Impact of interventional therapy on top of standard drug therapy on left ventricular structure and function in HFrEF patients complicating with middle aortic syndrome caused by Takayasu arteritis / 中华心血管病杂志

Objective: To evaluate the impact of interventional therapy on top of drug therapy on cardiac function and structure in heart failure with reduced ejection fraction (HFrEF) patients complicating with middle aortic syndrome caused by Takayasu arteritis (TA-MAS). Methods: It was a retrospective longitudinal study. The data of patients with TA-MAS and HFrEF, who received interventional therapy on top of drug therapy in Fuwai Hospital from January 2010 to September 2020, were collected and analyzed. Baseline clinical data (including demographic data, basic treatment, etc.) were collected through the electronic medical record system. Changes of indexes such as New York Heart Association (NYHA) classification, N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular end diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI) before and after therapy were analyzed. Results: A total of 10 patients were collected. There were 8 females in this patient cohort, age was (18.4±5.0) years and onset age was (15.3±5.0) years. All 10 patients received standard heart failure medication therapy in addition to hormone and/or immunosuppressive anti-inflammatory therapy, but cardiac function was not improved, so aortic balloon dilatation and/or aortic stenting were performed in these patients. The median follow-up was 3.3(1.3, 5.6) years. On the third day after interventional therapy, the clinical symptoms of the 10 patients were significantly improved, NYHA classfication was restored from preoperative Ⅲ/Ⅳ to Ⅱ at 6 months post intervention(P<0.05). Compared with preoperation, NT-proBNP (P=0.028), LVEDD (P=0.011) and LVMI (P=0.019) were significantly decreased, LVEF was significantly increased (P<0.001) at 6 months after operation. Compared with preoperation, NT-proBNP (P=0.016), LVEDD (P=0.023) and LVMI (P=0.043) remained decreased, LVEF remained increased (P<0.001) at 1 year after operation. Conclusion: Results from short and medium term follow-up show that interventional therapy on top of heart failure drug therpay can effectively improve left cardiac function and attenuate cardiac remodeling in patients with TA-MAS comorbid with HFrEF.

Pterostilbeno Reduz o Estresse Oxidativo no Pulmão e no Ventrículo Direito Induzido por Infarto do Miocárdio Experimental / Pterostilbene Reduces Experimental Myocardial Infarction-Induced Oxidative Stress in Lung and Right Ventricle

Resumo Fundamento O pterostilbeno (PS), um composto polifenólico natural e antioxidante, surge como uma intervenção promissora para minimizar danos do infarto agudo do miocárdio (IAM). Objetivo Este estudo teve como objetivo avaliar o desempenho do PS na promoção da homeostase redox nos pulmões e no ventrículo direito (VD) de animais infartados. Métodos Ratos Wistar machos (60 dias de idade) foram randomizados em três grupos: SHAM, IAM (infarto) e IAM+PS (IAM + pterostilbeno). Sete dias após o procedimento de IAM, os ratos foram tratados com PS (100 mg/kg/dia) por gavagem por oito dias. Os animais foram depois sacrificados e os pulmões e VD foram coletados para análise do balanço redox (diferenças foram consideradas significativas quando p<0,05). Resultados Nossos resultados mostram que o IAM desencadeia a interrupção redox no VD e nos pulmões, o que pode contribuir para danos induzido pelo IAM nesses órgãos. Consistentemente, o PS mitigou o estresse oxidativo e restaurou as defesas antioxidantes (Glutationa - GSH nos pulmões: SHAM = 0,79 ± 0,07; IAM = 0,67 ± 0,05; IAM + PS = 0,86 ± 0,14; p<0,05), indicando seu papel protetor neste cenário. Conclusão Nosso trabalho evidencia o potencial do uso de PS como abordagem terapêutica adjuvante após IAM para proteção dos tecidos pulmonares e cardíacos direitos.

Abstract Background Pterostilbene (PS), a natural and antioxidant polyphenolic compound emerges as a promising intervention in improving the myocardial infarction (MI) damages. Objetives This study aimed to evaluate PS actions in promoting redox homeostasis in lungs and right ventricle (RV) of infarcted animals. Methods Male Wistar rats (60 day-old) were randomized into three groups: SHAM, MI (infarcted), and MI+PS (MI+pterostilbene). Seven days after MI procedure, rats were treated with PS (100 mg/kg/day) via gavage for eight days. Animals were euthanized and the lungs and RV were harvested for analyses of redox balance (Differences were considered significant when p<0.05). Results Our results show that MI triggers a redox disruption scenario in RV and lungs, which can contribute to MI-induced damage on these organs. Consistently, PS mitigated oxidative stress and restored antioxidant defenses (GSH in lungs: SHAM= 0.79±0.07; MI=0.67±0.05; MI+PS=0.86±0.14; p<0.05), indicating its protective role in this scenario. Conclusions Our work evidences the PS potential use as an adjuvant therapeutic approach after MI focusing on protecting pulmonary and right-sided heart tissues.

Alprostadil attenuates myocardial ischemia/reperfusion injury by promoting antioxidant activity and eNOS activation in rats

Abstract Purpose: To investigate the effect of alprostadil on myocardial ischemia/reperfusion (I/R) in rats. Methods: Rats were subjected to myocardial ischemia for 30 min followed by 24h reperfusion. Alprostadil (4 or 8 μg/kg) was intravenously administered at the time of reperfusion and myocardial infarct size, levels of troponin T, and the activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in the serum were measured. Antioxidative parameters, nitric oxide (NO) content and phosphorylated endothelial nitric oxide synthase 3 (p-eNOS) expression in the left ventricles were also measured. Histopathological examinations of the left ventricles were also performed. Results: Alprostadil treatment significantly reduced myocardial infarct size, serum troponin T levels, and CK-MB and LDH activity (P<0.05). Furthermore, treatment with alprostadil significantly decreased malondialdehyde (MDA) content (P<0.05) and markedly reduced myonecrosis, edema and infiltration of inflammatory cells. Superoxide dismutase and catalase activities (P<0.05), NO level (P<0.01) and p-eNOS (P<0.05) were significantly increased in rats treated with alprostadil compared with control rats. Conclusion: These results indicate that alprostadil protects against myocardial I/R injury and that these protective effects are achieved, at least in part, via the promotion of antioxidant activity and activation of eNOS.

Impact of dexmedetomidine on hemodynamics in rabbits

Abstract Purpose: To evaluate the effects of single intravenous administration of Dexmedetomidine (DEX) on hemodynamics in rabbits. Methods: A total of 32 New Zealand white rabbits were randomly divided into the control group (Group C), Group D1 (2.75 μg/kg), Group D2 (5.5 μg/kg), and Group D3 (8.25 μg/kg) to compare systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), central venous pressure (CVP), left ventricular systolic pressure (LVSP), left ventricular end-stage diastolic pressure (LVEDP), left ventricular developmental pressure (LVDP), +dp/dtmax, -dp/dtmax, and t-dp/dtmax at different time points. Results: The levels of SBP, DBP, HR, LVSP, and LVEDP in Group D1, D2, and D3 were lower than that of Group C from T1 to T5 (P<0.05), but there was no significant difference at T6 and T7 (P>0.05). Compared with T0, the levels of SBP, DBP, HR, LVSP, LVEDP, and left arterial pressure (LAP) from T1 to T7 were decreased (P<0.05), but there was no significant difference in the other indexes (P>0.05). Conclusion: Dexmedetomidine can decrease blood pressure and heart rate in rabbits in a dose-dependent manner, but there is no effect on the myocardial systolic and diastolic function.

Mesenchymal stem cells reduce left ventricular mass in rats with doxorubicin-induced cardiomyopathy / Las células madre mesenquimales reducen la masa ventricular izquierda en ratas con miocardiopatía inducida por doxorrubicina

SUMMARY: Doxorubicin is a drug that used by a majority in the treatment of carcinomas. The most obvious known side effect is cardiomyopathy. Many studies have been carried out to eliminate side effects of the doxorubicin, and stem cell studies have been added in recent years. In this study, it was aimed to investigate fetal-derived mesenchymal stem cells (F-MSCs) treatment of doxorubicininduced cardiomyopathy by morphological methods. A total of 24 rats which were divided into three separate groups (Control, sham, treatment), each consisting of 8 male rats were used. In sham and treatment group, Adriamycin was administered in a single dose by tail injection to perform cardiotoxicity. In the treatment group, F-MSCs were intra-peritoneally administrated. Then, rats were euthanized and their hearts were photographed at the level of papillary muscle. and thickness, diameters and surface area levels were measured. Left ventricular mass (LVM) and left ventricular mass index (LVMI) were calculated after measurement. The sham group, LVM and LVMI levels were found to significantly lower (p<0.05) than control and treatment group. In the one hand, LVMI levels of rats in treatment group was statistically similar (p>0.05) to control group. Similarly, LVM levels of control and treatment groups were close to each other while this level of sham group was lower. It has been shown that F-MSC administrations in rats with doxorubicin-induced cardiomyopathy have adverse effect on LVM and LVMI values. In addition, the intra-peritoneal MSC administrations may be an alternative to other injection routes such as intra-venous and intra-cardiac administrations.

RESUMEN: La doxorrubicina es un medicamento usado ampliamente en el tratamiento de carcinomas. El efecto secundario más conocido es la miocardiopatía. Se han llevado a cabo muchos estudios para eliminar los efectos secundarios de la doxorrubicina, y en los últimos años se han agregado estudios con células madre. mediante métodos morfológicos, se intentó investigar el tratamiento de las células madre mesenquimales (F-MSCs) derivadas del feto, de la miocardiopatía inducida por doxorrubicina. Se utilizó un total de 24 ratas que se dividieron en tres grupos (control, simulación, tratamiento), cada uno de las cuales consistía en 8 ratas macho. En el tratamiento simulado y en el grupo tratamiento, se administró doxorrubicina en una dosis única mediante inyección en la cola de la rata para realizar cardiotoxicidad. En el grupo tratamiento, las FMSC se administraron intraperitonealmente. Luego, las ratas fueron sacrificadas y sus corazones fueron fotografiados a nivel de los músculos papilares, y se midieron los espesores, los diámetros y los niveles de área superficial. Después de las mediciones se calcularon la masa ventricular izquierda (MVI) y el índice de masa ventricular izquierda (IMVI). En el grupo simulado, los niveles de MVI y IMVI se encontraron significativamente inferiores (p <0.05) que en los grupos control y tratamiento. Por un lado, los niveles de IMVI de las ratas en el grupo de tratamiento fueron estadísticamente similares (p> 0,05) al grupo de control. De forma similar, los niveles de MVI de los grupos control y tratamiento se aproximaban uno al otro, mientras que este nivel era más bajo en el grupo simulado. Se ha demostrado que la administracion de F-MSC en ratas con miocardiopatía inducida por doxorrubicina tiene un efecto adverso sobre los valores de MVI y IMVI. Además, la administracion de MSC intraperitoneal puede ser una alternativa a otras rutas de inyección tal como las administración intravenosa e intracardíaca.

Lactate-upregulation of lactate oxidation complex-related genes is blunted in left ventricle of myocardial infarcted rats

Lactate modulates the expression of lactate oxidation complex (LOC)-related genes and cardiac blood flow under physiological conditions, but its modulatory role remains to be elucidated regarding pathological cardiac stress. The present study evaluated the effect of lactate on LOC-related genes expression and hemodynamics of hearts submitted to myocardial infarction (MI). Four weeks after MI or sham operation, isolated hearts of male Wistar rats were perfused for 60 min with Na+-lactate (20 mM). As expected, MI reduced cardiac contractility and relaxation with no changes in perfusion. The impaired cardiac hemodynamics were associated with increased reactive oxygen species (ROS) levels (Sham: 19.3±0.5 vs MI: 23.8±0.3 µM), NADPH oxidase (NOX) activity (Sham: 42.2±1.3 vs MI: 60.5±1.5 nmol·h−1·mg−1) and monocarboxylate transporter 1 (mct1) mRNA levels (Sham: 1.0±0.06 vs MI: 1.7±0.2 a.u.), but no changes in superoxide dismutase (SOD), catalase, NADH oxidase (NADox), and xanthine oxidase activities. Lactate perfusion in MI hearts had no additional effect on ROS levels, NADox, and NOX activity, however, it partially reduced mct1 mRNA expression (MI-Lactate 1.3±0.08 a.u.). Interestingly, lactate significantly decreased SOD (MI-Lactate: 54.5±4.2 µmol·mg−1·min−1) and catalase (MI: 1.1±0.1 nmol·mg−1·min−1) activities in MI. Collectively, our data suggest that under pathological stress, lactate lacks its ability to modulate the expression of cardiac LOC-related genes and the perfused pressure in hearts submitted to chronic MI. Together, these data contribute to elucidate the mechanisms involved in the pathogenesis of heart failure induced by MI.

The Role of Serotonin in Ventricular Repolarization in Pregnant Mice

PURPOSE: The mechanisms underlying repolarization abnormalities during pregnancy are not fully understood. Although maternal serotonin (5-hydroxytryptamine, 5-HT) production is an important determinant for normal fetal development in mice, its role in mothers remains unclear. We evaluated the role of serotonin in ventricular repolarization in mice hearts via 5Htr3 receptor (Htr3a) and investigated the mechanism of QT-prolongation during pregnancy. MATERIALS AND METHODS: We measured current amplitudes and the expression levels of voltage-gated K⁺ (Kv) channels in freshly-isolated left ventricular myocytes from wild-type non-pregnant (WT-NP), late-pregnant (WT-LP), and non-pregnant Htr3a homozygous knockout mice (Htr3a(−/−)-NP). RESULTS: During pregnancy, serotonin and tryptophan hydroxylase 1, a rate-limiting enzyme for the synthesis of serotonin, were markedly increased in hearts and serum. Serotonin increased Kv current densities concomitant with the shortening of the QT interval in WT-NP mice, but not in WT-LP and Htr3a(−/−)-NP mice. Ondansetron, an Htr3 antagonist, decreased Kv currents in WT-LP mice, but not in WT-NP mice. Kv4.3 directly interacted with Htr3a, and this binding was facilitated by serotonin. Serotonin increased the trafficking of Kv4.3 channels to the cellular membrane in WT-NP. CONCLUSION: Serotonin increases repolarizing currents by augmenting Kv currents. Elevated serotonin levels during pregnancy counterbalance pregnancy-related QT prolongation by facilitating Htr3-mediated Kv currents.

Pentoxifylline Attenuates Cardiac Remodeling Induced by Tobacco Smoke Exposure / A Pentoxifilina Atenua a Remodelação Cardíaca Induzida pela Exposição á Fumaça de Cigarros

Abstract Background: Tobacco smoke exposure is an important risk factor for cardiac remodeling. Under this condition, inflammation, oxidative stress, energy metabolism abnormalities, apoptosis, and hypertrophy are present. Pentoxifylline has anti‑inflammatory, anti-apoptotic, anti-thrombotic and anti-proliferative properties. Objective: The present study tested the hypothesis that pentoxifylline would attenuate cardiac remodeling induced by smoking. Methods: Wistar rats were distributed in four groups: Control (C), Pentoxifylline (PX), Tobacco Smoke (TS), and PX-TS. After two months, echocardiography, invasive blood pressure measurement, biochemical, and histological studies were performed. The groups were compared by two-way ANOVA with a significance level of 5%. Results: TS increased left atrium diameter and area, which was attenuated by PX. In the isolated heart study, TS lowered the positive derivate (+dp/dt), and this was attenuated by PX. The antioxidants enzyme superoxide dismutase and glutathione peroxidase were decreased in the TS group; PX recovered these activities. TS increased lactate dehydrogenase (LDH) and decreased 3-hydroxyacyl Coenzyme A dehydrogenases (OH-DHA) and citrate synthase (CS). PX attenuated LDH, 3-OH-DHA and CS alterations in TS-PX group. TS increased IL-10, ICAM-1, and caspase-3. PX did not influence these variables. Conclusion: TS induced cardiac remodeling, associated with increased inflammation, oxidative stress, apoptosis, and changed energy metabolism. PX attenuated cardiac remodeling by reducing oxidative stress and improving cardiac bioenergetics, but did not act upon cardiac cytokines and apoptosis.

Resumo Fundamento: Exposição à fumaça de cigarros é um fator significativo de risco para a remodelação cardíaca. Nesta condição, estão presentes inflamação, estresse oxidativo, anormalidades do metabolismo energético, apoptose e hipertrofia. A pentoxifilina tem propriedades anti-inflamatórias, anti-apoptóticas, anti-trombóticas e anti-proliferativas. Objetivo: O presente estudo testou a hipótese de que a pentoxifilina atenuaria a remodelação cardíaca induzida pelo fumo. Métodos: Ratos Wistar foram distribuídos em quatro grupos: Controle (C), Pentoxifilina (PX), Fumaça de Cigarro (FC), e PX-FC. Depois de dois meses, foram feitos ecocardiografia, medição de pressão arterial invasiva e estudos bioquímicos e histológicos. Os grupos foram comparados por ANOVA de duas vias com nível de significância de 5%. Resultados: FC aumentou o diâmetro e a área do átrio esquerdo, o que foi atenuado pela PX. No estudo de coração isolado, FC diminuiu a derivada positiva (+dp/dt), o que foi atenuado por PX. Os antioxidantes enzima superóxido-dismutase e glutationa peroxidase foram reduzidos no grupo FC; PX recuperou essas atividades. FC aumentou o lactato desidrogenase (LDH) e reduziu as desidrogenases 3-hidroxiacil Coenzima A (OH-DHA) e citrato sintase (CS). PX atenuou alterações de LDH, 3-OH-DHA e CS no grupo PX-FC. FC aumentou IL-10, ICAM-1 e caspase-3. PX não teve influência nestas variáveis. Conclusão: FC induziu remodelação cardíaca, associada a um aumento de inflamação, estresse oxidativo, apoptose e metabolismo energético alterado. PX atenuou remodelação cardíaca, reduzindo estresse oxidativo e melhorando bioenergética cardíaca, mas não agiu nas citocinas cardíacas nem na apoptose.

Effects of Growth Hormone on Cardiac Remodeling During Resistance Training in Rats / Efeitos do Hormônio do Crescimento na Remodelação Cardíaca Durante Treinamento Resistido em Ratos

Abstract Background: Although the beneficial effects of resistance training (RT) on the cardiovascular system are well established, few studies have investigated the effects of the chronic growth hormone (GH) administration on cardiac remodeling during an RT program. Objective: To evaluate the effects of GH on the morphological features of cardiac remodeling and Ca2+ transport gene expression in rats submitted to RT. Methods: Male Wistar rats were divided into 4 groups (n = 7 per group): control (CT), GH, RT and RT with GH (RTGH). The dose of GH was 0.2 IU/kg every other day for 30 days. The RT model used was the vertical jump in water (4 sets of 10 jumps, 3 bouts/wk) for 30 consecutive days. After the experimental period, the following variables were analyzed: final body weight (FBW), left ventricular weight (LVW), LVW/FBW ratio, cardiomyocyte cross-sectional area (CSA), collagen fraction, creatine kinase muscle-brain fraction (CK-MB) and gene expressions of SERCA2a, phospholamban (PLB) and ryanodine (RyR). Results: There was no significant (p > 0.05) difference among groups for FBW, LVW, LVW/FBW ratio, cardiomyocyte CSA, and SERCA2a, PLB and RyR gene expressions. The RT group showed a significant (p < 0.05) increase in collagen fraction compared to the other groups. Additionally, the trained groups (RT and RTGH) had greater CK-MB levels compared to the untrained groups (CT and GH). Conclusion: GH may attenuate the negative effects of RT on cardiac remodeling by counteracting the increased collagen synthesis, without affecting the gene expression that regulates cardiac Ca2+ transport.

Resumo Fundamento: Apesar de os efeitos benéficos do treinamento resistido (TR) sobre o sistema cardiovascular estarem bem estabelecidos, poucos estudos têm investigado os efeitos crônicos da administração de hormônio do crescimento (GH) sobre a remodelação cardíaca durante um programa de TR. Objetivo: avaliar os efeitos do GH sobre a remodelação cardíaca em suas características morfológicas e na expressão dos genes do trânsito de Ca2+ em ratos submetidos ao TR. Métodos: Ratos Wistar machos foram divididos em 4 grupos (n = 7 por grupo): controle (CT), GH, TR e TR com GH (TRGH). A dose de GH foi de 0,2 UI/kg, a cada dois dias, por 30 dias. O modelo de TR utilizado foi o salto vertical em água (4 séries de 10 saltos, 3 vezes/semana) durante 30 dias consecutivos. Após o período experimental, as seguintes variáveis foram analisadas: peso corporal final (PCF), peso do ventrículo esquerdo (PVE), razão PVE/PCF, área seccional de cardiomiócitos (ASC), fração de colágeno, creatina quinase fração músculo-cérebro (CK-MB) e expressão gênica de SERCA2a, fosfolambam (PLB) e rianodina (RyR). Resultados: Não houve diferença significativa (p > 0,05) entre os grupos para PCF, PVE, razão PVE/PCF, ASC, e expressão gênica de SERCA2a, PLB e RyR. O grupo TR mostrou um significativo aumento (p < 0,05) da fração de colágeno em comparação aos outros. Além disso, os grupos treinados (TR e TRGH) apresentaram maiores níveis de CK-MB em comparação aos não treinados (CT e GH). Conclusão: Esses resultados indicam que o GH pode atenuar os efeitos negativos do TR na remodelação cardíaca por contrabalançar o aumento da síntese de colágeno, sem afetar a expressão de genes que regulam o trânsito de Ca2+ cardíaco.

Effect of different anesthetic agents on left ventricular systolic function assessed by echocardiography in hamsters

Determination of left ventricular ejection fraction (LVEF) using in vivo imaging is the cardiac functional parameter most frequently employed in preclinical research. However, there is considerable conflict regarding the effects of anesthetic agents on LVEF. This study aimed at assessing the effects of various anesthetic agents on LVEF in hamsters using transthoracic echocardiography. Twelve female hamsters were submitted to echocardiography imaging separated by 1-week intervals under the following conditions: 1) conscious animals, 2) animals anesthetized with isoflurane (inhaled ISO, 3 L/min), 3) animals anesthetized with thiopental (TP, 50 mg/kg, intraperitoneal), and 4) animals anesthetized with 100 mg/kg ketamine plus 10 mg/kg xylazine injected intramuscularly (K/X). LVEF obtained under the effect of anesthetics (ISO=62.2±3.1%, TP=66.2±2.7% and K/X=75.8±1.6%) was significantly lower than that obtained in conscious animals (87.5±1.7%, P<0.0001). The K/X combination elicited significantly higher LVEF values compared to ISO (P<0.001) and TP (P<0.05). K/X was associated with a lower dispersion of individual LVEF values compared to the other anesthetics. Under K/X, the left ventricular end diastolic diameter (LVdD) was increased (0.60±0.01 cm) compared to conscious animals (0.41±0.02 cm), ISO (0.51±0.02 cm), and TP (0.55±0.01 cm), P<0.0001. The heart rate observed with K/X was significantly lower than in the remaining conditions. These results indicate that the K/X combination may be the best anesthetic option for the in vivo assessment of cardiac systolic function in hamsters, being associated with a lower LVEF reduction compared to the other agents and showing values closer to those of conscious animals with a lower dispersion of results.

Hemodynamic changes with high infusion rates of lipid emulsion. Experimental study in swine

PURPOSE: To evaluate hemodynamic changes caused by sole intravenous infusion of lipid emulsion with doses recommended for treatment of drug-related toxicity. METHODS: Large White pigs underwent general anesthesia, tracheal intubation was performed, and mechanical ventilation was instituted. Hemodynamic variables were recorded using invasive blood pressure and pulmonary artery catheterization. Baseline hemodynamic measurements were obtained after a 30-minute stabilization period. An intravenous bolus injection of 20% lipid emulsion at 1.5 ml/kg was administered. Additional hemodynamic measurements were made after 1 minute, followed by a continuous intravenous lipid infusion of 0.25 ml/kg/min. Further measurements were carried out at 10, 20 and 30 minutes, when the infusion was doubled to 0.5 ml/kg/min. Assessment of hemodynamic changes were then made at 40, 50 and 60 minutes. RESULTS: Lipid infusion did not influence cardiac output or heart rate, but caused an increase in arterial blood pressure, mainly pulmonary blood pressure due to increased vascular resistance. Ventricular systolic stroke work consequently increased with greater repercussions on the right ventricle. CONCLUSION: In doses used for drug-related toxicity, lipid emulsion cause significant hemodynamic changes with hypertension, particularly in the pulmonary circulation and increase in vascular resistance, which is a factor to consider prior to use of these solutions.

Audiological Findings in Patients with OculoAuriculo-Vertebral Spectrum

Introduction Oculo-auriculo-vertebral spectrum, also referred to as Goldenhar syndrome, is a condition characterized by alterations involving the development of the structures of the first and second branchial arches. The abnormalities primarily affect the face, the eyes, the spine, and the ears, and the auricular abnormalities are associated with possible hearing loss. Objective To analyze the audiological findings of patients with oculo-auriculo-vertebral spectrum through liminal pure-tone audiometry and speech audiometry test. Methods Cross-sectional study conducted on 10 patients with oculo-auriculo-vertebral spectrum and clinical findings on at least two of the following areas: orocraniofacial, ocular, auricular, and vertebral. All patients underwent tonal and vocal hearing evaluations. Results Seven patients were male and three were female; all had ear abnormalities, and the right side was the most often affected. Conductive hearing loss was the most common (found in 10 ears), followed by sensorineural hearing loss (in five ears), with mixed hearing loss in only one ear. The impairment of the hearing loss ranged frommild to moderate, with one case of profound loss. Conclusions The results show a higher frequency of conductive hearing loss among individuals with the oculo-auriculo-vertebral spectrum phenotype, especially moderate loss affecting the right side. Furthermore, research in auditory thresholds in the oculoauriculo- vertebral spectrum is important in speech therapy findings about the disease to facilitate early intervention for possible alterations. .

Ionic Mechanisms of Desflurane on Prolongation of Action Potential Duration in Rat Ventricular Myocytes

PURPOSE: Despite the fact that desflurane prolongs the QTC interval in humans, little is known about the mechanisms that underlie these actions. We investigated the effects of desflurane on action potential (AP) duration and underlying electrophysiological mechanisms in rat ventricular myocytes. MATERIALS AND METHODS: Rat ventricular myocytes were enzymatically isolated and studied at room temperature. AP was measured using a current clamp technique. The effects of 6% (0.78 mM) and 12% (1.23 mM) desflurane on transient outward K+ current (I(to)), sustained outward current (I(sus)), inward rectifier K+ current (I(KI)), and L-type Ca2+ current were determined using a whole cell voltage clamp. RESULTS: Desflurane prolonged AP duration, while the amplitude and resting membrane potential remained unchanged. Desflurane at 0.78 mM and 1.23 mM significantly reduced the peak I(to) by 20+/-8% and 32+/-7%, respectively, at +60 mV. Desflurane (1.23 mM) shifted the steady-state inactivation curve in a hyperpolarizing direction and accelerated inactivation of the current. While desflurane (1.23 mM) had no effects on I(sus) and I(KI), it reduced the L-type Ca2+ current by 40+/-6% (p<0.05). CONCLUSION: Clinically relevant concentrations of desflurane appear to prolong AP duration by suppressing Ito in rat ventricular myocytes.

Dendroaspis natriuretic peptide regulates the cardiac L-type Ca2+ channel activity by the phosphorylation of alpha1c proteins

Dendroaspis natriuretic peptide (DNP), a new member of the natriuretic peptide family, is structurally similar to atrial, brain, and C-type natriuretic peptides. However, the effects of DNP on the cardiac function are poorly defined. In the present study, we examined the effect of DNP on the cardiac L-type Ca2+ channels in rabbit ventricular myocytes. DNP inhibited the L-type Ca2+ current (ICa,L) in a concentration dependent manner with a IC50 of 25.5 nM, which was blocked by an inhibitor of protein kinase G (PKG), KT5823 (1 microM). DNP did not affect the voltage dependence of activation and inactivation of ICa,L. The alpha1c subunit of cardiac L-type Ca2+ channel proteins was phosphorylated by the treatment of DNP (1 microM), which was completely blocked by KT5823 (1 microM). Finally, DNP also caused the shortening of action potential duration in rabbit ventricular tissue by 22.3 +/- 4.2% of the control (n = 6), which was completely blocked by KT5823 (1 microM). These results clearly indicate that DNP inhibits the L-type Ca2+ channel activity by phosphorylating the Ca2+ channel protein via PKG activation.

Left and right ventricular power: outputs are the strongest hemodynamic correlates to allow identification of acute responders to vasodilator treatment in idiopathic pulmonary arterial hypertension / El poder del ventrículo derecho y del izquierdo: son parámetros hemodinámicos que correlacionan con la posibilidad de ser respondedor durante el reto agudo con vasodilatadores en la hipertensión arterial pulmonar idiopática

Introduction: Despite the prognostic importance of traditionally derived measurements, the significance of right heart catheterization (RHC) remains controversial. Thus, a continued search for hemodynamic markers that define better responsive patients is required. Since, right ventricular failure is the most fatal pathway, right (RVPO) and left (LVPO) ventricular power output are parameters that could provide input for a better understanding of the hemodynamics involved in idiopathic pulmonary artery hypertension (IPAH). Method: We retrospectively analyzed how demographics and outcome correlate with hemodynamics to identify responders among IPAH patients. Results: Ninety patients fulfilled the following criteria for inclusion in this study: (1) complete RHC at baseline; (2) an acute evaluation for vasodilators (AEFV, including a positive response, that is, an increase in CO, a decrease in both mPAP and pulmonary vascular resistance ≥ 20% from baseline, respectively); and (3) a long-term follow-up under accepted IPAH treatments. If RVPO decreased (p < 0.001) and LVPO increased (p < 0.012) during AEFV, it is considered that these findings reinforce our ability to identify responders; that is, patients that remained as responders after 6.4 ± 3 years under nifedipine treatment (37.7% of the studied IPAH population). After multivariate analysis, age, RVPO, and LVPO remained as independent variables (OR = 0.927, 95%CI: 0.87-0.98, p = 0.01; OR = 0.114, 95%CI: 0.00-0.91, p = 0.045; and OR = 171.5, 95% CI: 5.3-549, p = 0.004, respectively) when estimating the probability of being a responder. On this basis, an equation was derived to identify responders among IPAH patients, where the probability of being a responder = 1.0196-0.0631 (age) - 4.7693 (RVPO) + 3.8152 (LVPO), ROC: 0.76, 95% CI: 0.63-0.89; p = 0.001. Conclusion:based on the proposed equation, LVPO and RVPO could be used for the identification of responders among IPAH patients.

Introducción: A pesar de la importancia y del significado pronóstico que tienen las mediciones directas y las derivadas del cateterismo cardiaco derecho, éstas permanecen hasta el día de hoy en el terreno académico de la controversia. Por lo tanto, se requiere la continua búsqueda de marcadores hemodinámicos para estratificar a los enfermos con hipertensión arterial pulmonar idiopática. Particularmente, cuando la disfunción contráctil del ventrículo derecho es la vía final más común de esta patología. En esta circunstancia, la determinación del poder del ventrículo derecho y del ventrículo izquierdo representa parámetros que pudieran ser de utilidad para lograr un mejor entendimiento en la hemodinámica de la hipertensión arterial pulmonar idiopática. Método: De manera retrospectiva, analizamos los aspectos demográficos, los hemodinámicos y la sobrevivencia, y si éstos se vieron asociados a la posibilidad de ser enfermos respondedores entre los portadores de hipertensión arterial pulmonar idiopática. Resultados: Noventa enfermos llenaron los siguientes criterios para ser incluidos en el estudio: 1. Contar con cateterismo cardiaco derecho basal; 2. Tener valoración aguda con adenosina, en donde quedó definida una respuesta "positiva aguda" como: aumento del gasto cardíaco, disminución de la presión arterial pulmonar media y de la resistencia vascular pulmonar calculada (≥ 20% de la basal, respectivamente) y; 3. Contar con un seguimiento a largo plazo bajo la influencia de los tratamientos modernos aceptados para enfermos con hipertensión arterial pulmonar idiopática. Sí, el poder del ventrículo derecho disminuyó (p < 0.001) y el poder ventrículo izquierdo aumentó (p < 0.012) durante el reto vasodilatador agudo se consideró que éstos hallazgos reforzaban la habilidad para detectar a los sujetos respondedores con hipertensión arterial pulmonar idiopática; población de enfermos que guardó ese comportamiento hemodinámico durante 6.4 ± 3 años bajo la influencia de nifedipina (37% de la totalidad de la población con hipertensión arterial pulmonar idiopática). Después de efectuar un análisis multivariado, la edad, el poder del ventrículo derecho y del ventrículo izquierdo permanecieron como variables independientes (OR = 0.927, 95%IC: 0.87-0.98, p = 0.01; OR = 0.114, 95%IC: 0.00-0.91, p = 0.045; y OR = 171.5, 95%IC: 5.3-549, p = 0.004, respectivamente) para ser considerados "respondedores". Como resultado, se derivó una ecuación donde la probabilidad de ser respondedor = 1.0196-0.0631 (edad) - 4.7693 (poder del ventrículo derecho) + 3.8152 (poder del ventrículo izquierdo), ROC: 0.76, 95%CI: 0.63 - 0.89; p = 0.001. Conclusión: Con fundamento en los hallazgos de este estudio, la ecuación propuesta, el poder del ventrículo derecho y el ventrículo izquierdo pueden ser utilizados para identificar "respondedores" entre los enfermos con hipertensión arterial pulmonar idiopática.

Fluoxetine effects on mitochondrial ultrastructure of right ventricle in rats exposed to cold stress / Efeitos da fluoxetina sobre a ultraestrutura mitocondrial no ventrículo direito de ratos expostos ao estresse pelo frio

OBJECTIVE: To assess fluoxetine effects on mitochondrial structure of the right ventricle in rats exposed to cold stress. METHODS: The experimental study procedures were performed in 250-300g male EPM-Wistar rats. Rats (n=40) were divided into four groups: 1) Control group (CON); 2) Fluoxetine (FLU); 3) Induced hypothermia (IH) and; 4) Induced hypothermia treated with fluoxetine (IHF). Animals of FLU group were treated by the administration of gavages containing 0.75 mg/kg/day fluoxetine during 40 days. The induced hypothermia was obtained by maintaining the groups 3 and 4 in a freezer at -8ºC for 4 hours. The animals were sacrificed and fragments of the right ventricle (RV) were removed and processed prior to performing electron microscopic analysis. RESULTS: The ultrastructural changes in cardiomyocytes were quantified through the number of mitochondrial cristae pattern (cristolysis). The CON (3.85 percent), FLU (4.47 percent) and IHF (8.4 percent) groups showed a normal cellular structure aspect with preserved cardiomyocytes cytoarchitecture and continuous sarcoplasmic membrane integrity. On the other hand, the IH (34.4 percent) group showed mitochondrial edema and lysis in cristae. CONCLUSION: The ultrastructural analysis revealed that fluoxetine strongly prevents mitochondrial cristolysis in rat heart, suggesting a protector effect under cold stress condition.

OBJETIVO: Analisar os efeitos da fluoxetina sobre a estrutura mitocondrial do ventrículo direito de ratos expostos ao estresse pelo frio. MÉTODOS: Os procedimentos do estudo foram realizados em ratos Wistar-EPM (250-300g) machos. Os ratos (n=40) foram divididos em quatro grupos: 1) Controle (CON); 2) Fluoxetina (FLU); 3) Induzidos à hipotermia (IH) e; 4) Induzidos à hipotermia tratados com fluoxetina (IHF). O grupo FLU foi tratado com gavagem contendo 0,75 mg/kg/dia de fluoxetina durante 40 dias. O estresse induzido pelo frio foi realizado mantendo os grupos 3 e 4 em um freezer (-8ºC) por quatro horas. Os animais foram sacrificados e fragmentos do ventrículo direito (VD) foram removidos e processados antes de serem conduzidos para a microscopia eletrônica. RESULTADOS: As alterações ultraestruturais dos cardiomiócitos foram quantificadas pelo número padrão de cristas mitocondriais (cristólises). Os grupos CON (3,85 por cento), FLU (4,47 por cento) e IHF (8,4 por cento) mostraram aspecto normal de suas estruturas celulares com a citoarquitetura dos cardiomiócitos preservada com integridade sarcoplasmática contínua. Por outro lado, o grupo IH (34,4 por cento) apresentou edema mitocondrial e lise nas cristas. CONCLUSÃO: A análise ultraestrutural revelou que a fluoxetina previne fortemente cristólises mitocondriais em miocárdio de ratos, sugerindo possível efeito protetor na condição de estresse induzido pelo frio.

Idiopathic left ventricular tachycardia in children.

BACKGROUND: Idiopathic left ventricular tachycardia (ILVT) is a rare but well-recognized clinical entity. The clinical characteristics and prognosis of this form of ventricular tachycardia (VT) in Thai children is not known. OBJECTIVE: To define clinical presentations, drug therapies, roles of radiofrequency (RF) catheter ablation, and the short-term outcome of these children in Thailand. PATIENTS AND METHOD: From April 1999 to June 2007, 10 patients were diagnosed as ILVT by specific electrocardiographic features and therapeutic response. All patients had a structurally normal heart. Data were collected retrospectively. Baseline clinical information, 12-lead electrocardiography (ECG) during VT, responses to drug therapy, results of RF catheter ablation therapy, and outcome were determined. RESULTS: Median age at presentation was 9.5 years (range, 3.8 to 14.0 years). Three patients (30%) were male. Eight patients (80%) were diagnosed as supraventricular tachycardia (SVT) before ILVT diagnosis. Median duration from SVT diagnosis to the correct diagnosis was 1.5 years (range, 0 to 6.0 years). Palpitation and chest pain were usual clinical manifestations while congestive heart failure was the presentation in one due to incessant tachycardia. Two patients had recurrent VT episodes during acute febrile illnesses. The majority of patients responded to intravenous verapamil. RF catheter ablation was performed in 3 patients with recurrence of the VT in one. CONCLUSION: Prompt recognition of the ILVTespecially in the emergency department is very important. Verapamil is effective for acute termination as well as prevention of VT recurrence. When VT is refractory to medical therapy, RF catheter ablation is safe and effective. The short-term prognosis was good.

Lead reduces tension development and the myosin ATPase activity of the rat right ventricular myocardium

Lead (Pb2+) poisoning causes hypertension, but little is known regarding its acute effects on cardiac contractility. To evaluate these effects, force was measured in right ventricular strips that were contracting isometrically in 45 male Wistar rats (250-300 g) before and after the addition of increasing concentrations of lead acetate (3, 7, 10, 30, 70, 100, and 300 µM) to the bath. Changes in rate of stimulation (0.1-1.5 Hz), relative potentiation after pauses of 15, 30, and 60 s, effect of Ca2+ concentration (0.62, 1.25, and 2.5 mM), and the effect of isoproterenol (20 ng/mL) were determined before and after the addition of 100 µM Pb2+. Effects on contractile proteins were evaluated after caffeine treatment using tetanic stimulation (10 Hz) and measuring the activity of the myosin ATPase. Pb2+ produced concentration-dependent force reduction, significant at concentrations greater than 30 µM. The force developed in response to increasing rates of stimulation became smaller at 0.5 and 0.8 Hz. Relative potentiation increased after 100 µM Pb2+ treatment. Extracellular Ca2+ increment and isoproterenol administration increased force development but after 100 µM Pb2+ treatment the force was significantly reduced suggesting an effect of the metal on the sarcolemmal Ca2+ influx. Concentration of 100 µM Pb2+ also reduced the peak and plateau force of tetanic contractions and reduced the activity of the myosin ATPase. Results showed that acute Pb2+ administration, although not affecting the sarcoplasmic reticulum activity, produces a concentration-dependent negative inotropic effect and reduces myosin ATPase activity. Results suggest that acute lead administration reduced myocardial contractility by reducing sarcolemmal calcium influx and the myosin ATPase activity. These results also suggest that lead exposure is hazardous and has toxicological consequences affecting cardiac muscle.

AIDS in childhood: cardiac involvement with and without triple combination antiretroviral therapy / AIDS na infância: acometimento cardíaco com e sem a terapia anti-retroviral tríplice combinada

OBJETIVO: Descrever a prevalência de alterações cardíacas ao ecocardiograma em crianças com AIDS acompanhadas em serviço de referência aos 18±6 meses do diagnóstico confirmado de AIDS. MÉTODOS: Estudo transversal, com corte aos 18±6 meses do diagnóstico de AIDS. Incluídas 93 crianças com diagnóstico confirmado de AIDS por transmissão vertical, sem doença maligna, que, na avaliação cardiológica, realizaram ecocardiograma (eco). De forma exploratória avaliaram-se as alterações cardíacas nos pacientes sem uso (G1) e com uso (G2) de terapia combinada anti-retroviral. RESULTADOS: Quando do diagnóstico de AIDS, as crianças tinham em média 3,07 anos e 50,50 por cento eram do sexo feminino. Esquema de terapia combinado com anti-retrovirais foi utilizado por 47 pacientes (G2). O acometimento cardíaco esteve presente em 40 crianças (43,00 por cento). A presença de disfunção ventricular esquerda (G1:39,10 por cento;G2:10,60 por cento) e o aumento isolado de ventrículo esquerdo (G1:6,60 por cento;G2:14,90 por cento) foram os achados mais freqüentes. Observou-se associação significativa entre os grupos sem e com terapia anti-retroviral combinada quanto à presença de disfunção ventricular esquerda (RP=3,42; [1,41-8,26]; p =0,02) e de desnutrição (RP=1,79; [1,00-3,20]; p=0,04). CONCLUSÃO: O acometimento cardíaco foi freqüente nas crianças com AIDS, sendo a disfunção ventricular esquerda a alteração mais observada ao ecocardiograma. Houve diferença estatisticamente significativa entre os grupos com e sem tratamento tríplice combinado quanto à presença de disfunção ventricular esquerda e de desnutrição.

OBJECTIVE: To describe the prevalence of cardiac abnormalities in the echocardiogram of children with AIDS followed up in a reference service at 18±6 months of AIDS confirmed diagnosis. METHODS: A cross-section study with a cohort after 18±6 months of AIDS diagnosis. The study included a total of 93 children with a confirmed diagnosis of AIDS with vertical transmission, with no malignancies and who underwent echocardiogram (echo) during cardiologic evaluation. Cardiac abnormalities were assessed in patients who were not treated (G1) and patients who were treated (G2) with combination antiretroviral therapy. RESULTS: When diagnosed with AIDS, the children were on average 3.07 years old and 50.50 percent were female. The combination regimen with antiretroviral agents was used by 47 patients (G2). Cardiac involvement was present in 40 children (43.00 percent). The presence of left ventricular dysfunction (G1: 39.10 percent; G2: 10.60 percent) and the isolated enlargement of left ventricle (G1: 6.60 percent; G2: 14.90 percent) were the most frequent findings. We observed a significant association between the groups without and with combination antiretroviral therapy asregards the presence of left ventricular dysfunction (PR= 3.42; [1.41-8.26]; p = 0.02) and malnutrition (PR = 1.79; [1.00-3.20]; p = 0.04). CONCLUSION: Cardiac involvement was frequent in children with AIDS and left ventricular dysfunction was the most common abnormality on echocardiogram. There was a statistically significant difference between the groups with and without triple combination treatment as regards the presence of left ventricular dysfunction and malnutrition.

Effect of induced iron deficiency and iron supplementation on the myocardium of the left ventricle of post weaned male albino rat. A light and electron microscopic study

Numerous studies have demonstrated the negative impact of iron deficiency on the growth and development. This study was designed to evaluate the effect of iron deficiency on the myocardium of the left ventricle of heart as well as their recovery whether by the therapeutic administration of iron or by balanced diet. Thirty six post weaned male albino rats were divided into three groups. Group I [12 rats] represented the control group receiving balanced diet [containing 36 mg iron/kg diet] and was equally subdivided into subgroup I-A and subgroup I-B according to duration of the experiment. Group II [12 rats] in which iron deficiency state was induced using a deficient diet [5 mg iron/kg diet] for 6 weeks. Group III [12 rats] represented the recovery group. They received iron deficient diet [5 mg/kg] similar to group II and according to the recovery regimen, this group was further subdivided into subgroup III-A [received balanced diet for further 2 weeks] and subgroup III-B [received oral supplementation of iron [9.45 mg/kg. body weight/day] along with the balanced diet for 2 weeks. Blood samples were collected for measuring hemoglobin concentration and chemical analysis for iron. Animals were sacrificed and their hearts were processed for both light and electronmicroscopic examinations. Iron deficiency resulted in vacuolation of left ventricular myocytes, pyknotic nuclei with mitochondrial swelling and disorganization. The sarcomeres were irregularly organized with focal degeneration and discontinuity of myofilaments. There was apparent thickening of the left ventricular muscle fibers. Recovery groups revealed evidence of mild regeneration in subgroup III-A and nearly complete recovery in subgroup III-B. Iron supplementation is essential to recover the changes associating iron deficiency