RESUMO
Primary pulmonary hypoplasia is a rare, usually lethal, condition presenting only after birth without other congenital abnormalities. We describe the first case of fraternal twins diagnosed prenatally with primary pulmonary hypoplasia. Both had diffuse hypoplasia of the pulmonary arteries initially identified by fetal echocardiography and confirmed at autopsy following termination. These cases permit examination of the histopathology of this disease in the fetal stage of development.
Assuntos
Doenças em Gêmeos/diagnóstico por imagem , Doenças Fetais/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Aborto Induzido , Adulto , Autopsia , Feminino , Humanos , Pulmão/anormalidades , Pulmão/embriologia , Gravidez , Diagnóstico Pré-Natal , Gêmeos Dizigóticos , UltrassonografiaRESUMO
BACKGROUND: Calcium overload is a major cause of reperfusion myocardial injury. Multidetector computed tomography (MDCT) has been previously used in visualizing coronary artery calcium, but not calcium deposits in reperfused infarction. PURPOSE: To assess the ability of MDCT to 1) noninvasively visualize and characterize calcium deposits in reperfused infarcts, and 2) monitor regional wall swelling, regional systolic wall thickening, and infarct resorption. MATERIAL AND METHODS: Reperfused myocardial infarcts were created in seven pigs by 2-hour occlusion of the left anterior descending coronary artery (LAD) after coronary catheterization. A 64-slice MDCT scanner was used for non-contrast images to depict calcium deposits. Furthermore, cine and delayed contrast-enhanced (DE) MDCT imaging were acquired to assess the chronological changes (2-4 hours, 1 week, and 8 weeks) in regional wall swelling, systolic wall thickening, and infarct size. RESULTS: Non-contrast MDCT images depicted calcium deposits as "hot-spots." Attenuation of calcium deposits was greater (89+/-6 Hounsfield units [HU]) than remote myocardium (36+/-3 HU; P<0.05). Calcium deposits were not evident at 2-4 hours and were substantially smaller at 8 weeks compared to 1 week. Correlations were found between the extent of calcium deposits, ejection fraction (R=0.81), and infarction size (R=0.70). Cine MCDT images demonstrated transient wall swelling (edema formation and resorption) at 2-4 hours and differences in regional systolic wall thickening among infarcted, peri-infarcted, and remote myocardium. Calcium-specific von Kossa stain confirmed the presence of calcium deposits in infarcted myocardium. CONCLUSION: 64-slice MDCT has the potential to demonstrate the progression and regression of calcium deposits, interstitial edema, and infarction. The presence of calcium deposits was transient and associated with reperfused recent infarction. The extent of calcium deposits was positively correlated with infarction size and negatively with global left-ventricular function.
Assuntos
Angioplastia Coronária com Balão , Cálcio/metabolismo , Infarto do Miocárdio/diagnóstico por imagem , Miocárdio/metabolismo , Tomografia Computadorizada por Raios X , Animais , Meios de Contraste , Histocitoquímica , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Miocárdio/patologia , Sus scrofa , Função Ventricular EsquerdaRESUMO
Angiopoietin (Ang)-2, the natural antagonist of the Ang1/Tie2 receptor is a complex regulator of blood vessel plasticity that plays a pivotal role in both vessel sprouting [in the presence of vascular endothelial growth factor (VEGF)-A] and vessel regression (in the absence of VEGF-A). Based on the spatial and temporal expression of Ang2 throughout human gestation, we recently suggested that the Ang2 may play a pivotal role in placental angiogenesis. Further, to examine this tenet we have developed a novel murine model system in which in utero Ang2 gene delivery via a non-replicating adenoviral expression vector has the potential to manipulate the blood vessel phenotype in vivo during pregnancy. Ang2 overexpression selectively and rapidly remodels the labyrinth perivascular extracellular matrix, subsequently promoting plasticity of the maternal and fetal vessels, which appear honeycombed due to a 2-fold increase in blood vessel luminal area. High levels of Ang2 impair endothelial cell adhesiveness, leading to vascular leakiness with perivascular oedema, which increases placental weight. These observations suggest that the Ang2 overexpression may play a key role in placental vascular remodelling. Furthermore, we suggest a novel new model to study the pathobiology of placental vascularization and the effect of placental blood vessels on fetal phenotype.
Assuntos
Angiopoietina-2/fisiologia , Neovascularização Fisiológica , Placenta/irrigação sanguínea , Angiopoietina-2/análise , Angiopoietina-2/genética , Animais , Vasos Sanguíneos/citologia , Vasos Sanguíneos/crescimento & desenvolvimento , Endotélio Vascular/química , Matriz Extracelular/química , Feminino , Vetores Genéticos , Humanos , Camundongos , Modelos Animais , Neovascularização Fisiológica/fisiologia , Fenótipo , Placenta/química , Placentação , Gravidez , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Transcrição Gênica , Ativação Transcricional , TransfecçãoRESUMO
To investigate the genetic contribution to phenotypic variability in aneuploidy, we generated mice with trisomy 16 (Ts16) by mating [Rb(6.16)24Lub x Rb(16.17)7Bnr]F1 males with females from four inbred strains, BALB/cJ, C3H/HeJ, C57BL/6J, and DBA/2J. Among the four Ts16 strains that were generated, there were no significant differences in survival, weight, or length relative to euploid control littermates at either embryonic day (E) 14.5 or E17.5. All Ts16 fetuses at E14.5 had edema that ranged from mild to severe, increased amniotic fluid volume, and a thickened neck. At E17.5, Ts16 fetuses exhibited two distinct phenotypes, one with an edematous morphology and the other runt-like. None of these gross morphological abnormalities was strain-specific either in occurrence or frequency. At E10.5, there were pharyngeal arch artery (PAA) anomalies in all Ts16 embryos on the C3H/HeJ background, but none in trisomics on the other three backgrounds. However, at E17.5, there was in addition to ventricular and atrioventricular septal defects, a high frequency of aortic arch defects in Ts16 fetuses, irrespective of genetic background. Taken together, these findings indicate that there are at least two mechanistic responses to the presence of three copies of mouse chromosome 16 in the modeling of the cardiovascular system: one, development of PAA defects, is strongly influenced by genetic background; but the second, development of aortic arch anomalies in the absence of preexisting PAA anomalies, is not.
Assuntos
Camundongos Mutantes , Camundongos Transgênicos , Trissomia , Animais , Artérias/anormalidades , Região Branquial/irrigação sanguínea , Sistema Cardiovascular/embriologia , Cruzamentos Genéticos , Edema/genética , Feminino , Coração/embriologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Fenótipo , Especificidade da Espécie , Fatores de TempoRESUMO
BACKGROUND AND PURPOSE: The composition of carotid atherosclerosis was visualized by using 3D MRI at high resolution with 200-micrometer (3) voxels. Magnetic resonance signal characteristics were correlated with plaque components, including collagenous cap, necrotic core, and calcification, to define resolution and other requirements for future clinical carotid MRI. METHODS: Twenty-one en bloc carotid endarterectomy specimens were imaged ex vivo by 3D gradient-echo MRI by using a 1.5-T clinical scanner with repetition time, echo time, and flip angle of 40 ms, 18 ms, and 20 degrees, respectively. Plaques were placed in Gd-saline and imaged in a solenoid radiofrequency coil. For quantitative tissue-specific signal analysis, techniques were developed to match tissue sections analyzed by MRI and histology. RESULTS: Three-dimensional imaging resolved complex morphological features not visualized by density- or T(2)-weighted 2D spin-echo imaging. The collagenous cap, necrotic core, and areas of focal calcification showed differing signal characteristics: mean contrast-to-noise ratio for cap versus underlying core was 20. The signal distributions for media and necrotic core overlapped but were resolvable in most specimens. The signal from thrombus was variable. CONCLUSIONS: En bloc specimens provide a useful model for studying plaque MRI. By use of isotropic submillimeter resolution, the collagenous cap and underlying necrotic core typically can be distinguished, and calcification can be identified. Thrombus displays a wide variation in signal intensity. The techniques presented could facilitate future clinicohistological correlation studies for atherosclerotic plaque MRI.
Assuntos
Doenças das Artérias Carótidas/patologia , Imageamento por Ressonância Magnética/métodos , Calcinose/patologia , Colágeno/ultraestrutura , Hemorragia/patologia , Imageamento Tridimensional/métodos , Necrose , Sensibilidade e Especificidade , Trombose/patologia , Túnica Média/patologiaRESUMO
Mn superoxide dismutase (MnSOD), a mitochondrial antioxidant enzyme, has been shown to be essential for animal survival. MnSOD mutant mice (Sod2-/- mice) on the CD1 background develop severe dilated cardiomyopathy and usually die within 10 d after birth. To characterize better the phenotype and understand the mechanism of superoxide-mediated tissue damage in Sod2-/- mice, congenic Sod2-/- mice on inbred backgrounds were generated to ensure genetic homogeneity. When generated on a C57BL/6J background (B6
Assuntos
Acidose/metabolismo , Cardiomiopatia Dilatada/enzimologia , Morte Fetal/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Acidose/genética , Aconitato Hidratase/genética , Aconitato Hidratase/metabolismo , Animais , Cardiomiopatia Dilatada/genética , Catalase/genética , Catalase/metabolismo , Morte Fetal/genética , Genótipo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Rim/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Camundongos , Camundongos Knockout , Camundongos Mutantes , Mitocôndrias/metabolismo , Miocárdio/citologia , Miocárdio/metabolismo , Fenótipo , Superóxido Dismutase/deficiência , Regulação para CimaRESUMO
Mice inheriting both copies of MMU12 either maternally or paternally demonstrate imprinting effects. Whereas maternal uniparental disomy 12 (matUPD12) fetuses are growth retarded and die perinatally, paternal UPD12 (patUPD12) fetuses die during late gestation and exhibit placentomegaly and skeletal muscle maturation defects. To examine further the developmental consequences of UPD12, we intercrossed mouse stocks heterozygous for Robertsonian translocation chromosomes (8.12) and (10.12). We report that at 13.5-14.5 dg patUPD12 hearts exhibit increased ventricular diameter, thinner, less compact myocardium, and deep intertrabecular recesses when compared to controls. These data provide evidence for cardiac failure, a lethal condition, and suggest a role for an imprinted gene(s) in normal heart development.
Assuntos
Cardiomiopatias/embriologia , Cardiomiopatias/genética , Aberrações Cromossômicas/genética , Impressão Genômica/genética , Miocárdio/patologia , Animais , Aberrações Cromossômicas/embriologia , Cruzamentos Genéticos , Feminino , Morte Fetal/genética , Coração/embriologia , Heterozigoto , Cariotipagem , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Translocação Genética/genéticaRESUMO
BACKGROUND: Vascular endothelial growth factor (VEGF) is being investigated for therapeutic angiogenesis in ischemic myocardium. Primarily, transient delivery systems have been tested. The goal of this study was to investigate the effects of continuous expression of VEGF in myocardium by use of myoblast-mediated delivery. METHODS AND RESULTS: Primary murine myoblasts (5 x 10(5) cells in 10 microL of PBS with 0.5% BSA) expressing both the murine VEGF gene and the beta-galactosidase (beta-gal) gene from a retroviral promoter were implanted in the ventricular wall of immunodeficient mice (n=11) via a subdiaphragmatic approach. Control immunodeficient mice (n=12) were injected with the same number of myoblasts expressing only the beta-gal gene. Between days 14 and 16, surviving mice were euthanized and the hearts processed for histology. In the experimental group, 11 of 11 mice demonstrated failure to thrive by day 13; 5 deaths occurred between days 8 and 15. There were no complications in the control mice. Histochemistry documented successful implantation of myoblasts (positive beta-gal reaction product) in 6 of 6 surviving experimental mice and 12 of 12 controls. Histology disclosed intramural vascular tumors resembling hemangiomas in the VEGF-myoblast-injected myocardium in 6 of 6 surviving mice. beta-Gal-expressing cells were present at the site of the vascular tumors. Immunohistochemistry localized abundant endothelial nitric oxide synthase and CD31 (platelet and endothelial cell adhesion molecule) within the lesion, consistent with the presence of endothelial cells. CONCLUSIONS: In this model, unregulated continuous expression of VEGF is associated with (1) a high rate of failure to thrive/death and (2) formation of endothelial cell-derived intramural vascular tumors in the implantation site. These results underscore the importance of regulating VEGF expression for therapeutic angiogenesis.
Assuntos
Fatores de Crescimento Endotelial/biossíntese , Fatores de Crescimento Endotelial/genética , Técnicas de Transferência de Genes/efeitos adversos , Neoplasias Cardíacas/genética , Hemangioma/genética , Linfocinas/biossíntese , Linfocinas/genética , Miocárdio/metabolismo , Animais , Transplante de Células , Regulação da Expressão Gênica , Neoplasias Cardíacas/metabolismo , Neoplasias Cardíacas/patologia , Hemangioma/metabolismo , Hemangioma/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos SCID , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Miocárdio/patologia , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
Severe ischemic injury or infarction of myocardium may cause activation of matrix metalloproteinases (MMPs) and damage the interstitial matrix. However, it is unknown whether MMP activation and matrix damage occur after moderate ischemia and reperfusion that result in myocardial stunning without infarction, and if so whether such changes contribute to postischemic myocardial expansion and contractile dysfunction. To address these questions, open-chest anesthetized pigs underwent 90 min of regional ischemia (subendocardial blood flow 0.4 +/- 0.1 ml. g(-1). min(-1)) and 90 min of reperfusion. After ischemia plus reperfusion, histological and ultrastructural examination revealed no myocardial infarction or inflammatory cell infiltration. Myocardial MMP-9 content increased threefold with a fourfold increase in the active form (P < 0.001). Myocardial collagenase content doubled (P < 0.01) but remained in latent form. MMP-2 and tissue inhibitors of metalloproteinases were unaffected. Despite increases in MMPs, collagen ultrastructure (assessed by cell maceration scanning electron microscopy) was unaltered. Intracoronary administration of the MMP inhibitor GM-2487 did not prevent or attenuate myocardial expansion (assessed by regional diastolic dimensions at near-zero left ventricular pressure) or contractile dysfunction. We conclude that although moderate ischemia and reperfusion alter myocardial MMP content and activity, these effects do not result in damage to interstitial collagen, nor do they contribute to myocardial expansion or contractile dysfunction.
Assuntos
Colágeno/ultraestrutura , Hemodinâmica , Metaloproteinases da Matriz/metabolismo , Isquemia Miocárdica/patologia , Isquemia Miocárdica/fisiopatologia , Reperfusão Miocárdica , Miocárdio/metabolismo , Miocárdio/ultraestrutura , Animais , Pressão Sanguínea , Colagenases/metabolismo , Circulação Coronária , Feminino , Coração/fisiopatologia , Frequência Cardíaca , Metaloproteinase 9 da Matriz/metabolismo , Isquemia Miocárdica/metabolismo , Miocárdio Atordoado/metabolismo , Miocárdio Atordoado/patologia , Miocárdio Atordoado/fisiopatologia , Miocárdio/patologia , Suínos , Inibidores Teciduais de Metaloproteinases/metabolismo , Função Ventricular EsquerdaRESUMO
An hydropic fetus seen at 28-weeks gestation had a saccular aortic aneurysm in the descending thoracic aorta. Histology disclosed marked fibrointimal hyperplasia, thrombus, and attenuation of the tunica media. The remainder of the descending thoracic aorta showed fibrointimal hyperplasia. We speculate that the narrowed lumen and rigid aortic wall resulting from this vasculopathy provided an increased afterload leading to cardiac failure.
Assuntos
Aorta Torácica/patologia , Aneurisma da Aorta Torácica/complicações , Aneurisma da Aorta Torácica/patologia , Hidropisia Fetal/etiologia , Humanos , Recém-Nascido , MasculinoRESUMO
PURPOSE: To estimate and compare the fractional distribution volume (fDV) of gadodiamide injection and technetium 99m-diethylenetriaminepentaacetic acid (DTPA) in the reperfused myocardium of rat hearts subjected to various durations of ischemia. MATERIALS AND METHODS: Magnetic resonance (MR) imaging and autoradiography were performed in rats subjected to 20, 30, 40, or 60 minutes of regional ischemia followed by 1 hour of reperfusion. The fDVs of gadodiamide injection and (99m)Tc-DTPA were measured and compared by using inversion-recovery echo-planar imaging and autoradiographic phosphor imaging, respectively. RESULTS: The mean fDV of both tracers (gadodiamide and (99m)Tc-DTPA) in normal myocardium was 18% +/- 1, whereas that in the entire area at risk increased significantly (P <.05) with 20, 30, 40, and 60 minutes of ischemia to 32% +/- 1, 57% +/- 4, 66% +/- 2, and 68% +/- 2, respectively. The fDV was significantly (P <.05) greater in the core of infarction-78% +/- 4, 89% +/- 5, and 88% +/- 5 with 30, 40, and 60 minutes of ischemia, respectively-than in the normal myocardium or in the area at risk. CONCLUSION: The fDV of MR contrast material in the periinfarcted rim was significantly (P <. 05) greater than that in the normal myocardium, but significantly less than that in the core of infarcted myocardium.
Assuntos
Meios de Contraste/farmacocinética , Imagem Ecoplanar , Gadolínio DTPA/farmacocinética , Isquemia Miocárdica/metabolismo , Reperfusão Miocárdica , Miocárdio/metabolismo , Análise de Variância , Animais , Autorradiografia , Corantes , Estudos de Viabilidade , Indóis , Imageamento por Ressonância Magnética , Microscopia Eletrônica , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Isquemia Miocárdica/patologia , Miocárdio/patologia , Miocárdio/ultraestrutura , Compostos Organometálicos , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Ratos Sprague-Dawley , Pentetato de Tecnécio Tc 99m/farmacocinética , Fatores de Tempo , Sobrevivência de TecidosRESUMO
A 3-day-old premature infant with meconium peritonitis, periventricular leukomalacia, and pulmonary hypertension died with respiratory insufficiency. An autopsy disclosed intravascular squamous cells in the lungs, brain, liver, pancreas, and kidneys. Numerous pulmonary capillaries and arterioles were occluded by squamous cells, accounting for pulmonary hypertension. Brain parenchyma surrounding occluded cerebral vessels showed infarct and gliosis. A mediastinal lymph node filled with squamous cells alluded to the mechanism by which these cells from the peritoneal cavity likely entered the bloodstream--namely, via diaphragmatic pores connecting with lymphatics. Thus, disseminated intravascular meconium rarely may complicate meconium peritonitis and have devastating consequences.
Assuntos
Doenças Fetais/etiologia , Doenças do Prematuro/etiologia , Mecônio , Peritonite/etiologia , Doenças Vasculares/etiologia , Embolia/etiologia , Evolução Fatal , Feminino , Humanos , Recém-Nascido , Gravidez , Complicações na GravidezRESUMO
This study tested the hypothesis that regional low-flow ischemia and reperfusion alter myocardial material properties by causing non-elastic deformation. Twenty-two anesthetized, open-chest pigs were studied. Pigs underwent 90 min of regional low-flow ischemia (anterior LV subendocardial blood flow 29+/-7% of baseline) followed by 90 min reperfusion. LV pressure and regional subendocardial segment length were recorded to derive end-diastolic pressure vs segment length (EDP vs EDL) and preload-recruitable stroke work (PRSW) relations. In vivo, non-elastic myocardial deformation was inferred from increases in minimally loaded myocardial dimensions: the EDL at zero EDP (L0) and the EDL at which no regional external work was performed (Lw, the PRSW intercept). In 15 pigs, ultrastructural confirmation of non-elastic deformation was obtained from sarcomere dimensions measured by transmission electron microscopy after in situ perfusion fixation under non-ischemic conditions, after 90 min ischemia, or after 90 min ischemia plus 90 min reperfusion. Ischemia increased L0 and Lw to 1.17+/-0.05 and 1. 13+/-0.04 times baseline, respectively. After reperfusion, L0 and Lw remained increased to 1.09+/-0.03 and 1.15+/-0.02 times baseline (all P<0.05). After reperfusion, PRSW slope was not different from baseline, but regional external work remained depressed (0.38+/-0.03 times baseline) due to the persistent increase in Lw. Neither L0 nor Lw changed in the posterior (non-ischemic) region. In hearts fixed after ischemia or after ischemia plus reperfusion, sarcomere length was significantly greater and transverse distance between thick myofilaments was significantly smaller in the anterior (ischemic) subendocardium than in the posterior (non-ischemic) subendocardium (P<0.01). We conclude that regional low-flow ischemia and reperfusion cause non-elastic deformation of myocardium, manifest in vivo by increased minimally loaded myocardial dimensions (L0 and Lw) and ultrastructurally by increased sarcomere length and decreased transverse interfilament distance. Non-elastic deformation of myocardium may contribute to contractile dysfunction in low-flow ischemia and reperfusion.
Assuntos
Circulação Coronária/fisiologia , Traumatismo por Reperfusão Miocárdica/patologia , Animais , Velocidade do Fluxo Sanguíneo , Elasticidade , Hemodinâmica/fisiologia , Microscopia Eletrônica , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Suínos , Função Ventricular/fisiologiaRESUMO
Giving 500 mg/kg of fructose-1,6-bisphosphate intraperitoneally decreases hypoxic/ischaemic CNS injury of neonatal rats. Before administering fructose-1,6-bisphosphate to human neonates, its toxicity must be determined in neonatal animals. Thus, saline or 4,000, 6,000, or 8,000 mg/kg of fructose-1,6-bisphosphate was given intraperitoneally to normoxic 7 days old rats. One, 2, and 24 hr and 7 days later, blood Ca2+, PO(4)3-, blood urea nitrogen, and creatinine concentrations, and aspartate aminotransferase activity were measured. Organ pathology was determined at necropsy. Pups receiving 4,000 mg/kg of fructose-1,6-bisphosphate survived without evidence of injury or toxicity. All animals receiving 8,000 mg/kg and 27 percent of those receiving 6,000 mg/kg of fructose-1,6-bisphosphate died. Surviving fructose-1,6-bisphosphate-treated animals grew at the same rates and had similar weights as saline-treated animals. Nineteen percent of pups given 6,000 or 8,000 mg/kg of fructose-1,6-bisphosphate had mild perivascular fluid cuffing and/or microscopic pulmonary haemorrhage, but none of the animals given 4,000 mg/kg of the compound had evidence of injury. No other organ pathology was found in any of the animals. Renal and hepatic function were normal in all animals. Fructose-1,6-bisphosphate administration was associated with a significant increase in the fructose-1,6-bisphosphate concentration of blood. Administering 4,000 to 8,000 mg/kg of fructose-1,6-bisphosphate significantly decreased Ca2+ concentrations and increased PO(4)3- concentrations 1 and 2 hrs after fructose-1,6-bisphosphate administration. Similar changes in Ca2+ and PO(4)3- concentrations occurred after the administration of 10 mmol/kg of sodium phosphate. The wide margin of safety for fructose-1,6-bisphosphate (8 times the dose needed to prevent or reduce CNS injury) may render fructose-1,6-bisphosphate safe for use in neonates.
Assuntos
Frutosedifosfatos/toxicidade , Animais , Animais Recém-Nascidos , Relação Dose-Resposta a Droga , Frutosedifosfatos/sangue , Injeções Intraperitoneais , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
Atrioventricular (AV) block is a useful substrate for the study of cardiac physiology. The objective of this investigation was to develop a straightforward and reproducible model of permanent AV block in rats. Working through a sternotomy, we used an epicardial fat pad between the aortic root and the right atrial wall of the rat as a landmark for the site for injection of 70% ethanol (5-10 microl) into the myocardium 3 mm below the epicardial surface. Stable, complete heart block was produced in 23 of 28 rats (82%) with a success rate of 100% in the last 16 rats of the series. Saline injection produced no heart block in 15 rats. A separate group of 14 animals was allowed to recover. Chronic heart block was achieved in all ethanol-injected animals for up to 7 days before death. The survival rate in the recovered rats was 90% in the ethanol-injected group and 100% in the saline-injected control group. Acute hemodynamic changes following the production of heart block consisted of an increase in central venous pressure, a decrease in systolic blood pressure, a decrease in left ventricular pressure, and a decrease in change in pressure over time. Chronic hemodynamic changes demonstrated a return to baseline of the central venous pressure, a persistent decrease in systolic blood pressure, and a decrease in left ventricular pressure. After the rats were killed and the hearts were dissected, discrete areas of myocardial damage were identified histologically in the atrial septum near the AV conduction axis tissue in the ethanol-injected hearts. Complete heart block was associated only with lesions extending into the specialized muscle of the AV node or His bundle. Focal mild hemorrhage, inflammation, and damaged myocardial fibers were observed in the acute stage, whereas healing lesions were characterized by granulation tissue and fibrosis replacing conduction tissue. The simple technique described provides a reproducible model for permanent, complete heart block and the study of cardiac function.
Assuntos
Bloqueio Cardíaco/fisiopatologia , Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/fisiologia , Tecido Adiposo/fisiopatologia , Animais , Nó Atrioventricular/patologia , Nó Atrioventricular/fisiopatologia , Eletrocardiografia , Eletromiografia , Coração/fisiopatologia , Bloqueio Cardíaco/patologia , Sistema de Condução Cardíaco/efeitos dos fármacos , Sistema de Condução Cardíaco/fisiologia , Hemodinâmica/fisiologia , Modelos Biológicos , Miocárdio/patologia , Ratos , Ratos Sprague-Dawley , Fluxo Sanguíneo Regional/fisiologiaRESUMO
To determine whether precise left-sided accessory pathway localization is possible from the coronary sinus, electrocardiogram (ECG) characteristics from the coronary sinus pair demonstrating earliest activation via the accessory pathway were compared to simultaneous mitral annular ablation catheter ECGs at successful ablation sites in 48 patients. To define the coronary sinus-mitral annular relation, the coronary sinus to mitral annulus distance (D) was measured at sequential distances from the coronary sinus os in 10 cadaver hearts. Mitral annular ECGs demonstrated earliest activation via the accessory pathway more frequently than the earliest coronary sinus pair (p < 0.001), more frequent continuous electrical activity (p < 0.001), and more frequent accessory pathway potentials (p < 0.01). D was >10 mm at 20, 40, and 60 mm, respectively, from the coronary sinus os. Coronary sinus ECGs do not precisely localize left-sided accessory pathways, which may be due in part to an average anatomic separation of more than 10 mm between the coronary sinus and accessory pathways bridging the mitral annulus.
Assuntos
Nó Atrioventricular/anormalidades , Eletrocardiografia , Adulto , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/cirurgia , Nó Atrioventricular/cirurgia , Ablação por Cateter , Vasos Coronários/anatomia & histologia , Feminino , Cardiopatias Congênitas/diagnóstico , Humanos , Masculino , Valva Mitral/anatomia & histologiaRESUMO
BACKGROUND: Previous studies have demonstrated that ischemic preconditioning prevents lethal cell injury and, as a consequence, limits infarct size in rat heart. Although both apoptosis and necrosis have been shown to contribute to myocardial cell death after myocardial ischemia and reperfusion, the ability of ischemic preconditioning to prevent programmed cell death remains unknown. METHODS AND RESULTS: To test the hypothesis that ischemic preconditioning reduces irreversible ischemic injury in part by decreasing apoptosis, rats that underwent ischemic preconditioning and controls were subjected to 30 minutes of left coronary artery occlusion followed by 180 minutes of reperfusion. Ischemic preconditioning was achieved by five 5-minute cycles of ischemia, each followed by 5 minutes of reperfusion. Infarct size, determined by dual staining with triphenyltetrazolium chloride and phthalocyanine blue dye, was significantly reduced in preconditioned compared with nonpreconditioned rats (11.4+/-1.4% versus 58.7+/-1.4%; n=20 in each group; P<.001; infarct size/risk area). Genomic DNA from preconditioned hearts showed little or no oligonucleosome-sized fragments (200-bp multiples), whereas genomic DNA from nonpreconditioned hearts showed a typical nucleosome fragmentation. The TUNEL assay localized fewer and sparsely stained nuclei within the infarct zone of ischemic preconditioned hearts compared with nonpreconditioned hearts. Consistent with these findings, the number of cytosolic histone-associated low-molecular-weight DNA fragments was significantly decreased in preconditioned hearts compared with controls (0.17+/-0.02 versus 1.07+/-0.09 U; n=10 in each group; P<.001; absorbance 405 nm/490 nm). CONCLUSIONS: This study suggests that ischemic preconditioning reduces irreversible ischemic injury in part by decreasing apoptosis after prolonged ischemia and reperfusion.
Assuntos
Apoptose , Precondicionamento Isquêmico Miocárdico , Miocárdio/patologia , Animais , Citosol/metabolismo , DNA/metabolismo , Fragmentação do DNA , Feminino , Técnicas Genéticas , Genoma , Técnicas Imunoenzimáticas , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Ratos , Ratos Sprague-Dawley , Distribuição TecidualRESUMO
BACKGROUND: Recently, a colony of German shepherd dogs with inherited spontaneous cardiac arrhythmias and associated sudden death has been developed and characterized. Due to the median age of onset of the arrhythmia (4.5 months), the tendency for the arrhythmia to occur during REM sleep or after exercise, and the absence of structural heart disease, we hypothesized a developmental abnormality of the sympathetic innervation to the heart. METHODS AND RESULTS: We studied 11 dogs from this colony, ranging in age from 6 months to 6 years, and four 7-month-old German shepherd dogs unrelated to the colony as controls. We imaged the distribution of functional myocardial sympathetic innervation and perfusion with [123I]metaiodobenzylguanidine (MIBG) and 201Tl, respectively. Sympathetic nerve distribution was evaluated morphologically by immunocytochemical localization of tyrosine hydroxylase. All of the hearts showed evidence of a regional decrease in MIBG uptake, ranging from 5.3% to 53.4% of the myocardium, whereas control dogs showed homogeneous MIBG uptake. Immunocytochemical studies on sections from regions with decreased MIBG uptake showed a striking paucity of nerves compared with regions with normal MIBG uptake, confirming denervation. When the dogs were grouped into those with (n=6) and without (n=5) evidence of ventricular tachycardia on ambulatory ECG, the group with ventricular tachycardia showed 35+/-16.5% denervation, whereas the group without ventricular tachycardia showed 12+/-5.6% denervation (P<.02). CONCLUSIONS: Abnormal heterogeneous sympathetic innervation exists in these dogs with inherited ventricular arrhythmia and sudden cardiac death. Mechanisms relating the presence and extent of regional denervation to the incidence of ventricular arrhythmia remain to be defined.
Assuntos
Arritmias Cardíacas/patologia , Morte Súbita Cardíaca/patologia , Coração/inervação , Sistema Nervoso Simpático/anatomia & histologia , 3-Iodobenzilguanidina , Animais , Cães , Eletrocardiografia , Coração/anatomia & histologia , Coração/diagnóstico por imagem , Coração/fisiopatologia , Iodobenzenos/metabolismo , Miocárdio/metabolismo , Cintilografia , Taquicardia Ventricular/patologiaRESUMO
BACKGROUND: Although nitric oxide seems important to cardiovascular function, the ontogenesis of this chemical messenger in the heart is unknown. To investigate this issue, we determined the distribution of nitric oxide synthase (NOS) in the rat heart at different stages during development. METHODS: Immunohistochemistry and the NADPH-diaphorase reaction were used to localize NOS activity-specifically, the endothelial isoform (eNOS) and neuronal isoform (bNOS)-in fetal (14- and 18-day gestation), neonatal (0-, 3-, and 6-day gestation), 12-day-old, 1-month-old, and mature adult Fischer 344 rat hearts. RESULTS: There was sparse eNOS immunoreactivity in the endocardium of the youngest fetal hearts; antibody to eNOS did not localize any vessels within the noncompact myocardium at this stage. By the eighteenth day of embryonic development (e18), eNOS was present not only in endocardium but also in the intima of numerous small vessels within the compact myocardium. In the neonatal rat heart, vascular eNOS predominated, with extensive reaction product in arteries, veins, and numerous capillary size vessels within the myocardium; the endocardium also contained eNOS immunoreactivity. A similar distribution was maintained throughout the remainder of development. Only rare bNOS-immunoreactive neurons were detected in hearts at the three oldest ages. CONCLUSIONS: (1) At e14, eNOS is confined to the endocardium of the developing rat heart; (2) as the myocardium becomes compact, vascular eNOS predominates over endocardial eNOS; (3) at birth, there is extensive eNOS in a distribution similar to the mature pattern; and (4) there is very little bNOS-immunoreactive neural tissue in the rat heart at any stage.