The term ischemia-reperfusion injury describes the experimentally and clinically prevalent finding that tissue ischemia with inadequate oxygen supply followed by successful reperfusion initiates a wide and complex array of inflammatory responses that may both aggravate local injury as well as induce impairment of remote organ function. Conditions under which ischemia-reperfusion injury is encountered include the different forms of acute vascular occlusions (stroke, myocardial infarction, limb ischemia) with the respective reperfusion strategies (thrombolytic therapy, angioplasty, operative revascularization) but also routine surgical procedures (organ transplantation, free-tissue-transfer, cardiopulmonary bypass, vascular surgery) and major trauma/shock. Since the first recognition of ischemia-reperfusion injury during the 1970s, significant knowledge has accumulated and the purpose of this review is to present an overview over the current literature on the molecular and cellular basis of ischemia-reperfusion injury, to outline the clinical manifestations and to compile contemporary treatment and prevention strategies. Although the concept of reperfusion injury is still a matter of debate, it is corroborated by recent and ongoing clinical trials that demonstrated ischemic preconditioning, inhibition of sodium-hydrogen-exchange and administration of adenosine to be effective in attenuating ischemia-reperfusion injury.

Because early mortality was significantly higher in patients receiving endovascular treatment for proximal aortic disease, endovascular-based approaches proved to be feasible alternatives to hybrid surgical procedures, especially when they were performed for aneurysms located in the distal aortic arch. Whereas cerebral ischemia accompanies both surgical and endovascular involvement of the supra-aortic vessels, endoleaks and aneurysm growth remain hallmarks of endovascular supra-aortic repair. Because surgical revision had no impact on mortality, complete surgical debranching may become the option of choice for patients with good life expectancy suffering from proximal aortic arch disease, whereas total endovascular procedures could be particularly advantageous in patients with short life expectancy and distal aortic arch disease.

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The aim of this study was to determine the pathophysiological mechanisms of postcardiopulmonary bypass (CPB) intestinal dysfunction using an in vivo canine model of extracorporeal circulation. Six dogs underwent a 90 min hypothermic CPB with continuous monitoring of mean arterial blood pressure (MAP) and mesenteric blood flow (MBF). Reactive hyperemia and vasodilator responses of the superior mesenteric artery to acetylcholine and sodium nitroprusside were determined before and after CPB. Mesenteric lactate production, glucose consumption, creatine kinase (CK) release and venous free radicals were determined. CPB induced a significant fall (p < 0.05) in MAP and MBF. After CPB, reactive hyperemia (-26 +/- 15% versus -53 +/- 2%, p < 0.05) and the response to acetylcholine (-42 +/- 9 versus -55 +/- 6%, p < 0.05) were significantly decreased. Reperfusion increased lactate production (0.8 +/- 0.09 mmol/L versus 0.4 +/- 0.18, p < 0.05) and the CK release (446 +/- 98 U/L versus 5 +/- 19 U/L, p < 0.01). Endothelial dysfunction, conversion from aerobic to anaerobic metabolism, and intestinal cell necrosis seem to be responsible for intestinal complications associated with CPB.

Poly-ADP-ribose synthetase inhibition improves the recovery of myocardial and endothelial function after cardiopulmonary bypass with hypothermic cardiac arrest.

The L-arginine-nitric oxide (NO) pathway plays an important role in ischemia-reperfusion injury. In the present study we investigated the role of NO-precursor L-arginine on cardiac and pulmonary function after reversible hypothermic ischemia. Twelve anesthetized dogs underwent cardiopulmonary bypass. After 60 minutes of hypothermic cardiac arrest, reperfusion was started with application of either saline vehicle (control, n = 6) or L-arginine (40 mg/kg i.v. bolus then 3 mg/kg i.v. infusion during the first 20 minutes of reperfusion, n = 6). The vasodilative response to acetylcholine was significantly higher in the L-arginine group (P < 0.05). The preload recruitable stroke work of the left ventricle decreased significantly after reperfusion, however remained unchanged in the L-arginine group. Arterial blood gas analysis did not show any difference between the two groups. Plasma L-arginine concentration reached peak level at 20 minutes of administration (675.0 +/- 66.6 versus 207.7 +/- 14.5 in the L-arginine group, P < 0.05) and returned to baseline at 40 minutes, while in the control group remained unchanged during ischemia and reperfusion (276.2 +/- 71.6 versus 283.8 +/- 38.5, P< 0.05). Plasma nitrite concentration followed L-arginine changes parallel, however nitrate levels increased slower. Supplementation with L-arginine during reperfusion prevents myocardial and endothelial dysfunction, however does not have any overriding effect on pulmonary function. Considerably rapid elimination of plasma L-arginine was demonstrated during early reperfusion.

OBJECTIVES The pathophysiology of delirium after cardiac surgery is complex. The present study aims to determine perioperative risk factors and construct a scoring system for postoperative delirium based on the type of surgery. METHODS Three hundred patients undergoing coronary artery bypass grafting (CABG; n = 150) or valve and/or aortic surgery ± CABG (n = 150) were retrospectively evaluated. RESULTS The incidence of delirium (32%) was similar in subgroups (28.7% and 33.33%, P = 0.384). Delirium patients were older [71.3 (standard deviation: 8.5) vs 66.6 (standard deviation: 9.5), P &lt; 0.001; 70.0 (standard deviation: 9.6) vs 62.5 (standard deviation: 12.6), P &lt; 0.001] and required more packed red blood cell units [2.1 (standard deviation: 2.1) vs 4.2 (standard deviation: 4.0), P &lt; 0.001; 2.4 (standard deviation: 3.3) vs 5.4 (standard deviation: 5.9), P &lt; 0.001] and fresh frozen plasma units [6.1 (standard deviation: 2.9) vs. 8.0 (standard deviation: 4.2), P &lt; 0.001; 6.3 (standard deviation: 3.4) vs 10.8 (standard deviation: 7.2), P &lt; 0.001] in CABG and valve/aortic subgroups, respectively. Delirium was associated with longer operation time [298.3 (standard deviation: 98.4) vs 250.6 (standard deviation: 67.8) min, P &lt; 0.001], cardiopulmonary bypass (CPB) time [171.5 (standard deviation: 54.9) vs 140.98 (standard deviation: 45.8) min, P &lt; 0.001] and cardiac arrest time [112 (standard deviation: 35.9) vs 91.9 (standard deviation: 28.6), P &lt; 0.001] only in the valve/aortic group (versus non-delirium). Multivariate regression analysis identified an association between delirium and age [odds ratio: 1.056 (95% confidence interval: 1.002–1.113), P = 0.041], CPB time [odds ratio: 1.1014 (95% confidence interval: 1.004–1.025), P = 0.007], fresh frozen plasma transfusion [odds ratio: 1.127 (95% confidence interval: 1.006–1.262), P = 0.039] and atrial fibrillation [odds ratio: 4.801 (95% confidence interval: 1.844–12.502), P &lt; 0.001] after valve/aortic surgery (area under the curve 0.835, P &lt; 0.001) and between delirium and age [odds ratio: 1.089 (95% confidence interval: 1.023–1.160), P = 0.007] and ventilation time [odds ratio: 1.068 (95% confidence interval: 1.026–1.113), P = 0.001] after isolated CABG (area under the curve 0.798, P &lt; 0.001). The cross-validation of the results by k-fold logistic regression revealed for the entire patient cohort an overall average accuracy of the prediction model of 0.764, with a false-positive rate of 0.052 and a false-negative rate of 0.18. CONCLUSIONS Age, CPB time, ventilation, transfusion and atrial fibrillation are differently associated with delirium depending on the operative characteristics. Optimization of intraoperative parameters and use of risk calculators may enable early institution of pharmacotherapy and improve overall outcome after cardiac surgery.

The aim of the present study was to determine whether the ET(A) receptor antagonist LU135252 can protect the mesenterium against ischaemia/reperfusion (I/R) damage. Direct occlusion of the superior mesenteric artery was performed for 30 min in two groups of dogs. Declamping was followed by 90 min of reperfusion. Mesenteric release of ET-1 was studied in series 1 (n=6). In series 2, 5 min before cross-clamping, the treated group (n=7) received an intravenous bolus of LU135252 (5 mg/kg), whereas the control group (n=6) was given vehicle. Mean arterial blood pressure and mesenteric blood flow were recorded. Mesenteric venous and systemic arterial serum lactate and glucose, plasma creatine kinase and free radical concentrations were determined at 15 min intervals. Ischaemia for 30 min induced a significant increase (P<0.05) in mesenteric ET-1 release (1594+/-526 pg/min, compared with 343+/-258 pg/min at baseline), which had returned to baseline after 20 min of reperfusion. LU135252 administration significantly decreased mesenteric blood flow during ischaemia (204+/-23%) compared with controls (320+/-34%, P<0.05). In contrast, mesenteric blood flow was higher in the treated group (120+/-19% compared with 82+/-7%; P<0.05) after 90 min of reperfusion. Mesenteric lactate production was reduced by ET(A) antagonist administration under ischaemia (0.77+/-0.02 mmol/l) compared with controls (1.36+/-0.04 mmol/l; P<0.01). Lower levels of venous creatine kinase were present in the treated group during ischaemia as well as after reperfusion (120+/-7% compared with 150+/-16%; P<0.01). Administration of LU135252 also improved the total scavenger capacity of the mesenteric bed during ischaemia [(15.9+/-3.9)x10(6) compared with (6.4+/-3.6)x10(6) relative light units; P<0.05] and early reperfusion [(8.7+/-3.1)x10(6) compared with (1.1+/-2.9)x10(6) relative light units]. Thus ET-1 is involved in I/R-induced disturbances in the intestine. LU135252 seems to counteract these changes, in part by increasing the antioxidant capacity of the mesenterium.