1H NMR metabolic profiling of synovial fluid from patients with anterior cruciate ligament tears and hemarthrosis.

OBJECTIVE: To compare the metabolic profiles of synovial fluid (SF) from patients with anterior cruciate ligament tears and hemarthrosis (HA) with that of normal controls, using 1H NMR spectroscopy (NMRS). METHODS: Synovial fluid was collected from eleven patients undergoing arthroscopic debridement within 14 days following an anterior cruciate ligament (ACL) tear and hemarthrosis. Ten additional SF samples were obtained from the knees of osteoarthritis-free volunteers to serve as normal controls. The relative concentrations of twenty-eight endogenous SF metabolites (hydroxybutyrate, acetate, acetoacetate, acetone, alanine, arginine, choline, citrate, creatine, creatinine, formate, glucose, glutamate, glutamine, glycerol, glycine, histidine, isoleucine, lactate, leucine, lysine, phenylalanine, proline, pyruvate, threonine, tyrosine, valine, and the mobile components of glycoproteins and lipids) were evaluated using NMRS and quantified using CHENOMX metabolomics analysis software. Mean differences between groups were evaluated with t-tests controlling for multiple comparisons at an overall error rate of 0.10. RESULTS: Statistically significant increases in the levels of glucose, choline, the branched-chain amino acids leucine, isoleucine, and valine, and the mobile components of N-acetyl glycoproteins and lipids were observed in ACL/HA SF as compared with normal controls; lactate levels were reduced. CONCLUSIONS: Marked changes occur in the metabolic profiles of human knee fluid following ACL injury and hemarthrosis, suggestive of increased demand and accompanying inflammatory response; potentially increased lipid and glucose metabolism; and possible hyaluronan degradation within the joint following trauma.

Off-pump coronary artery bypass grafting provides complete revascularization with reduced myocardial injury, transfusion requirements, and length of stay: a prospective randomized comparison of two hundred unselected patients undergoing off-pump versus conventional coronary artery bypass grafting.

OBJECTIVE: Retrospective comparisons of selected patients undergoing off-pump versus conventional on-pump coronary artery bypass grafting have yielded inconsistent results and raised concerns about completeness of revascularization in off-pump coronary artery bypass grafting. METHODS: Two hundred unselected patients referred for elective primary coronary artery bypass grafting were randomly assigned to undergo off-pump coronary artery bypass grafting with an Octopus tissue stabilizer (Medtronic, Inc, Minneapolis, Minn) or conventional coronary artery bypass grafting with cardiopulmonary bypass by a single surgeon. Revascularization intent determined before random assignment was compared with the revascularization performed. All management followed strict, unbiased, criteria-driven protocols. Patients and nonoperative care providers were blinded to surgical group. RESULTS: Baseline characteristics were similar. The number of grafts performed per patient (mean +/- SD 3.39 +/- 1.04 for off-pump coronary artery bypass grafting, 3.40 +/- 1.08 for conventional coronary artery bypass grafting) and the index of completeness of revascularization (number of grafts performed/number of grafts intended, 1.00 +/- 0.18 for off-pump coronary artery bypass grafting, 1.01 +/- 0.09 for conventional coronary artery bypass grafting) were similar. Likewise, the index of completeness of revascularization was similar between groups for the lateral wall. Combined hospital and 30-day mortalities and stroke rates were similar. Postoperative myocardial serum enzyme measures were significantly lower after off-pump coronary artery bypass grafting, suggesting less myocardial injury. Adjusted postoperative thromboelastogram indices, fibrinogen, international normalized ratio, and platelet levels all showed significantly less coagulopathy after off-pump coronary artery bypass grafting. Patients undergoing off-pump coronary artery bypass grafting received fewer units of blood, were more likely to avoid transfusion altogether, and had a higher hematocrit at discharge. Cardiopulmonary bypass was an independent predictor of transfusion (odds ratio 2.42, P =.0073) by multivariate analysis. More patients undergoing off-pump coronary artery bypass grafting were extubated in the operating room and within 4 hours. Postoperative length of stay (in days) was shorter for off-pump coronary artery bypass grafting (5.1 +/- 6.5 for off-pump coronary artery bypass grafting, 6.1 +/- 8.2 for conventional coronary artery bypass grafting, P =.005 by Wilcoxon test). One patient (in the conventional coronary artery bypass grafting group) required angioplasty for graft closure within 30 days. CONCLUSIONS: When compared with conventional coronary artery bypass grafting with cardiopulmonary bypass, off-pump coronary artery bypass grafting achieved similar completeness of revascularization, similar in-hospital and 30-day outcomes, shorter length of stay, reduced transfusion requirement, and less myocardial injury.

The effects of freeze/thawing on human synovial fluid observed by 500 MHz 1H magnetic resonance spectroscopy.

OBJECTIVE: To investigate the effect of freeze/thaw and low temperature storage on the biomolecular profile of human synovial fluid (SF) using high resolution (500 MHz 1H) magnetic resonance spectroscopy (MRS). METHODS: SF was collected from 12 patients undergoing arthroscopic debridement for treatment of moderate osteoarthritis (OA). Six of the larger samples were divided into 5 parts and treated as follows: the first was analyzed with spin-echo MRS soon after arthroscopy (< 24 h); the 2nd, 3rd, and 4th parts were frozen (-75 degrees C) and thawed for a total of one, 5, and 10 freeze/thaw cycles, respectively, followed by MRS analysis; the 5th part was kept in -75 degrees C storage for > or = 1 year before MRS processing. The 6 smaller samples were divided into 2 parts, the first analyzed shortly after extraction (< or = 24 h), while the 2nd was processed after storage at -75 degrees C for > or = 1 year. Changes in measured metabolite levels were tested for significance using paired t tests. RESULTS: Freeze-thaw cycling had no statistically significant effect on the relative concentrations of endogenous metabolites measured by MRS, though it did alter individual sample results. Prolonged low temperature storage resulted in a significant drop (p < 0.05) in the signal intensities of glucose (45%), N-acetyl glycoproteins (39%), CH2-chain and CH3-terminal and resonances of lipoproteins (46 and 37%, respectively), valine (43%), leucine (35%), and isoleucine (43%). CONCLUSION: This study raises questions about routine procedures that may inadvertently affect the outcomes of quantitative SF analyses. Extended low temperature storage should be avoided as it permanently alters the biochemical profile of SF, possibly leading to erroneous conclusions about the nature of OA related changes in metabolite levels with disease progression.

Effects of hyperbaric oxygen on a human model of injury.

To determine whether intermittent exposures to hyperbaric oxygen enhance recovery from delayed-onset muscle soreness of the quadriceps, we conducted a randomized, controlled, double-blinded, prospective study using 66 untrained men between the ages of 18 and 35 years. After the induction of muscle soreness, these subjects were treated in a hyperbaric chamber over a 5-day period in two phases, with four groups (control, hyperbaric oxygen treatment, delayed treatment, and sham treatment) in the first phase; and three groups (3 days of treatment, 5 days of treatment, and sham treatment) in the second phase. The hyperbaric exposures involved 100% oxygen for 1 hour per day at 2.0 atm. The sham treatments involved 21% oxygen for 1 hour per day at 1.2 atm. We monitored recovery using a leg dynamometer to test eccentric torque of the nondominant quadriceps muscle before and immediately after exercise and at 48 and 96 hours after exercise. Pain was tested daily using visual analog pain scales. In phase 1 a significant difference in recovery of eccentric torque was noted in the treatment group compared with the other groups. In phase 2, the recovery of eccentric torque for the 5-day treatment group was significantly greater than for the sham group from immediately after exercise to 96 hours after exercise. The pain data did not differ significantly in any comparison in either phase. The results suggest that treatment with hyperbaric oxygen may enhance recovery of eccentric torque of the quadriceps muscle from delayed-onset muscle soreness.

1H NMR investigation of changes in the metabolic profile of synovial fluid in bilateral canine osteoarthritis with unilateral joint denervation.

OBJECTIVE: High resolution 1H-nuclear magnetic resonance (NMR) techniques have been used to compare the effects of unilateral knee-joint denervation on the biochemical profiles of synovial fluid in a bilateral canine model of osteoarthritis. METHOD: Paired synovial fluid samples were obtained from seven dogs all of which had previously undergone bilateral anterior cruciate ligament transection, unilateral knee denervation and contralateral sham nerve exposure. All synovial fluid samples were then analyzed using 500 MHz 1H-CPMG spin-echo NMR Spectroscopy to assess differences in endogenous metabolite levels between the paired fluids. RESULTS: The results indicate statistically significant increases in glycerol, hydroxybutyrate, glutamine/glutamate, creatinine/creatine, acetate and N-acetyl-glycoprotein concentrations in synovial fluids from denervated with respect to control knees. Furthermore, significant trends towards elevated lactate, alanine and pyruvate levels in the denervated knee fluids are consistent with our previous findings comparing NMR spectroscopy metabolic profiles of normal and osteoarthritic canine synovial fluids. CONCLUSION: This study lends support to the principle of neurogenic acceleration of OA in that the observed differences in metabolite concentrations found in the denervated knee fluids seem to correlate with metabolic changes resulting from aggravation of the OA process caused by joint denervation.

Comparative study of normal and osteoarthritic canine synovial fluid using 500 MHz 1H magnetic resonance spectroscopy.

High resolution 1H nuclear magnetic resonance spectroscopy has been used to investigate and compare the metabolic profiles of normal and osteoarthritic synovial fluids in a canine model of osteoarthritis. The spectra of osteoarthritic synovial fluid showed (a) increased concentrations of lactate, pyruvate, lipoprotein-associated fatty acids, and glycerol as well as the ketones hydroxybutyrate and hydroxyisobutyrate, (b) reduced levels of glucose, and (c) elevated levels of N-acetylglycoproteins, acetate, and acetamide compared with healthy normal canine synovial fluid. An increase was also observed in the concentrations of the amino acids alanine and isoleucine. These results suggest that (a) the intraarticular environment in canine osteoarthritis is more hypoxic and acidotic than in a normal joint, (b) lipolysis may play an increasingly important role as a source of energy in osteoarthritis, and (c) the N-acetylglycoprotein polymer component of synovial fluid (mostly hyaluronan) seems to be increasingly fragmented and degraded into acetate by way of an acetamide intermediate with progressive osteoarthritis. The observed changes in the biochemical profile of canine osteoarthritic synovial fluid may be useful in understanding alterations in joint metabolism consequent to arthritic diseases and helpful in identifying potential markers of osteoarthritis.

Advances in anesthesia for cardiac surgery: an overview for the 1990s.

Anesthetic care for patients undergoing cardiac surgery has changed dramatically in the past 10 years. Examples of such change include same-day admissions, "fast-track" protocols, selective use of pulmonary artery catheters, transesophageal echocardiography, and the introduction of new drugs such as phosphodiesterase inhibitors and antifibrinolytic agents. Under pressure from our peers and those funding health care, we are making major efforts to reduce costs and the length of hospitalization while maintaining high quality of care.