Niveles urinarios de angiotensina-(1-7) y angiotensina II en pacientes con estenosis aórtica de importante repercusión hemodinámica / Urinary levels of angiotensin-(1-7) and angiotensin II in patients with severe aortic stenosis

Objetivo:Reforzar el conocimiento sobre la fisiopatología de la estenosis aórtica. Métodos: Se compararon los niveles urinarios de angiotensina II y angiotensina-(1-7) entre dos muestras: a) 45 pacientes con estenosis aórtica de importante repercusión hemodinámica, sin hipertensión arterial sistémica y con funciones renal y sistólica ventricular izquierda normales; b) grupo de control con 21 voluntarios sin patología cardiovascular. Hipótesis nula: no habría diferencia entre los niveles urinarios. Resultados:El promedio de la concentración urinaria de angiotensina-(1-7) en pacientes con estenosis aórtica fue 2.102 pmoles/mL y de 5.591 pmoles/mL para el grupo control. La media obtenida en concentración urinaria de angiotensina II fue de 0.704 pmoles/mL en los pacientes con estenosis aórtica y 0.185 pmoles/mL en el grupo control. Utilizando la prueba t de Student determinamos que la diferencia en la concentración urinaria de angiotensina-(1-7) (p = 0.633) y la diferencia en la concentración urinaria de angiotensina II (p = 0.631), fueron estadísticamente significativas. Conclusión:Se documentó una diferencia estadísticamente significativa en los niveles urinarios de angiotensina II y angiotensina-(1-7) dentro del grupo de pacientes con estenosis aórtica de importante repercusión hemodinámica.

Objective:Strengthen knowledge about the pathophysiology of aortic stenosis. Methods: Urinary levels of angiotensin-(1-7) and angiotensin II were compared between two samples: A) forty five patients with severe aortic stenosis, without systemic arterial hypertension and with normal kidney and normal left ventricular systolic function; B) control group: twenty one persons without cardiovascular disease. Null hypothesis: there would be no difference between urinary levels. Results: The average of angiotensin-(1-7) urinary concentration in severe aortic stenosis patients was 2.102 pmol/mL and 5.591 pmol/mL for the control group. The average of Ang II was 0.704 pmol/mL and 0.185 pmol/mL respectively. Using t-Student test, we determine that the difference in urinary concentration of angiotensin-(1-7) [p = 0.633] and the difference of angiotensin II (p = 0.631), were statistically significant. Conclusion:documented a statistically significant difference in urinary levels angiotensin II and angiotensin-(1-7) within the group of patients with severe aortic stenosis.

Impacto del uso de rosuvastatina en los primeros días de un síndrome coronario agudo en la fiunción endotelial y el poder oxidativo / Influence of rosuvastatin in endothelial function and oxidative stress, in patients with acute coronary syndrome

PURPOSE: The endothelial function is the cornerstone of several cardiovascular disease. In this trial we compared how the Nitric Oxide (NO) and Oxidative Stress (OS) serum levels, as surrogate markers of endothelial function, change in patients who received (or not) rosuvastatin during the first seven days of an acute coronary syndrome (ACS). METHODS: Twenty-two patients with ACS (age:66 +/- 9 years, gender: ten female and 12 male) were randomized in two groups. Patients in the first group (G1) received the conventional treatment for an ACS, plus placebo. The other group (G2) additionally received a daily oral dose of 40 mg of rosuvastatin. We measured the blood levels of nitrates and OS in both groups twice: at baseline (admission to Intensive care unit) and seven days after. The statistical analysis was performed using the paired t-test or the Chi2 test depending of the variables. Statistical significance was considered with a p < 0.05. RESULTS: Groups (G1 and G2) differed statistically on age (G1=71 years +/- 10 vs. G2 63 +/- 9 years, p=0.04). After 7 days of the ACS onset, ON levels diminished on 21% (p=0.17) in G1, but raised on 24% in the group who re- ceived rosuvastatin (p=0.005), with statistically difference between groups (p=0.005). On the other hand, the OS, augmented statistically on both groups: G1 (17%, p<0.001) and G2 (13%, p<0.001), without any difference between groups (p=0.77). Conclusion: The endothelial dysfunction in the first days of an ACS is accentuated, but with the use of rosuvastatina, the endothelial function improves. In contrast, the OS increase in both groups, without differences between groups.

Inflamación en hipertensión arterial / Inflammation in high blood pressure

Inflammatory status is involved in the pathophysiology of several cardiovascular disorders and in the genesis of high blood pressure. In this disease inflammation results from the activity of several hematological cells as well as the presence of chemotactic factors, immunological reactivity and hyperactivity of vasoconstrictor systems as that of the renin-angiotensin. Clinical evaluation of hypertension recommends secreening of several proinflammatory substances in hypertensive patients in order to evaluate their level of cardiovascular risk. Interleukin-6 and C reactive protein have been considered the most usual risk biomarkers. Interleukin 6 is a potent proinflammatory compound which participates in the acute fase of the tissular reaction to lesions associated to immunological, ischemic or oxidative stress. C reactive protein participates during inflammation activating the first component of complement with disorganization of the phospholipidic array of the endothelial sarcolemmal membrane and the consequent endothelial dysfunction related to the genesis of high blood pressure.

De la reperfusión al post-acondicionamiento del miocardio con isquemia prolongada. Nuevo paradigma terapéutico de los síndromes coronarios agudos con elevación del segmento ST? De lo básico a lo clínico / Reperfusion and postconditioning in acute ST segment elevation myocardial infarction. A new paradigm for the treatment of acute myocardial infarction. From bench to bedside?

After prolonged periods of ischemia and energy depletion, the ischemic myocardial cell can be jeopardized by specific causes within the reperfusion period. These causes can be viewed as unwanted aspects of the recovery process itself limiting its efficiency. Three potential initial causes of immediate reperfusion injury, aside from oxygen radicals, have been experimentally investigated in detail, and are briefly discussed: 1. re-energization; 2. rapid normalization of tissue pH; and 3. rapid normalization of tissue osmolality. These potential causes are not entirely independent. Understanding of the basic causes has opened novel perspectives for specific interference with these serious pathomechanisms. The experimental results obtained in the last years encourage the development of therapeutic approaches to reduce infarct size by specific measures applied during the early phase of reperfusion. In the clinical setting, reperfusion therapy for acute myocardial infarction (AMI) has shown to reduce mortality, yet it may also have deleterious effects, including myocardial necrosis and no-reflow. Almost two decades ago, great hope arose from the description of ischemic preconditioning. Unfortunately, ischemic preconditioning is not feasible in the clinical practice because the coronary artery is already occluded at the time of hospital admission of the AMI patient. Recently, in the dog model, a phenomenon called [quot ]postconditioning[quot ] has been described. It has been reported previouly that reperfusion injury can be significantly reduced by modifying the conditions and the composition of the initial reperfusate. Whereas preconditioning is triggered by brief episodes of ischemia-reperfusion performed just before a prolonged coronary artery occlusion, postconditioning is induced by a comparable sequence of reversible ischemia-reperfusion, but it is applied [quot ]just after the prolonged[quot ] ischemic insult. Protection afforded by postconditioning is as potent as that provided by preconditioning. Unlike preconditioning, the experimental design of postconditioning allows direct application in the clinical practice, especially during PTCA. It has been reported very recently, that postconditioning patients with ST segment elevation AMI, during coronary angioplasty protects the human heart in this clinical scenario. Obtaining such a beneficial effect by a simple manipulation of reperfusion is of major potential clinical interest. Now more than ever,

Los flavonoides y el sistema cardiovascular: pueden ser una alternativa terapéutica? / Flavonoids and the cardiovascular system: can they be a therapeutic alternative?

It has been suggested that dietary intake of flavonoids may reduce the risk of cardiovascular diseases. On the other hand, in vitro and in vivo studies shows that flavonoids has a vast array of biological activities. Our aim in this review is to put in evidence the effect of flavonoids on several enzymatic systems that could act as potential therapeutic targets, based on the reports of diverse research groups, leaders in the natural products research area, have published through the years, and with the goal of consolidating those results with the findings provided by some epidemiological studies, could support the introduction of these compounds into the clinic.

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.

Re-encuesta Nacional de Hipertensión Arterial (RENAHTA): Consolidación Mexicana de los Factores de Riesgo Cardiovascular. Cohorte Nacional de Seguimiento / National Re-survey of Arterial Hypertension (RENAHTA). Mexican consolidation of the cardiovascular risk factors. National Follow-up Cohort

Propósito: A través de una Re-encuesta Nacional sobre Hipertensión Arterial Sistémica (HTAS) y Factores de Riesgo Cardiovascular, en población adulta con HTAS identificada en encuestas nacionales de salud del año 2000; Determinar: 1) Las tasas de morbilidad y mortalidad. 2) La incidencia e interrelación en el tiempo con otros factores de riesgo, tales como Obesidad, Dislipidemia, Diabetes y Tabaquismo. 3) Los principales factores de riesgo asociados a HTAS que influencian la aparición de complicaciones, necesidad y numero de días de hospitalización. 4) El grado de adherencia y tipo de medicación usada por el paciente hipertenso. Métodos: La Re-encuesta Nacional de Hipertensión (RENAHTA) fue realizada en el periodo 2003-2004. La encuesta es tipo III del método paso a paso descrito por la OMS. La población estudiada correspondió en su mayoría (73%) a individuos detectados en encuestas nacionales previas. El muestreo fue ponderado a priori tomando en cuenta una prevalencia nacional promedio de HTAS de 30.05% y su correspondiente para cada estado de la República. Error máximo permisible en la estimación = 0.28, Efecto de diseño = 4.5; y, Tasa de respuesta esperada (0.70). Resultados: De 14 567 como muestra inicial, 1165 (8%) sujetos fueron considerados como no hipertensos o falsos positivos en el año 2000. De los 13,402 pacientes restantes se informaron 335 muertes ocurridas en los primeros 2 años de seguimiento (2000-2002), lo que implicó una mortalidad anual de ˜1.15% en la población hipertensa. Así, 13,067 sobrevivientes, fueron sujetos a análisis. La edad al momento de la re-encuesta fue 45.6 ± 12.6. El (40.5%) fueron hombres (n=5,295), hubo diferencia estadísticamente significativa en la talla, pero no en el peso entre ambos géneros. El control de la HTAS subió de 14.6% en el 2000 a 19.2% en el 2004. Se duplicó la cifra de diabéticos de 16% a 30% (p < .001). El 54% de la población estudiada requirió de hospitalización al menos ...

Objective: Based on a National Re-survey on Hypertension (HTA) and other cardiovascular risk factors performed in Mexico during 2003 and 2004 in the adult population with HTA, as identified in the 2000 National Survey of Health, this study was planed to determine: 1) morbidity and mortality rates; 2) the incidence and interrelation with other risk factors, such as overweight, obesity, dyslipidemia, nephropathy and diabetes; 3) the main risk factors associated to HTA involved in its complications, need for hospitalization and number of days; and, 4) the degree of therapeutical adhesion and the type of antihypertensive drugs used. Methods: The survey was of type III using the step by step method described by WHO. Sampling was weighed a priori taking into account a national prevalence average of HTA of 30.05% and its corresponding rate for each federal state. Permissible maximum error in the estimation = 0.28. Effect of design = 4.5; and, Rate of awaited answer (0.70). Results: From the initial 14,567 interviewed patients, 1,165 (8%) subjects were considered non-hypertensive or false positives at the 2000 survey. From the 13,402 remaining patients, 335 died during the first 2 years of pursuit, which implies an annual mortality of ˜1.15% in the hypertensive population. Thus, 13,067 survivors were subjected to the final analysis. The mean age at the re-survey was 45.6 ± 12.6; 40.5% were men (n = 5,295). There was a statistically significant difference in height, but not in weight between both genders. The control HTAwas raised 14.6% in the year 2000 and 19.2% in 2004. The prevalence of diabetes was duplicated from 16% to 30% (< .001). Fifty four percent of the whole population required hospitalization at least once during the period of study. The rates of overweight, obesity, and dyslipidemia rose significantly (p < 0.05) independently from age, federal state, and gender. Conclusion: RENAHTA shows the impact of hypertension on the morbidity and mortality during the 3.1 ± 1.5 years of follow-up in Mexico. It alerts us on the need to reinforce the strategies of attention and prevention of this crucial risk factor and of screening the dynamic nonlinear interaction between the main cardiovascular risk factors in Mexico. New hypotheses are proposed forthe metabolic syndrome.

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.

Participación del óxido nítrico y los metabolitos del ácido araquidónico vía citocromo P450 en la regulación de la presión arterial / Participation of nitric oxide and arachidonic acid metabolites via cytochrome-p450 in the regulation of arterial blood pressure

El óxido nítrico y los metabolitos del ácido araquidónico vía citocromo P450 contribuyen a la regulación de la presión arterial. La modificación en la síntesis de estos autacoides conduce a hipertensión arterial, sin embargo, se desconoce si existe interacción. Por ello, decidimos estudiar el papel modulador del óxido nítrico y los metabolitos del ácido araquidónico vía citocromo P450, y su interacción, sobre la presión arterial y el contenido renal de citocromo P450. Ratas Wistar macho fueron divididas por grupos: 1) Control, 2) L-NAME (100mg/kg/d v.o.), 3) L-NAME + SnCl2 (10mg/kg/d i.p.) y 4) L-NAME + dexametasona (1mg/kg/d s.c.). Se determinó la presión arterial sistólica y la concentración de nitritos por HPLC en orina y sangre. Los valores de presión arterial sistólica fueron: control 97 ± 7 mmHg, L-NAME 151 ± 4.6 mmHg, L-NAME + SnCl2 133 ± 3 mmHg, y L-NAME + dexametasona 152 ± 4.5 mmHg. Los nitritos en orina fueron: 1) 1.832 ± 0.32, 2) 1.031 ± 0.23, 3) 1.616 ± 0.33 y 4) 1.244 ± 0.33 μmol/mL y en sangre: 1) 0.293 ± 0.06, 2) 0.150 ± 0.05, 3) 0.373 ± 0.13 y 4) 0.373 ± 0.07 μmol/mL. El contenido renal de citocromo P450 fue abatido con el tratamiento de L-NAME + SnCl2, y una respuesta semejante se observó con L-NAME + dexametasona. Tanto óxido nítrico como los metabolitos del ácido araquidónico vía CYP participan en la regulación de la presión arterial. Además, el óxido nítrico contribuye regulando parcialmente el contenido renal del citocromo P450.

Nitric oxide and cytochrome P450 arachidonic acid metabolites participate in blood pressure regulation. The synthesis of these autacoids leads to arterial hypertension. However, it is not known whether there is an interaction between them. Therefore, we studied the modulatory effect of nitric oxide and cytochrome P450-arachidonic acid metabolites, their interaction on blood pressure, and the renal content of cytochrome P450. Male Wistar rats were divided: 1) control, 2) L-NAME (100 mg/kg/d p.o.), 3) L-NAME + SnCl2 (10 mg/kg/d i.p.), and 4) L-NAME + dexamethasone (1 mg/kg/d s.c.). We measured blood pressure and collected urine and blood for nitric oxide measurement. NO2 was quantified by HPLC. Blood pressure was: control, 97 ± 7 mmHg; L-NAME, 151 ± 4.6 mmHg; L-NAME + SnCl2, 133 ± 3 mmHg, and L-NAME + dexamethasone 152 ± 4.5 mmHg. Urine nitrite concentration was: 1) 1.832 ± 0.32, 2) 1.031 ± 0.23, 3) 1.616 ± 0.33, and 4) 1.244 ± 0.33 μmol/mL, while the concentration in blood was: 1) 0.293 ± 0.06, 2) 0.150 ± 0.05, 3) 0.373 ± 0.13, and 4) 0.373 ± 0.07 μmol/ mL. L-NAME + SnCl2 decreased cytochrome P450 renal content, and L-NAME + dexamethasone showed a similar response. In conclusion, both, nitric oxide and CYP-arachidonic acid metabolites play a role in the regulation of blood pressure. Nitric oxide also partially regulates renal cytochrome P450 content. (Arch Cardiol Mex 2003; 73:98-104).

Estudio de la relación entre las características electromoleculares de los digitálicos y su acción farmacológica / Relationship between the electromolecular properties of digitalis compounds and their pharmacological properties

Pese a su reducido margen de seguridad, los digitálicos siguen utilizándose en el tratamiento de la insuficiencia cardiaca congestiva y la fibrilación auricular crónica. Con el descubrimiento de su estructura, se han realizado remodelaciones para disminuir su toxicidad. Investigaciones recientes reportan que la eficacia digitálica radica en la electronegatividad del anillo "D" esteroideo, generada por la lactona e hidroxilo que poseen estos compuestos. En el presente trabajo, damos cuenta de la importancia que tiene esta propiedad molecular, que aunada a la conformación estructural, dan lugar a cambios significativos en las propiedades farmacológicas como el inotropismo y el margen de seguridad. Así, evaluamos una serie de once compuestos derivados de digitoxigenina, con grupos que sustituyen sobre el anillo "D" al hidroxilo y/o la lactona, los cuales denominamos -OH, -Lac, D-01, D-02, D-03, D-07, D-14, D-15, D-20, D-21 y D-22. La electronegatividad y la energía conformacional de cada compuesto se determinaron por el método Duhamm. El estudio farmacológico se realizó en corazones aislados de cobayo con base en el modelo de Langendorff y, en corazón de perro conforme al modelo cardiopulmonar de Starling. Los resultados permiten observar que la modulación de la acción digitálica está centrada, estructuralmente, en los sustituyentes de la fracción "D". El efecto inotrópico positivo y el margen de seguridad, medido como el cociente de la dosis tóxica sobre la dosis inotrópica, están relacionados con el aumento de electronegatividad y con una disminución de las energías rotacional y translacional que definen la conformación molecular; en consecuencia, estas propiedades son imprescindibles en la eficacia digitálica.

In spite their reduced therapeutic index, digitalis-type drugs continue being used for treating diseases such as congestive heart failure and chronic atrial fibrillation. Thanks to the development of several methods, their structural determination has been feasible, so, structural modifications have been worked out to modulate their toxicity. Several reports realizes that efficacy for these digitalis-type drugs lies on the electronegativity centered on the steroidal moiety (D-ring) generated by either lactone and hydroxyl sub-stituents attached to the steroidal moiety. In this work, we report how electronegativity, and so structural conformation, does modify their pharmacological properties, e.g., inotropism and safety margin. Thus, we evaluated a series of eleven drugs derived from digitoxigenin, named -OH, -Lac, D-01, D-02, D-03, D-07, D-14, D-15, D-20, D-21 and D-22, with groups that substitute both lactone and hydroxyl groups on the steroidal D-ring. Electronegativity and conformational energy were determined by Duhamm's method. The pharmacological evaluation for these drugs was accomplished in guinea pigs isolated hearts (according to the model proposed by Langendorff) and dog's isolated heart (as established by Starling's in vivo model). The results may suggest that digitalis-like action lies on the substituents attached to the D-ring. Positive inotropic effect and therapeutic index are related with increases in electronegativity as well with decreases in rotational and traslational energies; therefore, these molecular properties have such importance for the digitalis efficacy. (Arch Cardiol Mex 2003; 73:11-17).