***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: BACKGROUND Endothelial dysfunction leading to neutrophil infiltration of tissues has been implicated in tissue injury caused by ischemia-reperfusion ( IR ) . Tissue injury during IR can be reduced by prior ischemic preconditioning ( IPC ) . In humans , it is unclear whether endothelial dysfunction occurs during IR or whether IPC offers protection against endothelial dysfunction and inflammatory cell activation . We studied the effects of experimental IR on endothelial and neutrophil function in the human forearm in vivo and examined the protection afforded by IPC . METHOD AND RESULTS The forearm was made ischemic for 20 minutes by inflating a blood pressure cuff to 200 mm Hg . We assessed endothelial function of conduit ( radial artery flow-mediated dilation ) and resistance vessels ( blood flow responses to intra-arterial infusion of the endothelium-dependent dilator acetylcholine ) in healthy volunteers before and after IR . IR reduced flow-mediated dilation of the radial artery at 15 minutes of reperfusion ( 7.7+/-1.5 % to 3.5+/-0.9 % ) and the dilator response of resistance vessels to acetylcholine at 15 , 30 , and 60 minutes of reperfusion . IR did not reduce the dilator response of the radial artery to glyceryltrinitrate and only caused a small reduction of glyceryltrinitrate-induced dilation of resistance vessels at 60 minutes of reperfusion . IR caused an increase in neutrophil CD11b expression and platelet-neutrophil complexes in the circulating blood .  IPC ( three 5-minute episodes of ischemia ) before IR prevented endothelial dysfunction and neutrophil activation . CONCLUSIONS A clinical ly relevant period of ischemia-reperfusion causes profound and sustained endothelial dysfunction and systemic neutrophil activation .  IPC attenuates both of these effects in humans OBJECTIVE : To investigate whether ischaemic preconditioning could reduce myocardial injury , as manifest by troponin T release , in patients undergoing elective coronary artery bypass surgery . DESIGN : R and omised controlled trial . SETTING : Cardiothoracic unit of a tertiary care centre . PATIENTS : Patients with three vessel coronary artery disease and stable angina admitted for first time elective coronary artery bypass surgery were invited to take part in the study ; 33 patients were r and omised into control or preconditioning groups . INTERVENTION : Patients in the preconditioning group were exposed to two additional three minute periods of myocardial ischaemia at the beginning of the revascularisation operation , before the ischaemic period used for the first coronary artery bypass graft distal anastomosis . MAIN OUTCOME MEASURE : Serum troponin T concentration at 72 hours after cardiopulmonary bypass . RESULTS : The troponin T assays were performed by blinded observers at a different hospital . All patients had undetectable serum troponin T ( < 0.1 microgram/l ) before cardiopulmonary bypass , and troponin T was raised postoperatively in all patients . At 72 hours , serum troponin T was lower ( P = 0.05 ) in the preconditioned group ( median 0.3 microgram/l ) than in the control group ( median 1.4 micrograms/l ) . CONCLUSIONS : The direct application of a preconditioning stimulus in clinical practice has been shown , for the first time , to protect patients against irreversible myocyte injury Objective : To evaluate the protective effects of ischemic preconditioning in a prospect i ve r and omized study involving a large population of unselected patients and to identify factors affecting the protective effects . Summary Background Data : Ischemic preconditioning is an effective protective strategy in several animal models . Protection has also been suggested in a small series of patients undergoing a hemihepatectomy with 30 minutes of inflow occlusion . Whether preconditioning confers protection in other types of liver resection and longer periods of ischemia is unknown . Therefore , we conducted a prospect i ve r and omized study to evaluate the impact of ischemic preconditioning in liver surgery . Methods : A total of 100 unselected patients undergoing major liver resection ( > bisegmentectomy ) under inflow occlusion for at least 30 minutes were r and omized during surgery to either receive or not receive an ischemic preconditioning protocol ( 10 minutes of ischemia followed by 10 minutes of reperfusion ) . Univariate and multivariate analyses were performed to identify independent factors affecting the protective effects of ischemic preconditioning .  ATP contents in liver were measured as a possible mechanism of protection . Results : Both groups ( n = 50 in each ) were comparable regarding age , gender , duration of inflow occlusion , and resected liver volumes . Postoperative serum transaminase levels were significantly lower in preconditioned than in control patients ( median peak AST 364 U/L vs. 520 U/L , P = 0.028 ; ALT 406 vs. 519 U/L , P = 0.049 ) . Regression multivariate analysis revealed an increased benefit of ischemic preconditioning in younger patients , in patients with longer duration of inflow occlusion ( up to 60 minutes ) , and in cases of lower resected liver volume ( < 50 % ) . Patients with steatosis were also particularly protected by ischemic preconditioning .  ATP content in liver tissue was preserved by ischemic preconditioning in young but not older patients . Conclusions : This study establishes ischemic preconditioning as a protective strategy against hepatic ischemia in humans . The strategy is particularly effective in young patients requiring a prolonged period of inflow occlusion , and in the presence of steatosis , and is possibly related to preservation of ATP content in liver tissue . Other strategies are needed in older patients Hepatic pedicle clamping ( HPC ) is widely used to control intraoperative bleeding during hepatectomy ; intermittent HPC is better tolerated but is associated with blood loss during each period of reperfusion . Recently , it has been shown that ischemic preconditioning ( IP ) reduces the ischemia-reperfusion damage for up to 30 minutes of continuous clamping in healthy liver . We evaluated the safety of IP for more prolonged periods of continuous clamping in 42 consecutive patients with healthy liver su bmi tted to hepatectomy .  IP was used in 21 patients ( group A ) ; mean + /- SD of liver ischemia was 54 + /- 19 minutes ( range , 27 - 110 ; in 7 cases > 60 minutes ) . In the other 21 patients , continuous clamping alone was used ( Group B ) ; liver ischemia lasted 36 + /- 14 minutes ( range , 13 - 70 ; in 2 cases > 60 minutes ) . Two patients in Group A ( 9.5 % ) and 3 in Group B ( 14.2 % ) received blood transfusions . In spite of the longer duration of ischemia ( P=.001 ) , patients with IP had lower aspartate aminotransferase ( AST ; P=.03 ) and alanine aminotransferase ( ALT ; P = not significant ) at postoperative day 1 , with a similar trend at postoperative day 3 . This was reconfirmed by multiple regression analysis , which showed that although postoperative transaminases increased with increasing duration of ischemia and of the operation in both groups , the increases were significantly smaller ( P<.001 ) with the use of preconditioning . In conclusion , the present study confirms that IP is safe and effective for liver resection in healthy liver and is also better tolerated than continuous clamping alone for prolonged periods of ischemia . This technique should be preferred to continuous clamping alone in healthy liver . Additional studies are needed to assess the role of IP in cirrhotic liver and to compare IP with intermittent clamping OBJECTIVES The purpose of this study was to determine whether administration of bradykinin reproduces the cardioprotective effects of ischemic preconditioning ( PC ) in patients undergoing percutaneous transluminal coronary angioplasty ( PTCA ) . BACKGROUND Experimental studies suggest that activation of the bradykinin B2 receptor is an important trigger of ischemic PC . However , it is unknown whether bradykinin can precondition human myocardium against ischemia in vivo . Multicenter clinical trials have demonstrated an anti-ischemic effect of angiotensin-converting enzyme inhibitors , which has been postulated to result from potentiation of bradykinin ; however , direct evidence for an anti-ischemic action of bradykinin in patients is lacking . METHODS Thirty patients were r and omized to receive a 10-min intracoronary infusion of bradykinin ( 2.5 microg/min ) or normal saline . Ten minutes later they underwent PTCA ( three 2-min balloon inflations 5 min apart ) . RESULTS In control patients , the ST-segment shift on the intracoronary and surface electrocardiogram was significantly greater during the first inflation than during the second and third inflations , consistent with ischemic PC . In bradykinin-treated patients , the ST-segment shift during the first inflation was significantly smaller than in the control group , and there were no appreciable differences in ST-segment shift during the three inflations . Measurements of chest pain score and regional wall motion during inflation ( quantitative two-dimensional echocardiography ) paralleled those of ST-segment shift . Infusion of bradykinin had no hemodynamic effects and no significant adverse effects . Thus , intracoronary infusion of bradykinin before PTCA rendered the myocardium relatively resistant to subsequent ischemia , and the degree of this cardioprotective effect was comparable to that afforded by the ischemia associated with the first balloon inflation in control subjects . In a separate cohort of seven patients given the same dose of bradykinin , coronary hyperemia resolved completely within 10 min after the end of the infusion , indicating that bradykinin-induced vasodilation can not account for the protective effects observed during the first balloon inflation . CONCLUSIONS Bradykinin preconditions human myocardium against ischemia in vivo in the absence of systemic hemodynamic changes . Pretreatment with bradykinin appears to be just as effective as ischemic PC and could be used prophylactically to attenuate ischemia in selected patients undergoing PTCA BACKGROUND The timing of onset of angina before myocardial infa rct ion in relation to outcome is unknown . METHODS AND RESULTS We prospect ively determined the importance of the time of onset of preinfa rct ion angina in relation to 30-day outcomes in the TIMI-9B study from st and ardized forms . Of the 3002 patients entered into the study , 425 reported angina before their myocardial infa rct ion . Patients with angina onset within 24 hours of infa rct ion had a lower 30-day cardiac event rate ( mortality , recurrent myocardial infa rct ion , heart failure , or shock ) at 4 % than those with onset of angina > 24 hours ( 17 % ; P=.030 ) . A history of any angina alone was not associated with reduced event rate . Peak creatine kinase levels tended to be lower in the group with angina within 24 hours . These benefits were not due to higher rates of use of antianginal medicines or aspirin and were not a consequence of differences in baseline characteristics or disease states ( hypertension , hypercholesterolemia ) among subgroups . CONCLUSIONS These temporal observations are consistent with the concept of preconditioning by preinfa rct ion angina but do not rule out other mechanisms AIM The cardioprotective effects afforded by volatile anesthetics , i.e. isoflurane , during heart surgery may be due to preconditioning of the myocardium through the activation of KATP channels . The aims of this study were to establish whether glibenclamide prevents the isoflurane-induced cardioprotection in diabetic patients undergoing coronary surgery ( CABG ) and whether this cardioprotective effect can be restored by preoperative shift from glibenclamide to insulin therapy . METHODS We enrolled 60 patients undergoing CABG . Twenty consecutive non-diabetic patients were r and omized to receive conventional anesthesia ( CA ) or conventional anesthesia plus isoflurane ( ISO ) ( added to the inspired oxygen before starting cardiopulmonary bypass ) ; 40 consecutive diabetic patients in chronic treatment with oral glibenclamide  were r and omized to conventional anesthesia ( G-CA ) , conventional anesthesia plus isoflurane ( G-ISO ) , conventional anesthesia after shifting to insulin ( I-CA ) or conventional anesthesia plus isoflurane after shifting to insulin ( I-ISO ) .  Serum levels of cardiac troponin I ( CTnI ) and CK-MB , as markers of ischemic injury , were obtained 1 , 24 , 48 and 96 hours , postoperatively . RESULTS Postoperative peak levels of CTnI and CK-MB were lower in ISO than in CA ( 0.5+/-0.3 vs 2.8+/-2.2 ng/ml , p<0.05 and 61+/-27 vs 79+/-28 U/L , p<0.05 , respectively ) , as well as in I-CA and I-ISO than G-CA and G-ISO groups ( 0.5+/-0.7 and 0.7+/-0.9 vs 3.5+/-3 and 2.7+/-2.5 ng/ml , p<0.05 ; 47+/-7 and 41+/-5 vs 85+/-28 and 50+/-23 U/L , p< 
    Output:
    
At present , there is no evidence for IP occurring in the human intestine , although animal studies attest to the possibility .
Ischemic preconditioning appears to be effective even when applied to a site remote to the organ exposed to ischemia .
However , these favorable effects are less evident in diabetic and elderly patients .
CONCLUSION Ischemic preconditioning is safe for use in elective cardiac , hepatic , and pulmonary surgery .
More studies with greater patient numbers need to be carried out in these areas to demonstrate the efficacy of IP in providing clinical benefit in terms of reducing morbidity and mortality .