaging. MATERIALS AND METHODS: Six dogs underwent MRI and angiography of both knees before and 12 weeks after right knee anterior cruciate ligament injury. Synovial vascularity was evaluated on CE-MRI, DCE-MRI, and Q-DSA by 2 independent observers. Synovial inflammation and vascularity were histologically scored independently. Cartilage lesions and osteophytes were analyzed macroscopically, and cartilage volumetry was analyzed by MRI. Vascularity and osteoarthritis markers on imaging were compared before and after osteoarthritis generation, and between the osteoarthritis model and the control knee, using linear mixed models accounting for within-dog correlation. RESULTS: In all knees, baseline imaging showed no abnormalities. Control knees did not develop significant osteoarthritis changes, synovial inflammation, or hypervascularization. In osteoarthritis knees, mean synovial enhancement score on CE-MR imaging increased by 13.1 ± 0.59 (P < .0001); mean synovial inflammation variable increased from 47.33 ± 18.61 to 407.97 ± 18.61 on DCE-MR imaging (P < .0001); and area under the curve on Q-DSA increased by 1058.58 ± 199.08 (P = .0043). Synovial inflammation, hypervascularization, and osteophyte formations were present in all osteoarthritis knees. Histology scores showed strong correlation with CE-MR imaging findings (Spearman correlation coefficient [SCC] = 0.742; P = .0002) and Q-DSA findings (SCC = 0.763; P < .0001) and weak correlation with DCE-MR imaging (SCC = -0.345; P = .329). Moderate correlation was found between CE-MR imaging and DSA findings (SCC = 0.536; P = .0004). CONCLUSIONS: In this early-stage knee osteoarthritis dog model, synovial inflammation and hypervascularization were found on imaging and confirmed by histology.

Immediate ACL reconstruction prevents microvascular pathophysiology in the uninjured MCL that is not fully reversed by delayed ACL reconstruction.

Anterior cruciate ligament (ACL) injury induces maladaptive vascular responses that degrade medial collateral ligament (MCL) function. The purpose of this study was to determine if early or delayed ACL reconstruction can prevent or reverse the abnormal changes in vascular function that occur in the uninjured MCL after ACL injury. Twenty-four rabbits were divided into four groups (n = 6); control, ACL-deficient (ACL-X), immediate ACL reconstructed (ACL-IR) and delayed ACL reconstructed (ACL-DR). After 8 weeks, MCLs were assessed for blood flow, responses to acetylcholine (ACh) and phenylephrine (Phe) and autoregulatory responses, using laser speckle perfusion imaging. In ACL-X knees, blood flow in the MCL increased by 2.5-fold compared to control. MCL hyperemia was diminished in ACL-DR knees and was unaltered in ACL-IR knees. MCL vasculature was unresponsive to ACh and Phe in ACL-X. These responses were partially restored by ACL reconstruction. Autoregulatory responses were not significantly different between groups. ACL-DR decreased hyperemia in the MCL and partially attenuated abnormal MCL vascular responses. ACL-IR was more effective at preventing MCL hyperemia and preserving vascular responsiveness to ACh and Phe. This suggests that the vascular alterations in the uninjured rabbit MCL are largely caused by abnormal mechanical loading resulting from ACL deficiency and can be prevented through early reconstruction. Early ACL reconstruction could limit the progression of microvascular dysfunction of the MCL, and preserve physiological joint homeostasis. This might prevent joint degeneration and delay the progression of osteoarthritis.

Differential function of nitric oxide in murine antigen-induced arthritis.

BACKGROUND: The aim of our study was to investigate the role of inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) production in different stages of murine antigen-induced arthritis (AiA). METHODS: Clinical, histological and microcirculatory parameters (measured by intravital fluorescence microscopy) were assessed in the knee joint during acute and chronic AiA after inhibition of iNOS with L-N(6)-(1-iminoethyl)lysine (L-NIL). Plasma concentrations of and were evaluated by the Griess reaction and the expression of iNOS, P- and E-selectin, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) by immunohistochemistry. RESULTS: In both stages of the disease, plasma concentrations of and were increased and iNOS was expressed. In the acute phase, swelling, leucocyte adhesion, leucocyte infiltration and expression of adhesion molecules were increased in arthritic animals treated with L-NIL in comparison with untreated arthritic animals. In the chronic phase, no change in the disease parameters could be detected after L-NIL treatment. CONCLUSION: Increased NO production induced by iNOS during the acute phase of AiA can be regarded as a protective response in the prevention of further leucocytic infiltration and joint destruction, whereas it seems to play a subordinate role in chronic AiA.

The surgical anatomy of the stifle joint in sheep.

OBJECTIVE: To provide a detailed description of the surgical anatomy of the stifle joint in sheep. STUDY DESIGN: The results from analysis of cadaveric dissections (14 stifle joints) and stifle radiographs (8 sets of mediolateral and craniocaudal radiographs) are presented. ANIMALS: Skeletally mature ewes of mixed breeds. CONCLUSIONS: Although the anatomy of the ovine stifle joint is similar to that of the human knee joint, a number of unique features were identified. These included the presence of the tendon of the m. extensor digitorum longus on the craniolateral aspect of the stifle joint, the absence of a cranial meniscofemoral ligament (ligament of Humphrey) in the caudal joint space, and attachment of the patellar tendon to the cranial pole of the patella (rather than to the distal pole, as in humans). The implications of these differences are discussed with reference to the suitability of the ovine stifle as a surgical model for the human knee joint.

Vascular supply of the equine stifle joint.

The vascular supply of the equine stifle joint was investigated, using latex vascular injections of pelvic limbs from 3 adult horses and 6 ponies. Vessels were grossly dissected to the small arteriole level. The primary source of blood supply was the femoral artery and its branches which entered the joint on the caudal and medial surfaces. The superficial vasculature arose from the caudal branch of the deep circumflex iliac artery cranially and laterally, and from the saphenous and descending genicular arteries medially. The deep vasculature arose from the popliteal artery and its branches on the caudal joint surface. These 2 layers of vessels arborized to form the vascular rete which surrounded the joint and gave off branches to supply the articular capsule and the intraarticular structures. Venous drainage paralleled arterial pathways.