Effect of del nido cardioplegia use on kidney injury after coronary bypass operations

SUMMARY OBJECTIVE: After cardiac surgery, acute kidney injury is observed at a rate of 5-30%, and the second most common cause of acute kidney injury in intensive care units is cardiac surgery. In this study, we aimed to investigate the effect of del Nido cardioplegia solution use on postoperative acute kidney injury development in patients who underwent coronary artery bypass grafting operation with cardiopulmonary bypass. METHODS: Consecutive patients who underwent an elective coronary artery bypass grafting operation with cardiopulmonary bypass in our clinic between March 15, 2019, and March 15, 2020, were included in the study retrospectively. The patients were divided into two groups as those who received del Nido cardioplegia solution (Group 1) and blood cardioplegia (Group 2), and factors affecting the development of renal failure were examined. RESULTS: A total of 350 consecutive patients were included in the study. There were 156 patients in the del Nido cardioplegia group and 194 patients in the blood cardioplegia group. Among the patient group, 74 (21.1%) patients developed acute kidney injury. The total acute kidney injury development rate was significantly higher in Group 2 (p=0.018). In multivariate logistic regression analysis, advanced age (OR 1.128; 95%CI 1.044-1.217; p=0.042), increased blood product use (OR 1.318; 95%CI 1.154-1.998; p=0.019), preoperative creatinine elevation (OR 2.434; 95%CI 1.655-4.639; p=0.005), and increased cardioplegia volume (OR 1.254; 95%CI 1.109-2.980; p=0.009) were independent predictors of acute kidney injury. CONCLUSION: With this study, we showed that the use of del Nido cardioplegia solution can reduce the incidence of acute kidney injury.

Blood mRNA Expression Profiles of Autophagy, Apoptosis, and Hypoxia Markers on Blood Cardioplegia and Custodiol Cardioplegia Groups

Abstract Introduction: Blood cardioplegia (BC) and Custodiol cardioplegia (CC) have been used for a long time in open heart surgery and are highly effective solutions. The most controversial issue among these two is whether there is any difference between them regarding myocardial damage after ischemia surgery. In this study, autophagy, apoptosis, and hypoxia markers were investigated and that way we evaluated the differences between BC and CC patients. Methods: A total of 30 patients were included in this study, using two different cardioplegic solutions. Three different whole blood samples of the patients were taken from a central vein (preoperatively, immediately postoperatively, and one day after surgery). Total ribonucleic acid was extracted from these samples. Quantitative real-time polymerase chain reaction was performed, and changes in gene expression were determined by the 2-∆∆Ct method of relative quantification. Results: In the CC group, Beclin gene expression level was found to be higher and this difference was statistically significant (P=0.0024). Similarly, cysteine-aspartic acid protease (caspase) 9 and hypoxia-inducible factor 1α messenger ribonucleic acid (mRNA) gene expression level increased and were significantly different in the CC group. In the BC group, Beclin and microtubule-associated protein light chain 3 expressions were higher in the samples taken one day after surgery. Caspases 3 and 8 gene expressions were significantly different in the BC group. Conclusion: As a result of the analysis performed between the two cardioplegia groups, it has been shown that CC harms the myocardium more than BC at the level of mRNA expression of related markers.

Comparison of del nido cardioplegia and blood cardioplegia in terms of development of postoperative atrial fibrillation in patients undergoing isolated coronary artery bypass grafting

Abstract Objective: Del Nido cardioplegia (DNC) has been used in pediatric cardiac surgery for many years with a single dose application and its usage in adult cardiac surgery has been increasing in recent years, with results being published. In this study, we aimed to investigate the effect of DNC on the development of postoperative atrial fibrillation (PoAF). Methods: In this retrospective observational comparative study, 255 patients who underwent isolated on-pump coronary artery bypass grafting, between January 2019 and November 2019, were enrolled. The patients were divided into two groups: DNC (n=132) and blood cardioplegia (BC) (n=123). Intraoperative and postoperative data were evaluated and compared in terms of the development of PoAF. Results: We found that the development of PoAF and the length of hospital stay remain significantly higher in the BC group (P=0.044, P<0.001, respectively). In addition, the aortic cross-clamp time and the cardioplegia volume delivered were significantly lower in the DNC group (P=0.042, P<0.001, respectively). In multivariate logistic regression analysis, only higher cardioplegia volume was determined as an independent predictor for PoAF development (OR 1.001; 95% CI 1.000-1.001; P=0.033). We did not found difference between groups in terms of troponin T, inotropic drug support, need for intraaortic balloon pump and mortality. Conclusion: This study showed that DNC can be used safely in adult coronary bypass surgery and PoAF development effect is reduced.

Reemplazo de aorta ascendente con paro circulatorio con hipotermia sistémica moderada y perfusión cerebral retrógrada / Total replacement of the ascending aorta with moderate systemic hypothermic circulatory arrest and retrograde cerebral perfusion

Resumen: Antecedentes: El daño neurológico es una complicación devastadora de la cirugía con paro circulatorio del cayado aórtico y aorta ascendente. La perfusión anterógrada del encéfalo permite disminuir la incidencia de esta complicación, pero es un procedimiento engorroso que interfiere el campo quirúrgico. Para procedimientos más simples que requieran de paro circulatorio de menor duración, la Perfusión Cerebral Retrógrada (PCR) es una alternativa válida. Objetivo: Evaluar nuestros resultados en la cirugía del reemplazo total de la aorta ascendente tubular con paro circulatorio con hipotermia sistémica moderada y PCR. Material y Método: Entre enero de 2015 y enero de 2020 se identificaron los pacientes en la Base de Datos del Servicio de Cirugía Cardiaca de nuestra institución, se revisaron los protocolos operatorios, registros de perfusión y epicrisis, para obtener datos demográficos, clínicos y quirúrgicos pertinentes. La supervivencia alejada se certificó a través del "Servicio Registro Civil e Identificación de Chile". Resultados: En el periodo en estudio, 27 pacientes (21 hombres) tuvieron un reemplazo total de la aorta ascendente tubular con paro circulatorio con hipotermia moderada y PCR. Ocho pacientes tenían una cirugía previa; 7 de estos un reemplazo valvular aórtico. El 75% de los otros 20 pacientes tenía una válvula aórtica bicúspide. El diámetro máximo de la aorta ascendente fue en promedio 53,7 mm (45 a 67), y fue reemplazada en el 52% de los casos con un tubo protésico de 34 mm (promedio:32,4 mm; margen:30 a 34 mm). En 20 pacientes se efectuó un reemplazo valvular aórtico (15 con prótesis biológica). El tiempo promedio de circulación extracorpórea fue 174,6 min (97 a 243) y la temperatura sistémica mínima promedio fue 21ºC (18 a 25). El tiempo promedio de paro circulatorio fue 22,3 min (12 a 40) y de PCR 13 min (6 a 27). No hubo mortalidad operatoria. La morbilidad más frecuente fue la fibrilación auricular (33%). Una paciente presentó un episodio convulsivo aislado y otro fue reoperado por hemorragia postoperatoria. Una paciente falleció a los 48 meses de su operación. Conclusión: El paro circulatorio con hipotermia sistémica moderada y PCR para la cirugía de reemplazo total de la aorta ascendente facilitó la operación, con baja mortalidad y morbilidad en este grupo de pacientes.

Abstract: Background. Neurological damage is a devastating complication of aortic arch and ascending aorta surgery with deep hypothermic circulatory arrest. Antegrade cerebral perfusion significantly decreases the incidence of this complication, but it is a cumbersome procedure that interfere the surgical field. For more simple procedures, requiring a shorter period of circulatory arrest, retrograde cerebral perfusion (RCP) would be a valid alternative. Objective. To evaluate the results of total surgical replacement of the tubular ascending aorta with moderate hypothermic circulatory arrest and retrograde cerebral perfusion (RCP). Methods. Patients operated between January 2015 and January 2020 were included.Demographic, clinical and surgical information was obtained from the operatives notes, perfusion registry and discharge reports. Long-term survival was certified by the "Chilean Civil and Identification Registry". Results. 27 patients (21 men) underwent a total replacement of the tubular ascending aorta with circulatory arrest with moderate hypothermia and RCP. Eight patients had been previously operated on;7 of them had a previous aortic valve replacement. Of the remaining 20 patients, 75% had a bicuspid aortic valve. Average maximum diameter of the ascending aorta was 53.7 mm (45 - 67). Average size of the ascending aorta replacement graft was 32.4 mm (30 -34). In 20 patients a concomitant aortic valve replacement was performed (15 with a biological valve). Mean extracorporeal circulation time was 174.6 min (97 - 243) and mean minimal systemic temperature was 21ºC (18 - 25). Mean circulatory arrest time was 22.3 min (12 - 40) and mean RCP time was 13 min (6 - 27), There was no operative mortality. Atrial fibrillation was the most frequent post-operative morbidity (33%). One patient presented an isolated convulsive episode and another was re-operated due to postoperative hemorrhage. One patient died, 48 months after her operation. Conclusion. Moderate hypothermic circulatory arrest with RCP simplifies total tubular ascending aorta replacement, with low mortality and morbidity.

Single-dose del nido cardioplegia vs. blood cardioplegia in aortic valve replacement surgery

Abstract Introduction: In this study, we aimed to compare Del Nido cardioplegia (DNC) with blood cardioplegia (BC) in aortic valve replacement. Methods: A two-year single-institute retrospective cohort study was accomplished. Subjects who underwent aortic valve replacement surgery were divided into two groups (DNC and BC) and outcomes were compared. Results: Preoperative demographics and clinical data of the patients in both groups were similar. The time until cardiac arrest following administration of the first dose of cardioplegia was statistically significantly shorter in the BC group (47.0 sec. 25-103) than in the DNC group (63.0 sec. 48-140) (P=0.012). Cross-clamping time was longer in the BC group (48.7±12.3 min. vs. 41.5±11.8 min.) (P=0.041). Cardiopulmonary bypass time was statistically significantly shorter in the DNC group (BC 60.8±18.5 min., DNC 53.7±15.2 min.) (P=0.046). The rate of postoperative use of intravenous positive inotropic support drugs (dopamine, dobutamine, norepinephrine, etc.) for more than two hours was significantly higher in the BC group (20 [23.5%] in the BC group and nine [17.3%] in the DNC group) (P=0.035). Creatine kinase myocardial band and troponin I levels were slightly lower in patients receiving DNC, but no statistically significant difference was detected. Conclusion: Del Nido cardioplegia is safe and can be used efficiently as an alternative to blood cardioplegia in isolated aortic valve replacement surgery.

Comparison of the operative and postoperative effects of del Nido and blood cardioplegia solutions in cardiopulmonary bypass surgery

Abstract Objective: Our goal was to compare the operative and postoperative effects of del Nido cardioplegia (DN group) and blood cardioplegia (BC group) performed in cardiac surgery. Methods: A total of 83 patients were included, separated into DN group and BC group. The operative and postoperative effects of the two groups were compared for the first 24 hours until extubation. The operative and postoperative complete blood count (CBC), biochemical values and clinical parameters were compared. Results: The first control activated clotting time (ACT) levels in DN group patients were lower (P=0.003) during the operation. The amount of cardioplegia in DN group were lower than that in BC group (P=0.001). The pump outflow and postoperative lactate level of DN group were lower than those of BC group (P=0.005, P=0.018, respectively), as well as the amounts of NaHCO3 (P=0.006) and KCl (P=0.001) used during the operation. The same occurred with the first monocytes (Mo) and mean corpuscular volume (MCV) levels in the postoperative intensive care unit (P=0.006, P=0.002). However, the first glucose level and the eosinophil (Eo) level were higher in DN group (P=0.011, P=0.047, respectively). Conclusion: In the operative evaluation, the amount of cardioplegia, the first ACT levels, the pump outflow lactate level and the amounts of NaHCO3 and KCl in DN group were lower. In postoperative evaluation, measured level of lactate, Mo and MCV in DN group were all lower; their glucose and Eo levels were higher.

Comparison between the effects of bretschneiders htk solution and cold blood cardioplegia on systemic endothelial functions in patients who undergo coronary artery bypass surgery: a prospective randomized and controlled trial

Abstract Objective: To investigate the effects of Bretschneider's histidine-tryptophan-ketoglutarate (HTK) solution and cold blood cardioplegia on systemic endothelial functions. Methods: A total of 50 patients who underwent isolated coronary artery bypass surgery between March 2018 and May 2018 were randomly divided into two groups - group 1 (Bretschneider's HTK solution, n=25) and group 2 (cold blood cardioplegia, n=25). Data related to the indicators of endothelial dysfunction were recorded. Flow-mediated dilation was measured together with the assessment of the values of endothelin-1, von Willebrand factor, and asymmetric dimethylarginine to identify endothelial dysfunction. Then, the two groups were compared regarding these values. Results: The most significant result of our study was that the endothelin-1 level was significantly higher in group 2 than in group 1 (P<0.001). The value of flow-mediated dilation was found to increase to a lesser degree on the postoperative days compared to the value at the day of admission in group 1 (P=0.002 and P=0.030, respectively). Conclusion: Cardiopulmonary bypass leads to endothelial dysfunction. Our results revealed that Bretschneider's HTK solution causes less severe endothelial injury than cold blood cardioplegia.

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.

Protección miocárdica en pediatría / Pediatric myocardial protection

La cardioplejía es la mejor solución para obtener un campo operatorio cardíaco seco y quieto; también es el principal componente de la protección miocárdica. No hay dudas de su eficiencia en la prevención de las lesiones isquémicas miocárdicas durante el clampeo transversal aórtico, aunque hay pocos datos, si los hay, basados en la evidencia sobre la mejor calidad y cantidad de la cardioplejía que se requiere para maximizar la protección miocárdica (la cual puede ser diferente de una patología a otra). Durante años el método de referencia fue la cardioplejía cristaloide fría intermitente, pero progresivamente se implementaron algunos perfeccionamientos. El cambio de una cardioplejía cristaloide a una sanguínea y de una fría a una templada fueron probablemente las dos modificaciones principales adoptadas por un gran número de cirujanos cardíacos. Estas modificaciones se implementaron inicialmente en la cirugía en adultos y luego se aplicaron en la cirugía pediátrica. El objetivo de esta reseña fue describir la base racional de estos cambios, así como la progresión del uso de la cardioplejía sanguínea templada intermitente en las unidades pediátricas, sus ventajas y resultados. Otros factores involucrados en la protección miocárdica y las perspectivas futuras se analizan brevemente...

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.

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.