***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: UNLABELLED In this prospect i ve study , we evaluated whether high thoracic epidural anesthesia ( TEA ) or i.v . clonidine , in addition to general anesthesia , affects the cardiopulmonary bypass- and surgery-associated stress response and incidence of myocardial ischemia by their sympatholytic properties . Seventy patients scheduled for elective coronary artery bypass graft ( CABG ) received general anesthesia with sufentanil and propofol . TEA was r and omly induced before general anesthesia and continued during the study period in 25 ( anesthetized dermatomes C6-T10 ) . Another 24 patients received i.v . clonidine as a bolus of 4 microg/kg before the induction of general anesthesia . Clonidine was then infused at a rate of 1 microg x kg(-1 ) x h(-1 ) during surgery and at 0.2 - 0.5 microg x kg(-1 ) x h(-1 ) postoperatively . The remaining 21 patients underwent general anesthesia as performed routinely ( control ) . Hemodynamics , plasma epinephrine and norepinephrine , cortisol , the myocardial-specific contractile protein troponin T , and other cardiac enzymes were measured pre- and postoperatively . During the preoperative night and a follow-up of 48 h after surgery , five-lead electrocardiogram monitoring was used for ischemia detection . Both TEA and clonidine reduced the postoperative heart rate compared with the control group without jeopardizing cardiac output or perfusion pressure . Plasma epinephrine increased perioperatively in all groups but was significantly lower in the TEA group . Neither TEA nor clonidine affected the increase in plasma cortisol . The release of troponin T was attenuated by TEA . New ST elevations > or = 0.2 mV or new ST depression > or = 0.1 mV occurred in > 70 % of the control patients but only in 40 % of the clonidine group and in 50 % of the TEA group . We conclude that TEA ( but not i.v . clonidine ) combined with general anesthesia for CABG demonstrates a beneficial effect on the perioperative stress response and postoperative myocardial ischemia . IMPLICATION S Thoracic epidural anesthesia combined with general anesthesia attenuates the myocardial sympathetic response to cardiopulmonary bypass and cardiac surgery . This is associated with decreased myocardial ischemia as determined by less release of troponin T. These findings may have an impact on the anesthetic management for coronary artery bypass grafting Background Most new perioperative myocardial ischemic episodes occur in the absence of hypertension or tachycardia . The ability of alpha2 ‐adrenoceptor agonists to inhibit central sympathetic outflow may benefit patients with coronary artery disease by increasing the myocardial oxygen supply‐ and ‐dem and ratio . Methods A r and omized double‐blind study design was used in 297 patients scheduled to have elective vascular surgical procedures to evaluate the effects of 2 micro gram/kg sup ‐1 oral clonidine ( n = 145 ) or placebo ( n = 152 ) on the incidence of perioperative myocardial ischemic episodes , myocardial infa rct ion , and cardiac death . Continuous real‐time S‐T segment trend analysis ( lead II and V5 ) was performed during anesthesia and surgery and correlated with arterial blood pressure and heart rate before and during ischemic events . Dose requirements for vasoactive and antiischemic drugs to control blood pressure and heart rate as well as episodes of myocardial ischemia ( i.e. , catecholamines , beta‐adrenoceptor antagonists , nitrates , and systemic vasodilators ) and fluid volume load were recorded . Results Administration of clonidine reduced the incidence of perioperative myocardial ischemic episodes from 39 % ( 59 of 152 ) to 24 % ( 35 of 145 ) ( P < 0.01 ) . Hemodynamic patterns , percentage of ischemic time , and the number of ischemic episodes per patient did not differ . Nonfatal myocardial infa rct ion developed after operation in four patients receiving placebo compared with none receiving clonidine ( day 2 to 21 ; P = 0.07 ) . The incidence of fatal cardiac events ( 1 vs. 2 ) was not different . Dose requirements for vasoactive and antiischemic drugs did not differ between the groups , but the amount of presurgical fluid volume was slightly greater in patients receiving clonidine ( 951 + /‐ 388 vs. 867 + /‐ 381 ml ; P < 0.03 ) . Conclusion A small oral dose of clonidine , given prophylactically , can reduce the incidence of perioperative myocardial ischemic episodes without affecting hemodynamic stability in patients with suspected or documented coronary artery disease OBJECTIVE : To evaluate whether clonidine , enoximone , and enalaprilat reduce ischaemia-related myocardial cell damage in cardiac surgery . DESIGN : Prospect i ve r and omised controlled trial . SETTING : Clinical investigation in a cardiac anaesthesia department of a university hospital . PATIENTS : 88 consecutive patients undergoing coronary artery bypass surgery . INTERVENTIONS : After induction of anaesthesia patients continuously received the alpha 2 agonist clonidine ( group 1 , n = 22 ) , the phosphodiesterase ( PDE ) III inhibitor enoximone ( group 2 , n = 22 ) , the angiotensin converting enzyme ( ACE ) inhibitor enalaprilat ( group 3 , n = 22 ) , or saline solution as placebo ( control group , n = 22 ) . The infusion was stopped immediately before the start of cardiopulmonary bypass . MAIN OUTCOME MEASURES : The ST segment was analysed and the activity of creatine kinase isoenzyme MB ( CKMB ) , cardiac troponin T ( TnT ) , and the BB isoenzyme of glycogen phosphorylase ( GPBB ) were measured before the start of infusion ( baseline ) , after weaning from cardiopulmonary bypass ( CPB ) , at the end of surgery , 5 h after CPB , and on the morning of the first and third postoperative days . RESULTS : Biometric data and time of cross-clamping were not significantly different in the four groups . Changes in the ST segment indicating ischaemia were least common in the enalaprilat group ( P < 0.05 ) . Postoperatively , CKMB activity was significantly higher in the clonidine and the control groups . Both new markers of myocardial cell damage increased more after CPB and postoperatively in the control patients ( TnT peak : ( mean ( SD ) ) 3.99 ( 0.35 ) microgram/1 ; GPBB peak : 82 ( 15 ) ng/ml ) and the clonidine-treated group ( TnT peak : 3.80 ( 0.3 ) microgram/1 ; GPBB peak : 85 ( 14 ) ng/ml ) . Enalaprilat-treated patients showed the smallest overall changes in st and ard ( CKMB ) and new serological markers of myocardial ischaemia ( TnT peak : 0.71 ( 0.1 ) microgram/1 ; GPBB peak : 44 ( 14 ) ng/ml ) . CONCLUSIONS : In patients treated with enalaprilat before CPB , both new , more sensitive markers of ischaemic myocardial tissue damage increased significantly less than in an untreated control group . Those treated with enoximone also had lower plasma concentration of TnT and GPBB than the control group , whereas clonidine did not reduce the concentration of these markers of myocardial ischaemia . Pharmacological interventions , such as the continuous infusion of the ACE inhibitor enalaprilat , before start of CPB may help to protect the heart against ischaemia/reperfusion injury The purpose of this study was to assess the efficacy of clonidine in achieving perioperative hemodynamic stability in patients undergoing coronary artery bypass grafting performed under high-dose alfentanil anesthesia . Twenty-four patients with left ventricular ejection fraction greater than 0.5 were prospect ively studied in a double-blind manner ; those requiring emergency procedures were excluded . They were r and omized to receive either oral clonidine or placebo together with their premedication . Induction of anesthesia was achieved with 10 mg of alfentanil infused over 5 minutes followed by a continuous infusion of 60 mg/h during 1 hour , or until sternotomy , and then 30 mg/h until the end of surgery . Hemodynamic responses to noxious stimuli were treated with additional alfentanil boluses and isoflurane when these were unsuccessful . Intraoperative hemodynamic profile analyses showed a continuous increase in systemic vascular resistance and mean arterial pressure in the clonidine group from the time of skin incision until the onset of bypass , whereas the cardiac output profiles remained similar in the two groups . The number of additional alfentanil boluses was similar . Isoflurane requirements ( 1/11 v 4/13 ) were not significantly different , but only a few patients required this therapy . The postbypass hemodynamic profiles were similar . Severe hemodynamic impairment occurred in the clonidine group during warming in the postoperative period : this group showed a drop in systemic vascular resistance index ( 1276 + /- 347 v 1757 + /- 415 dyn.sec.cm-5.m2 ) that could not be compensated for by an increase in cardiac output despite normal filling pressures , causing hypotension ( 66 + /- 10 v 79 + /- 16 mmHg ) . This hemodynamic status led to greater requirements for vasoactive agents and inotropics in this group . ( ABSTRACT TRUNCATED AT 250 WORDS The effects of clonidine , a central ly acting α2-adrenergic receptor agonist , on depth of fentanyl anesthesia and on cardiovascular response to laryngoscopy and intubation were studied . Twenty-four patients undergoing aortocoronary bypass surgery ( ACBS ) with a history of arterial hypertension , coronary artery disease ( NYHA class 3–4 ) , and well-preserved left ventricular function were assigned r and omly to either Group 1 ( n = 12 ) , who received st and ard pre-medication , or Group 2 ( n = 12 ) , who received clonidine 5 μ;g·kg-1 po in addition to st and ard premedication 90 min before estimated induction time . Depth of anesthesia was assessed by on-line aperiodic computerized analysis of the electroencephalogram ( Lifescan EEG Monitor ® ) . Fentanyl was administered in 250-μ;g increments to shift the EEG to the 0.5–3-Hz frequency range ( delta activity ) in all subjects . In both groups , the anesthetic regimen effectively prevented hyperdynamic cardiovascular responses to laryngoscopy and intubation . No significant differences in measured or derived hemodynamic variables were observed between the two groups during the awake control period , except for stroke volume index ( SVI ) , which was significantly greater in Group 1,44 ± 9 ml · beat-1 · M-2 compared with Group 2 , 35 ± 3.3 ml · beat-1 · m-2 ( P < 0.05 ) . By contrast , fentanyl requirements in Group 2 were significantly reduced by 45 % when compared with Group 1 , i.e. , from 110 ± 23 to 61 ± 19 μ;g · kg-1(P < 0.001 ) . The authors conclude that at a similar anesthetic depth , as assessed by the EEG shift into the lower frequency range ( 0.5–3 Hz ) , a markedly reduced fentanyl dose effectively prevented the hyperdynamic cardiovascular response to laryngoscopy and intubation in the group of patients premedicated with clonidine . This is likely explained by the known synergistic inhibitory action of opiates and α2-adrenoceptor agonists on central sympathetic outflow We studied 61 patients undergoing elective major non-cardiac surgery in a r and omized , double-blind , placebo-control clinical trial to test the hypothesis that the addition of clonidine to a st and ardized general anesthetic could safely provide postoperative sympatholysis for patients with known or suspected coronary artery disease . Patients were allocated r and omly to receive either placebo ( n = 31 ) or clonidine ( n = 30 ) . The treatment group received premedication with a trans-dermal clonidine system ( 0.2 mg/d ) the night prior to surgery , which was left in place for 72 h , and 0.3 mg oral clonidine 60–90 min before surgery . Clonidine  reduced enflurane requirements , intraoperative tachycardia , and myocardial ischemia ( 1/28 clonidine patients vs 5/24 placebo , P = 0.05 ) . However , clonidine decreased heart rates only during the first five postoperative hours ; the incidence of postoperative myocardial ischemia ( 6/28 clonidine vs 5/26 placebo ) did not differ between the two groups . Patients who experienced postoperative myocardial ischemia tended to have higher heart rates after surgery . Clonidine significantly reduced the plasma levels of 
    Output:
    
In the subgroup analysis , clonidine reduced the incidence of myocardial ischemia in patients undergoing cardiac and noncardiac surgery .
The meta- analysis suggests that perioperative clonidine reduces cardiac ischemic episodes in patients with known , or at risk of , coronary arterial disease without increasing the incidence of bradycardia .