***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 Continuous exposure to organic nitrates is associated with substantial tachyphylaxis . This study compares the development of tolerance during continuous intravenous treatment with nitroglycerin versus nicor and il over a 24-hour period . METHODS AND RESULTS Twenty patients with congestive heart failure and pulmonary capillary wedge pressure ( PCWP ) > or = 18 mm Hg were r and omly assigned to nitroglycerin or nicor and il in a double-blind , crossover study . Doses were titrated to obtain a reduction of PCWP of at least 30 % and then maintained . The mean pretreatment PCWP for nitroglycerin was 25.4 + /- 6.7 mm Hg , decreasing to 19.0 + /- 6.8 mm Hg at 24 hours . The values for nicor and il  were 24.3 + /- 6.3 mm Hg and 15.6 + /- 4.5 mm Hg , respectively . Between-treatment difference was significant ( p < 0.01 ) . The difference between the minimal PCWP value and the 24-hour PCWP value for nitroglycerin was 5.1 mm Hg vs 1.4 mm Hg for nicor and il ( p < 0.005 ) . The mean systemic vascular resistance was 1418 + /- 355 dynes.sec.cm-5 before nitroglycerin infusion , decreasing to 1312 + /- 353 dynes.sec.cm-5 at 24 hours . Corresponding values for  nicor and il were 1420 + /- 366 dynes.sec.cm-5 and 967 + /- 274 dynes.sec.cm-5 . Between-treatment difference was significant ( p = 0.005 ) . Tachyphylaxis developed in 12 ( 60 % ) patients during nitroglycerin infusion versus three patients ( 15 % ) during nicor and il infusion . CONCLUSION This study demonstrates that intravenous nicor and il administration results in significantly less hemodynamic tolerance over a 24-hour period compared with nitroglycerin . This finding may represent a clinical advantage for nicor and il in the short-term treatment of patients with congestive heart failure While recent guidelines for the treatment of acute heart failure syndromes ( AHFS ) recommend pharmacotherapy with vasodilators in patients without excessively low blood pressure ( BP ) , few reports have compared the relative efficiency of vasodilators on hemodynamics in AHFS patients . The present study aim ed to assess the differences in hemodynamic responses between intravenous carperitide and nicor and il in patients with AHFS . Thirty-eight consecutive patients were assigned to receive 48-h continuous infusion of carperitide ( n = 19 ; 0.0125–0.05 μg/kg/min ) or nicor and il ( n = 19 ; 0.05–0.2 mg/kg/h ) . Hemodynamic parameters were estimated at baseline , and 2 , 24 , and 48 h after drug administration using echocardiography . After 48 h of infusion , systolic BP was significantly more decreased in the carperitide group compared with that in the nicor and il group ( 22.1 ± 20.0 % vs 5.3 ± 10.4 % , P = 0.003 ) . While both carperitide and nicor and il significantly improved hemodynamic parameters , improvement of estimated pulmonary capillary wedge pressure was greater in the carperitide group ( 38.2 ± 14.5 % vs 26.5 ± 18.3 % , P = 0.036 ) , and improvement of estimated cardiac output was superior in the nicor and il group ( 52.1 ± 33.5 % vs 11.4 ± 36.9 % , P = 0.001 ) . Urine output for 48 h was greater in the carperitide group , but not to a statistically significant degree ( 4203 ± 1542 vs 3627 ± 1074 ml , P = 0.189 ) . Carperitide and nicor and il were differentially effective in improving hemodynamics in AHFS patients . This knowledge may enable physicians in emergency wards to treat and manage patients with AHFS more effectively and safely Background —The ischemic preconditioning response among elderly patients is known to be lower than in adult patients . Since mitochondrial ATP-sensitive potassium ( KATP ) channels exert preconditioning effects , we undertook this study to determine whether this attenuated activation of KATP channels influences the reduced responsiveness of elderly patients to ischemic preconditioning . Methods and Results —Fifty-six patients undergoing angioplasty for a major epicardial coronary artery were r and omly allocated to either an ischemic preconditioning group , a nicor and il ( an agonist of KATP channels ) group , or a glibenclamide ( an antagonist of KATP channels ) , group based on their age : adult groups ( n=26 ; age , ≤55 years ; mean age , 45±5 years ) and elderly groups ( n=30 ; age , ≥65 years ; mean age , 71±3 years ) . Ischemic preconditioning with a 120-second coronary occlusion significantly lowered the ischemic burden assessed by ST-segment shift , chest pain score , and myocardial lactate extraction ratios in the adult group . This did not occur in the elderly group . The impaired preconditioning responsiveness in the elderly patients was reversed by nicor and il administration or an ischemic period lengthened to 180 seconds . However , nicor and il-induced cardioprotection was abolished by administering glibenclamide in both the adult and elderly groups . Conclusions —The present study demonstrates that preconditioning significantly enhances the tolerance of the heart to subsequent ischemia in adults but not in senescent patients . Since prolonged ischemia and nicor and il are able to mimic preconditioning and can reverse impaired responsiveness , impaired preconditioning of the aged heart appears to be due to an attenuated activation of KATP channels BACKGROUND Nicor and il injection , a potent vasodilator with K(ATP ) channel opening action and nitrate-like action , has been used for treatment of unstable angina . In the present investigation , we examined the effect of intravenous nicor and il on hemodynamics in patients with acute decompensated heart failure ( ADHF ) . METHODS ADHF patients admitted to hospital with pulmonary artery wedge pressure (PAWP)≥18 mm Hg were enrolled . Patients received nicor and il by an intravenous bolus injection of 0.2mg/kg/5 min followed by continuous infusion at a rate of 0.05 , 0.10 , or 0.20mg/kg/h for 6h . RESULTS Nicor and il administration caused a significant decrease in PAWP and increase in the cardiac index ( CI ) that began immediately after the injection and were maintained during the continuous infusion . After 6h , nicor and il administration at 0.2mg/kg/5 min followed by 0.20mg/kg/h result ed in a decrease in PAWP ( 26.5 % , p<0.01 ) , an increase in CI ( 15.8 % , p<0.05 ) , and a decrease in total peripheral resistance ( 13.8 % , p<0.01 ) in a dose-dependent manner . Nicor and il  decreased blood pressure significantly , without an excessive decrease or negative impact even in patients with lower systolic blood pressure . CONCLUSION Intravenous administration of nicor and il , by bolus injection followed by continuous infusion , improves PAWP and CI in ADHF patients immediately and continuously as a potent vasodilator with combined preload and afterload reduction . These results demonstrate that nicor and il is a safe and effective new medication for the treatment of ADHF To evaluate whether hemodynamic tolerance develops to nicor and il , a nitrate and potassium channel opener , 14 patients with chronic heart failure ( CHF ) were treated with nicor and il and 11 were treated with nitroglycerin ( GTN ) . Doses of GTN or nicor and il were titrated to achieve a > or = 20 % reduction in pulmonary capillary wedge pressure ( PCWP ) within 1 hour , and the infusion was maintained at a constant rate for 24 hours . Both groups of patients had comparable hemodynamic parameters before drug infusions were started . The fall in PCWP was identical after 1 hour infusion of either GTN or nicor and il . In the GTN group , PCWP was not significantly different from the baseline value at 12 hours ; however , in the nicor and il group , PCWP remained significantly lower than the preinfusion value for 24 hours . During the study period changes in plasma atrial natriuretic peptide ( ANP ) concentrations paralleled and correlated with changes in PCWP ( r = 0.84 , p < 0.001 ) . These findings indicate that CHF patients develop hemodynamic tolerance to GTN within 12 hours of continuous infusion , but not to nicor and il , which remained hemodynamically effective during the 24-hour period of infusion . Furthermore , plasma ANP concentration may be a useful noninvasive index of hemodynamic tolerance during GTN or nicor and il therapy in patients with CHF Hemodynamic tolerance has been observed within several hours of continuous infusion of nitroglycerin ( NTG ) . We examined the hemodynamic parameters as well as femoral arterial and venous cyclic guanosine monophosphate ( cGMP ) concentrations during intravenous infusion of NTG or nicor and il , a nitrate and potassium channel opener , in patients with congestive heart failure . Doses of NTG or nicor and il were titrated to achieve a > or = 25 % reduction in pulmonary capillary wedge pressure ( PCWP ) within 1 hour , and the infusion was maintained at a constant rate for 24 hours . The reduction in PCWP and mean arterial blood pressure was identical after a 1-hour infusion of either NTG or nicor and il . In the NTG group , PCWP and mean blood pressure were not significantly different from the baseline value at 12 hours , but in the nicor and il group PCWP and mean blood pressure remained significantly lower than the preinfusion value for 24 hours . The cGMP production with NTG ( assessed by the difference between the plasma arterial and venous cGMP level ) paralleled the changes in PCWP , suggesting that the plasma arteriovenous cGMP difference is a biochemical indicator of nitrate tolerance . Although the sustained decrease in PCWP was observed in the nicor and il group , cGMP production with nicor and il was also attenuated at 24 hours of continuous infusion . These findings suggest that the absence of the hemodynamic tolerance of nicor and il , a nitrate and potassium channel opener , is likely due to its action as a potassium channel opener , and not to its nitrate activity The Impact Of Nicor and il in Angina ( IONA ) r and omized trial showed a significant reduction in coronary events , in patients with stable angina treated with a KATP channel opener , nicor and il . However , the impact of nicor and il on endothelial apoptosis remains to be examined . We tested the hypothesis that nicor and il has anti-apoptotic effects in endothelial cells ( ECs ) . Apoptosis was induced by serum starvation in the culture media in human umbilical vein endothelial cells . We examined the effects of nicor and il on endothelial cell apoptosis . Cell viability after serum starvation was significantly higher in the nicor and il-treated group compared with the control group ( 81 ± 8 % vs. 63 ± 3 % , P < 0.01 ) . Apoptosis , as detected by caspase 3 activation and Hoechst 33258 assay , induced by serum starvation was also effectively abrogated by the treatment of nicor and il ( 100 μM ) . The protective effects of nicor and il on endothelial survival were significantly inhibited by a specific mitochondrial KATP channel blocker , 5-Hydroxydecanoic acid . A mitochondrial permeability transition pore activator significantly abolished the anti-apoptotic effect of nicor and il in endothelial cells , indicating that the mechanism of protective effect of nicor and il is involved in the mitochondrial apoptotic pathway although it affects neither Bcl-2 nor Bax protein expression levels . In conclusion , nicor and il inhibits serum starvation-induced endothelial cell apoptosis possibly through mitochondrial KATP channels OBJECTIVES We assessed whether the intravenous administration of nicor and il , an adenosine triphosphate (ATP)-sensitive K+ channel opener , exerts beneficial effect on microvascular function and functional and clinical outcomes in patients with acute myocardial infa rct ion ( AMI ) . BACKGROUND Experimental studies documented that ATP-sensitive K+ channel opener exerts cardioprotection after prolonged ischemia . METHODS We r and omly divided 81 patients with a first anterior AMI into two groups , nicor and il ( n = 40 ) and control groups ( n = 41 ) . All patients received successful coronary angioplasty within 12 h after the symptom onset and underwent myocardial contrast echcardiography ( MCE ) with the intracoronary injection of sonicated microbubbles . In the nicor and il group , we injected 4 mg of nicor and il followed by the infusion at 6 mg/h for 24 h and by oral nicor and il ( 15 mg/day ) . R 
    Output:
    
AND IMPLICATION S The use of nicor and il in HF patients exerts substantial beneficial effects , suggesting that it may be an additional therapeutic agent for HF