Background: The world population aging is evident and as a consequence, there is an increase of chronic diseases prevalence such as diabetes mellitus (DM) and cardiovascular diseases. The latter represent the main cause of death in elderly, especially coronary artery disease (CAD) and stroke. The chronotropic incompetence (CI) is characterized by an attenuated heart rate response to exercise. It represents a predictor of mortality and adverse cardiovascular events, and is defined as the failure to achieve less than 80% of heart rate reserve. However, its physiopathological mechanisms have not been clearly defined. One of the hypothesis postulates that it represents an abnormality in cardiovascular autonomic control. The DM and its chronic complications, such as autonomic neuropathy, are independent risk factors for stroke. As a possible manifestation of autonomic dysfunction, CI may be useful for cardiovascular risk stratification in diabetic patients. Objective: Estimate the value of chronotropic incompetence for predicting stroke in elderly diabetic patients that were submitted to exercise stress echocardiography, events included acute myocardial infarction (AMI), stroke and death. Methods: This was a restrospective observational H that assessed 298 elderly diabetic patients (from a population of 8269). Exercise stress echocardiography was performed by all participants of the study from January, 2000 to December, 2010. After exclusion criteria, patients were divided into two groups: G1 (patients who failed to achieve 80% of the age-predicted chronotropic index during exercise echocardiography) and G2 (patients who were able to achieve 80% of the age-predicted chronotropic index during exercise echocardiography). Results: There were 109 (36,6%) patients with chronotropic incompetence. Concerning clinical features, there were differences between the groups with reference to male gender (p=0,01), previous dyspneia (p=0,02) and typical angina. Concerning exercise stress echocardiography variables, there were divergences between groups for WMSI at rest, WMSI after exercise, LV mass index and LA diameter. In relation to cardiovascular events, the G1 group presented stroke in a higher frequency (9,2 % vs. 3,2%; p= 0,27) with relative risk 2,89 and G1 95% 1,05 - 7,95. The CI group presented higher frequency of death in patients that had AMI (p =0, 015) and stroke (p =0, 004). Conclusion: Our data suggest that CI predicts a worse prognosis for the occurrence of stroke in elderly diabetics as well as mortality for patients who developed with stroke and AMI. / Fundamento: devido ao envelhecimento populacional acelerado, principalmente em países em desenvolvimento como o Brasil, há aumento da prevalência de doenças crônicas como diabetes mellitus (DM) e patologias cardiovasculares. As principais causas de morte tanto em idosos como em diabéticos são a doença arterial coronariana (DAC) e a doença cerebrovascular (DCV). A incompetência cronotrópica (IC), caracterizada como uma incapacidade de atingir ao menos 80% da frequência cardíaca (FC) de reserva é um fator preditor de mortalidade e de eventos cardiovasculares. Embora seu mecanismo subjacente não seja bem definido, algumas hipóteses vêm sendo propostas, dentre elas, a disfunção autonômica. As complicações crônicas do DM, como neuropatia autonômica, são fatores de risco independentes para DCV. A IC pode ser útil para estratificação do risco cardiovascular nesta população. A ecocardiografia sob estresse pelo esforço físico (EF) é uma metodologia segura e eficaz na avaliação de pacientes com IC. Objetivos: avaliar o valor prognóstico da IC em idosos diabéticos submetidos à EF, considerando como desfechos: IAM, DCV e óbito geral; secundariamente, comparar características clínicas e ecocardiográficas entre idosos diabéticos com e sem IC. Método: estudo de coorte retrospectiva de 298 pacientes idosos e diabéticos submetidos à EF de janeiro de 2001 a dezembro de 2010. Os pacientes foram divididos em dois grupos: G1 109 pacientes com IC e G2 189 pacientes sem IC.Resultados: na amostra estudada a frequência de IC foi de 36,6% e o seguimento foi de 53,7 ± 32,5 meses com mínimo de 5 e máximo de 122 meses. O grupo G1 apresentou maior frequência de: sexo masculino (62,4% vs. 46,6%;p= 0,01), queixa de dispneia prévia à EF (7,5% vs. 2,1%; p= 0,02), angina prévia à EF (17% vs. 8%; p= 0,02), maior diâmetro do átrio esquerdo (4,1 ± 0,48 vs. 3,9 ± 0,45; p= 0,02), maior índice de massa do ventrículo esquerdo (101,82 ± 28,56 vs. 95,16 ± 26,43; p= 0,05), maior índice de escore de motilidade do ventrículo esquerdo (IEMVE) no repouso (1,07 ± 0,18 vs. 1,03 ± 0,12; p= 0,04) e de maior IEMVE no esforço (1,1 ± 0,2 vs. 1,05 ± 0,16; p= 0,004). Foi observada maior frequência de DCV no grupo G1 (9,2 % vs. 3,2%; p= 0,27) com risco relativo 2,89 e IC 95% 1,05 - 7,95. Conclusão: a IC foi associada de forma independente à ocorrência de DCV em idosos diabéticos .

Background: The world population aging is evident and as a consequence, there is an increase of chronic diseases prevalence such as diabetes mellitus (DM) and cardiovascular diseases. The latter represent the main cause of death in elderly, especially coronary artery disease (CAD) and stroke. The chronotropic incompetence (CI) is characterized by an attenuated heart rate response to exercise. It represents a predictor of mortality and adverse cardiovascular events, and is defined as the failure to achieve less than 80% of heart rate reserve. However, its physiopathological mechanisms have not been clearly defined. One of the hypothesis postulates that it represents an abnormality in cardiovascular autonomic control. The DM and its chronic complications, such as autonomic neuropathy, are independent risk factors for stroke. As a possible manifestation of autonomic dysfunction, CI may be useful for cardiovascular risk stratification in diabetic patients. Objective: Estimate the value of chronotropic incompetence for predicting stroke in elderly diabetic patients that were submitted to exercise stress echocardiography, events included acute myocardial infarction (AMI), stroke and death. Methods: This was a restrospective observational H that assessed 298 elderly diabetic patients (from a population of 8269). Exercise stress echocardiography was performed by all participants of the study from January, 2000 to December, 2010. After exclusion criteria, patients were divided into two groups: G1 (patients who failed to achieve 80% of the age-predicted chronotropic index during exercise echocardiography) and G2 (patients who were able to achieve 80% of the age-predicted chronotropic index during exercise echocardiography). Results: There were 109 (36,6%) patients with chronotropic incompetence. Concerning clinical features, there were differences between the groups with reference to male gender (p=0,01), previous dyspneia (p=0,02) and typical angina. Concerning exercise stress echocardiography variables, there were divergences between groups for WMSI at rest, WMSI after exercise, LV mass index and LA diameter. In relation to cardiovascular events, the G1 group presented stroke in a higher frequency (9,2 % vs. 3,2%; p= 0,27) with relative risk 2,89 and G1 95% 1,05 - 7,95. The CI group presented higher frequency of death in patients that had AMI (p =0, 015) and stroke (p =0, 004). Conclusion: Our data suggest that CI predicts a worse prognosis for the occurrence of stroke in elderly diabetics as well as mortality for patients who developed with stroke and AMI. / Fundamento: devido ao envelhecimento populacional acelerado, principalmente em países em desenvolvimento como o Brasil, há aumento da prevalência de doenças crônicas como diabetes mellitus (DM) e patologias cardiovasculares. As principais causas de morte tanto em idosos como em diabéticos são a doença arterial coronariana (DAC) e a doença cerebrovascular (DCV). A incompetência cronotrópica (IC), caracterizada como uma incapacidade de atingir ao menos 80% da frequência cardíaca (FC) de reserva é um fator preditor de mortalidade e de eventos cardiovasculares. Embora seu mecanismo subjacente não seja bem definido, algumas hipóteses vêm sendo propostas, dentre elas, a disfunção autonômica. As complicações crônicas do DM, como neuropatia autonômica, são fatores de risco independentes para DCV. A IC pode ser útil para estratificação do risco cardiovascular nesta população. A ecocardiografia sob estresse pelo esforço físico (EF) é uma metodologia segura e eficaz na avaliação de pacientes com IC. Objetivos: avaliar o valor prognóstico da IC em idosos diabéticos submetidos à EF, considerando como desfechos: IAM, DCV e óbito geral; secundariamente, comparar características clínicas e ecocardiográficas entre idosos diabéticos com e sem IC. Método: estudo de coorte retrospectiva de 298 pacientes idosos e diabéticos submetidos à EF de janeiro de 2001 a dezembro de 2010. Os pacientes foram divididos em dois grupos: G1 109 pacientes com IC e G2 189 pacientes sem IC.Resultados: na amostra estudada a frequência de IC foi de 36,6% e o seguimento foi de 53,7 ± 32,5 meses com mínimo de 5 e máximo de 122 meses. O grupo G1 apresentou maior frequência de: sexo masculino (62,4% vs. 46,6%;p= 0,01), queixa de dispneia prévia à EF (7,5% vs. 2,1%; p= 0,02), angina prévia à EF (17% vs. 8%; p= 0,02), maior diâmetro do átrio esquerdo (4,1 ± 0,48 vs. 3,9 ± 0,45; p= 0,02), maior índice de massa do ventrículo esquerdo (101,82 ± 28,56 vs. 95,16 ± 26,43; p= 0,05), maior índice de escore de motilidade do ventrículo esquerdo (IEMVE) no repouso (1,07 ± 0,18 vs. 1,03 ± 0,12; p= 0,04) e de maior IEMVE no esforço (1,1 ± 0,2 vs. 1,05 ± 0,16; p= 0,004). Foi observada maior frequência de DCV no grupo G1 (9,2 % vs. 3,2%; p= 0,27) com risco relativo 2,89 e IC 95% 1,05 - 7,95. Conclusão: a IC foi associada de forma independente à ocorrência de DCV em idosos diabéticos .

The parmacological effects of guinea pig vasoactive intestinal peptide (VIP) were studied in isolated perfused guinea pig hearts. Bolus injections of VIP produced a dose-dependent tachycardia that was not affected by atenolol. A decrease in amplitude of ventricular contractions occurred in response to all doses of VIP. This response was preceded by a small increase in amplitude in 3 of 6 hearts at the highest dose. VIP produced a decrease in perfusion pressure which was prominent after coronary tone was elevated with [Arg8]-vasopressin. The present findings support speculation that VIP may have a role in the regulation of heart rate and coronary blood flow.

Philosophiae Doctor - PhD / Plants used in traditional medicines have served as sources of some of the drug compounds used in medicines today, and could still serve as leads for then development of new drugs to treat existing chronic diseases such as hypertension. This study was aimed at the isolation and identification of a cardio-active compound from L. leonurus, a plant commonly used in traditional medicines in South Africa for the treatment of hypertension and other cardiac problems. The possible mechanisms by which the isolated compound produced its effect on the cardiovascular system were explored using the anaesthetized normotensive rat model.Fractionation of the organic extracts of the leaves led to the isolation of a novel diterpene,(13S)-9 , 13 -epoxylabda-6 (19),15(14)diol dilactone (EDD) whose structure was elucidated using infra red (IR), nuclear magnetic resonance (NMR), mass spectroscopy(MS), and X-ray diffraction analysis. In anaesthetized normotensive male Wistar rats, EDD(0.5 mg/kg – 5.0 mg/kg; IV) produced slight non-significant decreases in systolic pressure(SP), diastolic pressure (DP), and mean arterial pressure (MAP) with the lower (0.5 mg/kg– 2.0 mg/kg) doses, while significant increases in SP, DP and MAP occurred with the higher (3.0 mg/kg – 5.0 mg/kg) doses. All doses of EDD administered also produced significant decreases in heart rate (HR).Prazosin and reserpine pre-treatment abolished the vasoconstrictive effect of EDD,suggesting an indirect vasoconstrictive effect for EDD via the release of catecholamines.Atenolol pre-treatment led to increases in the negative chronotropic effect of EDD, while the positive chronotropic effect of dobutamine was significantly decreased by EDD,suggesting the involvement of the 1 adrenoceptor in the negative chronotropic effect of EDD. In animals pre-treated with verapamil, a cardio-selective Ca2+ channel blocker, no significant changes in HR occurred with all EDD doses, but HR values were significantly lower than those obtained with EDD in non pre-treated animals.The results of this study indicate that (13S)-9 , 13 -epoxylabda-6 (19),15(14)diol dilactone, a novel dilactone diterpene isolated from the leaves of L. leonurus has an effect on the cardiovascular system. EDD exhibits a dual effect on the cardiovascular system by producing a vasoconstrictive effect accompanied by bradycardia. The vasoconstrictive effect of EDD is probably due to the release of catecholamines, while the negative chronotropic effect is probably due to 1 adrenoceptor antagonism. Further studies are however required to fully determine the mechanism by which EDD produces its cardiovascular effects.

Introdução: A disfunção do sistema nervoso autônomo (disfunção autonômica ou dissautonomia) tem sido associada à fisiopatologia da fibromialgia em pacientes adultos. A modulação cardíaca em resposta ao exercício foi demonstrada em uma série de estudos em adultos com fibromialgia que evidenciaram reduzida capacidade aeróbia, assim como o comprometimento autonômico cardíaco e incompetência cronotrópica, que é a incapacidade de aumentar a frequência cardíaca concomitante ao aumento da intensidade do exercício. No entanto, a capacidade aeróbica e a disautonomia, definidas a partir da avaliação dos parâmetros do teste de exercício cardiopulmonar, não foram estudadas em pacientes adolescentes com síndrome da fibromialgia (FMJ). Objetivo: Avaliar os parâmetros do teste de exercício cardiopulmonar em pacientes com FMJ e controles saudáveis e as possíveis correlações entre estes parâmetros e a qualidade de vida relacionada à saúde (QVRS), capacidade funcional e dor nos pacientes FMJ. Métodos: Estudo transversal multicêntrico incluindo 25 pacientes com FMJ e 25 controles saudáveis. Ambos os grupos participavam somente das aulas de educação física na escola. O teste de exercício cardiopulmonar de esforço em esteira permitiu avaliar a resposta cardiorrespiratória durante o exercício. A resposta cronotrópica foi avaliada pela medida da reserva cronotrópica. Foram avaliados dor, capacidade funcional e QVRS. Resultados: A mediana da idade atual foi similar nos pacientes com FMJ e controles saudáveis (15 vs. 15 anos, p=0,890), assim como o índice de massa corporal (p=0,332), gênero feminino (p=1,000) e estágios de Tanner (p=0,822). A mediana dos parâmetros da QVRS (escore total de saúde física e saúde psicossocial) foi significativamente menor nos pacientes com FMJ versus controles, de acordo com o autorrelato dos pacientes e de seus pais (p < 0,001). A mediana do pico FC [181 (150-198) vs. 197 (181-202) bpm, p < 0,001], da reserva cronotrópica (RC) [84 (53-98) vs. 99 (84-103) %, p < 0,001] e da FC de repouso à FC de pico [96 (65-181) vs. 127 (61-185) bpm, p=0,010] foram significantemente menores nos pacientes com FMJ quando comparados aos controles saudáveis. A mediana do ?FCR1 [15 (3-39) vs. 35 (9-52) bpm, p < 0,001], deltaFCR2 [37 (20-57) vs. 51 (32-94) bpm, p < 0,001], VO2 de pico [32.34 (24.24-39.65) vs. 36.4 (28.56-52.71) ml/kg/min, p=0,005], velocidade máxima [5 (4-6.3) vs. 5.9 (4.0-6.3) mph, p=0,001], tempo de exaustão [11.5 (8.5-14.5) vs. 14 (11-18) minutos, p < 0,001] e capacidade de trabalho [3.37 (2.04-5.6) vs. 3.89 (2.91-6.55) W/kg, p=0,006] foram significativamente menores nos pacientes com FMJ quando comparados aos controles. A frequência da incompetência cronotrópica (<= 80%) foi significativamente maior nos pacientes com FMJ versus controles (p=0,0006). Conclusões: Este estudo identificou incompetência cronotrópica e recuperação atenuada da FC em pacientes com FMJ, indicando disfunção autonômica / Introdução: Autonomic nervous system dysfunction (also named autonomic disturbance or dysautonomia) has been linked to physiopathology of adult patients with fibromyalgia. Cardiac modulation in response to exercise in case series of adult fibromyalgia revealed reduced aerobic capacity, as well as cardiac autonomic impairment and chronotropic incompetence, which is the inability to increase heart rate with an increase in exercise intensity. However, to our knowledge treadmill cardiorespiratory test and to assess aerobic capacity and dysautonomia has not been studied in adolescents with JFM patients. Objective: To assess cardiorespiratory exercise test parameters in Juvenile fibromyalgia syndrome (JFM) patients and healthy controls and possible correlations between these parameters and health-related quality of life (HRQL), functional ability and pain in JFM patients. Methods: A multicenter cross-sectional study included 25 JFM patients and 25 healthy controls. Both groups were engaged only in the physical education classes in school. A treadmill graded cardiorespiratory test was performed and heart-rate (HR) response during exercise was evaluated by the chronotropic reserve (CR). Pain, functional ability and HRQL were assessed. Results: The median current age was similar in JFM and controls (15 vs. 15years, p=0.890), as well as body mass index (p=0.332), female gender (p=1.000) and Tanner stages (p=0.822). The medians of HRQL parameters (total score/physical health/psychosocial health) were significantly lower in JFM versus controls according to patient and parent self-reports (p<0.001). The median of peak HR [181 (150-198) vs. 197 (181-202) bpm, p < 0.001], chronotropic reserve [84 (53-98) vs. 99 (84-103)%, p < 0.001] and resting to peak [96 (65-181) vs. 127 (61-185) bpm, p=0.010] were significantly lower in JFM compared to controls. The median of ?HRR1 [15 (3-39) vs. 35 (9-52) bpm, p < 0.001], deltaHRR2 [37 (20-57) vs. 51 (32-94) bpm, p < 0.001], peak VO2 [32.34 (24.24-39.65) vs. 36.4 (28.56-52.71) ml/kg/min, p=0.005]; peak speed [5 (4-6.3) vs. 5.9 (4.0-6.3) km/h, p=0.001], time to exhaustion [11.5 (8.5-14.5) vs. 14 (11-18) minutes, p < 0.001] and working capacity on power [3.37 (2.04-5.6) vs. 3.89 (2.91-6.55) W/kg, p=0.006] were significantly lower in JFM compared to controls. The frequency of chronotropic incompetence ( <= 80%) was significantly higher in JFM versus controls (p=0.0006). Conclusions: This study identified chronotropic incompetence and delayed HR recovery in JFM patients, indicating autonomic dysfunction

Introdução: A disfunção do sistema nervoso autônomo (disfunção autonômica ou dissautonomia) tem sido associada à fisiopatologia da fibromialgia em pacientes adultos. A modulação cardíaca em resposta ao exercício foi demonstrada em uma série de estudos em adultos com fibromialgia que evidenciaram reduzida capacidade aeróbia, assim como o comprometimento autonômico cardíaco e incompetência cronotrópica, que é a incapacidade de aumentar a frequência cardíaca concomitante ao aumento da intensidade do exercício. No entanto, a capacidade aeróbica e a disautonomia, definidas a partir da avaliação dos parâmetros do teste de exercício cardiopulmonar, não foram estudadas em pacientes adolescentes com síndrome da fibromialgia (FMJ). Objetivo: Avaliar os parâmetros do teste de exercício cardiopulmonar em pacientes com FMJ e controles saudáveis e as possíveis correlações entre estes parâmetros e a qualidade de vida relacionada à saúde (QVRS), capacidade funcional e dor nos pacientes FMJ. Métodos: Estudo transversal multicêntrico incluindo 25 pacientes com FMJ e 25 controles saudáveis. Ambos os grupos participavam somente das aulas de educação física na escola. O teste de exercício cardiopulmonar de esforço em esteira permitiu avaliar a resposta cardiorrespiratória durante o exercício. A resposta cronotrópica foi avaliada pela medida da reserva cronotrópica. Foram avaliados dor, capacidade funcional e QVRS. Resultados: A mediana da idade atual foi similar nos pacientes com FMJ e controles saudáveis (15 vs. 15 anos, p=0,890), assim como o índice de massa corporal (p=0,332), gênero feminino (p=1,000) e estágios de Tanner (p=0,822). A mediana dos parâmetros da QVRS (escore total de saúde física e saúde psicossocial) foi significativamente menor nos pacientes com FMJ versus controles, de acordo com o autorrelato dos pacientes e de seus pais (p < 0,001). A mediana do pico FC [181 (150-198) vs. 197 (181-202) bpm, p < 0,001], da reserva cronotrópica (RC) [84 (53-98) vs. 99 (84-103) %, p < 0,001] e da FC de repouso à FC de pico [96 (65-181) vs. 127 (61-185) bpm, p=0,010] foram significantemente menores nos pacientes com FMJ quando comparados aos controles saudáveis. A mediana do ?FCR1 [15 (3-39) vs. 35 (9-52) bpm, p < 0,001], deltaFCR2 [37 (20-57) vs. 51 (32-94) bpm, p < 0,001], VO2 de pico [32.34 (24.24-39.65) vs. 36.4 (28.56-52.71) ml/kg/min, p=0,005], velocidade máxima [5 (4-6.3) vs. 5.9 (4.0-6.3) mph, p=0,001], tempo de exaustão [11.5 (8.5-14.5) vs. 14 (11-18) minutos, p < 0,001] e capacidade de trabalho [3.37 (2.04-5.6) vs. 3.89 (2.91-6.55) W/kg, p=0,006] foram significativamente menores nos pacientes com FMJ quando comparados aos controles. A frequência da incompetência cronotrópica (<= 80%) foi significativamente maior nos pacientes com FMJ versus controles (p=0,0006). Conclusões: Este estudo identificou incompetência cronotrópica e recuperação atenuada da FC em pacientes com FMJ, indicando disfunção autonômica / Introdução: Autonomic nervous system dysfunction (also named autonomic disturbance or dysautonomia) has been linked to physiopathology of adult patients with fibromyalgia. Cardiac modulation in response to exercise in case series of adult fibromyalgia revealed reduced aerobic capacity, as well as cardiac autonomic impairment and chronotropic incompetence, which is the inability to increase heart rate with an increase in exercise intensity. However, to our knowledge treadmill cardiorespiratory test and to assess aerobic capacity and dysautonomia has not been studied in adolescents with JFM patients. Objective: To assess cardiorespiratory exercise test parameters in Juvenile fibromyalgia syndrome (JFM) patients and healthy controls and possible correlations between these parameters and health-related quality of life (HRQL), functional ability and pain in JFM patients. Methods: A multicenter cross-sectional study included 25 JFM patients and 25 healthy controls. Both groups were engaged only in the physical education classes in school. A treadmill graded cardiorespiratory test was performed and heart-rate (HR) response during exercise was evaluated by the chronotropic reserve (CR). Pain, functional ability and HRQL were assessed. Results: The median current age was similar in JFM and controls (15 vs. 15years, p=0.890), as well as body mass index (p=0.332), female gender (p=1.000) and Tanner stages (p=0.822). The medians of HRQL parameters (total score/physical health/psychosocial health) were significantly lower in JFM versus controls according to patient and parent self-reports (p<0.001). The median of peak HR [181 (150-198) vs. 197 (181-202) bpm, p < 0.001], chronotropic reserve [84 (53-98) vs. 99 (84-103)%, p < 0.001] and resting to peak [96 (65-181) vs. 127 (61-185) bpm, p=0.010] were significantly lower in JFM compared to controls. The median of ?HRR1 [15 (3-39) vs. 35 (9-52) bpm, p < 0.001], deltaHRR2 [37 (20-57) vs. 51 (32-94) bpm, p < 0.001], peak VO2 [32.34 (24.24-39.65) vs. 36.4 (28.56-52.71) ml/kg/min, p=0.005]; peak speed [5 (4-6.3) vs. 5.9 (4.0-6.3) km/h, p=0.001], time to exhaustion [11.5 (8.5-14.5) vs. 14 (11-18) minutes, p < 0.001] and working capacity on power [3.37 (2.04-5.6) vs. 3.89 (2.91-6.55) W/kg, p=0.006] were significantly lower in JFM compared to controls. The frequency of chronotropic incompetence ( <= 80%) was significantly higher in JFM versus controls (p=0.0006). Conclusions: This study identified chronotropic incompetence and delayed HR recovery in JFM patients, indicating autonomic dysfunction