Lidocaine and pinacidil added to blood versus crystalloid cardioplegic solutions: study in isolated hearts

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.

Coronary perfusion pressure during antegrade cardioplegia in on-pump CABG patients

Abstract Objective: The aim of this study was to investigate whether aortic tension estimated by palpation and cardioplegia infusion line pressure provide results equivalent to those obtained with direct aortic intraluminal pressure measurement. Methods: Sixty consecutive patients who underwent coronary artery bypass graft surgeries with extracorporeal circulation were analyzed. Sanguineous cardioplegic solution in a ratio of 4:1 was administered using a triple lumen antegrade cannula. After crossclamping, cardioplegia was infused and aortic root pressure was recorded by surgeon (A) considering the aortic tension he felt in his fingertips. At the same time, another surgeon (B) recorded his results for the same measurement. Concomitantly, the anesthesiologist recorded intraluminal pressure in the aortic root and the perfusionist recorded delta pressure in cardioplegia infusion line. None of the participants involved in these measurements was allowed to be informed about the values provided by the other examiners. Results: The Bland-Altman test showed that a considerable variation between aortic wall tension was found as measured by palpation and by intraluminal pressure, with a bias of -9.911±18.75% (95% limits of agreement: -46.7 to 26.9). No strong correlation was observed between intraluminal pressure and cardioplegia line pressure (Spearman's r=0.61, 95% confidence interval 0.5-0.7; P<0.0001). Conclusion: These findings reinforce that cardioplegia infusion should be controlled by measuring intraluminal pressure, and that palpation and cardioplegia line pressure are inaccurate methods, the latter should always be used to complement intraluminal measurement to ensure greater safety in handling the cardioplegia circuit.

Single-dose lignocaine-based blood cardioplegia in single valve replacement patients

Abstract OBJECTIVE: Myocardial protection is the most important in cardiac surgery. We compared our modified single-dose long-acting lignocaine-based blood cardioplegia with short-acting St Thomas 1 blood cardioplegia in patients undergoing single valve replacement. METHODS: A total of 110 patients who underwent single (aortic or mitral) valve replacement surgery were enrolled. Patients were divided in two groups based on the cardioplegia solution used. In group 1 (56 patients), long-acting lignocaine based-blood cardioplegia solution was administered as a single dose while in group 2 (54 patients), standard St Thomas IB (short-acting blood-based cardioplegia solution) was administered and repeated every 20 minutes. All the patients were compared for preoperative baseline parameters, intraoperative and all the postoperative parameters. RESULTS: We did not find any statistically significant difference in preoperative baseline parameters. Cardiopulmonary bypass time were 73.8±16.5 and 76.4±16.9 minutes (P=0.43) and cross clamp time were 58.9±10.3 and 66.3±11.2 minutes (P=0.23) in group 1 and group 2, respectively. Mean of maximum inotrope score was 6.3±2.52 and 6.1±2.13 (P=0.65) in group 1 and group 2, respectively. We also did not find any statistically significant difference in creatine-phosphokinase-MB (CPK-MB), Troponin-I levels, lactate level and cardiac functions postoperatively. CONCLUSION: This study proves the safety and efficacy of long-acting lignocaine-based single-dose blood cardioplegia compared to the standard short-acting multi-dose blood cardioplegia in patients requiring the single valve replacement. Further studies need to be undertaken to establish this non-inferiority in situations of complex cardiac procedures especially in compromised patients.

Histidine-tryptophan-ketoglutarate solution decreases mortality and morbidity in high-risk patients with severe pulmonary arterial hypertension associated with complex congenital heart disease: an 11-year experience from a single institution

Cardioplegic reperfusion during a long term ischemic period interrupts cardiac surgery and also increases cellular edema due to repeated solution administration. We reviewed the clinical experiences on myocardial protection of a single perfusion with histidine-tryptophan-ketoglutarate (HTK) for high-risk patients with severe pulmonary arterial hypertension associated with complex congenital heart disease. This retrospective study included 101 high-risk patients undergoing arterial switch operation between March 2001 and July 2012. We divided the cohort into two groups: HTK group, myocardial protection was carried out with one single perfusion with HTK solution; and St group, myocardial protection with conventional St. Thomas' crystalloid cardioplegic solution. The duration of cardiopulmonary bypass did not differ between the two groups. The mortality, morbidity, ICU stay, post-operative hospitalization time, and number of transfusions in HTK group were lower than those in St group (P<0.05). Univariate and multivariate analysis showed that HTK is a statistically significant independent predictor of decreased early mortality and morbidity (P<0.05). In conclusion, HTK solution seems to be an effective and safe alternative to St. Thomas' solution for cardioplegic reperfusion in high-risk patients with complex congenital heart disease.

Modalidades de parada cardíaca induzida: hipercalemia e hipocalcemia - revisão de literatura / Modes of induced cardiac arrest: hyperkalemia and hypocalcemia - Literature review

A entrada de sódio e cálcio desempenham efeito chave no miócito submetido à parada cardíaca por hiperpotassemia. Eles provocam edema celular, acidose, consumo de trifosfato de adenosina e desencadeiam processo de morte celular programada. A parada cardíaca provocada por hipocalcemia mantém os níveis intracelulares de trifosfato de adenosina, melhora o rendimento diastólico e reduz o consumo de oxigênio, o que pode ser traduzido em melhor proteção do miócito às lesões provocadas pela parada cardíaca induzida.

The entry of sodium and calcium play a key effect on myocyte subjected to cardiac arrest by hyperkalemia. They cause cell swelling, acidosis, consumption of adenosine triphosphate and trigger programmed cell death. Cardiac arrest caused by hypocalcemia maintains intracellular adenosine triphosphate levels, improves diastolic performance and reduces oxygen consumption, which can be translated into better protection to myocyte injury induced by cardiac arrest.

Comparação da dimensão fractal e entropia de Shannon em miócitos de ratos submetidos à cardioplegia utilizando solução histidina-triptofano-cetoglutarato e histidina-triptofano com glutamato / Comparison of fractal dimension and Shannon entropy in myocytes from rats treated with histidine-tryptophan-glutamate and histidine-tryptophan cetoglutarate

Introdução: As soluções que provocam parada cardíaca eletiva estão em constante evolução, porém, o composto ideal ainda não foi encontrado. Os autores comparam uma nova solução cardioplégica com histidina-triptofano-glutamato (Grupo 2) com histidina-triptofano-cetoglutarato (Grupo 1) em modelo de coração isolado de rato. Objetivo: Quantificar a dimensão fractal e entropia de Shannon em miócitos de rato submetidos à cardioplegia utilizando solução histidina-triptofano com glutamato em modelo experimental, considerando-se os marcadores caspase, IL-8 e Ki-67. Métodos: Vinte 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 imunohistoquímicas para caspase, IL-8 e KI-67. Resultados: A dimensão fractal e a entropia de Shannon dos corações submetidos à parada cardíaca eletiva nos grupos 1 e 2 não foram diferentes. Conclusão: A quantidade de informações avaliada pela entropia de Shannon e a distribuição das mesmas (dada pela dimensão fractal) nas lâminas de coração de rato submetidas à cardioplegia com solução histidina-triptofano-acetoglutarato ou histidina-triptofano-glutamato não foram diferentes, o que mostra que a solução de histidina-triptofano-glutamato é tão boa quanto a histidina-triptofano-cetoglutarato na preservação dos miócitos em modelo de coração isolado de rato. .

Introduction: Solutions that cause elective cardiac arrest are constantly evolving, but the ideal compound has not yet been found. The authors compare a new cardioplegic solution with histidine-tryptophan-glutamate (Group 2) and other one with histidine-tryptophan-cetoglutarate (Group 1) in a model of isolated rat heart. Objective: To quantify the fractal dimension and Shannon entropy in rat myocytes subjected to cardioplegia solution using histidine-tryptophan with glutamate in an experimental model, considering the caspase markers, IL-8 and KI-67. Methods: Twenty male Wistar rats were anesthetized and heparinized. The chest was opened, the heart was withdrawn and 40 ml/kg of cardioplegia (with histidine-tryptophan-cetoglutarate or histidine-tryptophan-glutamate 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 min with Ringer-Locke solution. Analyzes were performed for immunohistochemical caspase, IL-8 and KI-67. Results: The fractal dimension and Shannon entropy were not different between groups histidine-tryptophan-glutamate and histidine-tryptophan-acetoglutarate. Conclusion: The amount of information measured by Shannon entropy and the distribution thereof (given by fractal dimension) of the slices treated with histidine-tryptophan-cetoglutarate and histidine-tryptophan-glutamate were not different, showing that the histidine-tryptophan-glutamate solution is as good as histidine-tryptophan-acetoglutarate to preserve myocytes in isolated rat heart. .

Aperfeiçoamento em técnica de perfusão cardioplégica no pinçamento único de aorta - resultados iniciais / Improvement in cardioplegic perfusion technique in single aortic clamping - initial results

INTRODUÇÃO: O método mais comumente utilizado para a proteção miocárdica é o de administrar-se solução cardioplégica na circulação coronária. Entretanto, a proteção pode ser alcançada através da perfusão intermitente do sistema coronariano com sangue do próprio paciente, que é realizada por meio de múltiplas sequências de pinçamento e abertura do clamp aórtico ou por meio do pinçamento único e canulação acessória da raiz aórtica. Objetivo: Avaliar o desfecho clínico e a ocorrência de eventos neurológicos no período intra-hospitalar dos pacientes submetidos à cirurgia de revascularização do miocárdio com a técnica proposta aqui neste estudo. Métodos: Descreve-se uma técnica de proteção miocárdica no uso do pinçamento único de aorta que consiste na canulação acessória da raiz aórtica com sistema aperfeiçoado para perfusão coronária intermitente, foi realizado estudo observacional transversal prospectivo onde foram estudados 50 pacientes (idade média 58,5±7.19 anos) submetidos à cirurgia de revascularização do miocárdio sob a técnica proposta. Foram avaliadas variáveis clínicas e laboratoriais pré e pós-operatórias. Resultados: O nível médio de pico da CKMB pós-operatória foi de 51,64±27,10 U/L no segundo pós-operatório e da troponina I foi de 3,35±4,39 ng/ml no quarto pós-operatório, e estiveram dentro do limite da normalidade. Não foi observado nenhum óbito e um paciente evoluiu com alteração neurológica leve. A monitorização hemodinâmica não revelou alterações. Conclusão: A cirurgia de rev...

Introduction: The most common method used for myocardial protection is administering cardioplegic solution in the coronary circulation. Nevertheless, protection may be achieved by intermittent perfusion of the coronary system with patient's own blood. The intermittent perfusion may be performed by multiple sequences of clamping and opening of the aortic clamp or due single clamping and accessory cannulation of the aortic root as in the improved technique proposed in this study, reperfusion without the need for multiple clamping of the aorta. Objective: To evaluate the clinical outcome and the occurrence of neurological events in in-hospital patients submitted to myocardial revascularization surgery with the "improved technique" of intermittent perfusion of the aortic root with single clamping. Methods: This is a prospective, cross-sectional, observational study that describes a myocardial management technique that consists of intermittent perfusion of the aortic root with single clamping in which 50 patients (mean age 58.5±7.19 years old) have been submitted to the myocardial revasculrization surgery under the proposed technique. Clinical and laboratory variables, pre- and post-surgery, have been assessed. Results: The mean peak level of post-surgery CKMB was 51.64±27.10 U/L in the second post-surgery and of troponin I was 3.35±4.39 ng/ml in the fourth post-surgery, within normal limits. No deaths have occurred and one patient presented mild neurological disorder. Hemodynamic monitoring has not indicated any changes. Conclusion: The myocardial revascularization surgery by perfusion with the improved technique with intermittent aortic root with single clamping proved to be safe, enabling satisfactory clinical results. .

Development of cardioplegic solution without potassium: experimental study in rat / Desenvolvimento de solução cardioplégica sem potássio: estudo experimental em ratos

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.

Clinical and ultramicroscopic myocardial randomized study of beating versus arrested heart for mitral surgery / Estudo randomizado clínico e ultramicroscópico na cirurgia valvar mitral com o coração com atividade elétrica versus sem atividade elétrica

INTRODUCTION: Beating heart surgery on normothermic bypass simulates physiologic cardiac status. OBJECTIVES: This study compared clinical and transmission electron microscopic aspects of myocardial protection during mitral valve replacement using warm retrograde perfusion in empty beating versus arrested heart with cold blood anterograde cardioplegia. METHODS: Randomized study to evaluate myocardial cellular ischemia-reperfusion of both techniques to replace the mitral valve. Thirty-four patients were randomly assigned into group A (beating heart) and group B (arrested heart). The following parameters were assessed: echocardiography, blood chemistry, hemoglobin, lactate. During the surgical procedure a total of 102 myocardial biopsies were performed for ultrastructural analysis from anterior left ventricular wall: before cardiopulmonary bypass, before aortic desclamping and 10 minutes after reperfusion. RESULTS: Elevation of lactate at 3 hours during the procedure was higher in group A, but similar at the end of surgery (P=0.06). Cardioversion was necessary in 5/17 (A) vs. 13/17 (B) P=0.07. Median intraoperative systemic temperature was significantly lower in the group B compared to A (32oC vs. 36oC), P<0.001. There was no significant difference of the ultramicroscopic aspects of the heart biopsies before, during and after surgery in both groups. Cellular and mitochondrial transient abnormalities such as mitochondrial swelling, glycogen loss and cytosol swelling were detected independently of the moment of the biopsies. CONCLUSION: Myocardial protection and ultrastructural abnormalities were similar for both types of mitral valve replacement beating or arrested heart techniques.

INTRODUÇÃO: A cirurgia valvar mitral pode ser realizada com o coração com atividade elétrica, vazio e normotérmico com pinçamento aórtico, perfusão sanguínea no seio coronário, simulando um estado fisiológico. OBJETIVOS: Comparar as manifestações clínicas e ultramicroscópicas do miocárdio, na cirurgia valvar mitral, com o coração com atividade elétrica versus sem atividade elétrica. MÉTODOS: Estudo randomizado constituído de 34 pacientes: grupo A (batendo) e grupo B (parado). Os parâmetros foram: hematológico, bioquímico, ecocardiográfico, lactato. Foram realizadas 102 biopsias da parede anterior do ventrículo esquerdo preparadas para análise ultraestrutural: antes da circulação extracorpórea, antes do despinçamento aórtico e 10 minutos após a interrupção da circulação extracorpórea. RESULTADOS: Verificou-se elevação do lactato 3 horas após o início do procedimento, que foi maior no grupo A (P=0,06), todavia semelhantes no final da cirurgia. A cardioversão foi necessária em (A) 5/17 vs. (B) 13/17, P=0,07. A temperatura intraoperatória média foi significativamente menor no grupo B em relação ao grupo A (32oC vs. 36oC), P<0,001. A análise ultramicroscópica das amostras das biopsias do coração antes da circulação extracorpórea, ao término do pinçamento aórtico e após a saída da circulação extracorpórea, revelou anormalidades transitórias semelhantes no citoplasma, núcleos e mitocôndrias em ambos os grupos, independentemente do momento das biopsias. CONCLUSÃO: A proteção miocárdica na cirurgia valvar mitral apresentou aspectos semelhantes na preservação da integridade ultraestrutural dos cardiomiócitos quando realizada com o coração com ou sem atividade elétrica.

Recovery response of melatonin in induced myocardial infarction in adult male rabbits

Because myocardial infarction [MI] is a major cause of morbidity and mortality worldwide, protecting and remedy of the heart from the ischemia is the focus of intense research. This study aims to investigate the effects and the possible mechanism of melatonin in isoproterenol [ISO] induced acute MI in rabbits by studying electrocardiography [ECG], its angiogenic role, anti-inflammatory and antioxidants effects as well as histopathological changes of the cardiac muscle. A total of 50 rabbits were randomly divided into 5 groups, each of which were 10 rabbits: [I] Control group: received vehicle only, [II] Melatonin group: received melatonin in a dose of 10 mg/kg by intraperitoneal injection [i.pj, [III] MI group: MI was induced with ISO [85 mg /kg] administered subcutaneously twice at an interval of 24 h. [IV] Prophylactic group: melatonin injection was done for 7 days and induction of infarction with ISO was done at the 6[th] and 7[th] day of the experiment and [V] Therapeutic group: Injected with ISO in the 1[st] and 2[nd] day and melatonin was given for 7 days starting at day one of induced infarction. The following parameters were evaluated: ECG, heart weight/ body weight [HW/BW] ratio, serum levels of cardiac marker enzymes [creatinine kinase-MB [CK-MB], laclate dehydrogenase [LDH] and cardiac troponin-T [cTnT]]., inflammatory markers [serum tumor necrosis factor-a [TNFa] and cardiac myloperoxidase [MPO] enzyme], cardiac total peroxides level, total antioxidant capacity [TAC], oxidative stress index [OSI], angiogenic markers [cardiac vascular endothelial growth factor [VEGF] and inducihle nitric oxide [iNO]], and histopathological changes of the cardiac muscle. ISO induced MI rabbits showed significant pathological changes in the ECG pattern [elevated ST-segment and decreased R amplitude], significant increased HW/BW ratio, significant increased serum levels of cardiac marker enzymes [CK-MB, LDH and cTnT]. Also, inflammatory markers [serum TNF-alpha and cardiac MPO], angiogenic markers [VEGF and iNO], total peroxides and OS I were significantly higher whereas TAC were significantly lower in MI group as compared to control group. The histopathological findings of the myocardial tissue evidenced myocardial damage in ISO induced MI rabbits. Administration of melatonin in prophylactic and therapeutic groups revealed that melatonin has an efficient anti-inflammatory and antioxidant activity, reduced the cardiac marker enzymes and the pathological ECG patterns, ameliorated the increase in the HW/BW ratio and augmented myocardial angiogenesis. Also, decreased myocardial damage was evidenced by the histopathological findings with melatonin administration. The mending effects of melatonin in prophylactic group were more prominent than in the therapeutic group. The present study clearly demonstrated the cardioprotective effects of melatonin in a model of induced myocardial infarction which could be due to its anti-inflammatory, membrane stabilizing and free radical scavenging properties. Interestingly, this study is the first to prove the cardioprotective effect of melatonin via its angiogenic effect. Thereby, it should be considered for prophylactic and as a novel adjunctive therapy for attenuating ischemic myocardial damage

Sanguineous normothermic, intermittent cardioplegia, effects on hypertrophic myocardium: morphometric, metabolic and ultrastructural studies in rabbits hearts / Efeitos da cardioplegia sanguínea normotérmica intermitente, em miocárdio hipertrófico: estudos morfométricos, metabólicos e ultraestruturais em corações coelhos

OBJECTIVES: The present investigation aimed to study the protective effect of intermittent normothermic cardioplegia in rabbit's hypertrophic hearts. METHODS: The parameters chosen were 1) the ratio heart weight / body weight, 2) the myocardial glycogen levels, 3) ultrastructural changes of light and electron microscopy, and 4) mitochondrial respiration. RESULTS: 1) The experimental model, coarctation of the aorta induced left ventricular hypertrophy; 2) the temporal evolution of the glycogen levels in hypertrophic myocardium demonstrates that there is a significant decrease; 3) It was observed a time-dependent trend of higher oxygen consumption values in the hypertrophic group; 4) there was a significant time-dependent decrease in the respiratory coefficient rate in the hypertrophic group; 5) the stoichiometries values of the ADP: O2 revealed the downward trend of the values of the hypertrophic group; 6) It was possible to observe damaged mitochondria from hypertrophic myocardium emphasizing the large heterogeneity of data. CONCLUSION: The acquisition of biochemical data, especially the increase in speed of glycogen breakdown, when anatomical changes are not detected, represents an important result even when considering all the difficulties inherent in the process of translating experimental results into clinical practice. With regard to the adopted methods, it is clear that morphometric methods are less specific. Otherwise, the biochemical data allow detecting alterations of glycogen concentrations and mitochondria respiration before the morphometric alterations should be detected.

OBJETIVOS: O presente estudo teve como objetivo estudar o efeito protetor da cardioplegia normotérmica intermitente em corações hipertróficos de coelhos. MÉTODOS: Os parâmetros escolhidos foram: 1) relação peso cardíaco/peso corporal; 2) níveis de glicogênio nos músculos cardíacos; 3) alterações ultraestruturais por microscopia óptica e eletrônica; e 4) respiração mitocondrial. RESULTADOS: 1) O modelo experimental de coarctação da aorta induziu hipertrofia ventricular esquerda; 2) a evolução temporal dos níveis de glicogênio no miocárdio hipertrófico demonstra que há diminuição significativa; 3) observou-se tendência dependente do tempo para maiores valores do consumo de oxigênio para o grupo hipertrófico; 4) houve diminuição dependente do tempo da taxa de coeficiente respiratório no grupo hipertrófico; 5) os valores estequiométricos da ADP: O2 revelou a tendência decrescente no grupo hipertrófico; 6) observaram-se lesões mitocondriais do miocárdio hipertrófico, enfatizando a grande heterogeneidade dos dados. CONCLUSÃO: A aquisição de dados bioquímicos, principalmente o aumento na velocidade de quebra do glicogênio, quando mudanças anatômicas não são detectadas, representa um resultado importante, mesmo quando se consideram todas as dificuldades inerentes ao processo translacional de resultados experimentais para a prática clínica. No que diz respeito aos métodos adotados, é evidente que os métodos morfométricos são menos específicos. Os dados bioquímicos permitem a detecção de alterações das concentrações de glicogênio e respiração mitocondrial antes das alterações morfométricas serem detectadas.

Fatores associados à sobrevida em pacientes submetidos a transplante cardíaco utilizando microcardioplegia sanguínea retrógrada / Associated factors with survivals in patients undergoing orthotopic heart transplant using retrograde blood microcardioplegia

INTRODUÇÃO: Uma grande variedade de técnicas e soluções é utilizada na preservação do coração durante o transplante, o que demonstra a falta de método ideal na prática clínica. A administração da cardioplegia de forma retrógrada propicia perfusão contínua, o que pode conferir melhor recuperação inicial do coração transplantado. O objetivo deste trabalho é descrever a experiência de um único centro onde todos os pacientes receberam a mesma solução de conservação de órgão e foram submetidos a microcardioplegia sanguínea retrógrada contínua durante o implante do enxerto e avaliar fatores de mortalidade precoce e tardia com a utilização desta técnica. MÉTODOS: Este é um estudo retrospectivo, observacional e descritivo, realizado em um único centro. RESULTADOS: No período do estudo, foram realizados 35 transplantes cardíacos, sendo que 15 (42,9%) pacientes encontravam-se em choque cardiogênico. A probabilidade de sobrevida foi 74,8±7,8%, 60,4±11,3% e 15,1±13,4% ao final de 1 ano, 5 anos e 10 anos de seguimento, respectivamente. O tempo médio de sobrevida foi de 96,6 meses. CONCLUSÃO: A utilização da solução cardioplégica para proteção de órgãos e a estratégia de iniciar a perfusão com microcardioplegia sanguínea retrógrada contínua forneceu proteção adequada.

BACKGROUND: Several techniques and cardioplegic solutions have been used for heart preservation during transplant procedures. Unfortunately, there is a lack of ideal method for myocardial preservation in the clinical practice. The use of retrograde cardioplegia provides continuous infusion of cardioplegic solution during the graft implantation. This strategy may provide better initial recovery of the graft. The objective of this study is to describe the experience of a single center where all patients received the same solution for organ preservation and were subjected to continuous retrograde blood microcardioplegia during implantation of the graft and to evaluate factors associated to early and late mortality with this technique. METHODS: This is a retrospective, observational and descriptive study of a single center. RESULTS: During the study period were performed 35 heart transplants. Fifteen (42.9%) patients were in cardiogenic shock. The probability of survival was 74.8±7.8%, 60.4±11.3% and 15.1±13.4% at 1 year, 5 years and 10 years of follow-up, respectively. The median survival time was 96.6 months. CONCLUSION: The use of myocardial protection with retrograde cardioplegic solution may reduce the risks associated morbidity due to cold ischemia time during the heart transplant, and we suggest that this benefit may be even greater in cases of cold ischemia time longer ensuring protection to the myocardium.

Comparative experimental study of myocardial protection with crystalloid solutions for heart transplantation / Estudo comparativo experimental da proteção miocárdica com soluções cristalóides para transplante cardíaco

BACKGROUND: There is a growing need to improve myocardial protection, which will lead to better performance of cardiac operations and reduce morbidity and mortality. Therefore, the objective of this study was to compare the efficacy of myocardial protection solution using both intracellular and extracellular crystalloid type regarding the performance of the electrical conduction system, left ventricular contractility and edema, after being subjected to ischemic arrest and reperfusion. METHODS: Hearts isolated from male Wistar (n=32) rats were prepared using Langendorff method and randomly divided equally into four groups according the cardioprotective solutions used Krebs-Henseleit-Buffer (KHB), Bretschneider-HTK (HTK), St. Thomas-1 (STH-1) and Celsior (CEL). After stabilization with KHB at 37ºC, baseline values (control) were collected for heart rate (HR), left ventricle systolic pressure (LVSP), maximum first derivate of rise left ventricular pressure (+dP/dt), maximum first derivate of fall left ventricular pressure (-dP/dt) and coronary flow (CF). The hearts were then perfused at 10ºC for 5 min and kept for 2 h in static ischemia at 20ºC in each cardioprotective solution. Data evaluation was done using analysis of variance in completely randomized One-Way ANOVA and Tukey's test for multiple comparisons. The level of statistical significance chosen was P<0.05. RESULTS: HR was restored with all the solutions used. The evaluation of left ventricular contractility (LVSP, +dP/ dt and -dP/dt) showed that treatment with CEL solution was better compared to other solutions. When analyzing the CF, the HTK solution showed better protection against edema. CONCLUSION: Despite the cardioprotective crystalloid solutions studied are not fully able to suppress the deleterious effects of ischemia and reperfusion in the rat heart, the CEL solution had significantly higher results followed by HTK>KHB>STH-1.

INTRODUÇÃO: Existe crescente necessidade de aprimorar a proteção miocárdica, para melhor desempenho das operações cardíacas e diminuição da morbimortalidade. Portanto, o objetivo deste estudo foi comparar a eficácia da proteção miocárdica usando tanto solução cristaloide tipo intracelular como extracelular quanto ao desempenho do sistema de condução elétrica, contratilidade do ventrículo esquerdo e edema, após parada isquêmica e posterior reperfusão. MÉTODOS: Corações isolados de ratos Wistar foram montados em Langendorff e aleatoriamente divididos em quatro grupos. de acordo com as soluções cardioprotetoras utilizadas Krebs-Henseleit-Buffer (KHB), Bretschneider-HTK (HTK), St. Thomas-1(STH-1) e Celsior (CEL). Após a estabilização com KHB a 37ºC, valores basais (controle) foram coletados para frequência cardíaca (FC), pressão sistólica do ventrículo esquerdo (PSVE), derivada máxima de aumento da pressão ventricular esquerda (+dP/dt), derivada máxima de queda da pressão ventricular esquerda (-dP/dt) e fluxo coronariano (FCo). Os corações foram então perfundidos a 10ºC por 5 min e mantidos por 2 h em isquemia estática a 20ºC em cada solução cardioprotetora. Avaliação dos dados foi por análise de variância inteiramente casualizados em One-Way ANOVA e teste de Tukey para comparações múltiplas. O nível de significância estatística escolhido foi P<0,05. RESULTADOS: Houve recuperação da FC com todas as soluções utilizadas. A avaliação da contratilidade ventricular esquerda (PSVE, +dP/dt e -dP/dt) demonstrou que o tratamento com a solução CEL foi melhor em comparação às outras soluções. Ao analisar o CF, a solução HTK indicou melhor proteção contra edema. CONCLUSÃO: Apesar das soluções cristaloides cardioprotetoras estudadas não serem capazes de suprimir os efeitos deletérios da isquemia e reperfusão no coração de ratos, a solução CEL apresentou resultado superior seguido por HTK>KHB>STH-1.

Atrial septal defect closure on cardiopulmonary bypass in a sickle cell anemia: Role of hydroxyurea and partial exchange transfusion.

Partial exchange transfusion during cardiopulmonary bypass, while conducting cardiac surgery may be a useful technique in patients with high level of sickle hemoglobin. Along with this preoperative use of hydroxyurea and alternative analgesic modalities such as transcutaneous electrical nerve stimulation in postoperative period may be beneficial, in our opinion. A 16-year-old female of Turner's syndrome having sickle cell anemia scheduled for closure of arterial septal defect on cardiopulmonary bypass was managed with partial exchange transfusion and warm cardioplegia.

Análise ultra-estrutural do miocárdio usando solução cardioplégica cristalóide com e sem procaína em pacientes submetidos à troca valvar aórtica / Ultrastructural study of the myocardium using cardioplegic crystalloid solution with and without procaine in patients undergoing aortic valve replacement

OBJETIVO: Avaliar as alterações ultra-estruturais de dois tipos de cardioplegia (com e sem procaína) em corações de pacientes submetidos a troca valvar aórtica eletiva. MÉTODOS: Foram estudados 18 pacientes submetidos a circulação extracorpórea para troca valvular aórtica eletiva, no Hospital de Clínicas de Porto Alegre num período de 10 meses. Cada paciente foi distribuído aleatoriamente em dois grupos: grupo A - oito pacientes que receberam solução cardioplégica sem procaína; grupo B - Dez pacientes que receberam solução cardioplégica com procaína. Em ambos os grupos, o saco pericárdico foi irrigado com solução salina hipotérmica. As biópsias miocárdicas foram realizadas em três momentos: I - antes da parada isquêmica, II- no final do período isquêmico e III-15 minutos após a reperfusão. RESULTADOS: A avaliação ultra-estrutural comparando os grupos nos três momentos não demonstrou diferenças significativas, sendo a média dos escores no grupo A, nos momentos I, II, e III, de 0,1 ± 0,2; 0,4 ± 0,3 e 0,4 ± 0,4. No grupo B, a médio dos escores foi 0,2 ± 0,2; 0,4 ± 0,3 e 0,7 ± 0,2, respectivamente), nos momentos I, II, e III. A curva de CK-MB foi similar entre os dois grupos. O retorno espontâneo do ritmo cardíaco, pós-despinçamento, ocorreu em 70% dos pacientes no grupo B e, em 12,5% no grupo A (p=0,024). CONCLUSÃO: As duas soluções testadas protegeram o miocárdio de forma eficaz e não foi possível demonstrar, em nível ultra-estrutural, a superioridade da solução contendo procaína. Constatou-se que o retorno ao ritmo espontâneo do coração após o despinçamento aórtico foi significativamente maior no grupo que utilizou procaína adicionada à solução.

OBJECTIVE: The aim of this study was to assess whether the presence of procaine in crystalloid cardioplegic solution increases myocardial protection at the ultra structural level. METHODS: Eighteen patients that underwent aortic valve replacement in the Hospital de Clínicas de Porto Alegre over a 10-month period were studied. They were randomly allocated into two groups: group A - eight patients receiving cardioplegia without procaine; group B - ten patients receiving cardioplegia with procaine. Myocardial biopsies were performed in three different periods: 1st - before ischemic arrest, 2nd - at the end of ischemic arrest, and 3rd -15 minutes after reperfusion. RESULTS: The ultra structural analysis comparing the groups in the three moments did not show any statistically significant difference. The mean score in group A at moment I, II and III was 0.1 ± 0.2; 0.4 ± 0.3; 0.4 ± 0.4, and group B 0.2 ± 0.2; 0.4 ± 0.3; 0.7 ± 0.2. Comparative analysis of CK-MB was similar. The spontaneous return to sinus rhythm after aortic declamping in group B occurred in 70% and in group A 12.5% (p=0.024). CONCLUSION: Both cardioplegic solutions tested were equally effective in myocardial preservation, and we could not demonstrate at the ultrastructural level any benefit when procaine was added. The spontaneous return to sinus rhythm after aortic declamping was significantly greater when procaine was added.

Proteção miocárdica ao coração hipertrofiado: o eterno desafio: [revisão] / Myocardial protection to the hypertrophied heart: the eternal challenge: [review]

A proteção miocárdica permitiu enorme avanço na moderna cirurgia cardíaca, reduzindo a mortalidade e permitindo que operações cada vez mais complexas pudessem ser realizadas. A alteração na população eleita para procedimentos cirúrgicos cardiológicos mudou significativamente nas últimas décadas, com o aumento de pacientes mais idosos, com função ventricular deprimida e miocárdio hipertrofiado. Essa última condição, desde os primórdios da cirurgia cardíaca, constituiu-se em grande desafio. Diversas técnicas de proteção ao miocárdio hipertrofiado foram descritas, porém com resultados não alentadores. As características da hipertrofia miocárdica no adulto com cardiopatia cirúrgica apresentam particularidades desafiadoras. Nesse artigo, procuramos atualizar o estado da arte sobre a proteção miocárdica ao coração hipertrofiado.

The myocardial protection allowed great advance in cardiac surgery, decreasing the mortality and making more feasible complex surgeries. Latterly, the patient population elected for cardiac procedures has been changing towards elderly patients with ventricular function depressed and myocardial hypertrophy. The myocardial hypertrophy condition represents a great challenge since the beginning of the cardiac surgery. Several techniques have been described to protect the myocardial hypertrophy, however with no satisfactory results. In this manuscript we present the state of the art technique of myocardial protection.

Myocardial protection by continuous, blood, antegrade-retrograde cardioplegia in rabbits

PURPOSE: To study the effectiveness of the continuous, blood, antegrade-retrograde cardioplegia in an experimental model of isolated heart, evaluating ventricular function. METHODS: Rabbits were divided into four groups: Control-C(n=10); ischemic crystalloid cardioplegia-IC(n=10); ischemic blood cardioplegia-IB(n=10); ischemic non cardioplegia-INC(n=10). After the ischemic protocol period the ventricular function was analyzed by the intra-ventricular balloon technique. RESULTS: the intra-ventricular developed pressure (IVDP) was: C(92.90±6.86mmHg); IC(77.78±6.15mmHg); IB(93.64±5.09mmHg); INC(39.46 ±8.91mmHg) p<0.005. The first derivative of intra-ventricular pressure in its positive deflection was: C(1137.50± 92.23mmHg/sec); IC(1130.62 ±43.78mmHg/sec); IB(1187.58± 88.38mmHg/sec); INC(620.02± 43.80mmHg/se) p<0.005. The first derivate pressure in its negative deflection was: C(770.00± 73.41mmHg/sec); IC(610.03 ±47.43mmg/sec); IB(762.53 ±46.02mmHg/sec); INC(412.35 ±84.36mmHg/sec) p<0,005. The stress-strain angular logarithmic coefficient was: C(0.108± 0.02); IC(0.159± 0.038); IB(0.114 ±0.016); INC(0.175± 0.038) p<0.05. CONCLUSION: The ischemic group protected by blood cardioplegia showed better ventricular function than ischemic group protected by crystalloid cardioplegia and the non protected group.

OBJETIVO: Estudar a eficácia e a segurança da cardioplegia sanguínea, aterógrada-retrógrada contínua, por meio da avaliação da função ventricular. MÉTODOS: Os coelhos foram divididos em quatro grupos: Controle-C(n=10); isquêmico e cardioplegia cristaloide-IC(n=10; isquêmico e cardioplegia sanguínea-IB(n=10; isquêmico sem cardioplegia-INC(n=10. Após o período isquêmico do protocolo a função ventricular foi analisada pela técnica do balão intra-ventricular. RESULTADOS: a pressão desenvolvida intra-ventricular (IVDP) foi: C(92,90± 6,86mmHg); IC(77,78± 6,15mmHg); IB(93,64 ±5,09mmHg); INC(39,46 ±8,91mmHg) p<0,005. a primeira derivada temporal da pressão ventricular na sua deflexão positiva: C(1137,50± 92,23mmHg/sec); IC(1130,62 ±43,78mmHg/sec); IB(1187,58± 88,38mmHg/sec); INC(620,02± 43,80mmHg/se) p<0,005. A primeira derivada da pressão ventricular na sua deflexão negativa: C(770,00± 73,41mmHg/sec); IC(610,03 ±47,43mmg/sec); IB(762,53 ±46,02mmHg/sec); INC(412,35 ±84,36mmHg/sec) p<0,005. A relação do coeficiente angular logarítmico foi: C(0,108± 0,02); IC(0,159± 0,038); IB(0,114 ±0,016); INC(0,175± 0,038) p<0,05. CONCLUSÃO: No modelo experimental estudado o grupo isquêmico protegido pela cardioplegia sanguínea apresentou melhor função ventricular que os grupos protegidos por cardioplegia cristalóide e não protegido.

Solução cardioplégica polarizante: estado da arte / Polarizing cardioplegic solution: state of the art

A exegese do termo cardioplegia remete aos significados de lesão, golpe, ataque ou ferimento, bem diferente, portanto, do sentido em que o termo é empregado na maior parte dos centros de cirurgia cardíaca do Brasil e do mundo, ou seja, como correspondendo à proteção miocárdica. Daí a melhor denominação de solução cardioplégica, para caracterizar as soluções empregadas com finalidade de promover a parada cardíaca controlada do coração. A parada cardíaca induzida por solução cardioplégica pode acontecer por hiperpolarização, despolarização ou com bloqueadores da bomba de cálcio. No presente trabalho, discorreremos sobre os principais agentes que promovem a parada cardíaca por hiperpolarização da membrana miocárdica. Com a solução hiperpolarizante, o coração pára no perído diastólico, havendo uma redução ainda maior no seu gasto energético, o que propicia melhores condições ao coração quando este reinicia sua contração ao final do procedimento cirúrgico

Comparative study between cold and warm cardioplegia in cabg operations

The objective of this study is to prospectively evaluate two different cardioplegia techniques: intermittent cold cardioplegia and warm blood cardioplegia. Between During the period between August 2002 and April 2003, 35 consecutive patients undergoing elective CABG were studied in a prospective randomized trial. The patients were randomized in 2 groups: group I [20 patients] received intermittent cold crystalloid cardioplegia [15øO] and group H [15 patients] received undiluted warm blood [37øO], antigrade cardioplegia enriched with potassium and magnesium. Patients were predominantly male and the mean age was 56-5 years in group I and 54 +/- 5 in group IL There was no significant statistical difference between the 2 groups as regard the risk factors for CAD [smoking, hypertension, diabetes and hyperlipidemia]. Preoperative ejection fraction [EF] was 54 +/- 2% in group I and 52 +/- 2% in group II with P=0.380338 [NS]. The cross clamp time was 55 +/- 5 mm in group I and 53 +/- min in group II with P 0.429421 [NS]. The CPB time was 99-16 min in group I and 95 +/- 17 min in group II with P=0.108781 [NS]. Vasocon-strictive drugs were used in 7 patients [35%] in group I as compared to 5 patients [33%] in group II with P>0.05 [NS]. The total volume of crystalloid solution infused during CPB was 1332 +/- 309 ml. for group I and 1520 +/- 227 ml for group II with P=0.000263 [HS]. Hematocrit value during CPB was 29 +/- 2% in group I and 32 +/- 3% in group II with P=0.037741 [S]. The patients continued on mechanical ventilator for 9 +/- 1 hours in group I and 8.5 +/- 1 hours in group H. The postoperative chest tubes drainage was 460 +/- 153 ml in group I and 530 +/- 59 ml in group II with P=0.086227[NS]. Hematocrit value after CR8 was 35 +/- 4% in group I and 34 +/- 3% in group II with P=0.505103[NS]. The patients stayed in the ICU for 2.9-0.6 days in group I and 3.2 +/- 0.5 days in group H with P=0.334282[NS]. There is no statistical dfference between the 2 groups before aortic cross-clamping as regard serum lactate and troponin I. One minute after unclamping, the serum lactate was 0.9 +/- 0.3 mmoles/l in group I and 0.7 +/- 0.4 mmoles/l in group H with no significant difference [P>0.05] ponin I was 0.4 +/- 0.3 g/l in group I and 0.6-0.3 g/l in group II with P>0. 05 [NS]. The findings of our study did not reveal any significant difference between the warm blood cardioplegia and the cold cardioplegia in terms of myocardial protection, either for clinical or biological data