In vivo blood flow after rotator cuff reconstruction in a sheep model: comparison of single versus double row.

PURPOSE: Arthroscopic double-row (DR) suture anchor repair of rotator cuff tears has been shown to be superior to most single-row (SR) techniques with regard to footprint reconstruction, load to failure and tendon-to-bone contact pressures. The hypothesis of this study was that the greater contact pressures of DR techniques would compromise blood flow to a higher degree than SR repair. The aim of this experimental study was to evaluate the effect of a DR and a SR technique on tendon blood flow in a sheep model. METHODS: Eighteen sheep underwent detachment and immediate repair of the infraspinatus tendon using either a Mason-Allen or a suture-bridge technique. Tendon blood flow was measured using laser Doppler flowmetry before detachment, immediately after repair and 12 weeks thereafter. Six regions of interest were measured, three over the lateral and three over the medial aspect of the footprint. RESULTS: Immediately after repair, tendon blood flow decreased significantly in both repair groups (P = 0.004). In the SR group, blood flow decreased by 100.1 arbitrary units (AU) (83.6 %) after repair, in the DR by 81.4 AU (90.5 %). Subgroup analysis showed blood flow over the lateral aspect of the footprint decreased by 126.3 AU (92.2 %) in the SR and 84.4 AU (90.9 %) in the DR group, whereas over the medial aspect, it decreased by 73.9 AU (72.0 %) in the SR and 78.5 AU (90.1 %) in the DR group. None of the differences between the groups were significant. At 12 weeks, measured blood flow in the DR group had increased to 90.1 AU (100.2 %) compared to the native tendons and was at 72.5 AU (60.5 %) for the SR group. Again, the difference between SR and DR group was not statistically significant (n.s.). Assessment for retears showed that 4 of 8 tendons (50 %) in the DR group and 3 of 9 tendons (33.3 %) in the SR group had to be classified as re-ruptures. CONCLUSION: Suture anchor repair leads to an intraoperative decrease in tendon blood flow regardless of the repair technique. A significant difference between SR and DR repair was not found. These findings indicate that tendon blood flow should not be a factor to determine the use of either repair technique over the other.

Role of arginine vasopressin and terlipressin as first-line vasopressor agents in fulminant ovine septic shock.

PURPOSE: To compare the effects of first-line therapy with low-dose arginine vasopressin (AVP) or terlipressin (TP) on mesenteric blood flow, plasma AVP levels, organ function and mortality in ovine septic shock. METHODS: Twenty-four adult ewes were anesthetized and instrumented for chronic hemodynamic monitoring. A flow-probe was placed around the superior mesenteric artery, and feces were extracted from the cecum. Following baseline measurements, feces were injected into the peritoneal cavity. When mean arterial pressure (MAP) decreased to less than 60 mmHg, animals were randomly assigned to receive AVP (0.5 mU kg(-1) min(-1)), TP (1 microg kg(-1) h(-1)) or saline (n = 8 each). A norepinephrine infusion was titrated to maintain MAP at 70 +/- 5 mmHg in all groups. RESULTS: Cardiovascular pressures, cardiac output, mesenteric blood flow, and lung tissue concentrations of 3-nitrotyrosine and hemoxygenase-1 were similar among groups throughout the study period. TP infusion resulted in lower plasma AVP concentrations, reduced positive net fluid balance, increased central venous oxygen saturation and slightly prolonged survival compared to control and AVP-treated animals. However, TP treatment was associated with higher liver transaminases and lactate dehydrogenase versus control animals after 12 h. CONCLUSIONS: This study provides evidence that the effects of low-dose TP differ from those of AVP, not only as TP has a longer half life, but also because of different mechanisms of action. Although low-dose TP infusion may be superior to sole norepinephrine or AVP therapy in septic shock, the safety of this therapeutic approach should be determined in more detail.

Collagen IX is indispensable for timely maturation of cartilage during fracture repair in mice.

Fracture repair recapitulates in adult organisms the sequence of cell biological events of endochondral ossification during skeletal development and growth. After initial inflammation and deposition of granulation tissue, a cartilaginous callus is formed which, subsequently, is remodeled into bone. In part, bone formation is influenced also by the properties of the extracellular matrix of the cartilaginous callus. Deletion of individual macromolecular components can alter extracellular matrix suprastructures, and hence stability and organization of mesenchymal tissues. Here, we took advantage of the collagen IX knockout mouse model to better understand the role of this collagen for organization, differentiation and maturation of a cartilaginous template during formation of new bone. Although a seemingly crucial component of cartilage fibrils is missing, collagen IX-deficient mice develop normally, but are predisposed to premature joint cartilage degeneration. However, we show here that lack of collagen IX alters the time course of callus differentiation during bone fracture healing. The maturation of cartilage matrix was delayed in collagen IX-deficient mice calli as judged by collagen X expression during the repair phase and the total amount of cartilage matrix was reduced. Entering the remodeling phase of fracture healing, Col9a1(-/-) calli retained a larger percentage of cartilage matrix than in wild type indicating also a delayed formation of new bone. We concluded that endochondral bone formation can occur in collagen IX knockout mice but is impaired under conditions of stress, such as the repair of an unfixed fractured long bone.

Integrity of actin fibers and microtubules influences metastatic tumor cell adhesion.

Tumor cell adhesion within host organ microvasculature, its stabilization and invasion into host organ parenchyma appear to be important steps during formation of distant metastasis. These interactions of circulating tumor cells with the host organs occur in the presence of fluid shear forces and soluble and cellular environmental conditions of the blood that can modulate their cellular responses and possibly their metastatic efficiency. Cytoskeletal components, such as actin filaments and microtubules, can regulate biophysical characteristics and cellular signaling of the circulating cells. Therefore, we investigated the role of these cytoskeletal structures for early steps during metastasis formation in vivo and in vitro. Using an intravital observation technique, tumor cell adhesion of colon carcinoma cells within the hepatic microcirculation of rats and their invasion into liver parenchyma was observed. Disruption of actin filaments increased cell adhesion, whereas tubulin disruption inhibited adhesive interactions in vivo. The impairment of the cytoskeleton modulated adhesion-mediated cell signaling via focal adhesion kinase (FAK) and paxillin under flow conditions in vitro. In the presence of fluid flow, focal adhesions were enlarged and hyperphosphorylated, whereas stress fibers were reduced compared to static cell adhesion. Disruption of microtubules, however, partially inhibited these effects. Combining the in vivo and in vitro results, our study suggested that changes in cell rigidity and avidity of cell adhesion molecules after disruption of cytoskeletal components appear to be more important for initial adhesive interactions in vivo than their interference with adhesion-mediated cellular signal transduction.