Effect of continuous and interval exercise training on the PETCO2 response during a graded exercise test in patients with coronary artery disease

OBJECTIVE: The purpose of this study was to evaluate the following: 1) the effects of continuous exercise training and interval exercise training on the end-tidal carbon dioxide pressure (PETCO2) response during a graded exercise test in patients with coronary artery disease; and 2) the effects of exercise training modalities on the association between PETCO2 at the ventilatory anaerobic threshold (VAT) and indicators of ventilatory efficiency and cardiorespiratory fitness in patients with coronary artery disease. METHODS: Thirty-seven patients (59.7 +/- 1.7 years) with coronary artery disease were randomly divided into two groups: continuous exercise training (n = 20) and interval exercise training (n = 17). All patients performed a graded exercise test with respiratory gas analysis before and after three months of the exercise training program to determine the VAT, respiratory compensation point (RCP) and peak oxygen consumption. RESULTS: After the interventions, both groups exhibited increased cardiorespiratory fitness. Indeed, the continuous exercise and interval exercise training groups demonstrated increases in both ventilatory efficiency and PETCO2 values at VAT, RCP, and peak of exercise. Significant associations were observed in both groups: 1) continuous exercise training (PETCO(2)VAT and cardiorespiratory fitness r = 0.49; PETCO(2)VAT and ventilatory efficiency r = -0.80) and 2) interval exercise training (PETCO(2)VAT and cardiorespiratory fitness r = 0.39; PETCO(2)VAT and ventilatory efficiency r = -0.45). CONCLUSIONS: Both exercise training modalities showed similar increases in PETCO2 levels during a graded exercise test in patients with coronary artery disease, which may be associated with an improvement in ventilatory efficiency and cardiorespiratory fitness.

Angiotensin II type 2 receptor (AT2R) is associated with increased tolerance of the hyperthyroid heart to ischemia-reperfusion

Background Thyroid hormone induces cardiac hypertrophy and preconditions the myocardium against Ischemia/Reperfusion (I/R) injury. Type 2 Angiotensin II receptors (AT2R) are shown to be upregulated in cardiac hypertrophy observed in hyperthyroidism and this receptor has been reported to mediate cardioprotection against ischemic injury. Methods The aim of the present study was to evaluate the role of AT2R in the recovery of myocardium after I/R in isolated hearts from T3 treated rats. MaleWistar rats were treated with triiodothyronine (T3; 7 μg/100 gBW/day, i.p.) in the presence or not of a specific AT2R blocker (PD123,319; 10 mg/Kg) for 14 days, while normal rats served as control. After treatment, isolated hearts were perfused in Langendorff mode; after 30 min of stabilization, hearts were subjected to 20 min of zero-flow global ischemia followed by 25 min, 35 min and 45 min of reperfusion. Results T3 treatment induced cardiac hypertrophy, which was not changed by PD treatment. Post-ischemic recovery of cardiac function was increased in T3-treated hearts after 35 min and 45 min of reperfusion as compared to control and the ischemic contracture was accelerated and intensified. AT2R blockade was able to return the evaluated functional parameters of cardiac performance (LVDP, +dP/dtmáx and −dP/dtmin) to the control condition. Furthermore, AT2R blockade prevented the increase in AMPK expression levels induced by T3, suggesting its possible involvement in this process. Conclusion AT2R plays a significant role in T3-induced cardioprotection.

Cell therapy prevents structural, functional and molecular remodeling of remote non-infarcted myocardium

Background/objectives: Therapy using bone marrow (BM) cells has been tested experimentally and clinically due to the potential ability to restore cardiac function by regenerating lost myocytes or increasing the survival of tissues at risk after myocardial infarction (MI). In this study we aimed to evaluate whether BM-derived mononuclear cell (MNC) implantation can positively influence the post-MI structural remodeling, contractility and Ca(2 +)-handling proteins of the remote non-infarcted tissue in rats. Methods and results: After 48 h of MI induction, saline or BM-MNC were injected. Six weeks later, MI scars were slightly smaller and thicker, and cardiac dilatation was just partially prevented by cell therapy. However, the cardiac performance under hemodynamic stress was totally preserved in the BM-MNC treated group if compared to the untreated group, associated with normal contractility of remote myocardium as analyzed in vitro. The impaired post-rest potentiation of contractile force, associated with decreased protein expression of the sarcoplasmic reticulum Ca2 +-ATPase and phosphorylated-phospholamban and overexpression of Na(+)/Ca(2 +) exchanger, were prevented by BM-MNC, indicating preservation of the Ca(2 +) handling. Finally, pathological changes on remodeled remote tissue such as myocyte hypertrophy, interstitial fibrosis and capillary rarefaction were also mitigated by cell therapy. Conclusions: BM-MNC therapy was able to prevent cardiac structural and molecular remodeling after MI, avoiding pathological changes on Ca(2 +)-handling proteins and preserving contractile behavior of the viable myocardium, which could be the major contributor to the improvements of global cardiac performance after cell transplantation despite that scar tissue still exists.

Exercise Performance and Dynamic Hyperinflation in Lymphangioleiomyomatosis

Rationale: Lymphangioleiomyomatosis (LAM) is characterized by exercise performance impairment. Although airflow limitation is common, no previous studies have evaluated the prevalence and impact of dynamic hyperinflation (DH) in LAM. Objectives: To investigate the dynamic responses during maximal exercise and the prevalence, predictors, and repercussions of DH in LAM. Methods: Forty-two patients with LAM performed symptom-limited incremental cycle exercise and pulmonary functions tests (PFTs) and were compared with 10 age-matched healthy women. Dyspnea intensity, inspiratory capacity, oxygen saturation, and cardiac, metabolic, and respiratory variables were assessed during exercise. Patients with LAM also performed a 6-minute walk test (6MWT). Measurements and Main Results: Patients with LAM had higher baseline dyspnea, poorer quality of life, obstructive pattern, air trapping, and reduced diffusing capacity of carbon monoxide in PFTs. Although they had the same level of regular physical activity, their maximal exercise performance was reduced and was associated with ventilatory limitation, greater desaturation, and dyspnea. The prevalence of DH was high in LAM (55%), even in patients with mild spirometric abnormalities, and was correlated with airflow obstruction, air trapping, and diffusing capacity of carbon monoxide. Compared with the non-DH subgroup, the patients who developed DH had a ventilatory limitation contributing to exercise cessation on cycling and higher desaturation and dyspnea intensity during the 6MWT. Conclusions: Ventilatory limitation and gas exchange impairment are important causes of exercise limitation in LAM. DH is frequent in LAM, even in patients with mild spirometric abnormalities. DH was associated with the severity of disease, higher dyspnea, and lower oxygen saturation. In the 6MWT, desaturation and dyspnea were greater in patients with DH.

Performance of rest myocardial perfusion imaging in the management of acute chest pain in the emergency room in developing nations (PREMIER trial)

Background. Rest myocardial perfusion imaging (MPI) is effective in managing patients with acute chest pain in developed countries. We aimed to define the role and feasibility of rest MPI in low-to-middle income countries. Methods and Results. Low-to-intermediate risk patients (n = 356) presenting with chest pain to ten centers in eight developing countries were injected with a Tc-99m-based tracer, and standard imaging was performed. The primary outcome was a composite of death, non-fatal myocardial infarction (MI), recurrent angina, and coronary revascularization at 30 days. Sixty-nine patients had a positive MPI (19.4%), and 52 patients (14.6%) had a primary outcome event. An abnormal rest-MPI result was the only variable which independently predicted the primary outcome [adjusted odds ratio (OR) 8.19, 95% confidence interval 4.10-16.40, P = .0001]. The association of MPI result and the primary outcome was stronger (adjusted OR 17.35) when only the patients injected during pain were considered. Rest-MPI had a negative predictive value of 92.7% for the primary outcome, improving to 99.3% for the hard event composite of death or MI. Conclusions. Our study demonstrates that rest-MPI is a reliable test for ruling out MI when applied to patients in developing countries. (J Nucl Cardiol 2012;19:1146-53.)

The effect of acute magnesium loading on the maximal exercise performance of stable chronic obstructive pulmonary disease patients

OBJECTIVE: The potential influence of magnesium on exercise performance is a subject of increasing interest. Magnesium has been shown to have bronchodilatatory properties in asthma and chronic obstructive pulmonary disease patients. The aim of this study was to investigate the effects of acute magnesium IV loading on the aerobic exercise performance of stable chronic obstructive pulmonary disease patients. METHODS: Twenty male chronic obstructive pulmonary disease patients (66.2 +/- 8.3 years old, FEV1: 49.3 +/- 19.8%) received an IV infusion of 2 g of either magnesium sulfate or saline on two randomly assigned occasions approximately two days apart. Spirometry was performed both before and 45 minutes after the infusions. A symptom-limited incremental maximal cardiopulmonary test was performed on a cycle ergometer at approximately 100 minutes after the end of the infusion. ClinicalTrials.gov: NCT00500864 RESULTS: Magnesium infusion was associated with significant reductions in the functional residual capacity (-0.41 l) and residual volume (-0.47 l), the mean arterial blood pressure (-5.6 mmHg) and the cardiac double product (734.8 mmHg.bpm) at rest. Magnesium treatment led to significant increases in the maximal load reached (+8 w) and the respiratory exchange ratio (0.06) at peak exercise. The subgroup of patients who showed increases in the work load equal to or greater than 5 w also exhibited significantly greater improvements in inspiratory capacity (0.29 l). CONCLUSIONS: The acute IV loading of magnesium promotes a reduction in static lung hyperinflation and improves the exercise performance in stable chronic obstructive pulmonary disease patients. Improvements in respiratory mechanics appear to be responsible for the latter finding.

Myocardial performance in conscious streptozotocin diabetic rats

Abstract Background In spite of a large amount of studies in anesthetized animals, isolated hearts, and in vitro cardiomyocytes, to our knowledge, myocardial function was never studied in conscious diabetic rats. Myocardial performance and the response to stress caused by dobutamine were examined in conscious rats, fifteen days after the onset of diabetes caused by streptozotocin (STZ). The protective effect of insulin was also investigated in STZ-diabetic rats. Methods Cardiac contractility and relaxation were evaluated by means of maximum positive (+dP/dtmax) and negative (-dP/dtmax) values of first derivative of left ventricular pressure over time. In addition, it was examined the myocardial response to stress caused by two dosages (1 and 15 μg/kg) of dobutamine. One-way analysis of variance (ANOVA) was used to compare differences among groups, and two-way ANOVA for repeated measure, followed by Tukey post hoc test, to compare the responses to dobutamine. Differences were considered significant if P < 0.05. Results Basal mean arterial pressure, heart rate, +dP/dtmax and -dP/dtmax were found decreased in STZ-diabetic rats, but unaltered in control rats treated with vehicle and STZ-diabetic rats treated with insulin. Therefore, insulin prevented the hemodynamic and myocardial function alterations observed in STZ-diabetic rats. Lower dosage of dobutamine increased heart rate, +dP/dtmax and -dP/dtmax only in STZ-diabetic rats, while the higher dosage promoted greater, but similar, responses in the three groups. In conclusion, the results indicate that myocardial function was remarkably attenuated in conscious STZ-diabetic rats. In addition, the lower dosage of dobutamine uncovered a greater responsiveness of the myocardium of STZ-diabetic rats. Insulin preserved myocardial function and the integrity of the response to dobutamine of STZ-diabetic rats. Conclusion The present study provides new data from conscious rats showing that the cardiomyopathy of this pathophysiological condition was expressed by low indices of contractility and relaxation. In addition, it was also demonstrated that these pathophysiological features were prevented by the treatment with insulin.

Noninvasive and invasive evaluation of cardiac dysfunction in experimental diabetes in rodents

Abstract Background Because cardiomyopathy is the leading cause of death in diabetic patients, the determination of myocardial function in diabetes mellitus is essential. In the present study, we provide an integrated approach, using noninvasive echocardiography and invasive hemodynamics to assess early changes in myocardial function of diabetic rats. Methods Diabetes was induced by streptozotocin injection (STZ, 50 mg/kg). After 30 days, echocardiography (noninvasive) at rest and invasive left ventricular (LV) cannulation at rest, during and after volume overload, were performed in diabetic (D, N = 7) and control rats (C, N = 7). The Student t test was performed to compare metabolic and echocardiographic differences between groups at 30 days. ANOVA was used to compare LV invasive measurements, followed by the Student-Newman-Keuls test. Differences were considered significant at P < 0.05 for all tests. Results Diabetes impaired LV systolic function expressed by reduced fractional shortening, ejection fraction, and velocity of circumferential fiber shortening compared with that in the control group. The diabetic LV diastolic dysfunction was evidenced by diminished E-waves and increased A-waves and isovolumic relaxation time. The myocardial performance index was greater in diabetic compared with control rats, indicating impairment in diastolic and systolic function. The LV systolic pressure was reduced and the LV end-diastolic pressure was increased at rest in diabetic rats. The volume overload increased LVEDP in both groups, while LVEDP remained increased after volume overload only in diabetic rats. Conclusion These results suggest that STZ-diabetes induces systolic and diastolic dysfunction at rest, and reduces the capacity for cardiac adjustment to volume overload. In addition, it was also demonstrated that rodent echocardiography can be a useful, clinically relevant tool for the study of initial diabetic cardiomyopathy manifestations in asymptomatic patients.