Direct evidence for substantial mobilization of copper in the coronary flow immediately following prolonged, but not short, cardiac ischemia is presented. In the first coronary flow fraction (CFF) of reperfusion (0.15 ml), after 35 min of ischemia, the level of copper (as well as of iron) was 8-to 9-fold higher than the preischemic value. The levels in subsequent CFFs decreased and reached the preischemic value, indicating that both metals appear in a burst at the resumption of coronary flow. When the first CFF was used in a reaction mixture containing ascorbate and salicylate, the latter underwent chemical hydroxylation and was converted to its dihydroxybenzoate derivatives. Likewise, this CFF promoted the ascorbate-driven DNA degradation. Subsequent 150 CFFs were serially collected and demonstrated low activities. Following 18 min of ischemia, the copper level in the first CFF of reperfusion was only 15% over the preischemic value. In contrast, the mobilization of iron into coronary flow was significant but markedly lower than after 35 min. The levels of copper and the redox activity of the frst CFF correlated well with the degree of loss of cardiac function, after 18 and 35 min of ischemia, respectively. After 18 min of ischemia, cardiac function was about 50% and the damage is considered reversible, whereas after 35 min the functional loss exceeded 80% and is considered irreversible. These results are in accord with the causative role that copper and iron can play in heart injury following ischemia, by virtue of their capacity to catalyze the production of hydroxyl radicals, and could lead to the development of new modalities for intervention in tissue injury.

Background The efficacy of intravenous acetaminophen compared to its oral formulation for postoperative analgesia is unknown. We hypothesized that the addition of acetaminophen to a multimodal analgesia regimen would provide improved pain management in patients following total knee arthroplasty (TKA) and that the effect of acetaminophen would be variable based upon route of delivery. Methods The study was a single center, randomized, double-blinded, placebo-controlled clinical trial on the efficacy of intravenous versus oral acetaminophen in patients undergoing unilateral TKA. One hundred and seventy-four subjects were randomized to one of three groups: intravenous acetaminophen group (IV Group, n=57) received 1-gram intravenous acetaminophen and oral placebo prior to post-anesthesia care unit (PACU) admission; oral acetaminophen group (PO Group, n=58) received 1-gram oral acetaminophen and volume-matched intravenous normal saline; placebo group (Placebo Group, n=59) received oral placebo and volume-matched intravenous normal saline. Pain scores were obtained every 15 minutes during PACU stay. Average pain scores, maximum pain score, and pain scores before physical therapy were compared among the three groups. Secondary outcomes included total opiate consumption, time to PACU discharge, time to rescue analgesia, and time to breakthrough pain. Results The average PACU pain score was similar in the IV Group (0.56 ±0.99 [mean ±SD]) compared to the PO Group (0.67 ±1.20) (P=0.84) and Placebo Group (0.58 ±0.99) (P=0.71). Total opiate consumption at 6 hours (0.47mg hydromorphone equivalents ±0.56 vs 0.54 ±0.53 vs 0.54 ±0.61; P=0.69) and 24 hours (1.25 ±1.30 vs 1.49 ±1.34 vs 1.36 ±1.31; P=0.46) were also similar between the IV, PO, and Placebo Groups. No significant differences were found between all groups for any other outcome. Conclusion Neither intravenous nor oral acetaminophen provides additional analgesia in the immediate postoperative period when administered as an adjunct to multimodal analgesia in patients undergoing TKA in the setting of a spinal anesthetic.

Intact rat ventricular trabeculae were injected with the salt form of fura 2, and the fura 2 ratio signal (R) was used to report intracellular Ca2+ concentration ([Ca2+]i). The fixed end relaxation phase of a twitch is associated with a slowing of the decay of the R signal, or even a reversal, to form a distinct bump, indicating a transient rise in [Ca2+]i. The bump is most prominent at 30°C, and motion artifact is not its cause. Increasing doses of 2,3-butanedione monoxime caused progressive attenuation of the twitch and bump. Increasing the bathing Ca2+ concentration potentiated the twitch and enhanced the bump. Imposed muscle shortening during relaxation caused a much quicker force decline, and this led to the appearance of a much more prominent associated bump. The amplitude of the bump depends on the amplitude of twitch force and the rate of relaxation. These findings can be explained, as in skeletal muscle, by making cross-bridge attachment and Ca2+ binding to troponin C strongly cooperative; therefore, the bump during fast relaxation is produced by a reversal of this cooperativity, leading to rapid dissociation of Ca2+ from troponin C into the myoplasm.

Cuff leakage varies greatly among ETT types and is affected by cuff pressure, PEEP, PIP, and mode.