Targeting the adenosinergic system in restless legs syndrome: A pilot, "proof-of-concept" placebo-controlled TMS-based protocol.

Restless Legs Syndrome (RLS) is a common sleep disorder characterized by an urge to move the legs that is responsive to movement (particularly during rest), periodic leg movements during sleep, and hyperarousal. Recent evidence suggests that the involvement of the adenosine system may establish a connection between dopamine and glutamate dysfunction in RLS. Transcranial magnetic stimulation (TMS) is a non-invasive electrophysiological technique widely applied to explore brain electrophysiology and neurochemistry under different experimental conditions. In this pilot study protocol, we aim to investigate the effects of dipyridamole (a well-known enhancer of adenosinergic transmission) and caffeine (an adenosine receptor antagonist) on measures of cortical excitation and inhibition in response to TMS in patients with primary RLS. Initially, we will assess cortical excitability using both single- and paired-pulse TMS in patients with RLS. Then, based on the measures obtained, we will explore the effects of dipyridamole and caffeine, in comparison to placebo, on various TMS parameters related to cortical excitation and inhibition. Finally, we will evaluate the psycho-cognitive performance of RLS patients to screen them for cognitive impairment and/or mood-behavioral dysfunction, thus aiming to correlate psycho-cognitive findings with TMS data. Overall, this study protocol will be the first to shed lights on the neurophysiological mechanisms of RLS involving the modulation of the adenosine system, thus potentially providing a foundation for innovative "pharmaco-TMS"-based treatments. The distinctive TMS profile observed in RLS holds indeed the potential utility for both diagnosis and treatment, as well as for patient monitoring. As such, it can be considered a target for both novel pharmacological (i.e., drug) and non-pharmacological (e.g., neuromodulatory), "TMS-guided", interventions.

How to assess nonresponsiveness to vasodilator stress.

Myocardial perfusion imaging (MPI) is a powerful tool for the functional assessment of ischemia in patients with suspected or known coronary artery disease (CAD). Given that the diagnostic accuracy and prognostic value of MPI and post-test management are highly dependent on achieving an adequate stress vasodilatory response, it is critical to identify those who may not have adequately responded to vasodilator pharmacological stress agents such as adenosine, dipyridamole, and regadenoson. Caffeine, a potent inhibitor of the adenosine receptor, is a compound that can affect vasodilatory hemodynamics, result in false negative studies, and potentially alter management in cases of inaccurate test results. Vasodilator non-responsiveness can be suspected by examining hemodynamics, quantitative positron emission tomography (PET) metrics such as myocardial flow reserve (MFR), and splenic response to stress. Quantitative MFR values of 1-1.2 should raise suspicion for nonresponsiveness in the setting of normal perfusion, along with the absence of a splenic switch off. Newer metrics, such as splenic response ratio, can be used to aid in the identification of potential nonresponders to pharmacologic vasodilators.

The Impact of Dipyridamole on Disease-Associated Microglia Phenotypic Transformation in White Matter Lesions Induced by Chronic Cerebral Hypoperfusion.

White matter lesions (WMLs) resulting from chronic cerebral hypoperfusion (CCH) are the leading cause of vascular dementia (VaD). This study aimed to investigate whether dipyridamole could alleviate WMLs by regulating the phenotype of disease-associated microglia (DAM) through equilibrative nucleoside transporter 2 (ENT2) and adenosine A2A receptor (Adora2a) and to clarify the underlying molecular mechanisms. CCH rat models were constructed to mimic VaD. Morris water maze and Luxol Fast Blue staining were employed to assess cognitive function and quantify the severity of WMLs, respectively. Immunofluorescent staining was performed to analyze the activation of glial cells and the phenotypic transformation of DAM. Additionally, levels of ENT2, proteins in the NF-κB and ERK1/2 pathways and inflammatory cytokines were detected. The results indicated that dipyridamole diminished the activation and proliferation of microglia and astrocytes, increased the expression of myelin basic protein and ameliorated WMLs and cognitive decline in CCH rats. Further study revealed that dipyridamole decreased the expression of ENT2 and inhibited the activation of ERK1/2 and NF-κB signaling pathways, which ultimately converted DAM to anti-inflammatory phenotype and suppressed the levels of TNF-α, IL-1ß, IL-6 in WMLs. However, Adora2a inhibitor (SCH58261) attenuated above effects. Our study demonstrates that dipyridamole facilitates the conversion of DAM to the anti-inflammatory phenotype through ENT2/Adora2a pathway and inhibits the activation of ERK1/2 and NF-κB signaling pathways, thereby alleviating neuroinflammation in WMLs. The current findings establish the basis for using dipyridamole to treat VaD.

Enzyme-Induced Shape-Shifting Peptide Nanocarrier Coloaded with Paclitaxel and Dipyridamole Inhibits Platelet Function and Tumor Metastasis.

Tumor-associated platelets can bind to tumor cells and protect circulating tumor cells from NK-mediated immune surveillance. Tumor-associated platelets secrete cytokines to induce the epithelial-mesenchymal transition (EMT) in tumor cells, which promotes tumor metastasis. Combining chemotherapeutic agents with antiplatelet drugs can reduce the occurrence of metastasis, but the systemic application of chemotherapeutic agents and antiplatelet drugs is prone to causing serious side effects. Therefore, delivering drugs to the tumor microthrombus site for long-lasting inhibition is a problem that needs to be addressed. Here, we show that small molecule peptide nanoparticles containing the Cys-Arg-Glu-Lys-Ala (CREKA) peptide can deliver the platelet inhibitor dipyridamole (DIP) and the chemotherapeutic drug paclitaxel (PTX) to tumor tissues, thereby inhibiting tumor-associated platelet function while killing tumor cells. The drug-loaded nanoparticles PD/Pep1 inhibited platelet-tumor cell interactions, were effectively taken up by tumor cells, and underwent morphological transformation induced by alkaline phosphatase (ALP) to prolong the retention time of the drugs. After intravenous injection, PD/Pep1 can target tumors and inhibit tumor metastasis. Thus, this small molecule peptide nanoformulation provides a simple strategy for efficient drug delivery and shows promise as a novel cancer therapy platform.

Construction and study of blood purification membrane modified with PDE inhibitor: Investigation of antiplatelet activity and hemocompatibility.

The recent "cell-based theory" of coagulation suggests that platelets serve as the site of coagulation factor reactions, making platelets an effective target for inhibiting membrane thrombosis. Unfortunately, there is limited research on how blood purification membranes affect platelet intracellular signaling. In this study, we modified polyethersulfone (PES) membranes with the platelet phosphodiesterase (PDE) inhibitor dipyridamole (DIP) and investigated the effects of the DIP/PES (DP) membranes on platelet adhesion, activation, aggregation, and secretion, as well as the role of the PDE-cyclic adenosine monophosphate (cAMP) intracellular signaling pathway. Additionally, we evaluated the hemocompatibility and preliminary in vivo safety of DP membranes. Our results demonstrate that the modified DP membranes effectively inhibited platelet adhesion, membrane CD62P expression, and plasma soluble P-selectin activation levels. Furthermore, we confirmed that DP membranes achieved platelet aggregation inhibition and reduced platelet factor 4 and ß-thromoglobulin secretion levels by inhibiting platelet intracellular PDE-cAMP signaling. Moreover, the modified DP membranes exhibited good anticoagulant and red blood cell membrane stability and complement resistance and demonstrated preliminary biocompatibility in mouse experiments. Collectively, these findings highlight the potential application of DP dialysis membranes in blood purification for critically ill patients.

The possible protective effects of dipyridamole on ischemic reperfusion injury of priapism

ABSTRACT Purpose To investigate the protective effects against ischemia reperfusion injury of dipyridamole in a model of induced priapism in rats. Materials and Methods Twenty-four male Sprague-Dawley rats were divided into four groups, control, P/R, P/R+DMSO and P/R+D. 3ml blood specimens were collected from vena cava inferior in order to determine serum MDA, IMA, TAS, TOS and OSI values, and penile tissue was taken for histopathological examination in control group. Priapism was induced in P/R group. After 1h, priapism was concluded and 30 min reperfusion was performed. In P/R+DMSO group 1ml/kg DMSO was administered intraperitoneally 30 min before reperfusion, while in P/R+D group 10mg/kg dipyridamole was administered intraperitoneally 30 min before reperfusion. Blood and penis specimens were collected after the end of 30 min reperfusion period. Sinusoidal area (µm2), tears in tunica albuginea and injury parameters in sinusoidal endothelium of penis were investigated. Results Histopathological examination revealed no significant changes in term of sinusoidal area. A decrease in tears was observed in P/R+D group compared to P/R group (p<0.05). Endothelial injury decreased in P/R+D group compared to P/R group (p>0.05). There were no significant differences in MDA and IMA values between groups. A significant increase in TOS and OSI values was observed in P/R+D group compared to P/R group. A significant decrease in TAS levels was observed in P/R+D group compared to the P/R group. Conclusions The administration of dipyridamole before reperfusion in ischemic priapism model has a potential protective effect against histopathological injury of the penis.

Diferencias en la estimación de isquemia en SPECT de perfusión miocárdica con 99mTc-sestamibi usando bases de datos cuantitativos de ejercicio y dipiridamol / Different ischemia size estimation on exercise and dipyridamole quantitative databases with 99mTc-sestamibi myocardial SPECT

Introducción. Frecuentemente los estudios de perfusión miocárdica con dipiridamol (DIP) son analizados cuantitativamente usando bases de datos de ejercicio (EXE). Objetivo. Comparar un grupo de pacientes con enfermedad coronaria conocida, procesados con bases de datos de DIP y EXE. Métodos. Se analizó los SPECT de perfusión miocárdica con Tc99m-Sestamibi y DIP de 20 hombres y 19 mujeres. Luego de su procesamiento, las imágenes de DIP SPECT fueron comparadas con bases de datos de mapas polares de EXE y DIP. Se analizó la extensión (en pixeles) y la severidad (DS) de los defectos y de las zonas reversibles. Resultados. Hubo concordancia de 92 por ciento en las interpretaciones de los estudios que tenían necrosis, isquemia o ambos (kappa: 0,859). El tamaño de los defectos de estrés fue el mismo con ambas bases de datos tanto en hombres como en mujeres. Sin embargo, en hombres la reversibilidad fue mayor (156,4 +/- 107,7 versus 128,6 +/-113,6 píxeles; p=0,0251) y más severa (699,6 +/- 665,8 versus 486,6 +/- 551,9 SD; p=0,0003) con EXE. En mujeres la reversibilidad fue menor (92,8 +/- 110,3 versus 113 +/- 121,9 pixeles; p=0,0024) y menos severa (278,5 +/- 356,7 versus 363,8 +/-432,7 SD; p=0,0009) con EXE. Conclusiones. Los pacientes que se sometieron a DIP fueron clasificados correctamente como isquemia, necrosis o ambos usando bases de datos de mapas polares de EXE. No obstante, la base de datos EXE subestimó la extensión de los defectos en mujeres y la sobreestimó en hombres.

Background. Frequently, dipyridamole (DIP) myocardial perfusion SPECT is analyzed quantitatively using an exercise (EXE) database. Objective. To compare a group of patients with known coronary artery disease, processed with DIP and EXE polar maps. Method. We studied 20 males and 19 females with DIP Tc99m-Sestamibi myocardial SPECT. After similar processing, the DIP SPECT images were read using both EXE and DIP polar map databases. We analyzed defect and reversibility extension (in pixels) and severity in standard deviations. Results. Agreement to classify patients as having necrosis, ischemia or both was 92 percent (kappa: 0.859). Stress defect size was similar with both databases in males and females. However, in males reversibility resulted larger (156.4 +/- 107.7 versus 128.6 +/- 113.6 pixels; p=0.0251) and more severe (699.6 +/- 665.8 versus 486.6 +/- 551.9 SD; p=0.0003) with EXE. In females, reversibility resulted smaller (92.8 +/- 110.3 versus 113.0 +/- 121.9 pixels; p=0.0024) and less severe (278.5 +/- 356.7 versus 363.8 +/- 432.7 SD; p=0,0009) with EXE. Conclusion. Patients undergoing DIP stress were correctly classified as presenting ischemia, necrosis or both by EXE polar map database. However, EXE database underestimated ischemia extension in females and overestimated it in males.

Valor diagnóstico de la gammagrafía de perfusión miocárdica con 99mTc-Tetrofosmina en mujeres previamente revascularizadas / Diagnostic value of myocardial perfusion imaging with 99mTc-tetrofosmin in a population of women previously revascularized

Fundamento y objetivo: Se trata de un estudio transversal donde se han determinado los valores de sensibilidad y especificidad del estudio de perfusión miocárdica con 99mTc-Tetrofosmina en protocolo de un día tras estímulo farmacológico con dipiridamol, en una población de mujeres previamente revascularizadas, así como la relación con los territorios vasculares coronarios, tomando como referencia la coronariografía. Pacientes: Se han estudiado con carácter retrospectivo 53 historias clínicas de mujeres sometidas a una prueba de perfusión miocárdica y a una coronariografía de control. Resultados: Los valores de sensibilidad y especificidad para la población fueron de 64,29 por ciento y 75,0 por ciento respectivamente. Por territorio arterial coronario, los valores de sensibilidad y especificidad para la arteria DA fueron de 68,75 por ciento y 75,0 por ciento respectivamente, para la Cx de 37,93 por ciento y 88,89 por ciento, y para la CD de 46,43 por ciento y 60,71 por ciento. Conclusiones: En las mujeres que han sido previamente revascularizadas, la gammagrafía de perfusión miocárdica con 99mTc-Tetrofosmina y dipiridamol en protocolo de un día parece ser una prueba idónea para realizar el seguimiento de pacientes.

Background: This is a cross-sectional study to identify the values of sensitivity and specificity of myocardial perfusion imaging with 99mTc-tetrofosmin one-day protocol after pharmacological stimulation with dipyridamole in a population of women previously revascularized and the relationship of findings to coronary vascular territories, with coronary angiography as a gold standard. Patients We studied retrospectively 53 medical records of women undergoing myocardial perfusion test and control coronary angiography. Results: The sensitivity and specificity for the population were 64.29 percent and 75.0 percent respectively. For coronary artery territory, the values of sensitivity and specificity for the LAD were 68.75 percent and 75.0 percent respectively, for Cx of 37.93 percent and 88.89 percent, and for the RCA 46.43 percent and 60.71 percent. Conclusions: In women who have been previously revascularized, myocardial perfusion scintigraphy with 99mTc-tetrofosmin and dipyridamole in one-day protocol seems to be a suitable test to monitor patients.

Valor diagnóstico adicional de la disfunción sistólica inducida para la detección de enfermedad coronaria mediante resonancia magnética cardiaca de estrés con dipiridamol / Additional diagnostic value of systolic dysfunction induced by dipyridamole stress cardiac magnetic resonance used in detecting coronary artery disease

Introducción y objetivos. La perfusion con dipiridamol en resonancia magnética cardiaca (RMC) de estrés se utiliza para la detección de enfermedad de las arterias coronarias (EAC). Sin embargo, se carece de información sobre el valor diagnóstico de la disfunción sistólica (DS) inducida con dipiridamol. Este estudio se centra en investigar si la DS inducida aporta un valor diagnóstico adicional junto con la perfusión para la detección de las EAC. Métodos. Se sometió a 166 pacientes a una RMC con dipiridamol y a una angiografía coronaria cuantitativa. Se definió EAC para valores ≥ 70% de estenosis. Se analizó la extensión de la DS en reposo, la DS con dipiridamol, la DS inducida, el déficit de perfusión (DP) de primer paso en estrés y el realce tardío. Resultados. En un análisis multivariable, el DP (1,6 [1,33-1,91]; p < 0,0001) y la DS inducida (1,8 [1,18- 2,28]; p < 0,007) se relacionaron independientemente con la EAC y tuvieron sensibilidades/especificidades del 92%/62% y el 43%/96%, respectivamente. Los pacientes se clasificaron en grupo 1, sin isquemia, grupo 2, DP pero sin DS inducida, y grupo 3, DS inducida independientemente del DP. El grupo 3 presentó una mayor prevalencia de EAC que los grupos 1 y 2 (el 96 frente al 22 frente al 79%; p = 0,001) y un riesgo de EAC dos veces mayor (2,34 [1,07-5,13]; p = 0,034) que el grupo 2. Comparado con el grupo 2, el grupo 3 presentó más segmentos hipoperfundidos (6,2 ± 2,6 frente a 7,4 ± 3,4; p = 0,044) y más vasos patológicos (1,4 ± 1 frente a 1,8 ± 0,9; p = 0,036). Añadiendo la DS inducida a la perfusión y a la información clínica, se mejoró el test estadístico C del modelo multivariable para predecir la EAC (0,81 frente a 0,87; p = 0,02). Conclusiones. La DS inducida, junto con la imagen de perfusión, ofrece un valor diagnóstico adicional para la detección de EAC y permite la identificación de pacientes con isquemia severa y alta probabilidad de EAC (AU)

Introduction and objectives. Dipyridamole stress perfusion cardiac magnetic resonance (CMR) is used to detect coronary artery disease (CAD). However, few data are available on the diagnostic value of the systolic dysfunction induced by dipyridamole. This study investigated whether the induction of systolic dysfunction supplements the diagnostic information provided by perfusion imaging in the detection of CAD. Methods. Overall, 166 patients underwent dipyridamole CMR and quantitative coronary angiography, with CAD being defined as a stenosis ≥70%. Systolic dysfunction at rest, systolic dysfunction with dipyridamole, induced systolic dysfunction, and stress first-pass perfusion deficit (PD) and delayed enhancement were quantified. Results. In the multivariate analysis, PD (hazard ratio [HR] =1.6; 95% confidence interval [CI], 1.33-1.91; P<0001) and induced systolic dysfunction (OR=1.8; 95% CI, 1.18-2.28; P<.007) were independently associated with CAD and had a sensitivity and specificity of 92% and 62% and 43% and 96%, respectively. Patients were categorized as having no isquemia (Group 1), PD but no induced systolic dysfunction (Group 2), or induced systolic sysfunction irrespective of PD (Group 3). In Group 3, the prevalence of CAD was higher than in Group 1 or 2 (96% vs 22% and 79%, respectively; P=.001) and the risk of CAD was 2-fold higher than in Group 2 (OR=2.34; 95% CI, 1.07-5.13; P=.034). Compared with Group 2, more hypoperfused segments were observed in Group 3 (6.2 [2.6] vs 7.4 [3.4]; P=.044), and more diseased vessels (1.4 [1.0] vs 1.8 [0.9]; P=.036). Adding induced systolic dysfunction to perfusion and clinical data improved the multivariate model’s C-statistic for predicting CAD (0.81 vs 0.87; P=.02). Conclusions. Combining induced systolic dysfunction with perfusion imaging increases the diagnostic accuracy of detecting CAD and enables patients with severe ischemia and a high probability of CAD to be identified (AU)

Anticoagulantes orales y antiagregantes plaquetarios / Oral anticoagulants and blood platelet antiaggregates

En el siguiente artículo se describen los diferentes tipos de anticoagulantes orales y antiagregantes plaquetarios. Se especifican sus modos de acción, sus efectos adversos y precauciones y advertencias de cada uno de ellos (AU)

Disfunción diastólica y alteraciones segmentarias de la contractilidad ventricular inducida por infusión intravenosa del dipiridamol: estudio ecocardiográfico comparativo

Para efectos diagnósticos, se evaluaron los cambios inducidos sobre los signos Doppler de flujo transmitral por una infusión intravenosa de dipiridamol (0.14 mgs/Kg/min durante 4 min) en 10 enfermos coronarios y en 10 sujetos sanos. Durante el período de máxima acción farmacológica del dipiridamol, en el grupo coronario 4 pacientes presentaron angina (vs. 0 en el grupo control), en 6 se detectaron trastornos segmentarios de la contarctilidad (vs. 0 en el grupo control) y en todos se acentuaron o aparecieron signos de disfunción diastólica ventricular izquierda sobre las ondas Doppler de flujo transmitral (vs. 0 en el grupo control). La relación de velocidades pico E/A fue <1 en todos los enfermos coronarios y >1 en todos los sujetos sanos. La fracción porcentual del llenado temprano (E/T por ciento), se incrementó en todos los sujetos sanos (59.5 por ciento ñ 4.5 basal a 67 por ciento ñ 2.6 por ciento durante Dip.), mientras que en grupo coronario disminuyó en 9 de 10 pacientes (49.2 por ciento ñ 12.8 por ciento basal a 42 por ciento ñ 10 por ciento Dip.), p<0.001. La fracción porcentual del llenado tardío (A/T por ciento) aumentó en todos los casos, pero fue significativamente mayor en el grupo coronario. La duración del llenado total (DLLT) fue menor en el grupo coronario, indicando una prolongación del período de relajación isovolumétrico. Estos hallazgos sugieren que la isquemia generada por la infusión IV. de dipiridamol en pacientes con enfermedad coronaria,produce anormalidades en el patrón de flujo transmitral caracterizados por disminución del llenado ventricular durante la fase rápida temprana a expensas de su incremento durante la diástole tardía. Estos cambios pueden ser cuantificados y empleados como método diagnóstico de alta sensibilidad y especificidad

Efeito da ticlopidina e do dipiridamol sobre a agregaçäo e contagem das plaquetas de pacientes com agina crônica estável / The effect of ticlopidine and dipyridamole on platelet aggregation and count in patients with chronic stable angina pectoris

Objetivo - Comparar o efeito da ticlopidina e do dipiridamol sobre a agregaçäo e a contagem plaquetárias nos pacientes com insuficiência coronariana crônica estável. Casuística e Métodos - Foram estudados 80 pacientes com idade média de 58,3 ñ 5,8 anos, portadores de insuficiência coronariana crônica estável, divididos em dois grupos de 40 pacientes e cada grupo tratado com ticlopidina ou dipiridamol. A agreagaçäo e contagem de plaquetas foram realizadas antes do início das drogas, e na primeira e quarta semanas de tratamento. Resultados - Ao final da quarta semana de tratamento observou-se hipogregabilidades espontânea, induzida pelo aDP e pela adrenalina em, respectivamente, 82,5%, 72,5% e 67,5% dos pacientes do grupo dipiridamol, a hipoagregabilidade espontânea, induzida pelo aDO e pela adrenalina foi, respectivamene, de 40%, 30% e 27,5% (p < 0,001). A contagem das plaquetas permaneceu inalterada para ambos os grupos. Conclusäo - O efeito antiagregante plaquetário da ticlopidina é significantemente maior que o do dipiridamol, e pode ser droga alternativa na prevençäo de complicaçöes cardiovasculares

Estudio de perfusión miocárdica con talio-201 - dipiridamol: aspectos farmacológicos y aplicaciones clínicas en el diagnóstico de cardiopatía coronaria / Study of myocardial perfusion with thallium-201-dipiridamol: pharmaceutical aspects and clinical applications in the diagnosis of coronary cardiopathy

Diversas condiciones clínicas impiden efectuar ejercicio isotónico en correa sin fin o bicicleta ergométrica en casos en los que la evolución no invasiva de la insuficiencia coronaria es importante con fines diagnósticos o pronósticos o para evaluar los resultados de tratamientos médicos o quirúrgicos. El dipiridamol, droga que tiene potente acción vasodilatadora mediada por un aumento del nivel circulante dde adenosina, asociado a marcadores radioactivos de perfusión coronaria (Talio-201; isonitrilo Tc-99m) ha demostrado ser una alternativa muy útil y segura cuyo rendimiento es comparable con la técnica Talio-ejercicio. El dipiridamol produce vasodilatación y aumenta 3 a 5 veces el flujo coronario por espacio de 30 a 60 minutos, lo que permite evidenciar áreas miocárdicas hipoperfundidas. La seguridad de la prueba dipiridamol-Talio es muy grande. No obstante suele desencadenar angina y alteraciones isquémicas del electrocardiograma, los que se antagonizan rápida y totalmente con aminofilina

Avaliaçäo dos efeitos do dipiridamol oral macerado no teste ergométrico / Evaluation of the effects of macerated oral dipyridamole on the ergometric test

Dezoito doentes do sexo masculino, com idades de 42 a 72 anos (média 60,6), com aterosclerose coronária confirmada à cinecoronariografia, em programa de reabilitaçäo e que faziam uso regular de dipiridamol, foram submetidos a três testes ergométricos: controle (TE1) e 40 minutos após a administraçäo oral de dipiridamol macerado, nas doses de 150 mg (TE2) e 300 mg (TE3), respectivamente. A comparaçäo dos dados do TE2 e do TE1 mostrou que no TE2 foi maior o infradesnivelamento do segmento ST na menor carga máxima atingida e também no pico do esforço. A comparaçäo dos dados do TE3 com os do TE1 revelou que no TE3: 1) o infradesnivelamento do segmento ST foi maior no pico do esforço e na menor carga máxima atingida; 2) a freqüência cardíaca atingida e o produto FC x PA no pico do esforço foram menores; 3) o tempo total de angina e o tempo para seu desaparecimento, após esforço, foram maiores. As demais variáveis näo sofreram modificaçöes significativas. Estes dados sugerem que a sobrecarga do exercício físico, após a administraçäo de dipiridamol, desencadeou grau mais acentuado de isquemia miocárdica, cuja intensidade foi proporcional a dose utilizada

Açäo da Heparina, da associaçäo da Heparina com ácido Acetilsalicílico - Dipiridamol e da fístula arteriovenosa na prevençäo de retrombose após trombectomia venosa: estudo experimental em coelho

O presente experimento foi realizado com a finalidade de verificar a açäo da heparina, da associaçäo da heparina com o ácido acetilsalicílico (AAS) e dipiridamol, e da fístula arteriovenosa como tratamento auxiliares na prevençäo da retrombose venosa após trombectomia, em condiçöes de fluxo sangüíneo venoso diminuído. Em 48 coelhos machos foi induzida a trombose na veia jugular externa esquerda e suas tributárias pela injeçäo de trombina em um segmento venoso, no qual o fluxo sangüíneo foi interrompido por 10 minutos. Após 48 horas essas veias foram desobstruídas por meio de trombectomia com auxílio do cateter de Fogarty, sendo os coelhos em seguida distribuídos por sorteio em 4 grupos de 12 animais: Grupo1- controle- no qual todos os tempos cirúrgicos dos demais grupos foram realizados, exceto a confecçäo da fístula arteriovenosa e ministraçäo de drogas; Grupo2 - nos animais foi ministrada a heparina sódica (600 UI/Kg) via subcutânea a cada 8 horas, iniciada 30 minutos antes da trobectomia; Grupo3- nestes, além da heparina ministrada no mesmo esquema do grupo2, foi associado o AAS e o dipiridamos, via intramuscular, respectivamente nas doses de 10 mg/kg de peso uma vez por dia e 0,5 mg;kg de peso, repetida a cada 8 horas; Grupo4- nos animais, após a trombectomia, foi feita uma fístula arteriovenosa entre a artéria carótida esquerda e a veia maxilar esquerda. Os coelhos foram avaliados 48 horas após a trombectomia.

Efeitos agudos do dipiridamol sobre o desempenho funcional e sobre as alteraçöes da sinergia de contraçäo do ventrículo esquerdo em pacientes portadores de cardiopatia isquêmica / Acute effects of dypiridamol on the functional performance and synergy of the left ventricle contraction in patients with ischemic cardiopathy

O dipiridamol foi usado por via intravenosa lenta (5 min), na dose de 0,3 mg/kg de peso, durante estudo hemodinâmico e cineangiocardiográfico, em 21 pacientes, 15 homens e 6 mulheres, com média de idade de 52 + ou - 9 anos e diagnóstico de cardiopatia isquêmica aterosclerótica. Foram estudados os índices do desempenho funcional do ventrículo esquerdo (VE) e a motilidade segmentar de suas paredes, quer em situaçäo basal, quer aos 5 minutos após o uso do medicamento, verificando-se: 1) Aumento da velocidade máxima de encurtamento do elemento contrátil (V max.), do débito cardíaco (DC) e do volume sistólico (VS) (p <0,05); 2) Ausência de alteraçöes estatísticamente significativas nas demais variáveis estudadas, bem como na motilidade dos segmentos do miocárdio ventricular esquerdo. Concluiu-se que: 1) O dipiridamol causou uma tendência a melhorar o desempenho do VE como músculo (considerando-se o aumento da V max) e como bomba (considerando-se o aumento do DC e VS), embora näo tenha alterado os demais índices de avaliaçäo do desempenho ventricular esquerdo; 2) O dipiridamol näo alterou a sinergia de contraçäo do miocárdio ventricular isquêmico

Vasodilatadores e circulção coronária colateral: I. Dipiridamol; estudo em coração isolado / Vasodilator agents and collateral coronary circulation: I. Dipyridamole; study in isolated heart

Em 8 cäes anestesiados, foram estabelecidas preparaçöes coraçäo-pulmäo isoladas, mantendo-se a resistência periférica para assegurar pressäo arterial média constante (PA) de 80 mmHg. A artéria coronária descendente anterior (DA) foi ligada e um cateter introduzido distalmente. Foram controlados fluxo sistêmico (FS), EGG e fluxo colateral (FCCo), medido pelo cateter na DA. Estas variáveis foram estudadas antes e 5, 15 e 30 min depois da injeçäo de 10mg de dipiridamol. Os resultados obtidos demonstram que, mantendo-se a PA em 80 mmHg, o fluxo coronário permanece constante (p < 0,01) mesmo na vigência de variaçöes do fluxo sistêmico de 30 a 50% do controle. Na presente investigaçäo, näo foi possível constatar o fenômeno "steal effect" descrito para o dipiridamol