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1.
J Card Surg ; 37(9): 2592-2599, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35775747

RESUMO

BACKGROUND: Remote ischemic preconditioning (rIPC) has been applied to attenuate tissue injury. We tested the hypothesis that rIPC applied to fetal lambs undergoing cardiac bypass (CB) reduces fetal systemic inflammation and placental dysfunction. METHODS: Eighteen fetal lambs were divided into three groups: sham, CB control, and CB rIPC. CB rIPC fetuses had a hindlimb tourniquet applied to occlude blood flow for four cycles of a 5-min period, followed by a 2-min reperfusion period. Both study groups underwent 30 min of normothermic CB. Fetal inflammatory markers, gas exchange, and placental and fetal lung morphological changes were assessed. RESULTS: The CB rIPC group achieved higher bypass flow rates (p < .001). After CB start, both study groups developed significant decreases in PaO2 , mixed acidosis, and increased lactate levels (p < .0004). No significant differences in tissular edema were observed on fetal lungs and placenta (p > .391). Expression of Toll-like receptor 4 and intercellular adhesion molecule-1 in the placenta and fetal lungs did not differ among the three groups, as well as with vascular cell adhesion molecule-1 (VCAM-1) of fetal lungs (p > .225). Placental VCAM-1 expression was lower in the rIPC group (p < .05). Fetal interleukin-1 (IL-1) and thromboxane A2 (TXA2) levels were lower at 60 min post-CB in the CB rIPC group (p < .05). There were no significant differences in tumor necrosis factor-α, prostaglandin E2, IL-6, and IL-10 plasma levels of the three groups at 60-min post-bypass (p > .133). CONCLUSION: Although rIPC allowed increased blood flow during fetal CB and decreased IL-1 and TXA2 levels and placental VCAM-1, it did not prevent placental dysfunction in fetal lambs undergoing CB.


Assuntos
Precondicionamento Isquêmico , Molécula 1 de Adesão de Célula Vascular , Animais , Feminino , Feto , Interleucina-1 , Placenta , Gravidez , Ovinos
2.
Am J Respir Cell Mol Biol ; 49(6): 1019-28, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23841477

RESUMO

The pressure-loaded right ventricle (RV) adversely affects left ventricular (LV) function. We recently found that these ventricular-ventricular interactions lead to LV myocardial fibrosis through transforming growth factor-ß1 (TGF-ß1) signaling. We investigated the mechanisms mediating biventricular fibrosis in RV afterload and their potential modification by angiotensin receptor blockade. An adjustable pulmonary artery band (PAB) was placed in rabbits. In sham-operated control rabbits, the band was left uninflated (n = 6). In the RV afterload group, the PAB was sequentially inflated to generate systemic RV pressure at 28 days (n = 8). In a third group, the PAB was inflated to systemic levels, and the angiotensin receptor blocker losartan was added (n = 6). Five weeks after surgery, the animals were killed for assessments of biventricular hypertrophy, fibrosis, apoptosis, and the components of their signaling pathways. PAB animals developed biventricular hypertrophy, fibrosis, and apoptosis, versus sham rabbits, in which these conditions were decreased with losartan. RV and LV TGF-ß1, connective tissue growth factor (CTGF) (CCN2), endothelin-1 (ET-1), endothelin receptor B, and matrix metalloproteinase 2/9 mRNA levels were increased in PAB animals versus sham animals, and decreased with losartan. Given the marked biventricular CTGF up-regulation in PAB and down-regulation with losartan, we investigated CTGF signaling. RV and LV Smad 2/3/4 protein levels and LV RhoA mRNA levels were increased with PAB and reduced with losartan. In conclusion, isolated RV afterload induces biventricular fibrosis and apoptosis, which are reduced by angiotensin receptor blockade. Adverse ventricular-ventricular interactions induced by isolated RV afterload appear to be mediated through TGF-ß1-CTGF and ET-1 pathways.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Hipertensão/fisiopatologia , Fator de Crescimento Transformador beta1/fisiologia , Disfunção Ventricular Direita/fisiopatologia , Remodelação Ventricular/fisiologia , Animais , Apoptose , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Endotelina-1/genética , Endotelina-1/metabolismo , Hipertensão Pulmonar Primária Familiar , Fibrose , Hipertensão/tratamento farmacológico , Hipertensão/patologia , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Losartan/farmacologia , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Coelhos , Receptor de Endotelina B/genética , Receptor de Endotelina B/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta1/genética , Disfunção Ventricular Direita/tratamento farmacológico , Disfunção Ventricular Direita/patologia , Remodelação Ventricular/efeitos dos fármacos
3.
Thorac Cardiovasc Surg ; 60(1): 17-23, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22222683

RESUMO

BACKGROUND: An acute increase in right ventricular (RV) afterload leads to RV dilation, reduced systolic function, and low cardiac output. It has previously been shown, experimentally, that an additional increase of left ventricular afterload by aortic constriction can reverse some of these changes. We studied the clinically more relevant effects of intravenous vasopressors on this phenomenon in an animal model. METHODS: Acute RV failure was induced by pulmonary artery constriction in adult New Zealand white rabbits. We then assessed the effect of aortic constriction on the functional performance of the failing RV using conductance catheters. We compared the impact of aortic constriction on RV contractility with the effects of 0.05, 0.1, 0.5, and 1 mcg/kg × min(-1) norepinephrine and epinephrine. RESULTS: Aortic constriction lead to increased RV end-systolic pressure-volume relation (RVESPVR 3.2 (±0.6) versus 5.2 (±0.7) mm Hg/mL (p = 0.0002). Cardiac output (131 (±23.7) versus 134.8 (±32.5) mL/min), and heart rate remained unchanged. Administration of norepinephrine and epinephrine lead to similar effects on RV contractility with the maximum increase in RVESPVR observed with 0.5 mcg/kg × min(-1) norepinephrine (RVESPVR 4.8 (±0.4) mm Hg/mL, p = 0.007). However, in contrast to aortic constriction, cardiac output also markedly increased during vasopressor therapy, the most significant effect seen with 1 mcg/kg × min(-1) epinephrine (214.8 (±46.8) mL/min, p = 0.04). CONCLUSIONS: Aortic constriction improves RV contractility but not cardiac output in acute right heart failure. A comparable effect on RV functional performance with increased cardiac output was achieved by administration of systemic vasopressors. These data may have implications for management of clinical right heart failure.


Assuntos
Epinefrina/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Norepinefrina/farmacologia , Vasoconstritores/farmacologia , Disfunção Ventricular Direita/tratamento farmacológico , Função Ventricular Direita/efeitos dos fármacos , Doença Aguda , Animais , Aorta/fisiopatologia , Aorta/cirurgia , Débito Cardíaco/efeitos dos fármacos , Modelos Animais de Doenças , Epinefrina/administração & dosagem , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Infusões Intravenosas , Ligadura , Contração Miocárdica/efeitos dos fármacos , Norepinefrina/administração & dosagem , Artéria Pulmonar/cirurgia , Coelhos , Fatores de Tempo , Vasoconstritores/administração & dosagem , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/fisiopatologia
4.
PLoS One ; 15(2): e0217732, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32012157

RESUMO

BACKGROUND: Ventricle retraining has been extensively studied by our laboratory. Previous studies have demonstrated that intermittent overload causes a more efficient ventricular hypertrophy. The adaptive mechanisms involved in the ventricle retraining are not completely established. This study assessed vascular endothelial growth factor (VEGF) expression in the ventricles of goats submitted to systolic overload. METHODS: Twenty-one young goats were divided into 3 groups (7 animals each): control, 96-hour continuous systolic overload, and intermittent systolic overload (four 12-hour periods of systolic overload paired with 12-hour resting period). During the 96-hour protocol, systolic overload was adjusted to achieve a right ventricular (RV) / aortic pressure ratio of 0.7. Hemodynamic evaluations were performed daily before and after systolic overload. Echocardiograms were obtained preoperatively and at protocol end to measure cardiac masses thickness. At study end, the animals were killed for morphologic evaluation and immunohistochemical assessment of VEGF expression. RESULTS: RV-trained groups developed hypertrophy of RV and septal masses, confirmed by increased weight and thickness, as expected. In the study groups, there was a small but significantly increased water content of the RV and septum compared with those in the control group (p<0.002). VEGF expression in the RV myocardium was greater in the intermittent group (2.89% ± 0.41%) than in the continuous (1.80% ± 0.19%) and control (1.43% ± 0.18%) groups (p<0.023). CONCLUSIONS: Intermittent systolic overload promotes greater upregulation of VEGF expression in the subpulmonary ventricle, an adaptation that provides a mechanism for increased myocardial perfusion during the rapid myocardial hypertrophy of young goats.


Assuntos
Cardiomegalia/metabolismo , Artéria Pulmonar/cirurgia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Pressão Sanguínea , Cardiomegalia/cirurgia , Cabras , Ventrículos do Coração/metabolismo , Ventrículos do Coração/cirurgia , Masculino , Sístole , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/genética
5.
Artif Organs ; 33(3): 258-65, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19245525

RESUMO

We assessed a new experimental model of isolated right ventricular (RV) failure, achieved by means of intramyocardial injection of ethanol. RV dysfunction was induced in 13 mongrel dogs via multiple injections of 96% ethanol (total dose 1 mL/kg), all over the inlet and trabecular RV free walls. Hemodynamic and metabolic parameters were evaluated at baseline, after ethanol injection, and on the 14th postoperative day (POD). Echocardiographic parameters were evaluated at baseline, on the sixth POD, and on the 13th POD. The animals were then euthanized for histopathological analysis of the hearts. There was a 15.4% mortality rate. We noticed a decrease in pulmonary blood flow right after RV failure (P = 0.0018), as well as during reoperation on the 14th POD (P = 0.002). The induced RV dysfunction caused an increase in venous lactate levels immediately after ethanol injection and on the 14th POD (P < 0.0003). The echocardiogram revealed a decrease in the RV ejection fraction on the sixth and 13th PODs (P = 0.0001). There was an increased RV end-diastolic volume on the sixth (P = 0.0001) and 13th PODs (P = 0.0084). The right ventricle showed a 74% +/- 0.06% transmural infarction area, with necrotic lesions aged 14 days. Intramyocardial ethanol injection has allowed the creation of a reproducible and inexpensive model of RV failure. The hemodynamic, metabolic, and echocardiographic parameters assessed at different protocol times are compatible with severe RV failure. This model may be useful in understanding the pathophysiology of isolated right-sided heart failure, as well as in the assessment of ventricular assist devices.


Assuntos
Cães , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Animais , Modelos Animais de Doenças , Ecocardiografia , Etanol , Coração/fisiopatologia , Insuficiência Cardíaca/induzido quimicamente , Hemodinâmica , Humanos , Ácido Láctico/sangue , Masculino
6.
J Thorac Cardiovasc Surg ; 124(5): 999-1006, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12407385

RESUMO

OBJECTIVE: An experimental model with a reversible pulmonary trunk banding device was developed with the aim of inducing rapid ventricular hypertrophy. The device consists of an insufflatable cuff connected to a self-sealing button. METHODS: The right ventricles of 7 young goats (average weight, 8.7 kg) were submitted to systolic overload and evaluated according to the hemodynamic, echocardiographic, and morphologic aspects. Baseline biopsy specimens were taken from the myocardium for microscopic analysis. The device was implanted on the pulmonary trunk and inflated so that a 0.7 right ventricular/left ventricular pressure ratio was achieved. Echocardiographic and hemodynamic evaluations were performed every 24 hours. Systolic overload was maintained for 96 hours. The animals were then killed for morphologic study. Another 9 goats (average weight, 7.7 kg) were used for control right ventricular weight. RESULTS: The systolic right ventricular/pulmonary trunk pressure gradient varied from 10.1 +/- 4.3 mm Hg (baseline) to 60.0 +/- 11.0 mm Hg (final). Consequently, the right ventricular/left ventricular pressure ratio increased from 0.29 +/- 0.06 to 1.04 +/- 0.14. The protocol group showed a 74% increase in right ventricular mass when compared with the control group. Serial 2-dimensional echocardiography showed a 66% increase in right ventricular wall thickness. There was a 24% increase in the mean myocyte perimeter, and the myocyte area increased 61%. CONCLUSIONS: The device is easily adjustable percutaneously, enabling right ventricular hypertrophy in 96 hours of gradual systolic overload. This study suggests that the adjustable pulmonary trunk banding might provide better results for the 2-stage Jatene operation and for the failed atrial switch operations to convert to the double-switch operation.


Assuntos
Ventrículos do Coração/patologia , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Direita/etiologia , Valva Pulmonar/patologia , Animais , Pressão Sanguínea/fisiologia , Modelos Animais de Doenças , Ecocardiografia Doppler , Desenho de Equipamento/efeitos adversos , Cabras , Ventrículos do Coração/citologia , Ventrículos do Coração/fisiopatologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Hipertrofia Ventricular Direita/fisiopatologia , Microscopia , Modelos Cardiovasculares , Miócitos Cardíacos/metabolismo , Tamanho do Órgão/fisiologia , Valva Pulmonar/fisiopatologia , Volume Sistólico/fisiologia , Sístole/fisiologia , Função Ventricular Esquerda/fisiologia , Pressão Ventricular/fisiologia
7.
Eur J Cardiothorac Surg ; 25(2): 250-5, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14747122

RESUMO

OBJECTIVES: The natural history of tetralogy of Fallot (TOF) allows that a minority of patients reach adulthood without any treatment, representing mild forms of the disease. The aim of this study is the long-term evaluation of patients with TOF surgically treated in adulthood, in order to define its real benefit. METHODS: Between November 1982 and January 2001, 39 patients older than 18 years of age with tetralogy of Fallot underwent total correction. Mean age was 26.6 years (range 18-67) and 21 patients (53.8%) were females. A previous modified Blalock-Taussig shunt was performed in four patients (10.3%). Fifteen patients (38.5%) were in NYHA functional class III or IV. Mean hematocrit was 53.6+/-10% and the mean gradient across the right-ventricular outflow tract was 93.9+/-24.8 mmHg. The operation was performed via transatrial/transpulmonary approach in 16 patients (41%) and six patients (15.4%) required transannular patch. Pulmonary valvotomy was necessary in 13 patients (33.3%) and pulmonary valve replacement with bioprosthesis in 3 patients (7.7%). RESULTS: Hospital and late mortality were 5.1 and 7.7%, respectively. The mean follow-up was 45.1 months (range 1-194 months). Actuarial survival was 91.2+/-4.9%, 85.5+/-7.2% and 68.4+/-16.3% at 3, 7 and 15 years, respectively. In the latest follow-up, 27 (79.4%) of the survivals are presently in NYHA functional class I (P<0.001). Echocardiography has shown moderate/severe pulmonary insufficiency in 9 patients (26.5%), moderate pulmonary stenosis in 3 patients (8.8%) and residual ventricular septal defect in 4 patients (11.8%). Arrhythmias were identified in 38.9% of patients with symptoms suspicious of rhythm disturbances. There was impairment of right-ventricular function in 13 patients (38.2%). Three patients were reoperated on to close residual ventricular septal defects in two patients and for pulmonary valve replacement in one patient. CONCLUSIONS: The overall survival of surgically treated adult patients with TOF is acceptable. The great benefit of the complete repair at this age is the functional improvement. On the other hand, late complications closely related to chronic hypoxia, such as arrhythmia and ventricular dysfunction might direct for a more careful follow-up after the surgical correction.


Assuntos
Tetralogia de Fallot/cirurgia , Adolescente , Adulto , Fatores Etários , Idoso , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Reoperação , Tetralogia de Fallot/fisiopatologia , Resultado do Tratamento
8.
Ann Thorac Surg ; 95(4): 1422-8, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23434258

RESUMO

BACKGROUND: Traditional pulmonary artery banding (PAB) is not always suitable for mature subpulmonary ventricle retraining. We sought to assess in detail the myocardial morphologic adaptations of two different protocols for inducing right ventricular (RV) hypertrophy in an adult animal model. METHODS: Eighteen adult goats were distributed into three groups: sham (no systolic overload), traditional (continuous systolic overload), and intermittent (daily 12-hour systolic overload). Systolic overload was adjusted to achieve a 0.7 RV-to-aortic pressure ratio. All animals underwent weekly echocardiographic studies, and hemodynamic evaluations were performed 3 times a week. After 4 weeks, the animals were humanely killed for morphologic assessment. RESULTS: A 37.2% increase was observed in the RV wall thickness of the intermittent group (p<0.05), but no significant echocardiographic changes were observed in the other two groups. The intermittent and traditional groups had a 55.7% and 36.7% increase in RV mass, respectively, compared with the sham group (p<0.05). No differences were observed in myocardial water content of the three groups (p=0.27). RV myocardial fiber and nuclei diameters were increased in the intermittent group compared with the sham group (p<0.05). The area of collagen deposition in the RV interstitium was increased 98% in traditional group compared with the sham group (p<0.05). No significant cellular proliferation occurred in any group. CONCLUSIONS: This study suggests that a more effective and harmless hypertrophy can be achieved in adult animals using intermittent PAB compared with the traditional approach.


Assuntos
Ventrículos do Coração/fisiopatologia , Hipertrofia Ventricular Direita/terapia , Artéria Pulmonar/cirurgia , Função Ventricular Direita/fisiologia , Pressão Ventricular , Remodelação Ventricular/fisiologia , Animais , Modelos Animais de Doenças , Ecocardiografia , Cabras , Ventrículos do Coração/diagnóstico por imagem , Hipertrofia Ventricular Direita/diagnóstico por imagem , Hipertrofia Ventricular Direita/fisiopatologia , Ligadura , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/fisiopatologia , Resultado do Tratamento
9.
J Thorac Cardiovasc Surg ; 145(5): 1345-1351.e4, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-22925567

RESUMO

BACKGROUND: Ventricle retraining with abrupt systolic overload can cause myocardial edema and necrosis, followed by late ventricular failure. Intermittent systolic overload could minimize the inadequacy of conventional pulmonary artery banding. The present study compared ventricle function under dobutamine stress in 2 protocols of systolic overload in young goats. METHODS: Nineteen young goats were divided into 3 groups: sham (n = 7; no systolic pressure overload), continuous (n = 6; systolic overload maintained for 96 hours), and intermittent (n = 6; 4 periods of 12-hour systolic overload, paired with a 12-hour resting period). Echocardiographic and hemodynamic evaluations were performed daily. The myocardial performance index and ejection fraction were evaluated at rest and during dobutamine stress. The goats were then killed for morphologic evaluation. RESULTS: The intermittent group underwent less systolic overload than the continuous group (P < .05). Nevertheless, both groups had increased right ventricular and septal masses compared with the sham group (P < .0002). Echocardiography revealed a major increase in right ventricular wall thickness in the intermittent group (+64.8% ± 23.37%) compared with the continuous group (+43.9% ± 19.26%; P = .015). Only the continuous group remained with significant right ventricular dilation throughout the protocol (P < .001). The intermittent group had a significantly better myocardial performance index at the end of the protocol, under resting and dobutamine infusion, compared with the continuous group (P < .012). CONCLUSIONS: Both systolic overload protocols have induced rapid right ventricular hypertrophy. However, only the intermittent group had better preservation of right ventricular function at the end of the protocol, both at rest and during dobutamine infusion.


Assuntos
Ecocardiografia sob Estresse , Hipertrofia Ventricular Direita/diagnóstico por imagem , Artéria Pulmonar/cirurgia , Animais , Constrição , Modelos Animais de Doenças , Edema Cardíaco/diagnóstico por imagem , Edema Cardíaco/etiologia , Cabras , Hemodinâmica , Hipertrofia Ventricular Direita/etiologia , Hipertrofia Ventricular Direita/fisiopatologia , Contração Miocárdica , Artéria Pulmonar/fisiopatologia , Fatores de Tempo , Função Ventricular Direita , Pressão Ventricular
10.
J Thorac Cardiovasc Surg ; 144(6): 1494-501, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22818124

RESUMO

OBJECTIVES: Chronic right ventricular (RV) pressure overload results in pathologic RV hypertrophy and diminished RV function. Although aortic constriction has been shown to improve systolic function in acute RV failure, its effect on RV responses to chronic pressure overload is unknown. METHODS: Adjustable vascular banding devices were placed on the main pulmonary artery and descending aorta. In 5 animals (sham group), neither band was inflated. In 9 animals (PAB group), only the pulmonary arterial band was inflated, with adjustments on a weekly basis to generate systemic or suprasystemic RV pressure at 28 days. In 9 animals, both pulmonary arterial and aortic devices were inflated (PAB + AO group), the pulmonary arterial band as for the PAB group and the aortic band adjusted to increase proximal systolic blood pressure by approximately 20 mm Hg. Effects on the functional performance were assessed 5 weeks after surgery by conductance catheters, followed by histologic and molecular assessment. RESULTS: Contractile performance was significantly improved in the PAB + AO group versus the PAB group for both ventricles. Relative to sham-operated animals, both banding groups showed significant differences in myocardial histologic and molecular responses. Relative to the PAB group, the PAB + AO group showed significantly decreased RV cardiomyocyte diameter, decreased RV collagen content, and reduced RV expression of endothelin receptor type B, matrix metalloproteinase 9, and transforming growth factor ß genes. CONCLUSIONS: Aortic constriction in an experimental model of chronic RV pressure overload not only resulted in improved biventricular systolic function but also improved myocardial remodeling. These data suggest that chronically increased left ventricular afterload leads to a more physiologically hypertrophic response in the pressure-overloaded RV.


Assuntos
Aorta/efeitos dos fármacos , Insuficiência Cardíaca/cirurgia , Hipertensão Pulmonar/cirurgia , Hipertrofia Ventricular Direita/cirurgia , Função Ventricular Esquerda , Função Ventricular Direita , Pressão Ventricular , Remodelação Ventricular , Animais , Aorta/fisiopatologia , Pressão Arterial , Doença Crônica , Colágeno/metabolismo , Colagenases/metabolismo , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Constrição , Modelos Animais de Doenças , Endotelina-1/genética , Endotelina-1/metabolismo , Hipertensão Pulmonar Primária Familiar , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Hipertrofia Ventricular Direita/etiologia , Hipertrofia Ventricular Direita/metabolismo , Hipertrofia Ventricular Direita/patologia , Hipertrofia Ventricular Direita/fisiopatologia , Contração Miocárdica , Miocárdio/metabolismo , Miocárdio/patologia , Artéria Pulmonar/fisiopatologia , Artéria Pulmonar/cirurgia , Coelhos , Receptores de Endotelina/genética , Receptores de Endotelina/metabolismo , Recuperação de Função Fisiológica , Fatores de Tempo , Fator de Crescimento Transformador beta/metabolismo
11.
J Thorac Cardiovasc Surg ; 142(5): 1108-13, 1113.e1, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21907360

RESUMO

OBJECTIVE: Increased myocardial glucose-6-phosphate dehydrogenase (G6PD) activity occurs in heart failure. This study compared G6PD activity in 2 protocols of right ventricle (RV) systolic overload in young goats. METHODS: Twenty-seven goats were separated into 3 groups: sham (no overload), continuous (continuous systolic overload), and intermittent (four 12-hour periods of systolic overload paired with a 12-hour resting period). During a 96-hour protocol, systolic overload was adjusted to achieve a 0.7 RV/aortic pressure ratio. Echocardiographic and hemodynamic evaluations were performed before and after systolic overload every day postoperatively. After the study period, the animals were humanely killed for morphologic and G6PD tissue activity assessment. RESULTS: A 92.1% and 46.5% increase occurred in RV and septal mass, respectively, in the intermittent group compared with the sham group; continuous systolic overload resulted in a 37.2% increase in septal mass. A worsening RV myocardial performance index occurred in the continuous group at 72 hours and 96 hours, compared with the sham (P < .039) and intermittent groups at the end of the protocol (P < .001). Compared with the sham group, RV G6PD activity was elevated 130.1% in the continuous group (P = .012) and 39.8% in the intermittent group (P = .764). CONCLUSIONS: Continuous systolic overload for ventricle retraining causes RV dysfunction and upregulation of myocardial G6PD activity, which can elevate levels of free radicals by NADPH oxidase, an important mechanism in the pathophysiology of heart failure. Intermittent systolic overload promotes a more efficient RV hypertrophy, with better preservation of myocardial performance and and less exposure to hypertrophic triggers.


Assuntos
Glucosefosfato Desidrogenase/metabolismo , Hipertrofia Ventricular Direita/enzimologia , Miocárdio/enzimologia , Artéria Pulmonar/cirurgia , Disfunção Ventricular Direita/enzimologia , Fatores Etários , Animais , Aorta/fisiopatologia , Pressão Sanguínea , Modelos Animais de Doenças , Metabolismo Energético , Cabras , Hipertrofia Ventricular Direita/diagnóstico por imagem , Hipertrofia Ventricular Direita/etiologia , Hipertrofia Ventricular Direita/fisiopatologia , Ligadura , Miocárdio/patologia , Fatores de Tempo , Ultrassonografia , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/fisiopatologia , Função Ventricular Direita , Pressão Ventricular , Remodelação Ventricular
12.
Arq Bras Cardiol ; 95(3): 364-72, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20721519

RESUMO

BACKGROUND: Corrected transposition of great arteries often evolves with right ventricular dysfunction. The ventricular preparation for anatomic correction in adult patients has produced disappointing results. OBJECTIVE: To assess right ventricular hypertrophy (RV) induced by conventional and intermittent pulmonary banding (PB) in adult animals. METHODS: Nineteen adult goats were divided into three groups: conventional (six animals), intermittent (six animals) and control (seven animals). The Conventional group underwent fixed PB with cardiac tape, while the intermittent group received PB adjustable device, which generated systolic overload for 12 hours, alternated with 12 hours of rest of RV. The pressures of the RV, pulmonary artery and aorta were measured throughout the study. Echocardiography was performed weekly. After four weeks, the animals were euthanized for morphological evaluation of the ventricles. The Control group was put to euthanasia for analysis at baseline. RESULTS: Pressure overload was lower in the intermittent group (p = 0.001), compared to the conventional group. There was an increase in the thickness of the RV of the Intermittent group measured by echocardiography compared to their baseline values (p < 0.05). The myocardial performance index in the RV group was better in the Intermittent group (p = 0.024), compared to the Conventional group. The groups stimulated showed increased muscle mass compared to the Control group (p = 0.001). There was no difference in myocardial water content. CONCLUSION: The intermittent BP developed hypertrophy of better performance, suggesting this protocol as the preferred method of ventricular preparation.


Assuntos
Hemodinâmica/fisiologia , Hipertrofia Ventricular Direita/patologia , Artéria Pulmonar/fisiopatologia , Animais , Constrição , Feminino , Cabras , Hipertrofia Ventricular Direita/fisiopatologia , Modelos Animais , Cuidados Pré-Operatórios/métodos , Distribuição Aleatória , Sístole/fisiologia , Transposição dos Grandes Vasos/cirurgia
14.
J Thorac Cardiovasc Surg ; 133(6): 1510-6, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17532949

RESUMO

OBJECTIVES: Rapid ventricular conditioning induced by pulmonary artery banding has been recommended for patients with transposition of the great arteries who have lost the chance for the arterial switch operation or whose systemic (right) ventricle failed after the atrial switch. The present study was designed to experimentally evaluate 2 types of pulmonary artery banding (continuous and intermittent) and verify histologically the changes (hypertrophy or hyperplasia or both) of cardiomyocytes and vascular and interstitial cells from the stimulated ventricle beyond the neonatal period. METHODS: Twenty-one goats, 30 to 60 days old, were divided into 3 groups, each comprising 7 animals, as follows: control group (no surgical procedure); continuously stimulated group (systolic overload maintained for 96 hours); and intermittently stimulated group (4 periods of 12-hour systolic overload, alternated with a resting period of 12 hours). The animals were then killed for histologic and immunohistochemical analysis of the hearts. Murine monoclonal antibody Ki-67 was used as a proliferation cell marker. Myocardial collagen area fraction was determined by Sirius red staining. RESULTS: For both stimulated groups, a significant increase occurred in right ventricular cardiomyocytes and respective nuclei diameters compared with the controls (P < .05). The number of Ki-67-positive cardiomyocytes and interstitial/vessel cells from the right ventricle was augmented in both trained groups in relation to the left ventricle (P < .05). There was no significant difference in the right ventricular collagen area fraction from both trained groups compared with controls. CONCLUSIONS: Irrespective of the shorter training time (periods of overload intercalated with resting), the intermittent stimulation regimen was able to produce a similar training of the subpulmonary ventricle compared with the continuous stimulation regarding mass acquisition, cell hypertrophy, and hyperplasia.


Assuntos
Adaptação Fisiológica , Procedimentos Cirúrgicos Cardíacos/métodos , Miócitos Cardíacos/fisiologia , Artéria Pulmonar/cirurgia , Transposição dos Grandes Vasos/cirurgia , Análise de Variância , Animais , Proliferação de Células , Modelos Animais de Doenças , Ecocardiografia , Cabras , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Hiperplasia , Hipertrofia , Imuno-Histoquímica , Transposição dos Grandes Vasos/diagnóstico por imagem , Transposição dos Grandes Vasos/patologia , Transposição dos Grandes Vasos/fisiopatologia
15.
Ann Thorac Surg ; 84(6): 2081-4, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18036941

RESUMO

PURPOSE: We describe the first case in which a neonate with hypoplastic left heart syndrome was initially managed using a mini adjustable banding system. DESCRIPTION: Through a mid-sternotomy, a 5-day-old neonate underwent bilateral pulmonary artery banding using this new system, combined with placement of a main pulmonary artery to the innominate artery shunt. EVALUATION: The patient had an uneventful postoperative course. Three percutaneous adjustments of the banding system were necessary to keep the arterial oxygen saturation in the 75% to 85% range. On day 48 of life, she was submitted to stent placement (6 mm) within the atrial septum to treat a restrictive atrial septal defect. Afterward, seven additional percutaneous adjustments of the banding system were necessary. The Norwood operation and the bidirectional Glenn shunt were carried out on the day 106 of life. The bands were removed with no pulmonary artery distortion. CONCLUSIONS: The clinical use of this innovative pulmonary artery banding system was feasible, safe, and effective. This allowed for customization of the pulmonary blood flow according to the underlying clinical needs, resulting in a more precise balance between the pulmonary and systemic circulations.


Assuntos
Procedimentos Cirúrgicos Cardíacos/instrumentação , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Artéria Pulmonar/cirurgia , Feminino , Humanos , Síndrome do Coração Esquerdo Hipoplásico/fisiopatologia , Recém-Nascido , Cuidados Paliativos , Circulação Pulmonar
16.
Arq. bras. cardiol ; 95(3): 364-372, set. 2010. ilus, graf, tab
Artigo em Português | LILACS | ID: lil-560559

RESUMO

FUNDAMENTO: A transposição corrigida das grandes artérias frequentemente evolui com disfunção ventricular direita. O preparo ventricular para a correção anatômica em pacientes adultos apresenta resultados desapontadores. OBJETIVO: Analisar a hipertrofia do ventrículo direito (VD) induzida por dois tipos de bandagem pulmonar (BP), convencional e intermitente em animais adultos. MÉTODOS: Dezenove cabras adultas foram divididas em três grupos: Convencional (seis animais), Intermitente (seis animais) e Controle (sete animais). O grupo Convencional foi submetido à BP fixa com fita cardíaca, enquanto no grupo Intermitente foi usado dispositivo de BP ajustável, que gerava sobrecarga sistólica por 12 horas, alternada com 12 horas de descanso do VD. As pressões de VD, tronco pulmonar e aorta foram medidas durante todo o estudo. Ecocardiograma foi realizado semanalmente. Após quatro semanas, os animais foram eutanasiados para avaliação morfológica dos ventrículos. O grupo Controle foi submetido a eutanásia para análise em condições basais. RESULTADOS: A sobrecarga pressórica foi menor no grupo Intermitente (p=0,001), comparada ao grupo Convencional. Houve aumento na espessura do VD do grupo Intermitente, medida pelo ecocardiograma, comparado ao seu momento basal (p<0,05). O índice de performance miocárdica do VD foi melhor no grupo Intermitente (p=0,024), comparado ao Convencional. Os grupos estimulados apresentaram aumento da massa muscular em comparação ao grupo Controle (p=0,001). Não houve diferença no conteúdo de água miocárdica. CONCLUSÃO: A BP intermitente desenvolveu hipertrofia de melhor desempenho funcional, sugerindo este protocolo como método preferencial de preparo ventricular.


BACKGROUND: Corrected transposition of great arteries often evolves with right ventricular dysfunction. The ventricular preparation for anatomic correction in adult patients has produced disappointing results. OBJECTIVE: To assess right ventricular hypertrophy (RV) induced by conventional and intermittent pulmonary banding (PB) in adult animals. METHODS: Nineteen adult goats were divided into three groups: conventional (six animals), intermittent (six animals) and control (seven animals). The Conventional group underwent fixed PB with cardiac tape, while the intermittent group received PB adjustable device, which generated systolic overload for 12 hours, alternated with 12 hours of rest of RV. The pressures of the RV, pulmonary artery and aorta were measured throughout the study. Echocardiography was performed weekly. After four weeks, the animals were euthanized for morphological evaluation of the ventricles. The Control group was put to euthanasia for analysis at baseline. RESULTS: Pressure overload was lower in the intermittent group (p = 0.001), compared to the conventional group. There was an increase in the thickness of the RV of the Intermittent group measured by echocardiography compared to their baseline values (p < 0.05). The myocardial performance index in the RV group was better in the Intermittent group (p = 0.024), compared to the Conventional group. The groups stimulated showed increased muscle mass compared to the Control group (p = 0.001). There was no difference in myocardial water content. CONCLUSION: The intermittent BP developed hypertrophy of better performance, suggesting this protocol as the preferred method of ventricular preparation.


FUNDAMENTO: La transposición corregida de las grandes arterias frecuentemente evoluciona con disfunción ventricular derecha. La preparación ventricular para la corrección anatómica en pacientes adultos presenta resultados desalentadores. OBJETIVO: Analizar la hipertrofia del ventrículo derecho (VD) inducida por dos tipos de vendaje pulmonar (VP), convencional e intermitente en animales adultos. MÉTODOS: Diecinueve cabras adultas fueron divididas en tres grupos: Convencional (seis animales), Intermitente (seis animales) y Control (siete animales). El grupo Convencional fue sometido al VP fijo con cinta cardíaca, mientras que en el grupo Intermitente fue usado dispositivo de VP ajustable, que generaba sobrecarga sistólica por 12 horas, alternada con 12 horas de descanso del VD. Las presiones de VD, tronco pulmonar y aorta fueron medidas durante todo el estudio. Ecocardiograma fue realizado semanalmente. Después de cuatro semanas, los animales fueron eutanasiados para evaluación morfológica de los ventrículos. El grupo Control fue sometido a eutanasia para análisis en condiciones basales. RESULTADOS: La sobrecarga presórica fue menor en el grupo Intermitente (p=0,001), comparada al grupo Convencional. Hubo aumento en el espesor del VD del grupo Intermitente, medida por el ecocardiograma, comparado a su momento basal (p<0,05). El índice de performance miocárdica del VD fue mejor en el grupo Intermitente (p=0,024), comparado al Convencional. Los grupos estimulados presentaron aumento de la masa muscular en comparación al grupo Control (p=0,001). No hubo diferencia en el contenido de agua miocárdica. CONCLUSIÓN: EL VP intermitente desarrolló hipertrofia de mejor desempeño funcional, sugiriendo este protocolo como método preferencial de preparación ventricular.


Assuntos
Animais , Feminino , Hemodinâmica/fisiologia , Hipertrofia Ventricular Direita/patologia , Artéria Pulmonar/fisiopatologia , Constrição , Cabras , Hipertrofia Ventricular Direita/fisiopatologia , Modelos Animais , Cuidados Pré-Operatórios/métodos , Distribuição Aleatória , Sístole/fisiologia , Transposição dos Grandes Vasos/cirurgia
18.
Rev. bras. cir. cardiovasc ; 6(1): 38-44, jan.-abr. 1991. tab, graf
Artigo em Português | LILACS | ID: lil-164318

RESUMO

A diminuiçao da perfusao placentária com conseqüente distúrbio de trocas gasosas ocorre com freqüência após a circulaçao extracorpórea (CEC) fetal experimental. Com o objetivo de caracterizar a hemodinâmica placentária durante a CEC, foram colocadas em CEC sete placentas de ovelhas, isoladas in situ, através da canulaçao dos vasos umbilicais. O fluxo da CEC foi alterado de 15 a 300 ml/min/kg de peso fetal, em normotermia e hipotermia. A resistência vascular placentária (RVP) permaneceu constante durante uma pressao de perfusao e fluxo da CEC acima de 40 mmHg e 150 ml/min/kg, respectivamente. Abaixo destes valores, a relaçao da RVP com estes dois parâmetros foi inversamente proporcional. Um maior aumento da RVP foi observado durante a hipotermia. A implicaçao clínica destes achados reside no fato de que a diminuiçao do fluxo e da pressao de perfusao placentária durante a CEC pode conduzir a um ciclo vicioso, resultando em prejuízo adicional da perfusao placentária das trocas gasosas, sendo que a hipotermia agrava ainda mais esta disfunçao placentária.


Assuntos
Animais , Feminino , Gravidez , Feto/cirurgia , Gasometria , Pressão Sanguínea , Circulação Extracorpórea , Hematócrito , Placenta/fisiologia , Ovinos , Resistência Vascular
19.
Rev. bras. cir. cardiovasc ; 7(3): 157-64, jul.-set. 1992. ilus, graf
Artigo em Português | LILACS | ID: lil-164362

RESUMO

O aumento da resistência vascular placentária e distúrbios de trocas gasosas freqüentemente ocorrem após a circulaçao extracorpórea (CEC) letal. A utilizaçao de um circuito convencional de CEC que exclua a placenta da circulaçao através do clampeamento temporário do cordao umbilical pode proteger a vasculatura placentáriados estímulos que levam ao aumento da resistência vascular. Para avaliar atolerância placentária à parada normotérmica do fluxo sanguíneo umbílico-placentário, 9 placentas de ovelhas isoladas in-situ, foram colocadas em CEC através da canulaçao dos vasos umbilicais, com fluxo médio de artéria umbilical de 214 ml/min/kg. Após 30 minutos de estabelecimento da CEC, a circulaçao placentária foi interrompida por 30 minutos, simulando o clapeamento do cordao umbilical durante a CEC fetal total. Posteriormente, a circulaçao placentária foi restabelecida aos valores basais. A troca de gases placentária, o fluxo sangüíneo e a resistência vascular materno-placentários foram avaliados antes e depois da parada circulatória. Nao houve diferença estatisticamente significante entre os gradientes transplacentários de PO(2) e pCO(2') indicando que a interrupçao do fluxo sangúíneo placentário por 30 minutos, em condiçoes normotérmicas, nao afeta a funçao placentária. Este modelo sugere um método alternativo para a aplicaçao clínica da CEC letal, através da exclusao da circulaçao umbílico-piacentária durante a CEC fetal, eliminando-se, assim, os efeitos deletérios da CEC nas trocas gasosas plcentárias.


Assuntos
Humanos , Feminino , Gravidez , Feto/cirurgia , Placenta/fisiologia , Gasometria , Circulação Extracorpórea , Concentração de Íons de Hidrogênio , Microesferas , Ovinos , Resistência Vascular
20.
Rev. bras. cir. cardiovasc ; 13(3): 239-48, jul.-set. 1998. ilus, tab, graf
Artigo em Português | LILACS | ID: lil-223587

RESUMO

Um novo cateter-balao foi desenvolvido com o objetivo de induzir o preparo rápido do ventrículo pulmonar. O cateter apresenta três vias, uma para o balao e duas para medir pressoes, proximal e distal ao balao [ventrículo direito (VD) e tronco pulmonar (TP)]. Os coraçoes de 6 cabritos jovens (peso médio: 5,3 kg) foram submetidos à sobrecarga sistólica imposta pelo cateter e avaliados morfologicamente e pelo ecoardiograma. A via de saída do VD (VSVD) foi exposta através de toracotomia esquerda. Foram realizadas biópsias do miocárdio para estudos de microscopia óptica e eletrônica. O cateter-balao foi introduzido pelo VSVD e posicionado no TP. Após a convalescença pós-operatória, foi iniciado o treinamento do VD através da injeçao de 0,5 ml de água no balao. Posteriormente, volumes adicionais (0,5 ml) eram injetados no balao a cada 2 dias, causando sobrecarga sistólica progressiva. A avaliaçao ecocardiográfica foi realizada com intervalos de 1 a 2 dias. Os animais foram sacrificados após 2 a 3 semanas de treinamento do VD, para avaliaçao morfológica do coraçao. O diâmetro externo dos miócitos cardíacos, seccionados longitudinalmente, foi medido ao nível do núcleo, utilizando-se o sistema de análise de imagem (Quantimet-Leica). Secçoes de 1mu de espessura do VD foram examinados sob microscopia eletrônica para determinar a densidade de volume das mitocôndrias. O ecocardiograma revelou equalizaçao das massas musculares dos ventrículos com intervalo de 6 a 10 dias de treinamento do VD. A microscopia óptica, foi observado aumento significativo do diâmetro dos miócitos (p<0,001) e dos núcleos (p<0,003), embora sob a microscopia eletrônica nao tenha havido variaçao significativa da densidade média do volume de mitocôndrias do VD (p=0,385). O cateter-balao proposto neste trabalho permite a manipulaçao da luz do TP, possibilitando o preparo rápido e nao cirúrgico do ventrículo pulmonar e preservando a integridade anatômica das grandes artérias em pacientes com TGA.


Assuntos
Animais , Cateterismo , Pulmão/irrigação sanguínea , Ventrículos do Coração , Cabras
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