Mechanisms Involved in Exercise-Induced Cardioprotection: A Systematic Review

Background:Acute myocardial infarction is the leading cause of morbidity and mortality worldwide. Furthermore, research has shown that exercise, in addition to reducing cardiovascular risk factors, can also protect the heart against injury due to ischemia and reperfusion through a direct effect on the myocardium. However, the specific mechanism involved in exerciseinduced cardiac preconditioning is still under debate.Objective:To perform a systematic review of the studies that have addressed the mechanisms by which aerobic exercise promotes direct cardioprotection against ischemia and reperfusion injury.Methods:A search was conducted using MEDLINE, Literatura Latino-Americana e do Caribe de Informação em Ciências da Saúde, and Scientific Electronic Library Online databases. Data were extracted in a standardized manner by two independent researchers, who were responsible for assessing the methodological quality of the studies.Results:The search retrieved 78 studies; after evaluating the abstracts, 30 studies were excluded. The manuscripts of the remaining 48 studies were completely read and, of these, 20 were excluded. Finally, 28 studies were included in this systematic review.Conclusion:On the basis of the selected studies, the following are potentially involved in the cardioprotective response to exercise: increased heat shock protein production, nitric oxide pathway involvement, increased cardiac antioxidant capacity, improvement in ATP-dependent potassium channel function, and opioid system activation. Despite all the previous investigations, further research is still necessary to obtain more consistent conclusions.

New Exercise-Dipyridamole Combined Test for Nuclear Cardiology in Insufficient Effort: Appropriate Diagnostic Sensitivity Keeping Exercise Prognosis

AbstractBackground:Myocardial perfusion scintigraphy (MPS) in patients not reaching 85% of the maximum predicted heart rate (MPHR) has reduced sensitivity.Objectives:In an attempt to maintain diagnostic sensitivity without losing functional exercise data, a new exercise and dipyridamole combined protocol (EDCP) was developed. Our aim was to evaluate the feasibility and safety of this protocol and to compare its diagnostic sensitivity against standard exercise and dipyridamole protocols.Methods:In patients not reaching a sufficient exercise (SE) test and with no contraindications, 0.56 mg/kg of dipyridamole were IV administered over 1 minute simultaneously with exercise, followed by 99mTc-MIBI injection.Results:Of 155 patients, 41 had MPS with EDCP, 47 had a SE test (≥ 85% MPHR) and 67 underwent the dipyridamole alone test (DIP). They all underwent coronary angiography within 3 months. The three stress methods for diagnosis of coronary lesions had their sensitivity compared. For stenosis ≥ 70%, EDCP yielded 97% sensitivity, SE 90% and DIP 95% (p = 0.43). For lesions ≥ 50%, the sensitivities were 94%, 88% and 95%, respectively (p = 0.35). Side effects of EDCP were present in only 12% of the patients, significantly less than with DIP (p < 0.001).Conclusions:The proposed combined protocol is a valid and safe method that yields adequate diagnostic sensitivity, keeping exercise prognostic information in patients unable to reach target heart rate, with fewer side effects than the DIP.

Effects of One Resistance Exercise Session on Vascular Smooth Muscle of Hypertensive Rats

AbstractBackground:Hypertension is a public health problem and increases the incidence of cardiovascular diseases.Objective:To evaluate the effects of a resistance exercise session on the contractile and relaxing mechanisms of vascular smooth muscle in mesenteric arteries of NG-nitro L-arginine methyl ester (L-NAME)-induced hypertensive rats.Methods:Wistar rats were divided into three groups: control (C), hypertensive (H), and exercised hypertensive (EH). Hypertension was induced by administration of 20 mg/kg of L-NAME for 7 days prior to experimental protocols. The resistance exercise protocol consisted of 10 sets of 10 repetitions and intensity of 40% of one repetition maximum. The reactivity of vascular smooth muscle was evaluated by concentration‑response curves to phenylephrine (PHEN), potassium chloride (KCl) and sodium nitroprusside (SNP).Results:Rats treated with L-NAME showed an increase (p < 0.001) in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) compared to the initial period of induction. No difference in PHEN sensitivity was observed between groups H and EH. Acute resistance exercise reduced (p < 0.001) the contractile response induced by KCl at concentrations of 40 and 60 mM in group EH. Greater (p < 0.01) smooth muscle sensitivity to NPS was observed in group EH as compared to group H.Conclusion:One resistance exercise session reduces the contractile response induced by KCl in addition to increasing the sensitivity of smooth muscle to NO in mesenteric arteries of hypertensive rats.

Alternatives to Aerobic Exercise Prescription in Patients with Chronic Heart Failure

Background: Exercise is essential for patients with heart failure as it leads to a reduction in morbidity and mortality as well as improved functional capacity and oxygen uptake (v̇O2). However, the need for an experienced physiologist and the cost of the exam may render the cardiopulmonary exercise test (CPET) unfeasible. Thus, the six-minute walk test (6MWT) and step test (ST) may be alternatives for exercise prescription. Objective: The aim was to correlate heart rate (HR) during the 6MWT and ST with HR at the anaerobic threshold (HRAT) and peak HR (HRP) obtained on the CPET. Methods: Eighty-three patients (58 ± 11 years) with heart failure (NYHA class II) were included and all subjects had optimized medication for at least 3 months. Evaluations involved CPET (v̇O2, HRAT, HRP), 6MWT (HR6MWT) and ST (HRST). Results: The participants exhibited severe ventricular dysfunction (ejection fraction: 31 ± 7%) and low peak v̇O2 (15.2 ± 3.1 mL.kg-1.min-1). HRP (113 ± 19 bpm) was higher than HRAT (92 ± 14 bpm; p < 0.05) and HR6MWT (94 ± 13 bpm; p < 0.05). No significant difference was found between HRP and HRST. Moreover, a strong correlation was found between HRAT and HR6MWT (r = 0.81; p < 0.0001), and between HRP and HRST (r = 0.89; p < 0.0001). Conclusion: These findings suggest that, in the absence of CPET, exercise prescription can be performed by use of 6MWT and ST, based on HR6MWT and HRST

Serial High-Sensitivity Troponin T in Post-Primary Angioplasty Exercise Test

Abstract Background: The kinetics of high-sensitivity troponin T (hscTnT) release should be studied in different situations, including functional tests with transient ischemic abnormalities. Objective: To evaluate the release of hscTnT by serial measurements after exercise testing (ET), and to correlate hscTnT elevations with abnormalities suggestive of ischemia. Methods: Patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary angioplasty were referred for ET 3 months after infarction. Blood samples were collected to measure basal hscTnT immediately before (TnT0h), 2 (TnT2h), 5 (TnT5h), and 8 hours (TnT8h) after ET. The outcomes were peak hscTnT, TnT5h/TnT0h ratio, and the area under the blood concentration-time curve (AUC) for hscTnT levels. Log-transformation was performed on hscTnT values, and comparisons were assessed with the geometric mean ratio, along with their 95% confidence intervals. Statistical significance was assessed by analysis of covariance with no adjustment, and then, adjusted for TnT0h, age and sex, followed by additional variables (metabolic equivalents, maximum heart rate achieved, anterior wall STEMI, and creatinine clearance). Results: This study included 95 patients. The highest geometric means were observed at 5 hours (TnT5h). After adjustments, peak hscTnT, TnT5h/TnT0h and AUC were 59% (p = 0.002), 59% (p = 0.003) and 45% (p = 0.003) higher, respectively, in patients with an abnormal ET as compared to those with normal tests. Conclusion: Higher elevations of hscTnT may occur after an abnormal ET as compared to a normal ET in patients with STEMI.

Effect of Nebivolol on MIBG Parameters and Exercise in Heart Failure with Normal Ejection Fraction

Abstract Background: More than 50% of the patients with heart failure have normal ejection fraction (HFNEF). Iodine-123 metaiodobenzylguanidine (123I-MIBG) scintigraphy and cardiopulmonary exercise test (CPET) are prognostic markers in HFNEF. Nebivolol is a beta-blocker with vasodilating properties. Objectives: To evaluate the impact of nebivolol therapy on CPET and123I-MIBG scintigraphic parameters in patients with HFNEF. Methods: Twenty-five patients underwent 123I-MIBG scintigraphy to determine the washout rate and early and late heart-to-mediastinum ratios. During the CPET, we analyzed the systolic blood pressure (SBP) response, heart rate (HR) during effort and recovery (HRR), and oxygen uptake (VO2). After the initial evaluation, we divided our cohort into control and intervention groups. We then started nebivolol and repeated the tests after 3 months. Results: After treatment, the intervention group showed improvement in rest SBP (149 mmHg [143.5-171 mmHg] versus 135 mmHg [125-151 mmHg, p = 0.016]), rest HR (78 bpm [65.5-84 bpm] versus 64.5 bpm [57.5-75.5 bpm, p = 0.028]), peak SBP (235 mmHg [216.5-249 mmHg] versus 198 mmHg [191-220.5 mmHg], p = 0.001), peak HR (124.5 bpm [115-142 bpm] versus 115 bpm [103.7-124 bpm], p= 0.043), HRR on the 1st minute (6.5 bpm [4.75-12.75 bpm] versus 14.5 bpm [6.7-22 bpm], p = 0.025) and HRR on the 2nd minute (15.5 bpm [13-21.75 bpm] versus 23.5 bpm [16-31.7 bpm], p = 0.005), but no change in peak VO2 and 123I-MIBG scintigraphic parameters. Conclusion: Despite a better control in SBP, HR during rest and exercise, and improvement in HRR, nebivolol failed to show a positive effect on peak VO2 and 123I-MIBG scintigraphic parameters. The lack of effect on adrenergic activity may be the cause of the lack of effect on functional capacity.

Acute Effects of Exercise on Blood Pressure: A Meta-Analytic Investigation

Abstract Hypertension affects 25% of the world's population and is considered a risk factor for cardiovascular disorders and other diseases. The aim of this study was to examine the evidence regarding the acute effect of exercise on blood pressure (BP) using meta-analytic measures. Sixty-five studies were compared using effect sizes (ES), and heterogeneity and Z tests to determine whether the ES were different from zero. The mean corrected global ES for exercise conditions were -0.56 (-4.80 mmHg) for systolic BP (sBP) and -0.44 (-3.19 mmHg) for diastolic BP (dBP; z ≠ 0 for all; p < 0.05). The reduction in BP was significant regardless of the participant's initial BP level, gender, physical activity level, antihypertensive drug intake, type of BP measurement, time of day in which the BP was measured, type of exercise performed, and exercise training program (p < 0.05 for all). ANOVA tests revealed that BP reductions were greater if participants were males, not receiving antihypertensive medication, physically active, and if the exercise performed was jogging. A significant inverse correlation was found between age and BP ES, body mass index (BMI) and sBP ES, duration of the exercise's session and sBP ES, and between the number of sets performed in the resistance exercise program and sBP ES (p < 0.05). Regardless of the characteristics of the participants and exercise, there was a reduction in BP in the hours following an exercise session. However, the hypotensive effect was greater when the exercise was performed as a preventive strategy in those physically active and without antihypertensive medication.

Cardiorespiratory responses during and after water exercise in pregnant and non-pregnant women

PURPOSE: to compare the blood pressure and oxygen consumption (VO2) responses between pregnant and non-pregnant women, during cycle ergometer exercise on land and in water. METHODS: ten pregnant (27 to 29 weeks of gestation) and ten non-pregnant women were enrolled. Two cardiopulmonary tests were performed on a cycle ergometer (water and land) at the heart rate corresponding to VO2, over a period of 30 minutes each. Exercise measurements consisted of recording blood pressure every five minutes, and heart rate and VO2 every 20 seconds. Two-way ANOVA was used and α=0.05 (SPSS 17.0). RESULTS: there was no difference in cardiovascular responses between pregnant and non-pregnant women during the exercise. The Pregnant Group demonstrated significant differences in systolic (131.6±8.2; 142.6±11.3 mmHg), diastolic (64.8±5.9; 74.5±5.3 mmHg), and mean blood pressure (87.0±4.1; 97.2±5.7 mmHg), during water and land exercise, respectively. The Non-pregnant women Group also had a significantly lower systolic (130.5±8.4; 135.9±8.7 mmHg), diastolic (67.4±5.7; 69.0±10.1 mmHg), and mean blood pressure (88.4±4.8; 91.3±7.8 mmHg) during water exercise compared to the land one. There were no significant differences in VO2 values between water and land exercises or between pregnant and non-pregnant women. After the first five-minute recovery period, both blood pressure and VO2 were similar to pre-exercise values. CONCLUSIONS: for pregnant women with 27 to 29 weeks of gestation, water exercise at the heart rate corresponding to VO2 is physiologically appropriate. These women also present a lower blood pressure response to exercise in water than on land.

Fetal heart rate responses during maternal resistance exercise: a pilot study

PURPOSE: To determine fetal heart rate (FHR) responses to maternal resistance exercise for the upper and lower body at two different volumes, and after 25 minutes post-exercise.METHODS: Ten pregnant women (22-24 weeks gestation, 25.2±4.4 years of age, 69.8±9.5 kg, 161.6±5.2 cm tall) performed, at 22-24, 28-32 and 34-36 weeks, the following experimental sessions: Session 1 was a familiarization with the equipment and the determination of one estimated maximum repetition. For sessions 2, 3, 4 and 5,FHR was determined during the execution of resistance exercise on bilateral leg extension and pec-deck fly machines, with 1 and 3 sets of 15 repetitions; 50% of the weight load and an estimated repetition maximum. FHR was assessed with a portable digital cardiotocograph. Results were analyzed using Student's ttest, ANOVA with repeated measures and Bonferroni (α=0.05; SPSS 17.0).RESULTS: FHR showed no significant differences between the exercises at 22-24 weeks (bilateral leg extension=143.8±9.4 bpm, pec-deck fly=140.2±10.2 bpm, p=0.34), 28-30 weeks (bilateral leg extension=138.4±12.2 bpm, pec-deck fly=137.6±14.0 bpm, p=0.75) and 34-36 weeks (bilateral leg extension=135.7±5.8 bpm, pec-deck fly=139.7±13.3 bpm, p=0.38), between the volumes(bilateral leg extension at 22-24 weeks: p=0.36, at 28-30 weeks: p=0.19 and at 34-36 weeks: p=0.87; pec-deck fly at 22-24 weeks: p=0.43, at 28-30 weeks: p=0.61 and at 34-36 weeks: p=0.49) and after 25 minutes post-exercise.CONCLUSION: Results of this pilot study would suggest that maternal resistance exercise is safe for the fetus.

Effectiveness of an illustrated home exercise guide on promoting urinary continence during pregnancy: a pragmatic randomized clinical trial

OBJETIVO: Avaliar a efetividade de um manual de orientação de exercícios domiciliares (MOED) para o assoalho pélvico (AP) na promoção da continência urinária em gestantes primigestas.MÉTODOS: Ensaio clínico com 87 participantes, avaliadas 6 vezes durante a gestação e divididas aleatoriamente em 3 grupos: Grupo supervisionado (Gsup), que praticou exercícios com supervisão; Grupo observado (Gobs), que praticou exercícios sem supervisão, e Grupo referência (Gref), que não praticou exercícios. Incontinência urinária (IU) (desfecho primário) e força muscular perineal (FMP) (desfecho secundário) foram avaliadas por intermédio de diário de perdas urinárias e perineometria, respectivamente. Foram utilizados o teste de Kruskal-Wallis, seguido do teste post hoc de Dunn, para variáveis contínuas, e o teste do χ2 e testes Z, com correções de Bonferroni, para proporções, com nível de significância de 5%.RESULTADOS: O Gsup e o Gobs apresentaram 6,9% de gestantes incontinentes, enquanto o Gref apresentou 96,6% de incontinentes. Quanto à FMP, o Gsup e o Gobs apresentaram valores médios de contração de 10 e 8,9 cmH2O, respectivamente, enquanto o Gref apresentou valor de 4,7 cmH2O. Ambos os resultados significantes.CONCLUSÃO: A utilização de um MOED é eficaz na promoção da continência urinária e no aumento da FMP em gestantes primigestas, independentemente de supervisão permanente.

Serodiagnosis of Babesia equi in horses submitted to exercise stress

A complement fixation test (CFT), performed in microtitre plates, based upon the use of crude antigenic preparation of Babesia equi was adapted for the detection of antibodies in serum of infected horses. The indirect fluorescent antibody test (IFAT) and enzyme-linked immunosorbent assay (ELISA) were also used for the immunodiagnosis of B. equi. Serum samples from 15 apparently healthy horses, previously conditioned to a high-speed equine treadmill, were taken before and after exercise. All the samples analyzed were positive for B. equi infection. There were no significant differences (P<0.01) between these 3 tests, or the condition of rest or stress. The combined use of CFT and IFAT or ELISA should be recommended in order to enable veterinary services to more efficiently prevent introduction of infected horses into disease-free areas.

Do hematologic constituents really increase due to endurance exercise in horses?

The aim of this study was to evaluate the behavior of blood constituents in a group of horses that successfully completed long endurance rides in tropical conditions. Jugular vein puncture was done to collect blood before, during and after rides. Data were analyzed using a mathematic approach, based on the hematocrit and blood volume where the percentual change in plasma volume was used to correct the values of each variable analyzed. Significance was inferred when P<0.05. The proposed mathematical model to assess blood constituents concentrations allowed the observation of a different pattern of the variables behavior, pointing out that the approach followed by the authors could be more sensitive than ones that did not take this routine. In conclusion, the method used in this study enabled to monitor the physiological processes that actually occur during endurance effort in tropical conditions.

Low dose of dichloroacetate infusion reduces blood lactate after submaximal exercise in horses

The acute administration of an indirect activator of the enzyme pyruvate dehydrogenase (PDH) in human athletes causes a reduction in blood lactate level during and after exercise. A single IV dose (2.5m.kg-1) of dichloroacetate (DCA) was administered before a submaximal incremental exercise test (IET) with five velocity steps, from 5.0 m.s-1 for 1 min to 6.0, 6.5, 7.0 and 7.5m.s-1 every 30s in four untrained mares. The blood collections were done in the period after exercise, at times 1, 3, 5, 10, 15 and 20 min. Blood lactate and glucose (mM) were determined electro-enzymatically utilizing a YSI 2300 automated analyzer. There was a 15.3% decrease in mean total blood lactate determined from the values obtained at all assessment times in both trials after the exercise. There was a decrease in blood lactate 1, 3, 5, 10, 15 and 20 min after exercise for the mares that received prior DCA treatment, with respective mean values of 6.31±0.90 vs 5.81±0.50, 6.45±1.19 vs 5.58±1.06, 6.07±1.56 vs 5.26±1.12, 4.88±1.61 vs 3.95±1.00, 3.66±1.41 vs 2.86±0.75 and 2.75±0.51 vs 2.04±0.30. There was no difference in glucose concentrations. By means of linear regression analysis, V140, V160, V180 and V200 were determined (velocity at which the rate heart is 140, 160, 180, and 200 beats/minute, respectively). The velocities related to heart rate did not differ, indicating that there was no ergogenic effect, but prior administration of a relatively low dose of DCA in mares reduced lactatemia after an IET.

Monosodium glutamate (MSG)-obese rats develop glucose intolerance and insulin resistance to peripheral glucose uptake

Different levels of insulin sensitivity have been described in several animal models of obesity as well as in humans. Monosodium glutamate (MSG)-obese mice were considered not to be insulin resistant from data obtained in oral glucose tolerance tests. To reevaluate insulin resistance by the intravenous glucose tolerance test (IVGTT) and by the clamp technique, newborn male Wistar rats (N = 20) were injected 5 times, every other day, with 4 g/kg MSG (N = 10) or saline (control; N = 10) during the first 10 days of age. At 3 months, the IVGTT was performed by injecting glucose (0.75 g/kg) through the jugular vein into freely moving rats. During euglycemic clamping plasma insulin levels were increased by infusing 3 mU . kg-1 . min-1 of regular insulin until a steady-state plateau was achieved. The basal blood glucose concentration did not differ between the two experimental groups. After the glucose load, increased values of glycemia (P<0.001) in MSG-obese rats occurred at minute 4 and from minute 16 to minute 32. These results indicate impaired glucose tolerance. Basal plasma insulin levels were 39.9 ± 4 µU/ml in control and 66.4 ± 5.3 µU/ml in MSG-obese rats. The mean post-glucose area increase of insulin was 111% higher in MSG-obese than in control rats. When insulinemia was clamped at 102 or 133 µU/ml in control and MSG rats, respectively, the corresponding glucose infusion rate necessary to maintain euglycemia was 17.3 ± 0.8 mg . kg-1 . min-1 for control rats while 2.1 ± 0.3 mg . kg-1 . min-1 was sufficient for MSG-obese rats. The 2-h integrated area for total glucose metabolized, in mg . min . dl-1, was 13.7 ± 2.3 vs 3.3 ± 0.5 for control and MSG rats, respectively. These data demonstrate that MSG-obese rats develop insulin resistance to peripheral glucose uptake

Effects of caffeine on time to exhaustion in exercise performed below and above the anaerobic threshold

Controversy still exists concerning the potential ergogenic benefit of caffeine (CAF) for exercise performance. The purpose of this study was to compare the effects of CAF ingestion on endurance performance during exercise on a bicycle ergometer at two different intensities, i.e., approximately 10% below and 10% above the anaerobic threshold (AT). Eight untrained males, non-regular consumers of CAF, participated in this study. AT, defined as the intensity (watts) corresponding to a lactate concentration of 4 mM, was determined during an incremental exercise test from rest to exhaustion on an electrically braked cycle ergometer. On the basis of these measurements, the subjects were asked to cycle until exhaustion at two different intensities, i.e., approximately 10% below and 10% above AT. Each intensity was performed twice in a double-blind randomized order by ingesting either CAF (5 mg/kg) or a placebo (PLA) 60 min prior to the test. Venous blood was analyzed for free fatty acid, glucose, and lactate, before, during, and immediately after exercise. Rating of perceived exertion and time to exhaustion were also measured during each trial. There were no differences in free fatty acids or lactate levels between CAF and PLA during and immediately after exercise for either intensity. Immediately after exercise glucose increased in the CAF trial at both intensities. Rating of perceived exertion was significantly lower (CAF = 14.1 ± 2.5 vs PLA = 16.6 ± 2.4) and time to exhaustion was significantly higher (CAF = 46.54 ± 8.05 min vs PLA = 32.42 ± 14.81 min) during exercise below AT with CAF. However, there was no effect of CAF treatment on rating of perceived exertion (CAF = 18.0 ± 2.7 vs PLA = 17.6 ± 2.3) and time to exhaustion (CAF = 18.45 ± 7.28 min vs PLA = 19.17 ± 4.37 min) during exercise above AT. We conclude that in untrained subjects caffeine can improve endurance performance during prolonged exercise performed below AT and that the decrease of perceived exertion can be involved in this process