a total of 20 sedentary heart transplant recipients ( 18 men , 4911 years ) , 11 sedentary heart failure patients ( 8 men , 4310 years ) , and 7 sedentary healthy subjects ( 5 men 398 years ) were included in this study .
heart transplant recipients and heart failure patients with atrial fibrillation , a pacemaker , and noncardiovascular functional limitations like osteoarthritis were excluded from this study .
heart failure patients whose drug therapy was not optimized were also excluded from this study .
optimization was considered 50 mg / day or more of carvedilol for at least 3 months.18 healthy subjects did not have any risk factors for cardiovascular disease or noncardiovascular functional limitations .
this protocol was approved by the ethics committee of the heart institute , incor hcfmusp .
all patients were asked to refrain from both strenuous physical activity and the consumption of any stimulants ( eg , coffee , tobacco , alcohol ) 24 hours prior to the 6cwt .
the patients last meal was ingested at least 2 hours before the start of the test . before starting the 6cwt and blood sample collection
the 6cwt using the borg scale was performed on a treadmill with zero inclination and patient - controlled speed in a temperature - controlled room ( 2123c ) in the afternoon ( between 13:00 hours and 15:00 hours ) .
all patients were advised to keep walking during the test at a pace between  relatively easy and slightly tiring  ( between 11 and 13 on the borg scale ) .
the distance walked was recorded by the treadmill microprocessor ( series 2000 , marquette electronics , milwaukee , wi , usa ) .
encouragement was standardized with phrases like  if you can walk faster , increase the speed  ,
 you are doing very well ,  and  if it is tiring , you can reduce the speed . 
blood pressure was measured at rest and at the sixth minute by the auscultation method .
the electrocardiography ( max 1 , marquette electronics ) , ventilatory and gas exchange variables were continuously evaluated breath - by - breath by a computerized system ( vmax 229 model , sensormedics , yorba linda , ca , usa ) during the entire test but only collected at rest ( stand position ) and just after the 6-minute walking test .
the 6-minute walking test has been shown to reflect submaximal effort in heart failure patients19 and to reproduce the daily activities.20 blood samples were collected immediately before the 6-minute walking test with patients in the upright position and just after the exercise by the antecubital vein .
the norepinephrine assay was performed as previously reported.21 all heart failure patients were receiving carvedilol associated with an ace inhibitor or losartan .
patients took carvedilol , angiotensin - converting enzyme inhibitors , losartan , and isosorbide 5-mononitrate twice per day , one half of the daily dose in the morning ( 9:00 a.m. ) and the other half at night ( 9:00 p.m. ) .
diuretics , digoxin , and spironolactone were taken in the morning ( 9:00 a.m. ) .
all heart transplant recipients were receiving immunosuppressive therapy two times per day , one half of the daily dose in the morning and the other half at night .
the descriptive analysis is presented as the mean and standard deviation . to compare the norepinephrine levels between the 3 groups
data were analyzed using the statistical package for social sciences for windows , 11.5 ( spss inc , chicago , il ) .
a total of 20 sedentary heart transplant recipients ( 18 men , 4911 years ) , 11 sedentary heart failure patients ( 8 men , 4310 years ) , and 7 sedentary healthy subjects ( 5 men 398 years ) were included in this study .
heart transplant recipients and heart failure patients with atrial fibrillation , a pacemaker , and noncardiovascular functional limitations like osteoarthritis were excluded from this study .
heart failure patients whose drug therapy was not optimized were also excluded from this study .
optimization was considered 50 mg / day or more of carvedilol for at least 3 months.18 healthy subjects did not have any risk factors for cardiovascular disease or noncardiovascular functional limitations .
this protocol was approved by the ethics committee of the heart institute , incor hcfmusp .
all patients were asked to refrain from both strenuous physical activity and the consumption of any stimulants ( eg , coffee , tobacco , alcohol ) 24 hours prior to the 6cwt .
the patients last meal was ingested at least 2 hours before the start of the test . before starting the 6cwt and blood sample collection
the 6cwt using the borg scale was performed on a treadmill with zero inclination and patient - controlled speed in a temperature - controlled room ( 2123c ) in the afternoon ( between 13:00 hours and 15:00 hours ) .
all patients were advised to keep walking during the test at a pace between  relatively easy and slightly tiring  ( between 11 and 13 on the borg scale ) .
the distance walked was recorded by the treadmill microprocessor ( series 2000 , marquette electronics , milwaukee , wi , usa ) .
encouragement was standardized with phrases like  if you can walk faster , increase the speed  ,
 you are doing very well ,  and  if it is tiring , you can reduce the speed . 
blood pressure was measured at rest and at the sixth minute by the auscultation method .
the electrocardiography ( max 1 , marquette electronics ) , ventilatory and gas exchange variables were continuously evaluated breath - by - breath by a computerized system ( vmax 229 model , sensormedics , yorba linda , ca , usa ) during the entire test but only collected at rest ( stand position ) and just after the 6-minute walking test . the 6-minute walking test has been shown to reflect submaximal effort in heart failure patients19 and to reproduce the daily activities.20 blood samples were collected immediately before the 6-minute walking test with patients in the upright position and just after the exercise by the antecubital vein .
patients took carvedilol , angiotensin - converting enzyme inhibitors , losartan , and isosorbide 5-mononitrate twice per day , one half of the daily dose in the morning ( 9:00 a.m. ) and the other half at night ( 9:00 p.m. ) .
diuretics , digoxin , and spironolactone were taken in the morning ( 9:00 a.m. ) .
all heart transplant recipients were receiving immunosuppressive therapy two times per day , one half of the daily dose in the morning and the other half at night .
the descriptive analysis is presented as the mean and standard deviation . to compare the norepinephrine levels between the 3 groups
data were analyzed using the statistical package for social sciences for windows , 11.5 ( spss inc , chicago , il ) .
during rest , norepinephrine plasma level was higher in heart transplant recipients and healthy subjects .
just after the 6-minute walking test , heart transplant recipients norepinephrine plasma level was not different than that of heart failure patients and both these groups had a higher level of norepinephrine than did healthy subjects .
the main finding of this study is that norepinephrine remained increased just after the 6-minute walking test in heart transplant recipients .
this is the first report of the norepinephrine profile during a 6-minute walking test in heart transplant recipients .
that it s why we studied the neurohormonal profile in a 6-minute walking test . this way
the intensity of the 6-minute walking test , between 11 and 13 on the borg scale , was similar for all groups , which are expected to spend about the same metabolic or vo2 , regardless of physical status .
moreover , they were all clinically stable outpatients with optimized medication.22 prez - villa et al6 studied the neurohormonal profile of 37 heart failure patients on the waiting list for heart transplantation before and 1 , 4 , 9 , and 12 months after heart transplantation .
the authors concluded that the neurohormonal activation did not normalize after heart transplantation . in this study ,
plasma norepinephrine level was only recorded before and 1 month after heart transplantation , showing a tendency to decrease . in our study ,
the heart failure group had a higher level of resting norepinephrine compared with heart transplant recipients and healthy subjects .
the norepinephrine level of the heart transplant recipients did not differ from that of healthy subjects , probably by the partial reinnervation that occurred during the 8.5 years .
the progressive heart reinnervation through the years could have progressively decreased the necessity for norepinephrine plasma levels in heart transplant recipients .
the study by ferretti et al8 evaluated the neurohormonal profile of 17 heart transplant recipients and 9 healthy subjects at rest and at maximal exercise .
the resting norepinephrine plasma level was higher in heart transplant recipients than in healthy subjects . in our study
the time of heart transplantation , ie , different stages of reinnervation , between our heart transplant recipients and the ones in the study by ferretti et al was different ( 8.5 versus 3.4 years ) .
the norepinephrine plasma level was also higher in heart transplant recipients compared with that in healthy subjects .
this is in accordance with our results , despite the fact that our heart transplant recipients had performed a 6-minute walking test .
this study was limited by the study design ( cross - sectional ) , small study population , and the use of a single method of neurohormonal evaluation .
this study was limited by the study design ( cross - sectional ) , small study population , and the use of a single method of neurohormonal evaluation .
 objective : we sought to evaluate the neurohormonal activity in heart transplant recipients and compare it with that in heart failure patients and healthy subjects during rest and just after a 6-minute walking test.introduction:despite the improvements in quality of life and survival provided by heart transplantation , the neurohormonal profile is poorly described.methods:twenty heart transplantation ( 18 men , 4911 years and 8.53.3 years after transplantation ) , 11 heart failure ( 8 men , 4310 years ) , and 7 healthy subjects ( 5 men 398 years ) were included in this study . 
 blood samples were collected immediately before and during the last minute of the exercise.results:during rest , patients norepinephrine plasma level ( 659225 pg / ml ) was higher in heart transplant recipients ( 463167 pg / ml ) and heathy subjects ( 512132 ) , p<0.05 . 
 heart transplant recipient s norepinephrine plasma level was not different than that of healthy subjects . just after the 6-minute walking test , the heart transplant recipient s norepinephrine plasma level ( 1248692 pg / ml ) was not different from that of heart failure patients ( 1174653 pg / ml ) . 
 both these groups had a higher level than healthy subjects had ( 54595 pg / ml ) , p<0.05.conclusion : neurohormonal activity remains increased after the 6-minute walking test after heart transplantation . 
INTRODUCTION
MATERIALS AND METHODS
Study population
Six-minute walking test and blood norepinephrine
Current medication intake
Statistical analysis
RESULTS
DISCUSSION
Study limitation
CONCLUSION