Citations

Background Recent American Heart Association guidelines highlight the paucity of data on effectiveness and/or mechanisms underlying use of beta-adrenergic receptor (beta AR) antagonists after acute coronary syndromes in patients subsequently undergoing revascularization. It is important to assess whether beta AR antagonists might protect the heart and improve ventricular function in this scenario. The authors therefore used esmolol (an ultra-short-acting beta AR antagonist) to determine whether beta AR antagonist treatment improves left ventricular function in a canine model of acute reversible coronary ischemia followed by coronary reperfusion during cardiopulmonary bypass (CPB). The authors also tested whether the mechanism includes preserved beta AR signaling. Methods Dogs were randomized to either esmolol or saline infusions administered during CPB (n = 29). Pre-CPB and end-CPB transmyocardial left ventricular biopsies were obtained; plasma catecholamine concentrations, myocardial beta AR density, and adenylyl cyclase activity were measured. In addition, left ventricular systolic shortening and postsystolic shortening were determined immediately prior to each biopsy. Results While beta AR density remained unchanged in each group, isoproterenol-stimulated adenylyl cyclase activity decreased 26 +/- 6% in the control group but increased 38 +/- 10% in the esmolol group (pre-CPB to end-CPB, mean +/- SD, P = 0.0001). Left ventricular systolic shortening improved in both groups after release of coronary (LAD) ligature; however, the esmolol group increased to 72 +/- 23% of pre-CPB values compared to 48 +/- 12% for the control group (P = 0.0008). Conclusions These data provide prospective evidence that esmolol administration results in improved myocardial function. Furthermore, the mechanism appears to involve enhanced myocardial beta AR signaling.

Background There is limited information about the frequency of perioperative complications after elective primary orthopedic total hip and knee arthroplasty in contemporary practice. The purpose of this study was to determine the frequency of clinically relevant myocardial infarction, pulmonary embolism, deep venous thrombosis, and death within 30 days after elective primary hip or knee arthroplasty treated according to contemporary perioperative management. Methods The authors examined the medical records of consecutive patients undergoing hip or knee arthroplasty at their institution in a 10-yr period. Prospectively collected databases were used to identify patients with the diagnosis of myocardial infarction, pulmonary embolism, deep venous thrombosis, or death using strict validation criteria and diagnostic-certainty categories. Results A total of 10,244 patients underwent primary total hip or knee arthroplasty in the period of study. Of these, 224 patients had one or more adverse events (overall event rate: 2.2%; myocardial infarction: 0.4%; pulmonary embolism: 0.7%; deep venous thrombosis: 1.5%; death: 0.5%). Most adverse events (myocardial infarction, pulmonary embolism, and death) increased in frequency with older age, particularly for patients aged 70 yr or older. Myocardial infarction occurred more frequently in male patients. There were no differences in the overall event frequency between types of procedure. However, pulmonary embolism was highest in patients undergoing bilateral knee operations. Conclusions The overall frequency of serious complications within 30 days after primary total hip or knee arthroplasty with contemporary practice was 2.2%. Accurate knowledge of the perioperative risks associated with widely performed elective operations can be used to implement management strategies that may further improve patient outcomes and decrease cost.

Background The investigation examined whether primary alcohols could be used as tools to explore the mechanism of anesthetic actions in airway smooth muscle (ASM). The hypothesis was that, like volatile anesthetics, the primary alcohols relax intact ASM by decreasing intracellular Ca2+ concentration ([Ca2+]i) and by inhibiting agonist-induced increases in the force developed for a given [Ca2+]i (Ca2+ sensitivity). Method The effects of butanol, hexanol, and octanol on isometric force in canine tracheal smooth muscle were examined. The effects of hexanol on [Ca2+]i (measured with fura-2) and the relationship between force and [Ca2+]i were studied during membrane depolarization provided by KCl and during muscarinic stimulation provided by acetylcholine. Results The primary alcohols relaxed ASM contracted by KCl or acetylcholine in a concentration-dependent manner, with potency increasing as chain length increased. The alcohols could completely relax the strips, even during maximal stimulation with 10 microM acetylcholine (median effective concentrations of 28 +/- 12, 1.3 +/- 0.4, and 0.14 +/- 0.05 mM [mean +/- SD] for butanol, hexanol, and octanol, respectively). Hexanol decreased both [Ca2+]i and force in a concentration-dependent manner. Hexanol decreased Ca2+ sensitivity during muscarinic stimulation but had no effect on the force-[Ca2+]i relationship in its absence. Conclusions Primary alcohols produce reversible, complete relaxation of ASM, with potency increasing as chain length increases, by decreasing [Ca2+]i and inhibiting increases in Ca2+ sensitivity produced by muscarinic receptor stimulation. These actions mimic those of volatile anesthetics on ASM, a circumstance suggesting that the primary alcohols may be useful tools for further exploring mechanisms of anesthetic effects on ASM.