***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background — Accumulating evidence suggests that the ubiquitous anion nitrite ( NO2− ) is a physiological signaling molecule , with roles in intravascular endocrine nitric oxide transport , hypoxic vasodilation , signaling , and cytoprotection . Thus , nitrite could enhance the efficacy of reperfusion therapy for acute myocardial infa rct ion . The specific aims of this study were ( 1 ) to assess the efficacy of nitrite in reducing necrosis and apoptosis in canine myocardial infa rct ion and ( 2 ) to determine the relative role of nitrite versus chemical intermediates , such as S-nitrosothiols . Methods and Results — We evaluated infa rct size , microvascular perfusion , and left ventricular function by histopathology , microspheres , and magnetic resonance imaging in 27 canines subjected to 120 minutes of coronary artery occlusion . This was a blinded , prospect i ve study comparing a saline control group ( n=9 ) with intravenous nitrite during the last 60 minutes of ischemia ( n=9 ) and during the last 5 minutes of ischemia ( n=9 ) . In saline-treated control animals , 70±10 % of the area at risk was infa rct ed compared with 23±5 % in animals treated with a 60-minute nitrite infusion . Remarkably , a nitrite infusion in the last 5 minutes of ischemia also limited the extent of infa rct ion ( 36±8 % of area at risk ) . Nitrite improved microvascular perfusion , reduced apoptosis , and improved contractile function . S-Nitrosothiol and iron-nitrosyl-protein adducts did not accumulate in the 5-minute nitrite infusion , suggesting that nitrite is the bioactive intravascular nitric oxide species accounting for cardioprotection . Conclusions — Nitrite has significant potential as adjunctive therapy to enhance the efficacy of reperfusion therapy for acute myocardial infa rct ion OBJECTIVE --To assess the possible benefits of intravenous isosorbide dinitrate in acute myocardial infa rct ion and oral isosorbide mononitrate in subacute myocardial infa rct ion . METHODS --316 patients presenting with acute myocardial infa rct ion were entered into double blind placebo controlled clinical trials assessing infa rct size by enzyme release , ventricular size and function by echocardiography , reperfusion by continuous 12 lead ST segment monitoring and late potentials by high resolution electrocardiography . RESULTS --301 patients , of whom 292 ( 97 % ) received thrombolytic treatment , were r and omised on admission to intravenous isosorbide dinitrate or placebo . Overall , there was no significant effect of treatment on infa rct size , ST segment resolution , ventricular remodelling , or late potentials at day 3 . A trend was observed towards a reduction in infa rct size in patients with non-Q wave infa rct ion treated with isosorbide dinitrate . Heterogeneity of nitrate effect was observed in relation to the degree of ST segment elevation on presentation with a clear benefit of isosorbide dinitrate in patients with moderate ST segment elevation ( 472 U/l v 704 U/l , P = 0.003 ) and a trend towards a deleterious effect in patients with marked ST segment elevation ( 1152 U/l v 1058 U/l , P = 0.2 ) . ST segment re-elevation was more common among patients receiving nitrate treatment than in those assigned to placebo ( 29 v 16 , P < 0.05 ) . Some 160 patients underwent a further r and omisation to sustained release isosorbide mononitrate or placebo on day 3 . Echocardiographic volumes after 6 weeks of treatment were similar in the two groups . CONCLUSIONS --No benefit was observed with administration of nitrates in the treatment groups as a whole for either acute or subacute infa rct ion . There was , however , evidence of heterogeneity of effect in the different subgroups of acute infa rct ion , and the possibility that nitrates may have differing actions in different groups of patients should be considered This study was design ed to determine whether a sodium nitropruside infusion during the reperfusion ( payback ) period of cardiopulmonary bypass would minimize arrhythmias during the early postoperative period of coronary artery bypass surgery . A double-blind r and omized study was carried out in 38 patients with no previous history of ventricular arrhythmias . Seventeen received 5 % dextrose in water ( D5W ) and 21 received sodium nitroprusside at the rate of 2 microgram per kilogram per minute during the payback period . The pump flow was kept constant at 2.2 liters per square meter per minute , and mean pressure was maintained at greater than 50 mm Hg . There was a statistically significant difference between the two groups in the number of patients who developed ventricular arrhythmias ( 13 of 17 , or 76 % , in the D5W group versus 6 of 21 , or 29 % , in the sodium nitroprusside group ; p less than 0.005 ) . Twelve of the 13 patients in the D5W group experienced arrhythmias ( 6 ventricular tachycardia and 6 ventricular premature depolarization ) within the first 24 hours , compared to 5 of 12 patients in the nitroprusside group ( 3 ventricular tachycardia and 2 ventricular premature depolarization ) . Only 1 patient in each group developed ventricular arrhythmia after the first postoperative day . One patient in each group experienced atrial arrhythmia during the first 24 hours . After 24 hours , atrial arrhythmias developed in 5 patients in the D5W group ( 35 % ) and 3 patients in the sodium nitroprusside group ( 17 % ) ( p greater than 0.05 ) . The arterial pH ranged from 7.35 to 7.55 , with a Po2 greater than 70 torr and a serum potassium of 3.7 + /- 0.36 mEq per liter in the D5W group and 3.4 + /- 0.34 mEq per liter in the nitroprusside group during the period of arrhythmias . Sodium nitroprusside given during the payback period of cardiopulmonary bypass appears to minimize ventricular arrhythmias in the early postoperative period of coronary artery bypass surgery STUDY OBJECTIVE In order to assess the effects of inhaled nitric oxide ( iNO ) in preventing early-onset lung edema from occurring after lung transplantation , we measured extravascular lung water ( EVLW ) in a group of lung transplant recipients who were at high risk for developing ischemia-reperfusion-induced lung injury . DESIGN Prospect i ve , r and omized study . SETTING S Surgical ICU in a teaching hospital . PATIENTS Thirty double-lung transplant recipients . INTERVENTIONS Patients were r and omized to receive or not receive 20 ppm iNO at the time of reperfusion ( ie , before any occurrence of lung edema ) . In the NO group , iNO was then administered for a 12-h period . A double-dilution technique was used for the serial assessment of EVLW , intrathoracic blood volume , and cardiac index . St and ard hemodynamic and pulmonary parameters were also recorded during the first 3 postoperative days . MEASUREMENTS AND RESULTS Patients who received iNO did not have a different lung water content compared to control subjects ( p = 0.61 [ by analysis of variance ( ANOVA ) ] ) . Blood oxygenation ( ie , Pao(2)/fraction of inspired oxygen [ Fio(2 ) ] ratio ) did not differ between the two groups ( p = 0.61 [ by ANOVA ] ) . In both groups , EVLW and Pao(2)/Fio(2 ) ratio dropped significantly over time , regardless of the use of iNO ( p < 0.01 [ by ANOVA ] ) . CONCLUSIONS In the population studied , prophylactic iNO that was administered at 20 ppm had no effect on pulmonary edema formation and resolution following lung transplantation Free oxygen radicals are produced after coronary artery occlusion and reperfusion . Polyunsaturated fatty acids are oxidized by free radicals to lipid peroxides . Measurements of plasma malondialdehyde ( MDA ) formed by the breakdown of lipid peroxides are often used as markers of lipid peroxidation . The effect of intravenous nitroglycerin on plasma MDA levels was studied in 43 patients who received thrombolytic therapy for acute myocardial infa rct ion .  Plasma MDA levels in patients were elevated on admission to the hospital compared with healthy controls , and normalized within 48 hours . A greater increase in plasma MDA concentrations after thrombolysis was found in patients with noninvasive signs of reperfusion than in patients judged to have a persistent occlusion . In the 23 patients receiving immediate intravenous nitroglycerin infusion , plasma MDA levels did not change from baseline to 90 minutes ( 0.92+/-0.22 and 0.92+/-0.23 micromol/L , p=0.99 ) , whereas a significant increase was found in the 20 control patients who did not receive  nitroglycerin  ( from 0.83+/-0.22 to 1.01+/-0.30 micromol/L , p=0.0004 ) ( p=0.036 for the difference between groups ) . Successful reperfusion after thrombolytic therapy entails increased lipid peroxidation . Intravenous nitroglycerin reduces lipid peroxidation during myocardial ischemia and reperfusion & NA ; The authors studied the relationship between cardiac cytokine release and pump function and whether low‐dose application of sodium nitroprusside ( SNP ) improves cardiac performance during coronary artery bypass graft ( CABG ) creation . Cardiac reperfusion and application of nitric oxide have an influence on cytokine release . However , the functional consequences are unclear . Patients with CABGs ( n = 30 ) with severely compromised left ventricular ejection fraction ( < 40 % ) were treated with either SNP ( 0.5 & mgr;g/kg/min ) or placebo for the first 60 minutes of reperfusion after cardiac arrest . Interleukin (IL)‐6 , IL‐8 , and tumor necrosis factor (TNF)–&agr ; were determined in blood sample s from the radial artery and coronary sinus during reperfusion ( 5 , 35 , and 75 minutes ) . Hemodynamic measurements were performed before and after cardiopulmonary bypass and at the end of surgery . In all patients , the cardiac index at the end of surgery correlated negatively with levels of TNF‐&agr ; at 5 minutes ( r = 0.398 ; P < 0.05 ) , IL‐8 at 35 minutes ( r = 0.394 ; P < 0.05 ) , and IL‐6 at 75 minutes of reperfusion ( r = 0.421 ; P < 0.025 ) . Sodium nitroprusside  improved the cardiac index immediately after reperfusion ( 4.4 L/min/m2 ± 0.3 vs. 3.7 L/min/m2 ± 0.1 ; P = 0.014 ) and at the end of surgery ( 3.8 L/min/m2 ± 0.3 vs. 3.0 L/min/m2 ± 0.2 ; P = 0.023 ) . The negative correlation between cardiac index and transcardiac cytokines suggests that reducing cardiac inflammatory reaction improves postischemic cardiac function . This was achieved by treating CABG patients with the nitric oxide donor SNP at a dosage without vasodilatory action OBJECTIVE Acute renal failure remains a common and serious complication of cardiac surgery . In this r and omized trial , we aim ed to assess whether sodium nitroprusside ( SNP ) infusion during cardiopulmonary bypass ( CPB ) could prevent renal dysfunction after  coronary artery bypass grafting ( CABG )  surgery . METHODS Between October 2004 and May 2006 , 240 consecutive patients with stable angina undergoing elective CABG for multi-vessel coronary artery disease were prospect ively r and omized into control ( n=116 , 72 men , mean age 61.3+/-9.7 years ) or SNP groups ( n=124 , 81 men , 60.8+/-10.8 years ) .  SNP group received SNP after initiation of rewarming period during CPB at a dose of 0.1mg/kg/h and the infusion was concluded by weaning from CPB . The anesthetic and CPB regimes were st and ardized . Blood urea nitrogen ( BUN ) , serum creatinine ( SCr ) , estimated glomerular filtration rate ( eGFR ) , creatinine clearance ( C(Cr ) ) , urine output , serum cardiac specific troponin I ( cTnI ) , creatine kinase cardiac isoenzyme ( CKMB ) , and CPK were measured preoperatively and daily until day 5 after surgery . RESULTS There were no differences in baseline levels of BUN , SCr , eGFR , C(Cr ) , cTnI , CKMB , CPK levels and EuroSCORES between the groups . Although the duration s of cross clamp 
    Output:
    
In 20 ( 77 % ) of 26 studies and four ( 67 % ) of six high- quality studies , patients treated with NO-donor agents experienced reduced I/R injury compared with controls .
Despite a paucity of high- quality clinical investigations , the preponderance of evidence to date suggests that administration of NO-donor agents may be an effective treatment for I/R injury in human subjects