Orthotopic liver transplantation (OLT) is one of the most demanding surgical procedures performed. Intraoperative bleeding can be substantial and related to both surgical and nonsurgical causes. A less common but previously reported phenomenon is intraoperative cardiopulmonary thromboembolism precipitating major patient morbidity and mortality. In this paper, we present four cases of intraoperative thromboembolism during OLT. These cases were performed without the concomitant use of antifibrinolytic drugs. We performed a review and analysis of previously reported cases of intraoperative thromboembolism during OLT. Possible causes of thromboembolism, clinical management, use of thromboelastography, and the role of antifibrinolytic drugs are discussed.

OBJECTIVE: To examine the perioperative cardiac morbidity and mortality in patients undergoing major vascular surgery with beta-blockade after a positive stress test or cardiac catheterization. DESIGN: Retrospective review of a quality assurance database. SETTING: A university teaching hospital. PARTICIPANTS: A consecutive series of 31 patients undergoing peripheral vascular or aortic surgery after a positive stress test or catheterization between November 2001 and September 2003. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: All 31 patients had a preoperative positive stress test and/or cardiac catheterization, with 12 having multiple areas at risk for myocardial ischemia. None had an intervening coronary revascularization. Twenty-seven had at least one of the intermediate clinical predictors as defined by the American College of Cardiology and 7 had a left ventricular ejection fraction < 40%. Twenty-three patients had been on a beta-blocker and continued on it, while the remainder started on it de novo perioperatively. None of the patients suffered from myocardial infarction, congestive heart failure, or cardiac death perioperatively. CONCLUSIONS: This case series reports on the authors' experience with patients undergoing high-risk vascular surgery after a positive stress test or catheterization, but without an intervening coronary intervention. All patients received perioperative beta-blockade and had a very low adverse cardiac event rate. With reduction of adverse events by beta-blockade, the likelihood of a positive event may be reduced and the utility of the test in risk stratification may be questioned.

Naturally present antibacterial proteins play an important role in innate host defense. A synthetic peptide mimicking the C-terminal lipopolysaccharide (LPS)-binding domain of rabbit cathelicidin CAP18 was coupled to immunoglobulin (Ig) G to create CAP18(106-138)-IgG, a construct that, in concentrations equimolar to those of peptide alone, binds and neutralizes LPS and kills multiple gram-negative bacterial strains. The protective efficacy of CAP18(106-138)-IgG was evaluated in a model of cecal ligation and puncture in mice. A single intravenous administration of 20 mg/kg CAP18(106-138)-IgG protected against mortality, compared with sham-coupled IgG (P<.03). There was no protection offered by administration of equimolar peptide alone (P=.96). There was a trend toward protection in C3H/HeJ mice that are minimally sensitive to LPS (P=.06), suggesting that direct detoxification of LPS was not the only mechanism of protection. Chemical or genetic coupling of antimicrobial peptides to IgG may be a means of using these peptides to treat infections.

Positive pressure ventilation with large tidal volumes has been shown to cause release of cytokines, including interleukin (IL)-8. The mechanisms regulating lung stretch-induced cytokine production are unclear. We hypothesized that stretch-induced IL-8 production is dependent on the activation of the mitogen-activated protein kinases, c-Jun NH2-terminal kinases (JNK), p38, and/or extracellular signal-regulated kinase (ERK) 1/2. We exposed A549 cells, a type II-like alveolar epithelial cell line, to cyclic stretch at 20 cycles/min for 5 min-2 h. Cyclic stretch induced IL-8 protein production, IL-8 mRNA expression, and JNK activation, but only transient activation of p38 and ERK1/2. Inhibition of stretch-induced JNK activation by adenovirus-mediated gene transfer of stress-activated protein kinase (SEK-1), a dominant-negative mutant of SEK-1, the immediate upstream activator of the JNKs, and pharmacological JNK inhibitor II SP-600125 blocked IL-8 mRNA expression and attenuated IL-8 production. Inhibition of p38 and ERK1/2 did not affect stretch-induced IL-8 production. Stretch-induced activation NF-kappaB and activator protein (AP)-1 was blocked by NF-kappaB inhibitor and JNK inhibitor, respectively. An NF-IL-6 site was not essential for cyclic stretch-induced IL-8 promoter activity. Stretch also induced NF-kappaB-inducing kinase (NIK) activation, and inhibition of NF-kappaB attenuated IL-8 mRNA expression and IL-8 production. We conclude that stretch-induced transcriptional regulation of IL-8 mRNA and IL-8 production was via activation of AP-1 and NF-kappaB and was dependent on JNK and NIK activation, respectively.