Oral administration of TRPV4 inhibitor improves atrial calcium handling abnormalities in sterile pericarditis rats / 生理学报

Atrial Ca2+ handling abnormalities, mainly involving the dysfunction of ryanodine receptor (RyR) and sarcoplasmic reticulum Ca2+-ATPase (SERCA), play a role in the pathogenesis of atrial fibrillation (AF). Previously, we found that the expression and function of transient receptor potential vanilloid subtype 4 (TRPV4) are upregulated in a sterile pericarditis (SP) rat model of AF, and oral administration of TRPV4 inhibitor GSK2193874 alleviates AF in this animal model. The aim of this study was to investigate whether oral administration of GSK2193874 could alleviate atrial Ca2+ handling abnormalities in SP rats. A SP rat model of AF was established by daubing sterile talcum powder on both atria of Sprague-Dawley (SD) rats after a pericardiotomy, to simulate the pathogenesis of postoperative atrial fibrillation (POAF). On the 3rd postoperative day, Ca2+ signals of atria were collected in isolated perfused hearts by optical mapping. Ca2+ transient duration (CaD), alternan, and the recovery properties of Ca2+ transient (CaT) were quantified and analyzed. GSK2193874 treatment reversed the abnormal prolongation of time to peak (determined mainly by RyR activity) and CaD (determined mainly by SERCA activity), as well as the regional heterogeneity of CaD in SP rats. Furthermore, GSK2193874 treatment relieved alternan in SP rats, and reduced its incidence of discordant alternan (DIS-ALT). More importantly, GSK2193874 treatment prevented the reduction of the S2/S1 CaT ratio (determined mainly by RyR refractoriness) in SP rats, and decreased its regional heterogeneity. Taken together, oral administration of TRPV4 inhibitor alleviates Ca2+ handling abnormalities in SP rats primarily by blocking the TRPV4-Ca2+-RyR pathway, and thus exerts therapeutic effect on POAF.

Hypertrophic cardiomyopathy masked by pericarditis

Hypertrophic cardiomyopathy used to be regarded as a rare untreatable cause of sudden death in young male athletes. This report is the case of a middle-aged female patient with hereditary hypertrophic cardiomyopathy masked by superimposed pericarditis and revealed by autopsy. This case report illustrates how co-morbidity can hide a crucial diagnosis. This case report also illustrates the value of autopsy disclosing a familial disease that is increasingly recognized and dramatically more treatable than a few decades ago. Sudden death due to hypertrophic cardiomyopathy has become preventable, if the diagnosis is made soon enough. The lessons for patient care from this case include the importance of not missing the diagnosis of hypertrophic cardiomyopathy in female patients.

"Bread and butter" fibrinous pericarditis

Pericarditis is the inflammatory process involving the pericardium as a result of a systemic disease or a primary pericardium disorder.1 The actual incidence of pericarditis is difficult to ascertain,2 most probably because of under-reported or misdiagnosed cases. In the 19th century, Sir William Osler stated that pericarditis was one of the most serious diseases overlooked by practitioners.3 Even so, the rate of hospitalization by this diagnosis is estimated in 3.32 cases per 100,000 person-years, which corresponds to 0.2% of all causes of hospitalization in cardiology centers,4 with an incidence of 1.06% found in autopsy case series.5 Didactically, pericarditis can be morphologically classified in five types: (i) fibrinous; (ii) serous; (iii) purulent; (iv) hemorrhagic; or (v) caseous.6 The image presented herein refers to a typical fibrinous pericarditis, also known as "bread and butter" pericarditis.7 In such an entity, the pericardium, which is regularly smooth and bright, becomes opaque and granular, and macroscopically resembles two pieces of buttered bread pressed together then pulled apart. The histology shows the deposition of fibrin and leukocytic exudate involving the pericardial leaflets.8 Antonio Benivieni (1443-1502), a Florentine physician and a contemporary of Leonardo da Vinci, was assigned the first description of fibrinous pericarditis. However, René Laennec (1781-1826), also known for creating the stethoscope, was the first to register the analogy of this type of pericarditis with "buttered bread"9 in his book, A Treatise on the Diseases of the Chest and on Mediate Auscultation.10 The image presented in Figure 1 was obtained during the autopsy of a 25-year-old man who presented a 5-day history of high-grade fever, odynophagia, chest pain, and bloody sputum. He was hospitalized presenting marked leukocytosis with blasts in the peripheral blood smear and died 14 days later due to multiple organ failure. The autopsy revealed fibrinous pericarditis with a brighter yellow exudate than usual (probably due to hyperbilirubinemia, with direct and indirect bilirubin levels of 4.61 mg/dL and 2.07 mg/dL, respectively), lungs with "beefy red consolidation" due to alveolar edema, hemorrhage, hyaline membrane, and diffuse neutrophilic infiltrate. The patient's bone marrow was hypercellular at the expense of immature myeloid cells with areas of necrosis. The immunohistochemical study evidenced diffuse positivity for myeloperoxidase; CD117-positivity for 30% of the viable cells; CD34-positivity for 1% of the viable cells; and negativity for the terminal deoxynucleotidyl transferase­all of which were consistent with the diagnosis of M3 acute myeloid leukemia (French-American-British classification).11 Acute myocardial infarction, trauma/surgery, infection, uremia, systemic diseases, and neoplasia are among the most common causes of fibrinous pericarditis. Among the neoplasia, lung and breast malignancies stand out, followed by lymphomas and leukemia,12 although pericardial infiltration by nonlymphocytic leukemia is rarer.13 In a large case series of 420 postmortem examinations of the heart in acute leukemia,14 only 20 patients had symptoms of heart disease in life, and 9 of them had pericarditis at autopsy. In only 2 of the 9 patients, the pericarditis was the result of leukemic cell infiltrates into the pericardium; in 4 patients it was hemorrhagic; and in 2 it was pyogenic. Only 1 case remained with uncertain etiology, being fibrinous and unassociated with pericardial leukemic infiltrates, hemorrhages, or organisms, which also occurred in our case. The histopathologic study of the pericardium failed to reveal neoplastic cells, microorganisms, and viral inclusion; therefore, the precise etiology of the pericardial disease was not disclosed.

Fenetre pericardo-pleurale a l'Institut de Cardiologie d'Abidjan : indications et resultat

Objectif : Cette etude a ete motivee par des constats de recidives de pericardite liquidienne apres drainage pericardique par voie sous-xiphoidienne. Le but vise etait donc de faire un plaidoyer en faveur de la fenetre pericardo- pleurale au detriment du drainage pericardique classique par voie sous-xiphoidienne. Patients et methodes : Il s'agissait d'une etude prospective descriptive qui a ete realisee dans le service de chirurgie cardiovasculaire de l'institut de cardiologie d'Abidjan de mars 2008 a octobre 2012. Les donnees ont ete recueillies sur une fiche d'enquete a partir du suivi direct des patients qui ont beneficies d'une fenetre pericardo-pleurale. Les parametres etudies etaient; le sexe; l'age; l'indication operatoire; le nombre de ponction pleurale pour chaque patient apres ablation du drain pleural; le delai d'assechement pericardo-pleural pour chaque patient. Ont ete exclus de l'etude; les patients chez lesquels il a ete realise un drainage pericardique par voie sous-xiphoidienne (48 patients) un drainage pericardique et pleural par voie sous-xiphoidienne (13 patients) et un drainage pleural a thorax ferme (273 patients).Resultats : Vingt-quatre patients ont ete recenses dont 09 hommes et 15 femmes L'age moyen etait de 28 ans avec des extremes de 19 et 52ans. Les indications de la fenetre pleuro- pericardique etaient representees par : la pleuro-pericardite purulente (04cas); la pleuro-pericardite tuberculeuse (14 cas); la pleuro-pericardite neoplasique (02cas) et la pericardite idiopathique recidivante (04 cas). Aucun accident per- operatoire n'a ete observe. Seule les patients atteints de pleuro-pericardite neoplasique et de pericardite idiopathique recidivante ont eu besoin de ponction pleurales apres la fenetre pericardo-pleurale. Conclusion : La fenetre pericardo-pleurale a certains avantages ; Elle permet la biopsie d'une grande portion de pericarde et donc de favoriser le diagnostic anatomo-pathologique; elle permet en cas de reconstitution de l'epanchement pericardique l'evacuation vers la plevre qui est facilement accessible a la ponction transcutanee; les accidents per-operatoires sont moindres car le pericarde est vu sous un grand jour. Cette technique de drainage doit etre privilegiee tant que faire ce peut

Lesões epicárdicas na cardiopatia chagásica são reflexo de processo inflamatório / Epicardial lesions in Chagas' heart disease reflect an inflammatory process

OBJETIVO: Fornecer descrição anatomopatológica detalhada das lesões epicárdicas na cardiopatia chagásica crônica, avaliar sua incidência e discutir sua provável patogênese. MÉTODOS: Foram examinados os corações de 39 pacientes portadores de cardiopatia chagásica crônica submetidos a necropsia, com exame histológico das lesões epicárdicas. RESULTADOS: Manchas lácteas, caracterizadas por áreas bem definidas de cor branca do epicárdio, foram observadas em 80 por cento dos casos, predominantemente na face anterior do ventrículo direito. Histologicamente, foi observado abrupto espessamento fibroso do epicárdio, não havendo fibras elásticas, processo inflamatório ou vasos sangüíneos. Rosário chagásico, caracterizado por pequenos grânulos esbranquiçados, arredondados, seqüencialmente dispostos ao longo dos vasos coronarianos, esteve presente em 23 por cento dos corações. Apresentavam a mesma estrutura histológica que as manchas lácteas, mas de forma intrigante ocorriam apenas imediatamente acima de ramos arteriais coronarianos. Placa vilosa esteve presente na ponta ou na face anterior de 21 por cento dos corações, caracterizando-se pelo aspecto exofítico, provavelmente em decorrência da adesão pericárdica prévia localizada. A microscopia, foram observados focos de infiltrado inflamatório e proliferação vascular, típicos de epicardite em organização. Além das lesões descritas, havia células inflamatórias mononucleares esparsas, com agrupamentos focais, no epicárdio de praticamente todos os casos. CONCLUSÃO: Concluímos que as lesões epicárdicas da cardiopatia chagásica crônica são provavelmente conseqüentes à reação do epicárdio ao processo inflamatório crônico.

OBJECTIVE: Furnish a more detailed anatomicopathological description of the epicardial lesions in chronic chagasic cardiopathy, evaluate their incidence and discuss their probable pathogenesis METHODS: We examined the hearts of 39 chronic chagasic cardiopathy patients who underwent autopsies and submitted to histological analysis the epicardial lesions. RESULTS: Milk spots, characterized by well defined white areas in the epicardium were found in 80 percent of the cases, mainly on the anterior face of the right ventricle. Histological analysis revealed abrupt fibrous thickening of the epicardium, with no elastic fibers, inflammation or blood vessels. Chagasic rosary, characterized by small round whitish granules deposited sequentially along the coronary vessels were present in 23 percent of the hearts. They presented the same histological structure as the milk spots, but interestingly were only found immediately above the coronary artery branches. Villous plaque was found on the apex or anterior face of 21 percent of the hearts. It is characterized by an exophytic aspect, probably due to previous localized pericardial adhesion. Microscopic analysis revealed foci of inflammatory infiltrate and vascular proliferation, typical of epicarditis still under organization. In addition to the lesions described above, the vast majority of cases presented sparse mononuclear inflammatory cells with occasional foci. CONCLUSION: We concluded that epicardial lesions related to chronic chagasic heart disease are probably a result of epicardial reactions to chronic inflammatory process.

Pericardite aguda pós-influenza ou pós-vacina antiinfluenza: atualização / Acute pericarditis following Influenza infection or vaccine: update

As pericardites com etiologias idiopática e viral se confundem. Nem sempre existem achados clínicos que distinguem uma da outra, e é provável que muitos casos de pericardite idiopática sejam causados por infecções virais não reconhecidas. A influenza, virose que acomete principalmente o trato respiratório, pode também desencadear complicações cardíacas, como miocardites e pericardites. Por sua potencialidade mórbida, tem sido, nos últimos anos, alvo de campanhas nacionais de imunização por vacina. A pericardite pós-influenza e a pericardite pósvacina antiinfluenza são doenças cada vez mais enfrentadas pelo médico. O presente trabalho objetiva revisar a literatura mundial, fazendo uma atualização do tema delimitado

Pericarditis / Pericarditis

Se revisaron las historias clinicas de 31 pacientes admitidos entre mayo de 1989 a mayo de 1991 en el Servicio de Cardiologia de la Unidad Hospitalaria Nro 2 de la Caja Nacional de Salud de Cochabamba, 18 hombres y 13 mujeres comprendidos entre los 35 y 75 anos de edad. Las manifestaciones por las que fueron hospitalizados fueron de insuficiencia cardiaca congestiva, pero no padecian de valvulopatias, cardiopatias congenitas ni miocardiopatias demostrables. Por los estudios realizados se llego a la conclusion de que 28 eran portadores de pericarditis con derrame y 3 de pericarditis adhesiva, con tendencia a la pericarditis constricitva. La etiologia de 28 casos fue inflamatoria y de 3 metastasis maligna. Los resultdos fueron satisfactorios en 27 pacientes, 4 murieron y de estos: 2 tenian pericarditis de tipo inflamatorio y dos pericarditis cuyo liquido pericardico mostro alteraciones celulares malignas.

Pericarditis: aspectos clínicos y etiológicos / Pericarditis: clinical and ethiologic aspects

Se revisan la totalidad de historias clínicas correspondientes a los casos de pericarditis diagnósticados y hospitalizados en el lapso comprendido entre enero 1979 y diciembre de 1988, con un total de 120 pacientes, correspondiendo la mayoría al sexo masculino (79//), con un promedio de edad de 36 años. Casi las dos terceras partes corresponden a etiología idiopática y viral, y, en tercer lugar, pericarditis reumática, seguida de la posterior a infarto del miocardio. El síntoma más frecuente fue el dolor torácico (92//). En el 64// de los pacientes se demostró frote pericárdico. Más del 90// de los pacientes presentaron los hallazgos clásicos en el electrocardiograma. 60// de los pacientes evolucionaron sin complicaciones. La complicación más frecuente fue la insuficiencia cardíaca (18//). Al 40// de los pacientes se les realizó ecocardiograma demostrando en 67// grados variables de derrame pericárdico