No abstract

Aging is associated with insulin resistance, often attributable to obesity and inactivity. Recent evidence suggests that skeletal muscle insulin resistance in aging is associated with mitochondrial alterations. Whether this is true of the senescent myocardium is unknown. Twelve young (Y, 4 years old) and 12 old (O, 11 years old) dogs, matched for body mass, were instrumented with left-ventricular pressure gauges, aortic and coronary sinus catheters, and flow probes on left circumflex artery. Before surgery, all dogs participated in a 6-wk exercise program. Dogs underwent measurements of hemodynamics and plasma substrates before and during a 2-h hyperinsulinemic-euglycemic clamp to measure whole body and myocardial glucose and nonesterified fatty acid uptake. Following the protocol, myocardial and skeletal samples were obtained to measure components of the insulin-signaling cascade and mitochondrial structure. There was no difference in plasma glucose (Y, 90 Ϯ 4 mg/dl; O, 87 Ϯ 4 mg/dl), but old dogs had higher (P Ͻ 0.02) nonesterified fatty acids (Y, 384 Ϯ 48 mol/l; O, 952 Ϯ 97 mol/l) and plasma insulin (Y, 39 Ϯ 11 pmol/l; O, 108 Ϯ 18 pmol/l). Old dogs had impaired total body glucose disposition (Y, 11.5 Ϯ 1 mg⅐ kgThe impaired insulin action was associated with altered insulin signaling and glucose transporter (GLUT4) translocation. There were myocardial mitochondrial structural changes observed in association with decreased expression of uncoupling protein-3. Aging is associated with both whole body and myocardial insulin resistance, independent of obesity and inactivity, but involving altered mitochondrial structure and impaired cellular insulin action. myocardium; mitochondria; uncoupling protein-3 ADVANCED AGE IS ASSOCIATED with the development of whole body insulin resistance and increased incidence of type 2 diabetes in humans (4,9,14,33). Aging is also frequently accompanied by obesity and inactivity that predispose to the development of insulin resistance (6,16,17,32,39). However, it is unclear what independent role aging plays in the pathogenesis of insulin resistance in the absence of obesity and inactivity. Furthermore, it is unclear as to whether these abnormalities in insulin action extend to the senescent myocardium, where continuous contractile function makes inactivity less relevant.Recently, skeletal muscle insulin resistance in both advanced age (1, 28) and in lean offspring of patients with type 2 diabetes (10, 22, 29) was associated with altered mitochondrial protein expression (28) and density (10). These abnormalities were seen in association with increased intracellular lipid accumulation (22,28,29). However, it is unknown whether these same alterations are evident in the senescent myocardium, whether they are associated with altered insulin action, and whether they predispose to altered left ventricle (LV) hemodynamics in the absence of hyperglycemia or other conventional risk factors.Accordingly, the purpose of the present study was to determine whether aging alone was associated with bot...

Hospital-acquired infections add considerable morbidity and mortality to patient care. However, a detailed economic analysis of these infections on an individual case basis has been lacking. The authors examined both the hospital revenues and expenses in 54 cases of patients with central line-associated bloodstream infections (CLABs) over 3 years in 2 intensive care units and compared these financial data with patients who were matched for age, severity of illness on admission, and principal diagnosis. The average payment for a case complicated by CLAB was $64 894, and the average expense was $91733 with gross margin of -$26 839 per case and a total loss from operations of $1 449 306 in the 54 cases. The costs of CLABs and the associated complications averaged 43% of the total cost of care. The elimination of these preventable infections constitutes not only an opportunity to improve patient outcomes but also a significant financial opportunity.

Objective: Few large animal models exist for the study of aortic aneurysms. βaminopropionitrile (BAPN) is a compound known to cause aortic aneurysms by inhibiting lysyl oxidase, a collagen cross-linking enzyme. It is hypothesized that BAPN plus aneurysm induction surgery would result in significant aneurysm formation in swine with biologic properties similar to human disease. Methods: Initial experiments were performed in uncastrated male swine not treated with BAPN (surgery alone). Subsequently, uncastrated male swine were fed BAPN (0.15 grams/kilogram) for 7 days before undergoing surgery: the infrarenal aorta was circumferentially dissected and measured, balloon dilated, perfused with elastase (500 units) and Type 1 collagenase (8000 units), with extraluminal elastase application. In the BAPN groups, daily BAPN feedings continued until swine harvest at postoperative days 7, 14, and 28. Results: Swine undergoing surgery alone (n=12) had significantly less dilation at 28 days compared with BAPN + surgery swine (51.9±29.2% (0-100%) vs. 113.5±30.2% (52.9-146.2%); p<0.0003). Mean aortic dilation in animals undergoing treatment with surgery and BAPN was 86.9%±47.4% (range, 55.6-157.1%), 105.4%±58.1% (50-133.3%), and 113.5%±30.2% (52.9-146.2%) at 7, 14, and 28 days, respectively. In the BAPN + surgery group, significant elastolysis was present at all time points, while aortic wall collagen content was not significantly different. Smooth muscle cells were significantly depleted at 14 and 28 days, and M1 macrophages were increased at 14 and 28 days (p<0.05, all). Matrix metalloproteinase 2 was elevated at 7 days

BACKGROUND: Current ex vivo lung perfusion (EVLP) protocols aim to achieve perfusion flows of 40% of cardiac output or more. We hypothesized that a lower target flow rate during EVLP would improve graft function and decrease inflammation of donation after circulatory death (DCD) lungs. METHODS: A porcine DCD and EVLP model was utilized. Two groups (n = 4 per group) of DCD lungs were randomized to target EVLP flows of 40% (high-flow) or 20% (low-flow) predicted cardiac output based on 100 ml/min/kg. At the completion of 4 hours of normothermic EVLP using Steen solution, left lung transplantation was performed, and lungs were monitored during 4 hours of reperfusion. RESULTS: After transplant, left lung−specific pulmonary vein partial pressure of oxygen was significantly higher in the low-flow group at 3 and 4 hours of reperfusion (3-hour: 496.0 § 87.7 mm Hg vs. 252.7 § 166.0 mm Hg, p = 0.017; 4-hour: 429.7 § 93.6 mm Hg vs. 231.5 § 178 mm Hg, p = 0.048). Compliance was significantly improved at 1 hour of reperfusion (20.8 § 9.4 ml/cm H 2 O vs. 10.2 § 3.5 ml/cm H 2 O, p = 0.022) and throughout all subsequent time points in the low-flow group. After reperfusion, lung wet-to-dry weight ratio (7.1 § 0.7 vs. 8.8 § 1.1, p = 0.040) and interleukin-1b expression (927 § 300 pg/ng protein vs. 2,070 § 874 pg/ng protein, p = 0.048) were significantly reduced in the low-flow group. CONCLUSIONS: EVLP of DCD lungs with low-flow targets of 20% predicted cardiac output improves lung function, reduces edema, and attenuates inflammation after transplant. Therefore, EVLP for lung rehabilitation should use reduced flow rates of 20% predicted cardiac output.