Microcirculatory changes as a hallmark of aging in the heart and kidney / Cambios microcirculatorios como sello distintivo del envejecimiento en el corazón y riñón

SUMMARY: Changes in the microcirculation of multiple tissues and organs have been implicated as a possible mechanism in physiological aging. In particular, vascular endothelial growth factor is a secretory protein responsible for regulating angiogenesis via altering endothelial proliferation, survival, migration, extracellular matrix degradation and cell permeability. The aim of the present study was to evaluate the role of vascular endothelial growth factor in the progression of morphological alterations caused by physiological aging in the heart and kidney and to examine its relation to changes in capillary density. We used two age groups of healthy Wistar rats - 6- and 12-month- old. The expression of vascular endothelial growth factor was examined through immunohistochemistry and immunofluorescence and assessed semi-quantitatively. Changes in capillary density were evaluated statistically and correlated with the expression of vascular endothelial growth factor. We reported stronger immunoreactivity for vascular endothelial growth factor in the left compared to the right ventricle and also observed an increase in its expression in both ventricles in older animals. Contrasting results were reported for the renal cortex and medulla. Capillary density decreased statistically in all examined structures as aging progressed. The studied correlations were statistically significant in the two ventricles in 12-month-old animals and in the renal cortex of both age groups. Our results shed light on some changes in the microcirculation that take place as aging advances and likely contribute to impairment in the function of the examined organs.

Los cambios en la microcirculación de múltiples tejidos y órganos se han implicado como un posible mecanismo en el envejecimiento fisiológico. En particular, el factor de crecimiento endotelial vascular es una proteína secretora responsable de regular la angiogénesis mediante la alteración de la proliferación endotelial, la supervivencia, la migración, la degradación de la matriz extracelular y la permeabilidad celular. El objetivo del presente estudio fue evaluar el papel del factor de crecimiento del endotelio vascular en la progresión de las alteraciones morfológicas causadas por el envejecimiento fisiológico en el corazón y riñón y examinar su relación con los cambios en la densidad capilar. Utilizamos dos grupos de ratas Wistar sanas: 6 y 12 meses de edad. La expresión del factor de crecimiento del endotelio vascular se examinó mediante inmunohistoquímica e inmunofluorescencia y se evaluó semicuantitativamente. Los cambios en la densidad capilar se evaluaron estadísticamente y se correlacionaron con la expresión del factor de crecimiento del endotelio vascular. Informamos una inmunorreactividad más fuerte para el factor de crecimiento endotelial vascular en el ventrículo izquierdo en comparación con el derecho y también observamos un aumento en su expresión en ambos ventrículos en animales mayores. Se informaron resultados contrastantes para la corteza renal y la médula. La densidad capilar disminuyó estadísticamente en todas las estructuras examinadas a medida que avanzaba el envejecimiento. Las correlaciones estudiadas fueron estadísticamente significativas en los dos ventrículos en animales de 12 meses y en la corteza renal de ambos grupos de edad. Nuestros resultados arrojan luz sobre algunos cambios en la microcirculación que tienen lugar a medida que avanza el envejecimiento y probablemente contribuyan a un deterioro en la función de los órganos examinados.

Minoca, infarto con coronarias normales ¿La caída del paradigma? / MINOCA, infarction with normal coronaries. The fall of the paradigm ?

El infarto agudo de miocardio es la principal causa de muerte en el mundo, siendo la obstrucción coronaria aterosclerótica el hallazgo más frecuente. Sin embargo, el 6% de los pacientes no presenta lesiones angiográficamente significativas, definidas por obstrucción de la luz vascular mayor al 50%. Estos casos se han definido bajo el término MINOCA (myocardial infarction with non-obstructive coronary arteries). Suelen ocurrir en mujeres jóvenes, con factores de riesgo cardiovascular, elevación de biomarcadores cardíacos e infradesnivel del segmento ST en el electrocardiograma. Las principales etiologías son la miocarditis, el síndrome de Takotsubo y el infarto subendocárdico. Presentamos el caso de una mujer de 65 años con antecedentes de hipertensión arterial y bloqueo completo de rama izquierda previo, que ingresó con ángor, imagen de bloqueo completo de rama izquierda en el electrocardiograma con criterios de Sgarbossa negativos y biomarcadores cardíacos positivos. En el ecocardiograma evidenció trastorno en la motilidad de la pared inferolateral y en la coronariografía solo una lesión no significativa (40%) en segmento proximal de la arteria circunfleja. La cardiorresonancia, en la secuencia de realce tardío de gadolinio, mostró retención de contraste subendocárdico a nivel de los segmentos inferolateral medial con extensión lateroapical compatible con infarto correspondiente a territorio de arteria circunfleja. Este caso ilustra un ejemplo de MINOCA secundario a infarto subendocárdico con trombólisis espontánea, en el que la presentación clínica fue típica, sin embargo en la coronariografía no se observaron lesiones significativas, por lo que fue necesario complementar con otro método de imágenes: la cardiorresonancia.

Myocardial infarction is the leading cause of death in the world, being the coronary atherosclerotic obstruction the main finding. Although 6% of all the patients had no significant coronary arteries disease on coronary angiography, defined by lumen vascular obstruction greater than 50%. This type of cases was defined by the term MINOCA (myocardial infarction with non-obstructive coronary arteries). They are usually young women, with cardiovascular risk factors, high cardiac biomarkers with non-ST elevation in the electrocardiogram. The main etiologies are myocarditis, Takotsubo syndrome and subendocardial myocardial infarction. We present the case of a 65 years-old woman with history of hypertension and complete left bundle branch block, who was admitted to the emergency department with typical chest pain, complete left bundle branch block in the electrocardiogram, with negative Sgarbossa criteria and positive cardiac biomarkers. The echocardiography evidenced inferolateral regional wall motion abnormalities, and the coronary angiography a single non-significative lesion (40%) in the proximal segment of the circumflex artery. Cardiac magnetic resonance evidenced subendocardial late gadolinium enhancement in inferolateral medial with latero-apical extension segments consistent with circumflex artery-related infarction. This case illustrates an example of MINOCA secondary to myocardial infarction with posterior spontaneous thrombolysis, in which the clinical presentation was typical, however the coronary angiography showed non obstructive lesions. Therefore, another complementary imaging methods were needed such as the cardiac magnetic resonance.

Inadequações dos Esfigmomanômetros Utilizados em Serviços de Urgência e Emergência de uma Grande Capital Brasileira / Inadequacies of Sphygmomanometers Used in Emergency Care Services in a Large Capital City in Brazil

Fundamento: A hipertensão arterial é o principal fator de risco cardiovascular. A qualidade técnica dos esfigmomanômetros é condição fundamental para obtenção da correta medida da pressão arterial. Objetivos: Avaliar o perfil dos esfigmomanômetros disponíveis nos serviços de urgências de Belo Horizonte, Minas Gerais. Métodos: Realizamos um estudo transversal, observacional e não intervencionista para avaliar o perfil dos esfigmomanômetros disponíveis nos prontos atendimentos de adultos de hospitais públicos e privados do município de Belo Horizonte. Avaliamos 337 aparelhos de 25 hospitais, sendo 15 públicos (do total de 16) e 10 privados (do total de 12). Resultados: Foram observadas inadequações dos equipamentos em relação à validação pelo Instituto Nacional de Metrologia, Qualidade e Tecnologia ­ INMETRO, em 26% (88/337) dos equipamentos; calibração vencida em 39% (132/337) e não correspondência de marca aparelho/braçadeira em 54% (188/337). Em 13 dos 25 hospitais (52%), não havia disponibilidade de manguitos para braços de diferentes tamanhos além do padrão. Houve superioridade de adequação dos aparelhos aneroides e de mercúrio dos hospitais privados (p = 0,038 e p < 0,001, respectivamente) e dos eletrônicos nos públicos (p < 0,001). Conclusão: Conclui-se que 78% dos esfigmomanômetros disponíveis nos serviços de urgência/emergência de uma das maiores capitais brasileiras apresentavam inadequações técnicas, e em metade dos serviços não havia manguitos de diferentes tamanhos. Tal fato representa um alerta para a situação dos equipamentos disponíveis para atendimento da população no país

Background: Hypertension is the main risk factor for cardiovascular diseases. Technical quality of sphygmomanometers is a prerequisite for the correct measurement of arterial pressure. Objectives: To evaluate sphygmomanometers available in emergency services in the city of Belo Horizonte, Brazil. Methods: We performed a cross-sectional, observational, non-interventional study to evaluate characteristics of the sphygmomanometers available in adult emergency services of public and private hospitals in the city of Belo Horizonte, Brazil. We evaluated 337 sphygmomanometers of 25 hospitals ­ 15 (of 16) public hospitals and 10 (of 12) private hospitals. Results: Twenty-six percent (88/337) of devices were considered inadequate regarding the INMETRO (National Institute of Metrology, Quality and Technology) standards, 39.2% (132/337) for calibration dates, and 54% (188/337) for the mismatching between cuff's and device's brands. In 13 of 25 hospitals (52%), there were no spare cuffs in different sizes for different arm circumferences. Higher adequacy was found for aneroid and mercury sphygmomanometers used in private hospitals (p = 0.038 and p < 0.001, respectively) and electronic devices used in public hospitals (p < 0.001) compared with others.Conclusion: Seventy-eight percent of sphygmomanometers available in emergency services had technical inadequacies, and half of these services had no spare cuffs in different sizes available. These findings serve as a warning of the conditions of the equipment used in healthcare services provided to the general population in Brazil

Patterns of arterial vascularization in swine hearts / Padrões de vascularização arterial em corações de suínos

This study aimed to characterize the patterns of arterial vascularization in swine hearts. Ninety swine hearts were submitted to the Spalteholz diaphanization technique in order to dissect the coronary arteries. Three types of arterial vascularization patterns were characterized through the behaviorof the rami circumflexus and interventricularis, namely: balanced, right and left types. The balanced pattern was the most frequently (42.2%); in this case, the rami circumflexus and interventricularis occupied their respective sulci. The right type (40%) was further categorized into three vascularization subtypes. In the first, ramus circumflexus dexter branched from the ramus interventricularis subsinuosus. In the second, the arteria coronaria dextra branched from ramus interventricularis subsinuosus and ramus circumflexus. In the third model, arteria coronaria sinister branched from ramus interventricularis paraconalis. The left type (17.7%) exhibited two subtypes. In the first, ramus interventricularis paraconalis ran through the entire corresponding sulcus and the ventral third of sulcus interventricularis subsinuosus, and ramus interventricularis subsinuosus occupied the dorsal and middle third of its respective sulcus. In the second, ramus interventricularis subsinuosus branched from arteria coronaria dextra and ran through the dorsal and medium thirds of its respective sulcus, and the ventral third was occupied by the collateral branch of ramus circumflexus sinister. Our results reinforce the thesis that the blood distribution system through the coronary artery in swine is similar to human, not only in qualitative but also by a quantitative comparison.

Este estudo teve como objetivo caracterizar os padrões de vascularização arterial em corações de suínos. Para tanto, 90 corações de suínos foram submetidos à técnica de diafanização de Spalteholz com a finalidade de dissecar as artérias coronárias. Através do comportamento dos rami circumflexus e interventricularis caracterizou-se três modalidades de vascularização arterial do coração de suínos, sendo eles os tipos equilibrado, direito e esquerdo. O equilibrado foi observado com maior frequência (42,2%), neste caso os rami circumflexus e interventricularis das artérias coronárias ocupavam seus respectivos sulcos. O tipo direito (40%) apresentou três subtipos de vascularização. No primeiro o ramus circumflexus dexter ramificava-se formando o ramus interventricularis subsinuosus. No segundo, a arteria coronaria dextra emitia o ramus interventricularis subsinuosus e ramus circunflexus. E no terceiro modelo, da arteria coronaria sinistra emergia o ramus interventricularis paraconalis. O tipo esquerdo (17,7%) apresentou dois subtipos. No primeiro, o ramus interventricularis paraconalis percorria todo o sulco correspondente e o terço ventral do sulcus interventricularis subsinuosus, o ramus interventricularis subsinuosus ocupava os terços dorsal e médio do seu respectivo sulco. No segundo, o ramus interventricularis subsinuosus oriundo da arteria coronaria dextra percorria apenas os terços dorsal e médio do seu respectivo sulco, ficando o terço ventral ocupado por colateral do ramus circumflexus sinister. Nossos resultados reforçam a tese de que a distribuição do suprimento sanguíneo pela artéria coronária em suínos é semelhante ao humano, não apenas de maneira qualitativa, mas também do ponto de vista quantitativo.

Deficiency of sex hormones does not affect 17-ß-estradiol-induced coronary vasodilation in the isolated rat heart

The relaxation of coronary arteries by estrogens in the coronary vascular beds of naive and hypertensive rats has been well described. However, little is known about this action in gonadectomized rats. We investigated the effect of 17-ß-estradiol (E2) in coronary arteries from gonadectomized rats, as well as the contributions of endothelium-derived factors and potassium channels. Eight-week-old female and male Wistar rats weighing 220-300 g were divided into sham-operated and gonadectomized groups (n=9−12 animals per group). The baseline coronary perfusion pressure (CPP) was determined, and the vasoactive effects of 10 μM E2 were assessed by bolus administration before and after endothelium denudation or by perfusion with NG-nitro-L-arginine methyl ester (L-NAME), indomethacin, clotrimazole, L-NAME plus indomethacin, L-NAME plus clotrimazole or tetraethylammonium (TEA). The CPP differed significantly between the female and sham-operated male animals. Gonadectomy reduced the CPP only in female rats. Differences in E2-induced relaxation were observed between the female and male animals, but male castration did not alter this response. For both sexes, the relaxation response to E2 was, at least partly, endothelium-dependent. The response to E2 was reduced only in the sham-operated female rats treated with L-NAME. However, in the presence of indomethacin, clotrimazole, L-NAME plus indomethacin or L-NAME plus clotrimazole, or TEA, the E2 response was significantly reduced in all groups. These results highlight the importance of prostacyclin, endothelium-derived hyperpolarizing factor, and potassium channels in the relaxation response of coronary arteries to E2 in all groups, whereas nitric oxide may have had an important role only in the sham-operated female group.

Triangle of Brocq and Mouchet: anatomical study in brazilian cadavers and clinical implication

Introduction: The Brocq and Mouchet’s arterio-venous triangle is a well know topographic region that is composed by the intersection of the great cardiac vein (GCV), the circumflex artery (CA) and the anterior interventricular artery (AIA) of the left coronary artery. These structures are located between conus arteriosus and left auricle, on the left side of anterior surface of the heart. Material and methods: Twenty three hearts were dissected and evaluated regarding to Brocq and Mouchet’s arterio-venous triangle at the Department of Morphology of the Fluminense Federal University. All the specimens were dissected in male human cadavers. They were analyzed regarding to their disposition in the triangle and the relations between them. Results: The triangle was found in 20 hearts (86.9%); in the remaining 3 (11.1%) it was not formed. Regarding to the classification of the triangle, the pattern of distribution was as follows: “closed” in 5 (21.7%) hearts, “inferiorly open” in 9 (39.1%) hearts, “superiorly open” in 2 (8.7%) hearts and “completely opened” in 4 (17.4%). Conclusion: Our study may add important information to the anatomy of the heart specifically in brazilian population. These data may have relevant implications regarding to procedures in the heart.

Trans-esophageal echocardiography in off-pump coronary artery bypass grafting.

The two features of off-pump coronary artery bypass (OPCAB) grafting that lead to haemodynamic instability are, transient occlusion of the coronary arteries during distal anastomosis construction and displacement of the heart to provide access to the distal coronary arteries. The position of the heart as seen by trans-oesophageal echocardiography (TOE) can often provide an indication as to how much compression of the right or left ventricle has occurred. If either chamber is not filling, repositioning of the heart will be necessary. Close observation of the heart with TOE during periods of coronary occlusion may facilitate detection of worsening cardiac function as evidenced by weakening contraction, ventricular dilatation, or increasing mitral or tricuspid regurgitation. Haemodynamic change are more pronounced with displacement of the heart to access posterior than the anterior coronary arteries. Cardiac manipulations along with transient occlusion of coronary arteries during distal anastomosis may cause transient hypotension with increased filling pressures. TOE is helpful in this scenario as it helps to differentiate between cardiac dysfunction secondary to myocardial ischaemia (in which regional wall motion abnormalities will be present) from a much more common scenario where the increase in filling pressure is secondary to extra-cardiac compression and provides the ability to detect mitral regurgitation with a colour flow Doppler as well as assess the right heart function.

Myocardial Protective Effect of Tezosentan, an Endothelin Receptor Antagonist, for Ischemia-Reperfusion Injury in Experimental Heart Failure Models

The myocardial protective effects of endothelin antagonist in ischemic cardiomyopathy (ICMP), doxorubicin-induced cardiomyopathy (DOX) and pressure-overload hypertrophy by transverse aortic constriction (TAC) models have been predicted to be different. The objective of this experiment, therefore, is to evaluate the myocardial protective effect of tezosentan, an endothelin receptor antagonist, in various experimental heart failure models. Sprague-Dawley rats (6-8 weeks old, 200-300 g) were randomized to three experimental groups (n=30 each): ICMP; DOX; and TAC group. Each of these groups was randomly assigned further to the following subgroups (n=10 each): sham-operated ischemia-reperfusion subgroup (SHAM); tezosentan treated ischemia-reperfusion subgroup (Tezo); and tezosentan non-treated ischemia-reperfusion subgroup (N-Tezo). Total circulatory arrest was induced for 1 hr, followed by 2 hr of reperfusion. The left ventricular developed pressure, peak positive and negative first derivatives, and coronary blood flow were significantly different (P<0.05) among the SHAM, Tezo, and N-Tezo subgroups of the ICMP group at 30 min of reperfusion, but there were no statistically significant differences among the subgroups of the DOX and TAC groups. In conclusion, tezosentan, an endothelin receptor antagonist, showed myocardial protection effects only on the ischemic cardiomyopathy rat model, but not in the non-ischemic heart failure rat models.

Alterações hemodinâmicas devido ao uso de estabilizadores em revascularização do miocárdio: estudo experimental / Hemodynamic disorders related to beating heart surgery using cardiac stabilizers: experimental study

OBJETIVO: Estudar, em suínos, as alterações hemodinâmicas secundárias ao uso de estabilizadores para operações de revascularização do miocárdio sem circulação extracorpórea, um por sucção (Octopus) e outro por compressão (Speroni). MÉTODOS: Dez suínos submetidos à esternotomia e monitorizados com eletrocardiograma, débito cardíaco contínuo e pressões: arterial média, pulmonar média, atriais médias direita e esquerda, ventriculares diastólicas direita e esquerda, calculando-se volume sistólico e resistência vascular sistêmica. Estudaram-se os estabilizadores posicionados em três artérias: interventricular anterior, interventricular posterior e ramo marginal da circunflexa. Para cada animal foi sorteada a ordem de aplicação do estabilizador com relação ao tipo e à artéria. As mensurações foram realizadas antes e após aplicar-se o estabilizador. RESULTADOS: Na artéria interventricular anterior, ocorreram alterações somente com o Speroni, havendo queda do débito cardíaco, do volume sistólico e da pressão arterial média, com aumento da resistência vascular sistêmica. Na artéria interventricular posterior, constatamos alterações com o Speroni, havendo queda do débito cardíaco e do volume sistólico, com aumento da freqüência cardíaca. Com o Octopus houve aumento da freqüência cardíaca e da resistência vascular sistêmica, com queda do volume sistólico. No ramo marginal da circunflexa, ocorreu queda do débito cardíaco, do volume sistólico e da pressão arterial média com os dois estabilizadores, havendo também queda na pressão arterial pulmonar média e aumento da pressão atrial direita média com o estabilizador por compressão. CONCLUSÕES: Ambos os estabilizadores causaram alterações hemodinâmicas. O que atua por compressão provocou mais alterações do que o que atua por sucção.

OBJECTIVE: To study in swine the hemodynamic changes secondary to the use of stabilizers for off-pump coronary artery bypass graft surgeries by means of both a suction device "Octopus" and a compression device (Speroni). METHODS: Ten swine underwent median sternotomy. Monitoring of ECG, continuous cardiac output, mean arterial pressure, mean pulmonary artery pressure, mean right and left atrial pressures, and right and left ventricular diastolic pressure were performed. Stroke volume and systemic vascular resistance were calculated. Both stabilizers were studied placed on three vessels: anterior interventricular branch, posterior interventricular branch, and marginal branch of the circumflex branch. Each animal was randomly designed to application regarding the type of stabilizer and the target artery. The measurements were carried out 5 minutes before and after the stabilizer application. RESULTS: In the anterior interventricular branch changes have occurred only with the compression device, thus reducing cardiac output, stroke volume, and mean arterial pressure, but increasing the systemic vascular resistance. In the posterior interventricular branch changes have occurred with the compression device (Speroni), reducing cardiac output and stroke volume, but increasing the heart rate. With the suction device (octopus) there was an increase of both heart rate and systemic vascular resistance, but a decrease in stroke volume. In the marginal branch of the circumflex branch there was a decrease of cardiac output, stroke volume, and mean arterial pressure with both stabilizers. Also, there was a decrease in the mean pulmonary artery pressure and an increase in the mean right atrial pressure with the compression device (Speroni). CONCLUSION: Both stabilizers have caused hemodynamic changes. The compression device (Speroni) is more associated with changes than the suction device (Octopus).

Función endotelial / Endothelial function

The endothelium is the first line of tissue whose function is affected by the cardiovascular risk factors. The normal function of this vascular covering maintains the homeostasis of the vascular bed and its alterations favors the appearance of the initial lesions of various diseases including the atherosclerotic process. The endothelial function can be measured by means of non invasive methods and these measures can identify the people at higher risk to develop atherosclerosis and its complications and also the methodology has proven to be useful in the evaluation of the outcomes related to the therapeutic measures. The possibility of performing this methods in a safe, non invasive and reproducible way permits that the endothelial function could be used as screening tool for cardiovascular risk in open population.

El extracto acuoso de viscum album induce la expresión de las sintasas de oxido nítrico inducible y endotelial en corazón aislado y perfundido de cobayo. Evidencia del mecanismo de vasodilatación coronaria / Viscum album aqueous extract induces inducible and endothelial nitric oxide synthases expression in isolated and perfused guinea pig heart. Evidence of the coronary vasodilation mechanism

The pharmacological effect of a Viscum album aqueous extract was evaluated on the Langendorff isolated and perfused heart model in normotense male guinea pig hearts. Coronary vascular resistance, left intraventricular pressure, nitric oxide release in the perfusion liquid, cyclic guanosine monophosphate production, and analysis of inducible and endothelial nitric oxide synthases expression by Western Blot in ventricular tissue were recorded in absence and presence of blockers and inhibitors, such as 3 microM gadolinium chloride, 100 microM N(omega)-nitro-L-arginine methyl ester and 10 microM 1H-[1,2,4]oxadiazolo[4,2-a]quinoxalin-1-one. V. album aqueous extract exerts a significant decrease in the coronary vascular resistance, which courses with significant increases in nitric oxide and cyclic guanosine monophosphate production. Analysis of the expression of both nitric oxide synthases revealed that this extract significantly induces the expression of both isoforms in guinea pig hearts. These effects were inhibited by the presence of blockers and inhibitors. The coronary vasodilation induced by the extract is mediated by the nitric oxide/soluble guanylyl cyclase pathway. In addition, this extract shows a positive inotropic effect which that is tyramine-mediated by means of beta1-adrenergic stimulation.

Anatomical study of the anterior interventricular septal branches and their relationship with the blood supply of the septomarginal trabecula

The aim of this study was to examine the morphological features of the anterior interventricular septal branches that supply blood to the septomarginal trabecula and to correlate the anatomical observations with the angiographic characteristics analyzed by hemodynamic procedures. Forty human hearts were dissected after injecting colored latex into the left coronary artery. The vascularization of the septomarginal trabecula was always derived from the anterior interventricular artery, via the first, second and third anterior interventricular septal branches in 21 hearts (52.5%), 17 hearts (42.5%) and two hearts (5%), respectively, and the distances from the left coronary artery ostium ranged from 22 to 51 mm. The external diameter of these vessels at their origin varied from 1.0 to 2.35 mm and the vessels were analyzed based on specific requirements for surgical and hemodynamic methods of myocardial revascularization. Myocardial bridges were located over or before the origin of the vessels studied.

Estudio de los extractos de Magnolia grandiflora sobre el músculo cardíaco de cobayo / Study of Magnolia Grandiflora extracts in guinea pigs cardiac muscle

Se evaluó farmacológicamente los extractos de diversas variedades de Magnolia grandiflora sobre el músculo cardíaco. Se recolectó en el período de marzo a julio hojas y flores de Magnolia grandiflora nativa del Instituto Nacional de Cardiología "Ignacio Chávez", de la zona norte, poniente y oriente del Distrito Federal, de los estados de Puebla, Colima y Chiapas. Éstas se procesaron por separado y los extractos se obtuvieron por maceración con una mezcla de etanol-agua (1:3 v/v) a 4°C durante dos semanas. El análisis cualitativo se realizó por cromatografía en capa fina, columna y de líquidos de alta resolución (CLAR). El análisis funcional y molecular se efectuó por reactividad química específica y resonancia magnética protónica (RMN ¹H). La evaluación farmacológica se realizó en corazones aislados de cobayo macho. Los extractos, fracciones y compuestos se administraron en bolos seriados bajo un estudio de curvas dosis-respuesta gradual en donde se midió la presión intraventricular izquierda y la presión de perfusión coronaria, evaluando así el efecto inotrópico positivo y vasodilatador de los extractos de Magnolia grandiflora. Se identificó y aisló vulgarenol y 2-p-hidroxifenil-2-OH-etilamina, por lo que los resultados sugieren que su efecto vasodilatador e inotrópico positivo, se deben a la presencia de estas sustancias, las cuales se complementan con magnograndiólido y tiramina.

Several extracts from diverse Magnolia grandiflora varieties were pharmacological evaluated in the cardiac muscle. From March to July, flowers and leaves from Magnolia grandiflora, native from the National Institute of Cardiology "Ignacio Chávez", from north, west, and orient zones from Mexico City, and from Puebla, Colima and Chiapas states were collected. They were separately processed and the extracts were obtained by maceration with ethanol-water (1:3 v/v) at 4°C during two weeks. Qualitative analysis was accomplished with thin-layer, column and high-performance liquid chromatographies (HPLC). Functional and molecular analysis was made by specific chemical reactivity and by protonic magnetic resonance (RMN ¹H). Pharmacological evaluation was completed in isolated and perfused male guinea pigs hearts. Extracts, fractions, and compounds were administrated by serial bolus in a gradual dose-response curves study in which left intraventricular pressure and coronary perfusion pressure were recorded, evaluating by such the positive inotropic and vasodilator effects of Magnolia grandifloraextracts. Vulgarenol and 2-p-hydroxyphenyl-2-hydroxy-ethylamine were isolated and identified, and the obtained results suggest that its positive inotropic and vasodilator effects are owed to these substances, being complemented by magnograndiolide and tyramine.

Quantitative assessment of coronary flow reserve by the variables of time-intensity curve with myocardial contrast echocardiography / 华中科技大学学报（医学）（英德文版）

The reliability and reliable indexes of quantitative assessment of coronary flow reserve (CFR) by using time-intensity curve (TIC) via myocardial contrast echocardiography were investigated. The TIC variables were obtained by employing acoustic densitometry (AD) technique before and after acetylcholine (Ach) injection in 12 dogs. Meanwhile, the correlation between these variables and CFR was analyzed. Among the variables derived from TIC, peak intensity (PI), area under the curve (AUC) and descending slope (DS) were increased significantly (P < 0.05) with the increase of coronary blood flow after Ach injection. Conversely, time-to-peak (TP), half-time of descent (HT), and mean-transit-time (MTT) were decreased remarkably (P < 0.0001). The PI and AUC ratios from post- to pre-Ach injection were strongly associated with CFR with the correlation coefficient (r) being 0.8366 and 0.8824, respectively. It is reliable by using the variables derived from TIC with myocardial contrast echocardiography to quantitatively evaluate regional myocardial CFR. The PI and AUC ratios from post- to pre-Ach injection are the reliable indexes for quantitative assessment of CFR.

Study of the arterial coronary circulation in the dog (canis familiaris)

Study on arterial coronary circulation was performed in 30 dog hearts, by using the dissection and clearing techniques. We observed that the heart is supplied by the right coronary artery (a. coronaria dextra) and three branches of the left coronary artery ( a. coronaria sinistra): paraconal interventricular ( ramus interventricularis paraconalis), septal ( ramus septales ) and circumflex arteries (ramus circumflexus). The left coronary artery arose from a trunk in the ventral aortic sinus and, when there was no trunk formation, it was found two different origins in the aorta, corresponding to the circumflex and paraconal interventricular arteries. The latter, after originating right anterior ventricular, left anterior ventricular and septal ventricular arteries, ended next to the heart apex. The circumflex artery presented its course to the left up to the atrial face, where it ended as subsinuous interventricular artery. Arising from the circumflex artery, it was found the auricular ( rami auricularis), ventricular ( rami ventricularis) and septal (rami septales) branches and branches to the atrio-ventricular node ( nodus atrio-ventricularis). The septal artery (ramus septales) was observed to be originated from the paraconal interventricular artery, with lower frequence of the left coronary artery and in two cases of the circumflex artery. The right coronary artery presented no arterial trunk. In that place, there were two separate origins in the aorta or 2-3 origins in a common sinus. This artery emitted auricular, ventricular branches and to the atrio-ventricular node.

Hemodynamic Effects on Atherosclerosis-Prone Coronary Artery: Wall Shear Stress / Rate Distribution and Impedance Phase Angle in Coronary and Aortic Circulation

The objective of the present study was to evaluate the hemodynamic characteristics of an atherosclerosis-prone coronary artery compared to the aorta. We describe three- dimensional spatial patterns of wall shear stress (WSS) according to the impedance phase angle in pulsatile coronary and aorta models using in vivo hemodynamic parameters and computed numerical simulations both qualitatively and quantitatively. Angiography of coronary arteries and aortas were done to obtain a standard model of vascular geometry. Simultaneously to the physiologic studies, flow-velocity and pressure profiles from in vivo data of the intravascular Doppler and pressure wire studies allowed us to include in vitro numerical simulations. Hemodynamic variables, such as flow-velocity, pressure and WSS in the coronary and aorta models were calculated taking into account the effects of vessel compliance and phase angle between pressure and flow waveforms. We found that there were spatial fluctuations of WSS and in the recirculation areas at the curved outer wall surface of the coronary artery. The mean WSS of the calculated negative phase angle increased in the coronary artery model over that in the aorta model and the phase angle effect was most prominent on the calculated amplitude of WSS of the coronary artery. This study suggests that the rheologic property of coronary circulation, such as the fluctuation of WSS/WSR induces several hemodynamic characteristics. A separation of flow-velocity, a difference in phase between pressure conductance and blood flow and prominent temporal and/or spatial oscillatory fluctuations of the shear forces as a function of pulsatile flow might be important factors in atherogenesis and progression of atherosclerosis.

Membrane stretch increases the activity of Ca(2+)-activated K+ channels in rabbit coronary vascular smooth muscles

It has been proposed that Ca(2+)-activated K+ channels play an essential role in maintaining vascular tone during stretch of blood vessel. However, the underlying mechanism of stretch-induced change of Ca(2+)-activated K+ channel activities are still unknown. The present experiment was designed to investigate the effect of membrane stretch on these channels whose activity was measured from rabbit coronary smooth muscle cells using a patch clamp technique. Ca(2+)-activated K+ channel were identified by their Ca2+ and voltage dependencies and its large conductances as in other preparations. Perfusion of cells with a hypotonic solution, which mimics stretching the cell membrane by making a cell swelling, produced an increase in channel activity in cell-attached patch mode. The similar increase was observed when negative pressure was applied into the patch pipette for stretching the cell membrane within a patch area. In inside-out patch, stretch still increased channel activity even under the conditions which exclude the possible involvement of secondary messengers, or of transmembrane Ca2+ influx via stretch-activated cation channels. Pretreatment of arachidonic acid or albumin showed no effect on stretch-induced channel activation, excluding the possibility of fatty acids mediated channel activation during membrane stretch. These results indicate that the stretch may directly increase the activity of Ca(2+)-activated K+ channels in our experimental condition.