Effects of Exercise Training on Vascular Endothelial Function of Patients Submitted to Coronary Artery Bypass Graft
Effects of Exercise Training on Vascular Endothelial Function of Patients Submitted to Coronary Artery Bypass Graft
Objective: To observe the effects of exercise training on vascular endothelial function in
 patients undergoing coronary artery bypass graft (CABG) alone in phase III after six months
 of Cardiac rehabilitation programs (CRP).

 Methods: the investigators contacted all patients undergoing CABG alone in period of 1 year
 to participate in a CRP with duration of six months with three weekly sessions of 1 and half
 hour of the duration. All patients underwent biochemical blood tests, muscle strength testing
 of one repetition maximum (1-RM test) for upper and lower limbs, 6-minute walk test (6MWT),
 and evaluation of endothelial function (using flow-mediated vasodilation).
Introduction The cardiac rehabilitation optimizes a cardiac patient's physical,
 psychological, and social functioning, in addition to stabilizing, slowing, or even reversing
 the progression of the underlying atherosclerotic processes, thereby reducing morbidity and
 mortality. Patients who recently had had a myocardial infarction; or had undergone coronary
 artery bypass graft; or who had undergone percutaneous coronary interventions; or who are
 heart transplantation candidates or recipients; or have stable chronic heart failure,
 peripheral arterial disease with claudication, or other forms of CVD are candidates eligible
 for cardiac rehabilitation services ( , ).

 Recently, studies randomized clinical trials have reported the efficacy of the exercise
 training (ET) independently of format of exercise: aerobic, resistance, or combined exercise
 training in patients with coronary artery disease ( , ) and, others studies investigated the
 effects of ET on vascular endothelial function in patients with stable coronary artery
 disease ( ), ischemic heart disease ( ), recent myocardial infarction (4), and chronic heart
 failure (3, , ). ET is associated with an improvement in endothelial function, oxidative
 stress, and inflammation. Furthermore, the ET promotes beneficial effects on cardiovascular
 outcomes and decreases hospitalizations.

 Arterial endothelium function evaluated by flow-mediated vasodilation (FMD) is a predictor of
 long-term adverse cardiovascular outcomes in healthy subjects ( ). Vascular endothelial
 dysfunction is an independent risk factor for cardiovascular events and provides important
 prognostic data in addition to the more traditional risk factors ( ). Endothelial dysfunction
 plays an important role in patients with coronary atherosclerosis (both acute and chronic
 myocardial ischemia) and heart failure (3,5, ). Therefore, we aim to investigate the effect
 of combined exercise training on vascular endothelial function in sedentary patients
 submitted to coronary artery bypass graft (CABG) in late phase.

 Methods The protocol was approved by the local ethics committee of Associação de Caridade
 Santa Casa do Rio Grande Hospital, Rio Grande/RS - Brazil, under the protocol number
 003/2013. This study was non-randomized clinical trial. The written informed consent was
 obtained from all patients before of the onset of ET. The investigators invited all
 consecutive patients submitted to CABG alone at Cardiologic Hospital Doctor Pedro Bertoni of
 the Associação de Caridade Santa Casa do Rio Grande in the period of October, 2011 until
 October, 2012, who resided in the city of the Rio Grande (RS/Brazil), to participate of the
 ET. The investigators excluded the patients that performed others cardiologic procedures with
 the CABG. All patients were evaluated by cardiologist, and were ranked in Functional
 Classification of New York Heart Association (NYHA) such class I and II. Initially,
 twenty-four patients accepted and start to participate of ET, but only nine patients
 completed the program until the end.

 The program of exercise training (ET) was employed for 6 consecutive months with 3 sessions
 per week. The training of physical activity consisted of a combination of aerobic and
 resistance exercises for upper and lower limbs. Each session included: (1) 5-minute warm-up,
 (2) 30 minutes of aerobic exercise (performed in treadmills and stationary bikes); (3) 20
 minutes of resistance exercises with dumbbells for upper limbs and ankle support for lower
 limbs (exercises preformed in diagonals) that consisted of 6 sets of 10 resistance exercises
 repeated for upper limbs, and the same number of sets for lower limbs; and (4) 5-minute
 cool-down, totaling ninety minutes of session per day (90min/day) and, two hundred and
 seventy minutes per week (270min/week) ( ). Initialy, in aerobic exercises, the maximal HR to
 be achieved was established between 30-40% of HR at rest and, the aerobic exercise was
 limited by symptoms reported by patients. The initial weight of the dumbbells and ankle were
 established between 30-40% of one-repetition maximum test (1-RM test) and, gradually
 increased according to the symptoms reported by patients, without compensation of the trunk
 to perform the exercises, no history of muscle pain, and no muscle fatigue to complete all
 sessions. Heart rate (HR), respiratory rate (RR), saturation pulse of oxygen, and blood
 pressure were measured at the beginning, middle and end of each session. The intensity and
 the velocity of the exercise program were progressively increased.

 The baseline assessment was performed before the beginning of ET and, consisted of: blood
 chemistry (glycemia, insulin, glycohemoglobin, total-, high-, and low-density lipoprotein
 cholesterol, triglycerides); body mass index; strength of upper and lower limbs by 1-RM test
 of biceps brachialis and quadriceps, respectively; evaluation of functional capacity and;
 evaluation of vascular endothelial function.

 Cholesterol, triglycerides, high-density lipoproteins (HDLc) and, glucose urea were measured
 using LAB TEST commercial kits (Lagoa Santa, MG, Brazil) and analyzed in LAB MAX 240® (Tokyo,
 Japan) equipment. The low density lipoproteins (LDLc) was calculated by Friedewald's formula.
 Glucose levels were measured by Trinder assay (calorimetry) in the equipment LAB MAX 240®
 (Tokyo, Japan). The insulin was assessed by chemiluminescence method using the Immulite® DPC
 equipment (Diagnostic Products Corporation - DPC, Los Angeles, CA, USA). The glycosylated
 hemoglobin (HbA1c) was determined by enzymatic method using the equipment LAB MAX 240®
 (Tokyo, Japan).

 The 6-minutes walking test (6MWT) is used to assess the functional capacity of the
 individual, which is extremely important to evaluate tolerance and exercise capacities for
 the evaluation clinical and prognosis of patients with cardiovascular and pulmonary diseases
 ( , ). The 6MWT was performed on the first day in a linear corridor with 40 meters of length,
 and the researcher performed the test giving verbal commands to the patient, which should be
 done the best speed supported by him, and the researcher asked to the patient what their
 physical sensations. Data were collected before, at 3 minutes and at the end of the test for
 respiratory rate (RR), heart rate (HR), saturation pulse in portable pulse oximeter (Nonin®,
 model 9500, Plymouth, USA), and blood pressure systemic.

 Flow-mediated vasodilation (FMD) was measured to evaluating arterial endothelium-dependent
 vasodilation using a high-resolution vascular ultrasound (Logiq P6, GE Healtcare, GE
 Ultrasound Korea Ltda.) according to American Heart Association Guideline ( ) with
 adjustments ( , ). Settings of depth and gain imaging were kept constant throughout the
 study. Briefly, changing in brachial artery diameter after 60 s of reactive hyperemia, after
 deflation of a cuff placed around the upper arm and inflated to 50 mmHg above the systolic
 blood pressure during five min, was compared with a baseline measurement. To evaluate basal
 blood flow and flow immediately after cuff release obtained no later than 15 s after cuff
 deflation we used a pulsed-wave Doppler velocity signals (assessed using Doppler bean-vessel
 angle ≤60º). The increased diameter after a sublingual nitroglycerin spray (0.4 mg) was used
 as a measurement of endothelium-independent vasodilation. The vessel diameter responses to
 reactive hyperemia and to nitroglycerin were expressed as the percentage changing relative to
 diameter immediately before cuff inflation and to diameter immediately before drug
 administration. Measurements of brachial artery diameter were accomplished off line by two
 evaluators using a semiautomatic quantitative analysis system after interventions. The second
 evaluator performing measures was blind to first evaluator's measures. Differences larger
 than 0.01 mm between assessors (mean vessel diameter) repeated were repeated. All data were
 measured twice, and final values were present as mean.

 A nutritional counseling was performed, in wich the patients were instructed to avoid
 consumption of saturated fat and high-calorie foodstuff, to intake of dietary fiber, to
 maintain good hydration and to implement a fractionation of meals throughout the day, besides
 to receive instructions of food preparation, according to "I Diretriz sobre o Consumo de
 Gorduras e Saúde Cardiovascular" in "Arquivos Brasileiros de Cardiologia" of the "Sociedade
 Brasileira de Cardiologia" ( ).

 All tests were repeated after 6 months, and the results were compared to baseline tests. The
 training program was stopped at this point.

 The data are presented as the means ± SD. Distribution of variables was tested by Shapiro
 Wilk normality test. Baseline values were compared to values after 6 months of training
 program by use paired t-test. A value of P<0.05 was considered statistically significant.
Inclusion Criteria:

 -  resided in the city of the Rio Grande (RS/Brazil);

 -  age over 18 years-old;

 -  evaluation and medical authorization.

 Exclusion Criteria:

 -  the patients that performed others cardiologic procedures with the Coronary Artery
 Bypass Graft