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1.
NMR Biomed ; 35(9): e4752, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35483967

RESUMO

Here, we report on the development and performance of a robust 3-T single-voxel proton magnetic resonance spectroscopy (1 H MRS) experimental protocol and data analysis pipeline for quantifying brain metabolism during cardiopulmonary bypass (CPB) surgery in a neonatal porcine model, with the overall goal of elucidating primary mechanisms of brain injury associated with these procedures. The specific aims were to assess which metabolic processes can be reliably interrogated by 1 H MRS on a 3-T clinical scanner and to provide an initial assessment of brain metabolism during deep hypothermia cardiac arrest (DHCA) surgery and recovery. Fourteen neonatal pigs underwent CPB surgery while placed in a 3-T MRI scanner for 18, 28, and 37°C DHCA studies under hyperglycemic, euglycemic, and hypoglycemic conditions. Total imaging times, including baseline measurements, circulatory arrest (CA), and recovery averaged 3 h/animal, during which 30-40 single-voxel 1 H MRS spectra (sLASER pulse sequence, TR/TE = 2000/30 ms, 64 or 128 averages) were acquired from a 2.2-cc right midbrain voxel. 1 H MRS at 3 T was able to reliably quantify (1) anaerobic metabolism via depletion of brain glucose and the associated build-up of lactate during CA, (2) phosphocreatine (PCr) to creatine (Cr) conversion during CA and subsequent recovery upon reperfusion, (3) a robust increase in the glutamine-to-glutamate (Gln/Glu) ratio during the post-CA recovery period, and (4) a broadening of the water peak during CA. In vivo 1 H MRS at 3 T can reliably quantify subtle metabolic brain changes previously deemed challenging to interrogate, including brain glucose concentrations even under hypoglycemic conditions, ATP usage via the conversion of PCr to Cr, and differential changes in Glu and Gln. Observed metabolic changes during CPB surgery of a neonatal porcine model provide new insights into possible mechanisms for prevention of neuronal injury.


Assuntos
Ponte Cardiopulmonar , Creatina , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Ponte Cardiopulmonar/métodos , Creatina/metabolismo , Glucose/metabolismo , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Hipoglicemiantes/metabolismo , Fosfocreatina/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Suínos
3.
Ann Thorac Surg ; 107(2): 512-518, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30365966

RESUMO

BACKGROUND: Mitral valve (MV) regurgitation constitutes an increasing burden of adult and pediatric cardiac disease tending to worsen over time. Whether altered mechanical forces on leaflets cause valve disease is unknown. Here we show that MV leaflet coaptive strain disruption alters expression of genes critical to leaflet homeostasis. METHODS: We used a flow-culture bioreactor of rat MVs with flow-induced cyclic coaptation (cycling valve group; n = 4) or in a sustained open state (open valve group; n = 4). After 3 days of culture, leaflet RNA expression was profiled. RESULTS: More than 48 genes exhibited markedly changed expression when coaptive leaflet strain was disrupted for 3 days (change >fourfold; p < 0.05; cycling vs open valves). Genes exhibiting highly altered expression included Angpt2, Vegf, Cd74, RT1-Da (HLA-DRA), and Igfbp3. Pathway analysis indicated the most significant signaling pathways regulating the expression changes were Hif1α and Tnfα when MV closure was disrupted. CONCLUSIONS: Disruption of normal MV coaptive strain markedly alters the expression of leaflet genes, demonstrating that cyclic strain is critically important to leaflet homeostasis. We demonstrate a pattern of MV gene expression changes in which hypoxia signaling is prominently increased in response to disrupted strain cycles. Coaptive strain regulation of MV leaflet homeostasis implicates altered strain as a mechanism potentially initiating valve disease. Early repair may prevent progression of disease driven by altered coaptation.


Assuntos
Homeostase/fisiologia , Insuficiência da Valva Mitral/metabolismo , Valva Mitral/metabolismo , RNA/genética , Animais , Fenômenos Biomecânicos , Reatores Biológicos , Células Cultivadas , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Insuficiência da Valva Mitral/genética , Insuficiência da Valva Mitral/fisiopatologia , RNA/biossíntese , Ratos , Ratos Sprague-Dawley , Estresse Mecânico
4.
J Am Heart Assoc ; 5(8)2016 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-27464792

RESUMO

BACKGROUND: Aortic valve (AV) disease presents critical situations requiring surgery in over 2% of the US population and is increasingly the reason for cardiac surgery. Throughout the AV cycle, mechanical forces of multiple types and varying intensities are exerted on valve leaflets. The mechanisms whereby forces regulate leaflet homeostasis are incompletely understood. We used a novel flow bioreactor culture to investigate alteration of AV opening or closure on leaflet genes. METHODS AND RESULTS: Culture of rat AV was conducted in a flow bioreactor for 7 days at 37°C under conditions approximating the normal stroke volume. Three force condition groups were compared: Cycling (n=8); always open (Open; n=3); or always closed (Closed; n=5). From each culture, AV leaflets were pooled by force condition and RNA expression evaluated using microarrays. Hierarchical clustering of 16 transcriptome data sets from the 3 groups revealed only 2 patterns of gene expression: Cycling and Closed groups clustered together, whereas Open AV were different (P<0.05). Sustained AV opening induced marked changes in expression (202 transcripts >2-fold; P<0.05), whereas Closed AV exhibited similar expression pattern as Cycling (no transcripts >2-fold; P<0.05). Comparison with human sclerotic and calcific AV transcriptomes demonstrated high concordance of >40 Open group genes with progression toward disease. CONCLUSIONS: Failure of AV to close initiates an extensive response characterized by expression changes common to progression to calcific aortic valve disease. AV coaptation, whether phasic or chronic, preserved phenotypic gene expression. These results demonstrate, for the first time, that coaptation of valve leaflets is a fundamentally important biomechanical cue driving homeostasis.


Assuntos
Valva Aórtica/fisiologia , Doenças das Valvas Cardíacas/genética , Homeostase/genética , Animais , Fenômenos Biofísicos , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo/genética , Feminino , Regulação da Expressão Gênica , Análise em Microsséries , Modelos Cardiovasculares , Ratos Sprague-Dawley , Estresse Mecânico , Estresse Fisiológico/fisiologia , Regulação para Cima/genética
5.
ASAIO J ; 61(4): 443-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25794246

RESUMO

Durable mechanical support in situations of physiologic single ventricle has been met with little success so far, particularly in small children. We created an animal model to investigate whether pulsatile or continuous flow would be superior. Three 1 month old sheep (10-16 kg) were instrumented. Via sternotomy and with cardiopulmonary bypass, a large ventricular septal defect and atrial septal defect were created. The left ventricle was cannulated using a Berlin Heart inflow cannula. This was connected sequentially to a continuous flow device (Thoratec HeartMate X, Pleasanton, CA) and to a pulsatile device (Berlin Heart Excor, The Woodlands, TX). Outflow was via a Y-graft to both aorta and pulmonary artery, striving for equal flow to both. Atrial filling pressures were controlled with volume infusions over a wide range. Under comparable loading conditions, significantly higher maximum flow was obtained by HeartMate X than by Excor (4.95 ± 1.27 L/min [range, 3.84-6.34 L/min] for HeartMate X vs. 1.80 ± 0.85 L/min [range, 1.01-2.7 L/min] for Excor; p < 0.05). Judging from this limited animal study, in single ventricle scenarios, continuous flow devices may achieve higher pump flows than pulsatile devices when provided with similar filling pressures. Their clinical use should be investigated. More extensive experimental studies are needed.


Assuntos
Cardiopatias Congênitas/complicações , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/cirurgia , Coração Auxiliar , Fluxo Pulsátil/fisiologia , Animais , Modelos Animais de Doenças , Projetos Piloto , Carneiro Doméstico
6.
Echocardiography ; 32 Suppl 3: S190-4, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25693623

RESUMO

Pulmonary vascular shunting poses a major clinical risk. In this brief overview, we discuss the morphological aspects of shunting vessels in the lung, their development, and the regulation of their patency.


Assuntos
Fístula Arteriovenosa/embriologia , Fístula Arteriovenosa/patologia , Artéria Pulmonar/anormalidades , Artéria Pulmonar/embriologia , Veias Pulmonares/anormalidades , Veias Pulmonares/embriologia , Humanos , Modelos Anatômicos
7.
ASAIO J ; 61(3): 332-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25635937

RESUMO

Telemetric physiological monitoring systems (TPMS) have enabled accurate continuous measurement of animal blood pressures and flows. However, few studies describe approaches for use of TPMS in the great vessels or inside the heart. We describe our initial experiences using two types of TPMSs. Twelve lambs (20-37 kg) underwent sternotomy. Two lambs were not instrumented and were killed at 14 days to confirm normal sternal wound healing (sham group, n = 2). Ten lambs underwent placement of either standard indwelling pressure-monitoring catheter and perivascular-flow-probe (CFP group, n = 3) or TPMS implantation (TPMS group, n = 7). The TPMS used were EG1-V3S2T-M2 (EG1, n = 5; Transonic Endogear Inc.) and Physio Tel Digital L21 (PTD, n = 2; Data Sciences Inc.). Two deaths because of respiratory problems occurred in TPMS group, attributed to lung compression by the implanted device. In TPMS group, more consistent trends of blood pressures and flows were recorded, and management of animals was easier and less labor-intensive. Comparing the two TPMSs, the initiation and renewal costs for each case was $28 K vs. $20 K and $1,700 vs. $0, (PTD versus EG1, respectively). In conclusion, TPMS implantation was feasible via median sternotomy in lambs. Telemetric physiological monitoring systems significantly improve reliability of hemodynamic monitoring in chronic survival animal study. EG1 was less costly than PTD.


Assuntos
Modelos Animais de Doenças , Hemodinâmica/fisiologia , Monitorização Fisiológica/métodos , Telemetria/métodos , Animais , Ovinos , Esternotomia
8.
Ann Am Thorac Soc ; 10(5): 504-8, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24161053

RESUMO

Large-diameter, intrapulmonary arteriovenous anastomoses exist in human lungs. In developing fetuses, blood flows physiologically through pulmonary arteriovenous channels that appear to regress during lung maturation. Blood flow through intrapulmonary arteriovenous anastomoses is a normal occurrence during exercise or inhalation of reduced oxygen gas mixtures in most healthy humans. However, the importance of blood flow through these anastomoses to the efficiency of pulmonary gas exchange in normal and pathological states remains controversial. Newly reported three-dimensional dissections of human lung samples provide direct anatomic evidence of intrapulmonary arteriovenous anastomoses in the lungs of prematurely born infants, and suggest that these vessels contribute consequentially to the severe arterial hypoxemia experienced by infants who die of bronchopulmonary dysplasia. Surgical construction of a cavopulmonary anastomosis can also induce pathological arteriovenous shunting suggestive of a regression to the fetal state, possibly implicating an enigmatic hepatic factor in arteriovenous shunt regulation. These two observations support an important contribution of blood flow through intrapulmonary arteriovenous anastomoses to arterial hypoxemia under at least some pathological conditions. The degree to which these vessels contribute to arterial hypoxemia in other disease states where intrapulmonary shunting is present, such as hepatopulmonary syndrome, remains unknown.


Assuntos
Anastomose Arteriovenosa/fisiopatologia , Displasia Broncopulmonar/fisiopatologia , Hipóxia/fisiopatologia , Pulmão/fisiopatologia , Circulação Pulmonar/fisiologia , Troca Gasosa Pulmonar/fisiologia , Anastomose Arteriovenosa/fisiologia , Humanos , Pulmão/irrigação sanguínea , Pulmão/fisiologia
9.
J Thorac Cardiovasc Surg ; 145(6): 1460-4, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22944083

RESUMO

OBJECTIVE: Fetal cardiac surgery is a potential innovative treatment for certain congenital heart defects that have significant mortality and morbidity in utero or after birth, but it has been limited by placental dysfunction after fetal cardiac bypass. We have used the TinyPump device for fetal cardiac bypass in sheep fetuses at 90 to 110 days gestation. METHODS: Ten mixed-breed pregnant ewes were used over a period of 6 months, and 10 fetuses were placed on bypass for 30 minutes. Five fetuses with a mean gestational age of 104 ± 4.5 days and mean weight of 1.4 ± 0.4 kg were placed on bypass using the TinyPump device, and 5 fetuses with a mean gestational age of 119 ± 4.5 days and mean weight of 3.4 ± 0.4 kg were placed on bypass using the roller head pump. The fetuses were monitored for up to 3 hours after bypass or until earlier demise. RESULTS: Progressive respiratory and metabolic acidosis developed in all fetuses. The TinyPump group had a lower gestational age and weight compared with the roller head pump group. However, the rate of postbypass deterioration in the TinyPump group, as measured with blood gases, was noted to be significantly slower compared with the roller head pump group. CONCLUSIONS: We demonstrate the feasibility of the TinyPump device for fetal cardiac bypass in a fetal sheep model. The TinyPump group showed improved results compared with the roller head group despite more immature fetuses. The TinyPump device seems to be a promising device for future studies of fetal cardiac bypass in immature fetal sheep and in primates.


Assuntos
Ponte Cardiopulmonar/instrumentação , Coração Fetal/cirurgia , Coração Auxiliar , Animais , Feminino , Gravidez , Resultado da Gravidez , Ovinos
10.
J Thorac Cardiovasc Surg ; 144(4): 963-969.e1; discussion 969, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22917684

RESUMO

OBJECTIVES: This study investigated the time-dependent remodeling and growth potential of porcine small intestine submucosa as a biomaterial for the reconstruction of pulmonary arteries in a lamb model. METHODS: Left pulmonary arteries were partially replaced with small intestine submucosal biomaterial in 6 lambs. Two animals each were humanely killed at 1, 3, and 6 months. Computed tomographic angiography, macroscopic examination of the implanted patch, and microscopic analysis of tissue explants were performed. RESULTS: All animals survived without complications. Patency and arborization of the pulmonary arteries were detected 6 months after implantation. There was no macroscopic narrowing or aneurysm formation in the patch area. The luminal appearance of the patch was similar to the intimal layer of the adjacent native pulmonary artery. Scanning electron microscopy showed that the luminal surface of the patch was covered by confluent cells. Immunohistochemical examination confirmed endothelialization of the luminal side of the patch in all of the explanted patches. The presence of smooth muscle cells in the medial layer was confirmed at all time points; however, expression of elastin, growth of the muscular layer, and complete degradation of patch material were detectable only after 6 months. The presence of c-Kit-positive cells suggests migration of multipotent cells into the patch, which may play a role in remodeling the small intestine submucosal biomaterial. CONCLUSIONS: Our data confirmed that remodeling and growth potential of the small intestine submucosal biomaterial are time dependent. Additional experiments are required to investigate the stability of the patch material over a longer period.


Assuntos
Bioprótese , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Mucosa Intestinal/transplante , Intestino Delgado/transplante , Artéria Pulmonar/cirurgia , Animais , Animais Recém-Nascidos , Biomarcadores/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/ultraestrutura , Imuno-Histoquímica , Mucosa Intestinal/crescimento & desenvolvimento , Intestino Delgado/crescimento & desenvolvimento , Microscopia Eletrônica de Varredura , Modelos Animais , Células-Tronco Multipotentes/metabolismo , Células-Tronco Multipotentes/ultraestrutura , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/ultraestrutura , Desenho de Prótese , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/crescimento & desenvolvimento , Artéria Pulmonar/metabolismo , Artéria Pulmonar/ultraestrutura , Ovinos , Suínos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Transplante Heterólogo , Grau de Desobstrução Vascular
11.
Ann Thorac Surg ; 93(4): 1311-5, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22450088

RESUMO

In this case report, we evaluated cellular structure and the growth potential of a porcine small intestinal submucosal patch used for pulmonary artery augmentation in a 20-day-old newborn with pulmonary atresia. The patch was resected 2 months postoperatively due to apparent abnormal wall thickening and evaluated by histologic and immunohistologic staining.


Assuntos
Intestino Delgado/transplante , Artéria Pulmonar/cirurgia , Atresia Pulmonar/cirurgia , Animais , Remoção de Dispositivo , Matriz Extracelular/patologia , Matriz Extracelular/transplante , Feminino , Cardiopatias Congênitas/cirurgia , Humanos , Recém-Nascido , Intestino Delgado/patologia , Mucosa/transplante , Artéria Pulmonar/patologia , Procedimentos de Cirurgia Plástica , Reoperação , Suínos
12.
ASAIO J ; 58(1): 60-4, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22210652

RESUMO

Single ventricle congenital heart defects are usually palliated with the end result of a Fontan circulation. Despite improving results, this circulation is still associated with long-term failure. We previously developed an animal model of mechanical cavopulmonary circulation support that was successful in the acute and mid-term period. In the current study, we evaluated longer support durations in five Western-breed sheep. Through a right thoracotomy we instituted mechanical support from the inferior vena cava to the pulmonary artery, using a Heartmate II axial flow pump (Thoratec Corp., Pleasanton, CA). Postoperatively, the animals were anticoagulated with heparin iv. Hemodynamics, pump flow, anticoagulation, and hepatic and renal function were monitored daily. All animals survived the operation. Signs of moderate liver and kidney injury in general reversed quickly. Two animals had a fatal pump thrombosis. When anticoagulation was effective, hemodynamics and pump flow were maintained to normal values. Effective anticoagulation was difficult to achieve because of the high variability in response to heparin. Survival up to 18 days was accomplished. This study is the longest reported survival of animals with a mechanically assisted cavopulmonary circulation. The performance of the Thoratec Heartmate II has been good, but the issue of effective anticoagulation has not yet been solved.


Assuntos
Técnica de Fontan/métodos , Insuficiência Cardíaca/cirurgia , Animais , Anticoagulantes/uso terapêutico , Átrios do Coração/patologia , Cardiopatias Congênitas/cirurgia , Insuficiência Cardíaca/fisiopatologia , Coração Auxiliar , Hemodinâmica , Humanos , Modelos Animais , Modelos Cardiovasculares , Artéria Pulmonar , Ovinos , Fatores de Tempo , Resultado do Tratamento
13.
Artif Organs ; 34(11): 980-6, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21092040

RESUMO

The aim of this study is to evaluate the effect of temperature on cerebral oxygen metabolism at total body flow bypass and antegrade cerebral perfusion (ACP). Neonatal piglets were put on cardiopulmonary bypass (CPB) with the initial flow rate of 200mL/kg/min. After cooling to 18°C (n=6) or 25°C (n=7), flow was reduced to 100mL/kg/min (half-flow, HF) for 15min and ACP was initiated at 40mL/kg/min for 45min. Following rewarming, animals were weaned from bypass and survived for 4h. At baseline, HF, ACP, and 4 h post-CPB, cerebral blood flow (CBF) was measured using fluorescent microspheres. Cerebral oxygen extraction (CEO(2) ) and cerebral metabolic rate of oxygen (CMRO(2) ) were monitored. Regional cranial oxygen saturation (rSO(2) ) was continuously recorded throughout the procedure using near-infrared spectroscopy. At 18°C, CBF trended lower at HF and ACP and matched baseline after CPB. CEO(2) trended lower at HF and ACP, and trended higher after CPB compared with baseline. CMRO(2) at ACP matched that at HF. Cranial rSO(2) was significantly greater at HF and ACP (P<0.001, P<0.001) and matched baseline after CPB. At 25°C, CBF trended lower at HF, rebounded and trended higher at ACP, and matched baseline after CPB. CEO(2) was equal at HF and ACP and trended higher after CPB compared with baseline. CMRO(2) at ACP was greater than that at HF (P=0.001). Cranial rSO(2) was significantly greater at HF (P=0.01), equal at ACP, and lower after CPB (P=0.03). Lactate was significantly higher at all time points (P=0.036, P<0.001, and P<0.001). ACP provided sufficient oxygen to the brain at a total body flow rate of 100mL/kg/min at deep hypothermia. Although ACP provided minimum oxygenation to the brain which met the oxygen requirement, oxygen metabolism was altered during ACP at moderate hypothermia. ACP strategy at moderate hypothermia needs further investigation.


Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Ponte Cardiopulmonar , Circulação Cerebrovascular , Hipotermia Induzida , Consumo de Oxigênio , Oxigênio/sangue , Perfusão , Animais , Animais Recém-Nascidos , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Ácido Láctico/sangue , Espectrometria de Fluorescência , Espectroscopia de Luz Próxima ao Infravermelho , Suínos , Fatores de Tempo
14.
J Thorac Cardiovasc Surg ; 139(3): 530-5; discussion 535, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20176202

RESUMO

OBJECTIVE: Antegrade cerebral perfusion is widely used in neonatal heart surgery, yet commonly used flow rates have never been standardized. The objective of this study was to determine the antegrade cerebral perfusion flow rate that most closely matches standard cardiopulmonary bypass conditions. METHODS: Nine neonatal piglets underwent deep hypothermic cardiopulmonary bypass at a total body flow of 100 mL/kg/min (baseline). Antegrade cerebral perfusion was conducted via innominate artery cannulation at perfusion rates of 10, 30, and 50 mL/kg/min in random order. Cerebral blood flow was measured using fluorescent microspheres. Regional oxygen saturation and cerebral oxygen extraction were monitored. RESULTS: Cerebral blood flow was as follows: baseline, 60 +/- 17 mL/100 g/min; antegrade cerebral perfusion at 50 mL/kg/min, 56 +/- 17 mL/100 g/min; antegrade cerebral perfusion at 30 mL/kg/min, 36 +/- 9 mL/100 g/min; and antegrade cerebral perfusion at 10 mL/kg/min, 13 +/- 6 mL/100 g/min. At an antegrade cerebral perfusion rate of 50 mL/kg/min, cerebral blood flow matched baseline (P = .87), as did regional oxygen saturation (P = .13). Antegrade cerebral perfusion at 30 mL/kg/min provided approximately 60% of baseline cerebral blood flow (P < .002); however, regional oxygen saturation was equal to baseline (P = .93). Antegrade cerebral perfusion at 10 mL/kg/min provided 20% of baseline cerebral blood flow (P < .001) and a lower regional oxygen saturation than baseline (P = .011). Cerebral oxygen extraction at antegrade cerebral perfusion rates of 30 and 50 mL/kg/min was equal to baseline (P = .53, .48) but greater than baseline (P < .0001) at an antegrade cerebral perfusion rate of 10 mL/kg/min. The distributions of cerebral blood flow and regional oxygen saturation were equal in each brain hemisphere at all antegrade cerebral perfusion rates. CONCLUSION: Cerebral blood flow increased with antegrade cerebral perfusion rate. At an antegrade cerebral perfusion rate of 50 mL/kg/min, cerebral blood flow was equal to baseline, but regional oxygen saturation and cerebral oxygen extraction trends suggested more oxygenation than baseline. An antegrade cerebral perfusion rate of 30 mL/kg/min provided only 60% of baseline cerebral blood flow, but cerebral oxygen extraction and regional oxygen saturation were equal to baseline. An antegrade cerebral perfusion rate that closely matches standard cardiopulmonary bypass conditions is between 30 and 50 mL/kg/min.


Assuntos
Circulação Cerebrovascular , Perfusão/métodos , Perfusão/normas , Animais , Animais Recém-Nascidos , Fluxo Sanguíneo Regional , Suínos
15.
J Card Surg ; 24(5): 606-10, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19740304

RESUMO

BACKGROUND: Neurologic injury is a feared and serious long-term complication of cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). Postoperative hyperthermia was found to enhance postischemic neurologic injury. The use of core temperature as the reference point through CPB assumes parallel changes in brain temperature. We tested the hypothesis that regional and deep brain temperature (DBT) differ during cooling, DHCA, and rewarming. METHODS: Neonatal piglets (n = 9) were subject to CPB and cooled to rectal temperature (RT) of 18 degrees C, 30 minutes of DHCA were initiated, and subsequently the piglets were rewarmed to RT of 36.5 degrees C and weaned from CPB. Temperature probes were inserted into the DBT targeting the caudate and thalamic nuclei, their position confirmed by pathology. Superficial brain temperature was measured by a temperature probe inserted extradurally. RT, nasopharyngeal (NPT), and tympanic (TT) temperatures were recorded. RESULTS: During cooling the deep brain cooled faster and to lower temperatures compared to RT and TT; NPT reflected DBT accurately. During rewarming DBT was significantly higher than RT and TT. By the end of rewarming the difference between the deep brain and the RT reached statistical significance (30 minutes: 35.1 +/- 0.7 vs. 32.3 +/- 0.7 p < 0.05, respectively, 40 minutes: 37.5 +/- 0.3 vs. 34.7 +/- 0.8 p < 0.05, respectively). CONCLUSION: Deep brain hyperthermia routinely occurs during the last stages of rewarming following DHCA. DBT is accurately reflected by NPT and is directly correlated with inflow temperature. Therefore, during rewarming inflow temperatures should not exceed 36 degrees C and NPT should be closely monitored.


Assuntos
Encefalopatias/etiologia , Parada Circulatória Induzida por Hipotermia Profunda/efeitos adversos , Febre/etiologia , Análise de Variância , Animais , Temperatura Corporal , Ponte Cardiopulmonar , Consumo de Oxigênio , Reto , Fatores de Risco , Suínos , Membrana Timpânica
16.
ASAIO J ; 55(4): 406-11, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19471161

RESUMO

Total cavopulmonary connection (CPC) has a significant incidence of late failure due to increased systemic venous pressure and low cardiac output. Mechanical support could prevent failure by correcting hemodynamics. We established a model of inferior CPC using an axial flow pump (Thoratec HeartMate II, Thoratec Corp. Pleasanton, CA) in a group of ten 47-57 kg sheep and assessed hemodynamics and metabolism as a potential chronic treatment option for failed Fontan circulation. After pilot studies (n = 7), three animals underwent pump-supported inferior CPC to assess hemodynamic and metabolic responses. Pump inflow was connected to the inferior vena cava (IVC) and outflow to the main pulmonary artery. The IVC was ligated at the right atrium. Hemodynamic and biochemical parameters were recorded over four days. The first seven animals died from pump-related causes (graft kinking, three; pump thrombosis, one) or other causes (GI bleeding, one; suspected stroke, two). The subsequent three animals were electively euthanized on postoperative day four due to IRB requirements. Over the four day postoperative period, pump flow was 3.43 +/- 0.62 L/min and IVC pressure 4.05 +/- 3.21 mm Hg (mean +/- SD). Lactate levels remained normal. Low pressure and high-volume IVC flow was sustained by mechanical support. We will next attempt chronic pump implantation.


Assuntos
Hemodinâmica , Artéria Pulmonar/patologia , Veia Cava Inferior/fisiopatologia , Animais , Anticoagulantes/farmacologia , Técnica de Fontan/métodos , Átrios do Coração/patologia , Coração Auxiliar , Perfusão , Pressão , Ovinos , Estresse Mecânico , Trombose , Fatores de Tempo , Resultado do Tratamento
17.
Ann Thorac Surg ; 86(4): 1311-9, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18805183

RESUMO

BACKGROUND: Pluripotent cardiac progenitor cells resident in myocardium offer a potentially promising role in promoting recovery from injury. In pediatric congenital heart disease (CHD) patients, manipulation of resident progenitor cells may provide important new approaches to improving outcomes. Our study goals were to identify and quantitate populations of progenitor cells in human neonatal myocardium during the early postnatal period and determine the proliferative capacity of differentiated cardiac myocytes. METHODS: Immunologic markers of cell lineage (stage-specific embryonic antigen 4 [SSEA-4], islet cell antigen 1 [Isl1], c-kit, Nkx2.5, sarcoplasmic reticulum calcium-regulated ATPase type 2 [SERCA2]) and proliferation (Ki67) were localized in right ventricular biopsies from 32 CHD patients aged 2 to 93 days. RESULTS: Neonatal myocardium contains progenitor cells and transitional cells expressing progenitor and differentiated myocyte marker proteins. Some cells expressed the pluripotent cell marker c-kit and also coexpressed the myocyte marker SERCA2. Multipotent progenitor cells, identified by the expression of Isl1, were found. Ki67 was expressed in some myocytes and in nonmyocyte cells. A few cells expressing SSEA-4 and Isl1 were observed during the early postnatal period. Cells expressing c-kit, the premyocyte marker Nkx2.5, and Ki67 were found throughout the first postnatal month. A progressive decline in cell density during the first postnatal month was observed for c-kit+ cells (p = 0.0013) and Nkx2.5+ cells (p = 0.0001). The percentage of cells expressing Ki67 declined during the first 3 postnatal months (p = 0.0030). CONCLUSIONS: Cells in an incomplete state of cardiomyocyte differentiation continue to reside in the infant heart. However, the relative density of progenitor cells declines during the first postnatal month.


Assuntos
Proliferação de Células , Miócitos Cardíacos/fisiologia , Proteínas Proto-Oncogênicas c-kit/fisiologia , Regeneração/fisiologia , Células-Tronco/fisiologia , Análise de Variância , Procedimentos Cirúrgicos Cardíacos , Células Cultivadas , Feminino , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/cirurgia , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Masculino , Miócitos Cardíacos/patologia , Probabilidade , Proteínas Proto-Oncogênicas c-kit/metabolismo , Sensibilidade e Especificidade , Células-Tronco/patologia
18.
J Thorac Cardiovasc Surg ; 132(6): 1307-13, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17140947

RESUMO

OBJECTIVES: Regional low-flow perfusion has been used to minimize ischemic brain injury during complex heart surgery in children. However, optimal regional low-flow perfusion remains undetermined. Visible light spectroscopy is a reliable method for continuous determination of capillary oxygen saturation (SgvO2). We used visible light spectroscopy to follow deep and superficial brain SgvO2 during cardiopulmonary bypass, regional low-flow perfusion, and deep hypothermic circulatory arrest. METHODS: Visible light spectroscopy probes were inserted into the superficial and deep brain of neonatal (3.9-4.5 kg) piglets, targeting the caudate and thalamic nuclei. The piglets were subjected to cardiopulmonary bypass and cooled to a rectal temperature of 18 degrees C using pH stat. Regional low-flow perfusion was initiated through the innominate artery at 18 degrees C, and pump flows were adjusted to 40, 30, 20, and 10 mL/kg/min for 10-minute intervals followed by 30 minutes of deep hypothermic circulatory arrest. Regional low-flow perfusion was reestablished, and flows were increased in a stepwise manner from 10 to 40 mL/kg/min. SgvO2 was continuously monitored. Carotid flow was measured using a flow probe, and cerebral blood flow (milliliters per kilogram body weight per minute) was calculated. RESULTS: There were no significant differences between the deep and superficial brain tissue oxygenation during regional low flow brain perfusion before deep hypothermic circulatory arrest. However, after deep hypothermic circulatory arrest, the superficial brain SgvO2 was lower than the deep brain SgvO2 (24 +/- 12 vs 55.3 +/- 8, P = .05, at flows of 30 mL/kg/min, and 34.2 +/- 17 vs 62.5 + 8, P = .06, at a flow rate of 40 mL/kg/min). During regional low-flow perfusion, SgvO2 was maintained at flows of 30 to 40 mL/kg/min (cerebral blood flows of 15 to 21 mL/kg/min and 19 to 24 mL/kg/min, respectively), but was significantly lower at pump flows of 20 mL/kg/min (cerebral blood flow of 10 to 14 mL/kg/min) and 10 mL/kg/min (cerebral blood flow of 5 to 9 mL/kg/min) compared with the values obtained just before regional low-flow perfusion (pre-deep hypothermic circulatory arrest, 37 +/- 6 vs 65.5 +/- 4.4, P < .05, and 21.6 +/- 3.7 vs 65.5 +/- 4.4, P < .01, respectively; and post-deep hypothermic circulatory arrest, 32 +/- 4.5 vs 65.5 +/- 4.4, P < .05, and 16.6 +/- 4.7 vs 65.5 +/- 4.4, P < .01, respectively). CONCLUSIONS: Regional low-flow perfusion at pump flows of 30 to 40 mL/kg/min with resulting cerebral blood flows of 14 to 24 mL/kg/min was adequate in maintaining both deep and superficial brain oxygenation. However, lower pump flows of 20 and 10 mL/kg/min, associated with cerebral blood flow of 9 to 14 mL/kg/min, resulted in significantly reduced SgvO2 values.


Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Parada Circulatória Induzida por Hipotermia Profunda , Oximetria/métodos , Oxigênio/metabolismo , Animais , Animais Recém-Nascidos , Circulação Cerebrovascular , Oxigênio/análise , Perfusão , Fluxo Sanguíneo Regional , Análise Espectral , Suínos
19.
J Thorac Cardiovasc Surg ; 131(3): 659-65, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16515920

RESUMO

OBJECTIVE: Neonates with congenital heart disease might require surgical repair with deep hypothermic circulatory arrest, a technique associated with adverse neurodevelopmental outcomes. Antegrade cerebral perfusion is thought to minimize ischemic brain injury, although there are no supporting experimental data. We sought to evaluate and compare the extent of neurologic injury in a neonatal piglet model of deep hypothermic circulatory arrest and antegrade cerebral perfusion. METHODS: Neonatal piglets undergoing cardiopulmonary bypass were randomized to deep hypothermic circulatory arrest or antegrade cerebral perfusion for 45 minutes. Animals were killed after 6 hours of recovery, and brain tissue was stained for evidence of cellular injury and for the apoptotic markers activated caspase 3 and cytochrome c translocation from mitochondria to cytosol. RESULTS: Piglets from the antegrade cerebral perfusion group exhibited less apoptotic or necrotic injury (4 +/- 3 vs 29 +/- 12 cells per field, P = .03). The piglets undergoing antegrade cerebral perfusion also had less evidence of apoptosis, with fewer cells staining for activated caspase 3 (57 +/- 8 vs 93 +/- 9 cells per field, P = .001) or showing cytochrome c translocation (6 +/- 2 vs 15 +/- 4 cells per field, P = .02). CONCLUSIONS: The use of antegrade cerebral perfusion in place of deep hypothermic circulatory arrest reduces evidence of apoptosis and histologic injury in neonatal piglets. Neonates with congenital heart disease might benefit from antegrade cerebral perfusion during complex cardiac surgery to improve their overall neurologic outcome.


Assuntos
Isquemia Encefálica/patologia , Isquemia Encefálica/prevenção & controle , Ponte Cardiopulmonar/efeitos adversos , Neurônios/patologia , Animais , Animais Recém-Nascidos , Apoptose , Isquemia Encefálica/etiologia , Modelos Animais , Perfusão , Suínos
20.
Ann Thorac Surg ; 80(5): 1955-64, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16242503

RESUMO

Deep hypothermic circulatory arrest (DHCA) has been used for the past 50 years in the surgical repair of complex congenital cardiac malformations and operations involving the aortic arch; it enables the surgeon to achieve precise anatomical reconstructions by creating a bloodless operative field. Nevertheless, DHCA has been associated with immediate and late neurodevelopmental morbidities. This review provides an overview of the pathophysiology of neonatal hypoxic brain injury after DHCA, focusing on cellular mechanisms of necrosis, apoptosis, and glutamate excitotoxicity. Techniques and strategies in neonatal brain protection include hypothermia, acid base blood gas management during cooling, and pharmacologic interventions such as the use of volatile anesthetics. Surgical techniques consist of intermittent cerebral perfusion during periods of circulatory arrest and continuous regional brain perfusion.


Assuntos
Parada Circulatória Induzida por Hipotermia Profunda/efeitos adversos , Hipóxia Encefálica/fisiopatologia , Adulto , Animais , Morte Celular , Parada Circulatória Induzida por Hipotermia Profunda/métodos , Cardiopatias Congênitas/cirurgia , Humanos , Hipóxia Encefálica/etiologia , Hipóxia Encefálica/prevenção & controle , Lactente , Recém-Nascido
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