Inflammatory predictors of ongoing pain 2 years following knee replacement surgery.

INTRODUCTION: The prevalence of unrelieved pain following total knee arthroplasty (TKA) is substantial. OBJECTIVE: We asked if cytokine markers of inflammation in preoperative serum or knee synovial fluid (SF) would predict pain 2 years following TKA. METHODS: Demographic data and functional outcomes were recorded at baseline and 2 years with the WOMAC index. Serum and SF tissue samples were collected at the time of surgery. Linear regression modeling was used to determine the relationship between SF/serum inflammatory markers and a lesser improvement in self reported pain at two years follow-up. RESULTS: Of our 28 patient cohort, significant correlations between serum and SF levels were found for IL-1ß (p<0.002), MIP-1ß (p<0.001), adiponectin (p<0.001) and leptin (p<0.001). Adjusted analysis showed that greater SF concentrations of TNF-α, MMP-13 and IL-6 were independent predictors of less pain improvement at two years follow-up (p<0.05). CONCLUSIONS: Those patients, having ongoing pain despite no clinical or radiological cause, may have an inflammatory profile characterizing a predisposition to ongoing pain after TKA. LEVEL OF EVIDENCE: Prognosis study, Level 2.

Mast cell stabilization improves cardiac contractile function following hemorrhagic shock and resuscitation.

Hemorrhagic shock (HS) is associated with cardiac contractile dysfunction. Mast cell (MC) degranulation is hypothesized to mediate the cardiodepressant effect. Cardiac function was assessed after HS and resuscitation (HS/R) with the administration of the MC stabilizers to prevent MC degranulation. Anesthetized male Sprague-Dawley rats were randomized to sham-operated control or HS/R groups and underwent 60 min of HS followed by 2 h of resuscitated reperfusion. Animals in the HS/R groups were randomized to receive cromolyn (5 mg/kg), ketotifen (1 mg/kg), or saline 15 min before shock. Hearts were excised following HS or 2 h of reperfusion, and function was assessed on a Langendorff apparatus. A second group of randomized animals had serial blood samples taken to assess MC degranulation by quantifying levels of serum beta-hexosaminidase. Hearts were excised at 0 min (before HS) and following 60 min of HS (before resuscitation) for a histological evaluation of MC density and degranulation. In vivo MC stabilization using ketotifen and cromolyn improved cardiac peak systolic pressure (P < 0.05), contractility (P < 0.05), and relaxation (P < 0.05) compared with that of HS controls. Serum beta-hexosaminidase increased during HS/R and was inhibited by MC stabilization (P < 0.05). Degranulation was inhibited when assessed by histochemistry and immune fluorescence. The inhibition of MC degranulation can significantly improve cardiac function following HS/R.