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1.
Medicina (Kaunas) ; 58(2)2022 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-35208603

RESUMO

Background and Objectives: The cardioplegic arrest of the heart during cardiosurgical procedures is the crucial element of a cardioprotection strategy. Numerous clinical trials compare different cardioplegic solutions and cardioprotective protocols, but a relatively small number of papers apply to in vitro conditions using cultured cells. This work aimed to analyze whether it is possible to use the rat heart myocardium cells as an in vitro model to study the protective properties of St. Thomas cardioplegia (ST2C). Methods: The rat heart myocardium cells-H9C2 were incubated with cold cardioplegia for up to 24 h. After incubation, we determined: viability, confluency, and cell size, the thiol groups' level by modifying Ellman's method, Ki67, and Proliferating Cell Nuclear Antigen expression (PCNA). The impact on cells' morphology was visualized by the ultrastructural (TEM) study and holotomograpic 3D imaging. Results: The viability and confluency analysis demonstrated that the safest exposure to ST2C, should not exceed 4h. An increased expression of Ki67 antigen and PCNA was observed. TEM and 3D imaging studies revealed vacuolization after the longest period of exposure (24). Conclusions: According to obtained results, we conclude that STC can play a protective role in cardiac surgery during heart arrest.


Assuntos
Parada Cardíaca Induzida , Miocárdio , Animais , Soluções Cardioplégicas/química , Soluções Cardioplégicas/metabolismo , Soluções Cardioplégicas/farmacologia , Coração , Parada Cardíaca Induzida/métodos , Mioblastos , Miocárdio/metabolismo , Ratos
2.
Amino Acids ; 51(10-12): 1667-1680, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31712921

RESUMO

The unique capability of proton buffering is the rationale for using histidine (HIS) as a component of solutions for induction of cardiac arrest and myocardial protection in cardiac surgery. In humans, infusion of cardioplegic solution may increase blood plasma HIS from ~ 70 to ~ 21,000 µM. We examined the effects of a large intravenous dose of HIS on ammonia and amino acid concentrations and energy status of the body. Rats received 198 mM HIS intravenously (20 ml/kg) or vehicle. Samples of blood plasma, urine, liver, and soleus (SOL) and extensor digitorum longus (EDL) muscles were analysed at 2 or 24 h after treatment. At 2 h after HIS load, we found higher HIS concentration in all examined tissues, higher urea and ammonia concentrations in blood and urine, lower ATP content and higher AMP/ATP ratio in the liver and muscles, higher concentrations of almost all examined amino acids in urine, and lower glycine concentration in blood plasma, liver, and muscles when compared with controls. Changes in other amino acids were tissue dependent, markedly increased alanine and glutamate in the blood and the liver. At 24 h, the main findings were lower ATP concentrations in muscles, lower concentrations of branched-chain amino acids (BCAA; valine, leucine, and isoleucine) in blood plasma and muscles, and higher carnosine content in SOL when compared with controls. It is concluded that a load of large HIS dose results in increased ammonia levels and marked alterations in amino acid and energy metabolism. Pathogenesis is discussed in the article.


Assuntos
Nucleotídeos de Adenina/metabolismo , Aminoácidos/metabolismo , Amônia/metabolismo , Histidina/metabolismo , Administração Intravenosa , Aminoácidos/química , Animais , Soluções Cardioplégicas/química , Carnosina/metabolismo , Metabolismo Energético , Histidina/administração & dosagem , Histidina/análise , Ácidos Cetoglutáricos/metabolismo , Masculino , Especificidade de Órgãos , Ratos , Ratos Wistar , Distribuição Tecidual , Ureia/metabolismo
3.
Braz J Cardiovasc Surg ; 33(3): 211-216, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30043912

RESUMO

OBJECTIVE: The present study aimed the functional recovery evaluation after long term of cardiac arrest induced by Custodiol (crystalloid-based) versus del Nido (blood-based) solutions, both added lidocaine and pinacidil as cardioplegic agents. Experiments were performed in isolated rat heart perfusion models. METHODS: Male rat heart perfusions, according to Langendorff technique, were induced to cause 3 hours of cardiac arrest with a single dose. The hearts were assigned to one of the following three groups: (I) control; (II) Custodiol-LP; and (III) del Nido-LP. They were evaluated after ischemia throughout 90 minutes of reperfusion. Left ventricular contractility function was reported as percentage of recovery, expressed by developed pressure, maximum dP/dt, minimum dP/dt, and rate pressure product variables. In addition, coronary resistance and myocardial injury marker by alpha-fodrin degradation were also evaluated. RESULTS: At 90 minutes of reperfusion, both solutions had superior left ventricular contractile recovery function than the control group. Del Nido-LP was superior to Custodiol-LP in maximum dP/dt (46%±8 vs. 67%±7, P<0.05) and minimum dP/dt (31%±4 vs. 51%±9, P<0.05) variables. Coronary resistance was lower in del Nido-LP group than in Custodiol-LP (395%±50 vs. 307%±13, P<0.05), as well as alpha-fodrin degradation, with lower levels in del Nido-LP group (P<0.05). CONCLUSION: Del Nido-LP cardioplegia showed higher functional recovery after 3 hours of ischemia. The analysis of alpha-fodrin degradation showed del Nido-LP solution provided greater protection against myocardial ischemia and reperfusion (IR) in this experimental model.


Assuntos
Soluções Cardioplégicas/farmacologia , Parada Cardíaca Induzida/métodos , Lidocaína/farmacologia , Reperfusão Miocárdica/métodos , Pinacidil/farmacologia , Compostos de Potássio/farmacologia , Animais , Western Blotting , Soluções Cardioplégicas/química , Proteínas de Transporte/análise , Vasos Coronários/fisiopatologia , Glucose/química , Glucose/farmacologia , Coração/efeitos dos fármacos , Masculino , Manitol/química , Manitol/farmacologia , Proteínas dos Microfilamentos/análise , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Cloreto de Potássio/química , Cloreto de Potássio/farmacologia , Compostos de Potássio/química , Procaína/química , Procaína/farmacologia , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Tempo , Resistência Vascular/fisiologia , Função Ventricular Esquerda/fisiologia
4.
Rev. bras. cir. cardiovasc ; 33(3): 211-216, May-June 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-958403

RESUMO

Abstract Objective: The present study aimed the functional recovery evaluation after long term of cardiac arrest induced by Custodiol (crystalloid-based) versus del Nido (blood-based) solutions, both added lidocaine and pinacidil as cardioplegic agents. Experiments were performed in isolated rat heart perfusion models. Methods: Male rat heart perfusions, according to Langendorff technique, were induced to cause 3 hours of cardiac arrest with a single dose. The hearts were assigned to one of the following three groups: (I) control; (II) Custodiol-LP; and (III) del Nido-LP. They were evaluated after ischemia throughout 90 minutes of reperfusion. Left ventricular contractility function was reported as percentage of recovery, expressed by developed pressure, maximum dP/dt, minimum dP/dt, and rate pressure product variables. In addition, coronary resistance and myocardial injury marker by alpha-fodrin degradation were also evaluated. Results: At 90 minutes of reperfusion, both solutions had superior left ventricular contractile recovery function than the control group. Del Nido-LP was superior to Custodiol-LP in maximum dP/dt (46%±8 vs. 67%±7, P<0.05) and minimum dP/dt (31%±4 vs. 51%±9, P<0.05) variables. Coronary resistance was lower in del Nido-LP group than in Custodiol-LP (395%±50 vs. 307%±13, P<0.05), as well as alpha-fodrin degradation, with lower levels in del Nido-LP group (P<0.05). Conclusion: Del Nido-LP cardioplegia showed higher functional recovery after 3 hours of ischemia. The analysis of alpha-fodrin degradation showed del Nido-LP solution provided greater protection against myocardial ischemia and reperfusion (IR) in this experimental model.


Assuntos
Animais , Masculino , Soluções Cardioplégicas/farmacologia , Reperfusão Miocárdica/métodos , Compostos de Potássio/farmacologia , Pinacidil/farmacologia , Parada Cardíaca Induzida/métodos , Lidocaína/farmacologia , Fatores de Tempo , Resistência Vascular/fisiologia , Soluções Cardioplégicas/química , Proteínas de Transporte/análise , Western Blotting , Ratos Wistar , Vasos Coronários/fisiopatologia , Glucose/farmacologia , Glucose/química , Coração/efeitos dos fármacos , Manitol/farmacologia , Manitol/química , Proteínas dos Microfilamentos/análise
5.
Nat Protoc ; 12(12): 2623-2639, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29189769

RESUMO

This protocol describes the preparation of highly viable adult ventricular myocardial slices from the hearts of small and large mammals, including rodents, pigs, dogs and humans. Adult ventricular myocardial slices are 100- to 400-µm-thick slices of living myocardium that retain the native multicellularity, architecture and physiology of the heart. This protocol provides a list of the equipment and reagents required alongside a detailed description of the methodology for heart explantation, tissue preparation, slicing with a vibratome and handling of myocardial slices. Supplementary videos are included to visually demonstrate these steps. A number of critical steps are addressed that must be followed in order to prepare highly viable myocardial slices. These include identification of myocardial fiber direction and fiber alignment within the tissue block, careful temperature control, use of an excitation-contraction uncoupler, optimal vibratome settings and correct handling of myocardial slices. Many aspects of cardiac structure and function can be studied using myocardial slices in vitro. Typical results obtained with hearts from a small mammal (rat) and a large mammal (human) with heart failure are shown, demonstrating myocardial slice viability, maximum contractility, Ca2+ handling and structure. This protocol can be completed in ∼4 h.


Assuntos
Ventrículos do Coração/citologia , Microtomia/métodos , Miocárdio/citologia , Adulto , Animais , Soluções Cardioplégicas/química , Dissecação/métodos , Cães , Desenho de Equipamento , Humanos , Indicadores e Reagentes , Camundongos , Microtomia/instrumentação , Ratos , Preservação de Tecido/métodos
6.
Asian Cardiovasc Thorac Ann ; 25(7-8): 495-501, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28975821

RESUMO

Objective Blood cardioplegia, the gold-standard cardioprotective strategy, requires frequent dosing, resulting in hyperkalemia-induced myocardial edema. The aim of our study was to compare the efficacy and safety of a long-acting blood-based cardioplegia with physiological potassium levels versus the well-established cold blood St. Thomas' Hospital no. 1 cardioplegia solution in multivalve surgeries. Methods One hundred patients undergoing simultaneous elective aortic and mitral valve replacement ± tricuspid valve repair were randomized in two groups. In group 1, adenosine 12 mg was given via the aortic root after crossclamping, followed by a single dose of long-acting solution at 14℃ (30 mLckg-1); in group 2, an initial 30 mLckg-1 of St. Thomas' cardioplegia at 14℃ was administered, followed by 15 mLckg-1 every 20 min. Duration of cardiopulmonary bypass, inotropic score, arrhythmias, ventilation time, and the levels of interleukin-6, creatinine kinase-MB, and troponin I were compared. Results Mean cardiopulmonary bypass and crossclamp times were 134.04 ± 36.12 vs. 154.34 ± 34.26 ( p = 0.004) and 110.37 ± 24.80 vs. 132.48 ± 31.68 min ( p = 0.002), respectively, in the long-acting and St. Thomas' groups. Cardiac index, creatinine kinase-MB and troponin I levels were comparable. Interleukin-6 levels post-bypass were 61.72 ± 15.33 and 75.44 ± 31.78 pgcmL-1 ( p = 0.007) in the long-acting and St. Thomas' cardioplegia groups, respectively. Conclusions Single-dose long-acting cardioplegia gives a cardioprotective effect comparable to repeated doses of the well-established St. Thomas' Hospital no. 1 cold blood cardioplegia.


Assuntos
Soluções Cardioplégicas/uso terapêutico , Parada Cardíaca Induzida/métodos , Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca , Valvas Cardíacas/cirurgia , Adulto , Bicarbonatos/efeitos adversos , Bicarbonatos/química , Bicarbonatos/uso terapêutico , Cloreto de Cálcio/efeitos adversos , Cloreto de Cálcio/química , Cloreto de Cálcio/uso terapêutico , Soluções Cardioplégicas/efeitos adversos , Soluções Cardioplégicas/química , Ponte Cardiopulmonar , Cardiotônicos/administração & dosagem , Feminino , Parada Cardíaca Induzida/efeitos adversos , Doenças das Valvas Cardíacas/fisiopatologia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Valvas Cardíacas/fisiopatologia , Humanos , Hiperpotassemia/sangue , Hiperpotassemia/induzido quimicamente , Índia , Magnésio/efeitos adversos , Magnésio/química , Magnésio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Potássio/sangue , Cloreto de Potássio/efeitos adversos , Cloreto de Potássio/química , Cloreto de Potássio/uso terapêutico , Estudos Prospectivos , Respiração Artificial , Fatores de Risco , Cloreto de Sódio/efeitos adversos , Cloreto de Sódio/química , Cloreto de Sódio/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
7.
Ann Thorac Surg ; 103(5): 1550-1556, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28190549

RESUMO

BACKGROUND: The aim of this study was to evaluate outcome measures after the use of del Nido (dN) cardioplegia compared with conventional multidose high-potassium (non-dN) cardioplegia in neonates and infants. METHODS: We retrospectively analyzed data in patients, aged younger than 1 year, undergoing cardiopulmonary bypass (CPB) from January 2012 to August 2015. We changed our cardioplegia protocol from non-dN to dN administered in a single or infrequently dosed strategy in September 2013. The outcomes of the dN group (n = 107) are compared with the non-dN group (n = 118). We analyzed variables for demographic, intraoperative, early postoperative, and discharge variables. RESULTS: The two groups were similar in age, weight, height, CPB, and cross-clamp time; preoperative and postoperative echocardiographic systolic functions; first 24-hour postoperative urine output and inotropic score; length of stay; and mortality rate. The Society of Thoracic Surgeons/European Association for Cardio-Thoracic Surgery Congenital Heart Surgery (STAT) mortality category was significantly higher in the dN group (p = 0.03). The cardioplegia dosing interval was lower for the non-dN group (p < 0.001). The volume and doses of cardioplegia per patient were significantly higher in the non-dN group (p < 0.001). In a subanalysis, when the Norwood patients were excluded from both groups, the overall STAT mortality category difference was no longer significant. The demographic, early postoperative, and discharge variables still showed no significant difference when the two groups were compared. CONCLUSIONS: Similar outcomes can be achieved with less frequent interruption of the operation and lower volume of cardioplegia when using dN cardioplegia solution compared with conventional cardioplegia. The dN cardioplegia with extended ischemic interval can be used as an alternative strategy in the neonatal and infant population during cardiac operations.


Assuntos
Soluções Cardioplégicas/química , Parada Cardíaca Induzida/métodos , Cardiopatias Congênitas/cirurgia , Procedimentos Cirúrgicos Cardíacos , Soluções Cardioplégicas/administração & dosagem , Soluções Cardioplégicas/efeitos adversos , Feminino , Cardiopatias Congênitas/mortalidade , Humanos , Lactente , Recém-Nascido , Masculino , Potássio/administração & dosagem , Estudos Retrospectivos
8.
Sci Rep ; 6: 23572, 2016 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-27121996

RESUMO

This study investigated whether caridoplegia solution with Emulsified Isoflurane (EI) could improve cardiaoprotection in a dog CPB model of great similarity to clinical settings. Adult dogs were randomly assigned to receive one of the following cardioplegia solutions: St. Thomas with EI (group ST+EI), St. Thomas with 30% Intralipid (group ST+EL) and St. Thomas alone (group ST). The aorta was cross-clamped for two hours followed by reperfusion for another two hours, during which cardiac output was measured and dosages of positive inotropic agent to maintain normal hemodynamics were recorded. Serum level of cardiac troponin I (cTnI) and CK-MB were measured. Deletion of cardiac mitochondrial DNA was examined at the end of reperfusion. Compared with ST, ST+EI decreased the requirement of dopamine support while animals receiving ST+EI had a significantly larger cardiac output. ST+EI reduced post-CPB release of cTnI and CK-MB. Mitochondrial DNA loss was observed in only one of the tested animals from group ST+EI while it was seen in all the tested animals from group ST+EL and ST. Addition of emulsified isoflurane into cardioplegia solution protects against myocardial ischemia reperfusion injury. This protective effect might be mediated by preserving mitochondrial ultrastructure and DNA integrity.


Assuntos
Soluções Cardioplégicas/química , Ponte Cardiopulmonar , Isoflurano/administração & dosagem , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Animais , Soluções Cardioplégicas/administração & dosagem , Creatina Quinase Forma MB/sangue , DNA Mitocondrial/metabolismo , Modelos Animais de Doenças , Cães , Emulsões/química , Parada Cardíaca Induzida , Ventrículos do Coração/patologia , Isoflurano/química , Masculino , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Miocárdio/metabolismo , Estresse Oxidativo , Fosfolipídeos/química , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Óleo de Soja/química , Superóxido Dismutase/análise , Troponina I/sangue , Proteína X Associada a bcl-2/metabolismo
9.
Rev Bras Cir Cardiovasc ; 29(1): 83-8, 2014.
Artigo em Inglês, Português | MEDLINE | ID: mdl-24896167

RESUMO

INTRODUCTION: Cardiac arrest during heart surgery is a common procedure and allows the surgeon to perform surgical procedures in an environment free of blood and movement. Using a model of isolated rat heart, the authors compare a new cardioplegic solution containing histidine-tryptophan-glutamate (group 2) with the histidine-tryptophan-alphacetoglutarate (group 1) routinely used by some cardiac surgeons. OBJECTIVE: To assess caspase, IL-8 and KI-67 in isolated rat hearts using immunohistochemistry. METHODS: 20 Wistar male rats were anesthetized and heparinized. The chest was opened, cardioctomy was performed and 40 ml/kg of the appropriate cardioplegic solution was infused. The hearts were kept for 2 hours at 4ºC in the same solution, and thereafter, placed in the Langendorff apparatus for 30 minutes with Ringer-Locke solution. Immunohistochemistry analysis of caspase, IL-8, and KI-67 were performed. RESULTS: The concentration of caspase was lower in group 2 and Ki-67 was higher in group 2, both P<0.05. There was no statistical difference between the values of IL-8 between the groups. CONCLUSION: Histidine-tryptophan-glutamate solution was better than histidine-tryptophan-alphacetoglutarate solution because it reduced caspase (apoptosis), increased KI-67 (cell proliferation), and showed no difference in IL-8 levels compared to group 1. This suggests that the histidine-tryptophan-glutamate solution was more efficient than the histidine-tryptophan-alphacetoglutarate for the preservation of hearts of rat cardiomyocytes.


Assuntos
Soluções Cardioplégicas/farmacologia , Ácido Glutâmico/farmacologia , Glutaratos/farmacologia , Coração/efeitos dos fármacos , Histidina/farmacologia , Triptofano/farmacologia , Animais , Apoptose/efeitos dos fármacos , Soluções Cardioplégicas/química , Caspases/análise , Caspases/efeitos dos fármacos , Imuno-Histoquímica , Interleucina-8/análise , Interleucina-8/efeitos dos fármacos , Antígeno Ki-67/análise , Antígeno Ki-67/efeitos dos fármacos , Masculino , Miócitos Cardíacos , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Tempo
10.
Rev. bras. cir. cardiovasc ; 29(1): 83-88, Jan-Mar/2014. tab, graf
Artigo em Português | LILACS | ID: lil-710087

RESUMO

Introdução: A parada do coração durante a cirurgia cardíaca é procedimento comum e permite que o cirurgião realize os procedimentos cirúrgicos em ambiente isento de sangue e movimento. Os autores comparam, em modelo de coração isolado de rato, uma nova solução cardioplégica com histidina-triptofano-glutamato (grupo 2) com a histidina-triptofano-alfacetoglutarato (grupo 1) já utilizada de rotina por alguns cirurgiões cardíacos. Objetivo: Avaliar por análise imuno-histoquímica a caspase, a IL-8 e KI-67 em corações isolados de ratos. Métodos: 20 ratos machos de raça Wistar foram anestesiados e heparinizados. O tórax foi aberto, realizado cardiectomia e infundido 40 ml/kg de solução cardioplégica apropriada. Os corações foram mantidos por 2 horas na mesma solução a 4ºC e, após esse período, colocados em aparato de Langendorff por 30 minutos com solução de Ringer Locke. Foram feitas análises imuno-histoquímicas para caspase, IL-8 e KI-67. Resultados: A concentração de caspase estava menor no grupo 2 e da KI-67 estava mais elevada no grupo 2, ambos com P<0,05. Não houve diferença estatística entre os valores de IL-8 entre os grupos. Conclusão: A solução com histidina-triptofano-glutamato foi melhor que a com histidina-triptofano-cetoglutarato, pois reduziu a caspase (apoptose), aumentou o KI-67 (proliferação celular) e não apresentou valores diferentes de IL-8 (inflamação e necrose) que no grupo 1. Isso sugere que a solução histidina-triptofano-glutamato foi mais eficiente que a histidina-triptofano-cetoglutarato na preservação dos cardiomiócitos dos corações de ratos. .


Introduction: Cardiac arrest during heart surgery is a common procedure and allows the surgeon to perform surgical procedures in an environment free of blood and movement. Using a model of isolated rat heart, the authors compare a new cardioplegic solution containing histidine-tryptophan-glutamate (group 2) with the histidine-tryptophan-alphacetoglutarate (group 1) routinely used by some cardiac surgeons. Objective: To assess caspase, IL-8 and KI-67 in isolated rat hearts using immunohistochemistry. Methods: 20 Wistar male rats were anesthetized and heparinized. The chest was opened, cardioctomy was performed and 40 ml/kg of the appropriate cardioplegic solution was infused. The hearts were kept for 2 hours at 4ºC in the same solution, and thereafter, placed in the Langendorff apparatus for 30 minutes with Ringer-Locke solution. Immunohistochemistry analysis of caspase, IL-8, and KI-67 were performed. Results: The concentration of caspase was lower in group 2 and Ki-67 was higher in group 2, both P<0.05. There was no statistical difference between the values of IL-8 between the groups. Conclusion: Histidine-tryptophan-glutamate solution was better than histidine-tryptophan-alphacetoglutarate solution because it reduced caspase (apoptosis), increased KI-67 (cell proliferation), and showed no difference in IL-8 levels compared to group 1. This suggests that the histidine-tryptophan-glutamate solution was more efficient than the histidine-tryptophan-alphacetoglutarate for the preservation of hearts of rat cardiomyocytes. .


Assuntos
Animais , Masculino , Soluções Cardioplégicas/farmacologia , Ácido Glutâmico/farmacologia , Glutaratos/farmacologia , Coração/efeitos dos fármacos , Histidina/farmacologia , Triptofano/farmacologia , Apoptose/efeitos dos fármacos , Soluções Cardioplégicas/química , Caspases/análise , Caspases/efeitos dos fármacos , Imuno-Histoquímica , /análise , /efeitos dos fármacos , /análise , /efeitos dos fármacos , Miócitos Cardíacos , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Tempo
11.
Rev. bras. cir. cardiovasc ; 28(4): 524-530, out.-dez. 2013. ilus, tab
Artigo em Inglês | LILACS | ID: lil-703122

RESUMO

INTRODUCTION: Myocardial preservation during open heart surgeries and harvesting for transplant are of great importance. The heart at the end of procedure has to resume its functions as soon as possible. All cardioplegic solutions are based on potassium for induction of cardioplegic arrest. OBJECTIVE: To assess a cardioplegic solution with no potassium addition to the formula with two other commercially available cardioplegic solutions. The comparative assessment was based on cytotoxicity, adenosine triphosphate myocardial preservation, and caspase 3 activity. The tested solution (LIRM) uses low doses of sodium channel blocker (lidocaine), potassium channel opener (cromakalin), and actin/myosin cross bridge inhibitor (2,3-butanedione monoxime). METHODS: Wistar rats underwent thoracotomy under mechanical ventilation and three different solutions were used for "in situ" perfusion for cardioplegic arrest induction: Custodiol (HTK), Braile (G/A), and LIRM solutions. After cardiac arrest, the hearts were excised and kept in cold storage for 4 hours. After this period, the hearts were assessed with optical light microscopy, myocardial ATP content and caspase 3 activity. All three solutions were evaluated for direct cytotoxicity with L929 and WEHI-164 cells. RESULTS: The ATP content was higher in the Custodiol group compared to two other solutions (P<0.05). The caspase activity was lower in the HTK group compared to LIRM and G/A solutions (P<0.01). The LIRM solution showed lower caspase activity compared to Braile solution (P<0.01). All solutions showed no cytotoxicity effect after 24 hours of cells exposure to cardioplegic solutions. CONCLUSION: Cardioplegia solutions without potassium are promised and aminoacid addition might be an interesting strategy. More evaluation is necessary for an optimal cardioplegic solution development.


INTRODUÇÃO: Preservação do miocárdio durante cirurgias cardíacas abertas e de colheita para transplante são de grande importância. O coração ao final do processo tem de retomar as suas funções, logo que possível. Todas as soluções cardioplégicas são baseadas em potássio, para indução de parada cardioplégica. OBJETIVO: Comparar a uma solução cardioplégica sem adição de potássio à sua fórmula com duas outras soluções cardioplégicas disponíveis comercialmente. A avaliação comparativa foi baseada na citotoxicidade, preservação miocárdica (adenosina trifosfato, ATP) e atividade da caspase 3. A solução testada (LIRM) utiliza baixas doses de bloqueador de canal de sódio (lidocaína), abridor do canal de potássio (cromacalina) e inibidor da ponte actina/miosina (2,3-butanodiona monoxima). MÉTODOS: Ratos Wistar foram submetidos à toracotomia sob ventilação mecânica e três soluções diferentes foram utilizadas para perfusão in situ para a indução de parada cardioplégica: soluções Custodiol (HTK) Braile (G/A) e LIRM. Após parada cardíaca, os corações foram retirados e mantidos em câmara fria por 4 horas. Após esse período, o coração foi avaliado com microscopia de luz ótica, o conteúdo de ATP miocárdico e atividade da caspase 3. Todas as três soluções foram avaliadas quanto à citotoxicidade direta com células L929 e WEHI-164. RESULTADOS: A quantidade de ATP foi maior no grupo Custodiol em comparação às com outras duas soluções (P<0,05). A atividade de caspase foi menor no grupo HTK quando comparado às soluções LIRM e G/A (P<0,01). A solução LIRM demonstrou menor atividade da caspase em comparação à solução Braile (P<0,01). Todas as soluções não mostraram qualquer efeito de citotoxicidade após 24 horas de exposição das células às soluções cardioplégicas. CONCLUSÃO: Soluções cardioplégicas sem potássio são uma perspectiva e a adição de aminoácido pode ser uma estratégia interessante. Mais avaliações são necessárias para o desenvolvimento ideal da solução cardioplégica.


Assuntos
Animais , Ratos , Soluções Cardioplégicas/farmacologia , Parada Cardíaca Induzida/métodos , Coração/efeitos dos fármacos , Preservação de Órgãos/métodos , Trifosfato de Adenosina/análise , Soluções Cardioplégicas/química , /análise , Sobrevivência Celular/efeitos dos fármacos , Glucose/química , Glucose/farmacologia , Modelos Animais , Manitol/química , Manitol/farmacologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Cloreto de Potássio/química , Cloreto de Potássio/farmacologia , Potássio/química , Potássio/farmacologia , Procaína/química , Procaína/farmacologia , Ratos Wistar , Reprodutibilidade dos Testes , Bloqueadores dos Canais de Sódio/química , Fatores de Tempo
14.
J Extra Corpor Technol ; 45(1): 46-50, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23691784

RESUMO

The evolution of myocardial protection techniques has been both the source of milestone advancements and controversial debate in cardiac surgery. Our institution has modified a low-prime cardioplegia system (CPS) and adopted a single-dose cardioplegia solution (del Nido cardioplegia) for our congenital heart disease population. The goal of this article is to describe our CPS and outline our myocardial protection protocol. These techniques have allowed us to minimize circuit surface area, operate uninterrupted, and safely protect the myocardium during extended ischemic periods.


Assuntos
Soluções Cardioplégicas/química , Parada Cardíaca Induzida/instrumentação , Parada Cardíaca Induzida/métodos , Criança , Humanos , Miniaturização/instrumentação , Segurança do Paciente , Pediatria/instrumentação , Pediatria/métodos
15.
J Cardiothorac Surg ; 8: 60, 2013 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-23547937

RESUMO

BACKGROUND: The Krebs-Henseleit buffer is the best perfusion solution for isolated mammalian hearts. We hypothesized that a Krebs-Henseleit buffer-based cardioplegic solution might provide better myocardial protection than well-known crystalloid cardioplegic solutions because of its optimal electrolyte and glucose levels, presence of buffer systems, and mild hyperosmolarity. METHODS: Isolated Langendorff-perfused rat hearts were subjected to either global ischemia without cardioplegia (controls) or cardioplegic arrest for either 60 or 180 min, followed by 120 min of reperfusion. The modified Krebs-Henseleit buffer-based cardioplegic solution (mKHB) and St. Thomas' Hospital solution No. 2 (STH2) were studied. During global ischemia, the temperatures of the heart and the cardioplegic solutions were maintained at either 37°C (60 min of ischemia) or 22°C (moderate hypothermia, 180 min of ischemia). Hemodynamic parameters were registered throughout the experiments. The infarct size was determined through histochemical examination. RESULTS: Cardioplegia with the mKHB solution at moderate hypothermia resulted in a minimal infarct size (5 ± 3%) compared to that in the controls and STH2 solution (35 ± 7% and 19 ± 9%, respectively; P < 0.001, for both groups vs. the mKHB group). In contrast to the control and STH2-treated hearts, no ischemic contracture was registered in the mKHB group during the 180-min global ischemia. At normothermia, the infarct sizes were 4 ± 3%, 72 ± 6%, and 70 ± 12% in the mKHB, controls, and STH2 groups, respectively (P < 0.0001). In addition, cardioplegia with mKHB at normothermia prevented ischemic contracture and improved the postischemic functional recovery of the left ventricle (P < 0.001, vs. STH2). CONCLUSIONS: The data suggest that the Krebs-Henseleit buffer-based cardioplegic might be superior to the standard crystalloid solution (STH2).


Assuntos
Soluções Cardioplégicas/farmacologia , Cardiotônicos/farmacologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Animais , Soluções Cardioplégicas/química , Cardiotônicos/química , Glucose/química , Glucose/farmacologia , Parada Cardíaca , Frequência Cardíaca/efeitos dos fármacos , Masculino , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Ratos , Ratos Wistar , Estatísticas não Paramétricas , Trometamina/química , Trometamina/farmacologia , Fibrilação Ventricular , Pressão Ventricular/efeitos dos fármacos
16.
J Thorac Cardiovasc Surg ; 145(3): 812-8, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22964356

RESUMO

OBJECTIVE: We aimed to evaluate the efficacy and safety of a cold crystalloid cardioplegic solution with adenosine (1.2 mmol/L) instead of supranormal potassium. METHODS: Sixty low-risk patients scheduled for elective coronary artery bypass grafting (CABG) were randomized to receive standard cold crystalloid hyperkalemic cardioplegia (hyperkalemic group) or normokalemic cardioplegia in which supranormal potassium was replaced with 1.2 mmol/L adenosine (adenosine group). End points were postoperative release of troponin T and creatine kinase MB, hemodynamics measured by PiCCO arterial thermodilution catheters, perioperative release of markers of endothelial activation and injury, and clinical course. RESULTS: The adenosine group had a significantly shorter time to arrest than did the hyperkalemic group (mean ± standard deviation, 11 ± 5 vs 44 ± 18 seconds; P < .001). Three hearts in the adenosine group were probably not adequately drained and received additional hyperkalemic cardioplegia to maintain satisfactory cardioplegic arrest. There were no differences between groups with respect to perioperative release of markers of endothelial activation or injury and no differences between groups in postoperative release of troponin T or creatine kinase MB. Postoperative hemodynamics including cardiac index were similar between groups. The incidence of postoperative atrial fibrillation was significantly lower in the adenosine group than in the hyperkalemic group (4 vs 15; P = .01). CONCLUSIONS: Adenosine instead of hyperkalemia in cold crystalloid cardioplegia is safe, gives more rapid cardiac arrest, and affords similar cardioprotection and maintenance of hemodynamic parameters, together with a marked reduction in the incidence of postoperative atrial fibrillation.


Assuntos
Adenosina/farmacologia , Fibrilação Atrial/prevenção & controle , Soluções Cardioplégicas/química , Ponte de Artéria Coronária , Parada Cardíaca Induzida/métodos , Complicações Pós-Operatórias/prevenção & controle , Potássio/farmacologia , Fibrilação Atrial/epidemiologia , Biomarcadores/metabolismo , Distribuição de Qui-Quadrado , Creatina Quinase Forma MB/metabolismo , Soluções Cristaloides , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Incidência , Soluções Isotônicas/química , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Fatores de Tempo , Resultado do Tratamento , Troponina T/metabolismo
17.
Rev Bras Cir Cardiovasc ; 28(4): 524-30, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24598959

RESUMO

INTRODUCTION: Myocardial preservation during open heart surgeries and harvesting for transplant are of great importance. The heart at the end of procedure has to resume its functions as soon as possible. All cardioplegic solutions are based on potassium for induction of cardioplegic arrest. OBJECTIVE: To assess a cardioplegic solution with no potassium addition to the formula with two other commercially available cardioplegic solutions. The comparative assessment was based on cytotoxicity, adenosine triphosphate myocardial preservation, and caspase 3 activity. The tested solution (LIRM) uses low doses of sodium channel blocker (lidocaine), potassium channel opener (cromakalin), and actin/myosin cross bridge inhibitor (2,3-butanedione monoxime). METHODS: Wistar rats underwent thoracotomy under mechanical ventilation and three different solutions were used for "in situ" perfusion for cardioplegic arrest induction: Custodiol (HTK), Braile (G/A), and LIRM solutions. After cardiac arrest, the hearts were excised and kept in cold storage for 4 hours. After this period, the hearts were assessed with optical light microscopy, myocardial ATP content and caspase 3 activity. All three solutions were evaluated for direct cytotoxicity with L929 and WEHI-164 cells. RESULTS: The ATP content was higher in the Custodiol group compared to two other solutions (P<0.05). The caspase activity was lower in the HTK group compared to LIRM and G/A solutions (P<0.01). The LIRM solution showed lower caspase activity compared to Braile solution (P<0.01). All solutions showed no cytotoxicity effect after 24 hours of cells exposure to cardioplegic solutions. CONCLUSION: Cardioplegia solutions without potassium are promised and aminoacid addition might be an interesting strategy. More evaluation is necessary for an optimal cardioplegic solution development.


Assuntos
Soluções Cardioplégicas/farmacologia , Parada Cardíaca Induzida/métodos , Coração/efeitos dos fármacos , Preservação de Órgãos/métodos , Trifosfato de Adenosina/análise , Animais , Soluções Cardioplégicas/química , Caspase 3/análise , Sobrevivência Celular/efeitos dos fármacos , Glucose/química , Glucose/farmacologia , Manitol/química , Manitol/farmacologia , Modelos Animais , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Potássio/química , Potássio/farmacologia , Cloreto de Potássio/química , Cloreto de Potássio/farmacologia , Procaína/química , Procaína/farmacologia , Ratos , Ratos Wistar , Reprodutibilidade dos Testes , Bloqueadores dos Canais de Sódio/química , Fatores de Tempo
18.
J Extra Corpor Technol ; 44(3): 98-103, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23198389

RESUMO

Cardioplegia is an integral and essential method of myocardial protection for patients of all ages requiring cardiac surgery in which the heart must be stopped. Numerous cardioplegia solutions and delivery methods have been developed. The del Nido cardioplegia solution has been in use for 18 years at Boston Children's Hospital. This is a unique four parts crystalloid to one part whole blood formulation that is generally used in a single-dose fashion. Although the formulation was originally developed for use in pediatric and infant patients, its use for adult cardiac surgery has been expanding. National and international inquiries to our institution regarding this cardioplegia have been increasing over the last 2 years. We present the developmental history, supporting theory, and current protocol for use of what is now referred to as del Nido cardioplegia.


Assuntos
Soluções Cardioplégicas/administração & dosagem , Parada Cardíaca Induzida/métodos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Animais , Boston , Soluções Cardioplégicas/química , Criança , Parada Cardíaca Induzida/história , Parada Cardíaca Induzida/instrumentação , História do Século XX , Hospitais Pediátricos/história , Humanos , Modelos Animais , Pennsylvania
20.
Perfusion ; 27(2): 98-103, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22005886

RESUMO

BACKGROUND: The single dose cardioplegia technique for myocardial protection during congenital heart surgery is a viable alternative to multidose protocols. METHODS: Thirty-four pediatric patients with aortic cross clamp times greater than 90 minutes were grouped by modified adult (MA) multidose solution or del Nido (dN) single dose solution. Also, data from eight patients where the cross clamp times were greater than two hours on one dose of dN solution were included. RESULTS: In the 90-minute plus arm of the study, there were no significant differences between the groups when comparing the risk adjustment for congenital heart surgery (RACHS) (p=0.6), cardiopulmonary bypass times (CPB) (p=0.5), aortic cross camp times (p=0.5), weights (p=0.7) and number of intraoperative exogenous blood units (p=0.5). There were significant differences between the groups (p<0.05) in the number of cardioplegia doses and with perioperative glucose levels. In the greater than two hours group, the incidence of complete heart block (CHB) was 0.125% and there were no deaths or mechanical circulatory support (MCS) devices used. CONCLUSION: del Nido cardioplegia solution is a reasonable tool for myocardial protection during congenital heart surgery that significantly decreased the number of cardioplegic interventions and perioperative glucose values in our study groups.


Assuntos
Glicemia/análise , Soluções Cardioplégicas/uso terapêutico , Parada Cardíaca Induzida/métodos , Cardiopatias Congênitas/cirurgia , Adolescente , Adulto , Soluções Cardioplégicas/administração & dosagem , Soluções Cardioplégicas/química , Ponte Cardiopulmonar , Criança , Humanos , Incidência , Miocárdio/metabolismo , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
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