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.

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.

Comparative analysis of myocardial protection with htk solution and hypothermic hyperkalemic blood solution in the correction of acyanogenic congenital cardiopathies - a randomized study

Abstract Objective: The goal of the present study was to compare the myocardial protection obtained with histidine-tryptophan-ketoglutarate (HTK) cardioplegic solution (Custodiol®) and with intermittent hypothermic blood solution. Methods: Two homogenous groups of 25 children with acyanotic congenital heart disease who underwent total correction with mean aortic clamping time of 60 minutes were evaluated in this randomized study. Troponin and creatine kinase-MB curves, vasoactive-inotropic score, and left ventricular function were obtained by echocardiogram in each group. The values were correlated and presented through graphs and tables after adequate statistical treatment. Results: It was observed that values of all the studied variables varied over time, but there was no difference between the groups. Conclusion: We conclude that in patients with acyanotic congenital cardiopathies submitted to total surgical correction, mean aortic clamping time around one hour, and cardiopulmonary bypass with moderate hypothermia, the HTK crystalloid cardioplegic solution offers the same myocardial protection as the cold-blood hyperkalemic cardioplegic solution analyzed, according to the variables considered in our study model.

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.

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.

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

Utilidad de la terapéutica metabólica G-I-K en cirugía de cardiacos / On metabolic therapeutics G-I-K in surgery of cardiac patients

Se exponen en forma sintética los principios básicos de la terapéutica metabólica, en su modalidad de las venoclisis con glucosa, insulina y potasio, ya propuestas a su tiempo por el Dr. Demetrio Sodi Pallares. Se relata la sucesión cronológica de la aplicación de dicho tratamiento en las fases preoperatoria, transoperatoria y postoperatoria de cirugía cardiovascular. Se describen asimismo algunas observaciones personales de uno de los autores. Se concluye que la mezcla glucosa-insulina-potasio constituye un poderoso sistema donador de energía y el aporte generoso de esta última es muy útil para la protección del miocardio dañado en cirugía cardíaca y no cardíaca. Lo demuestra el gran número de publicaciones al respecto. Las más recientes señalan la reducción de los síndromes de bajo gasto debidos a intervenciones sobre las arterias coronarias, así como la baja del nivel de ácidos grasos circulantes tras las angioplastías primarias. Las soluciones mencionadas, en concentraciones mayores que las iniciales, podrían volverse una medida rutinaria en los centros de medicina y cirugía generales.

The basic principles of the metabolic therapeutics with glucose-insulin-potassium solutions, already proposed by Dr. Demetrio Sodi Pallares, are exposed. Chronologic succession of this treatment during the preoperative, transoperative and postoperative phases of heart surgery, as well as some personal observations of one of the authors, are described. The glucose-insulin-potassium solution is a powerful system, providing very useful energy to protect the injured myocardium during cardiovascular surgery. Many publications support this assertion. The most recent ones indicate a reduction of low output syndromes due to interventions on coronary arteries, as well as a significant diminution of circulating fatty acids after primary angioplasty. The mentioned solution, in higher concentrations than the initial one, could become routine therapeutics in medicine and surgery centers, in general.

Soluciones cristaloides y coloides, como sustitutas de la sangre en el cebado del circuito extracorpóreo durante la cirugía cardiovascular / Crystalloid and colloidal solutions as blood substitutes in the priming of the extracorporeal circuit during cardiovascular surgery

Se realizó un estudio cualitativo donde se exponen las características principales, objetivos de aplicación y las ventajas que ofrecen las diferentes soluciones coloidales y electrolíticas utilizadas en el cebado del circuito extracorpóreo. Como objetivo principal se exponen los argumentos necesarios que permiten al perfusionista combinar determinadas soluciones, para conservar la osmolaridad, la presión oncótica del plasma, mejorar el flujo microcirculatorio y evitar las transfusiones de sangre y hemoderivados innecesarias. También se mencionan diferentes técnicas para conservar el nivel del hematócrito, como son el uso de hemofiltros, concentrador de células y la aplicación de la cardioplejia sanguínea, que aunque su principal objetivo es la protección miocárdica, también sustituye los grandes volúmenes de líquido que caracteriza el uso de la cardioplejia cristaloide(AU)

The chief characteristics, objectives of application and the advantages the colloidal and electrolytic solutions used in the priming of the extracorporeal circuit offer are explained in this qualitative study. The necessary arguments that allow the perfusionist to combine certain solutions to conserve osmolarity, the oncotic pressure of plasma, to improve the microcirculatory flow and to avoid blood transfusions and unnecessary hemoderivatives, are dealt with as the fundamental aim. Reference is made to different techniques used to conserve the haematocrit level, such as: the use of haemofilters, cell concentrator and the application of blood cardioplegia, whose main goal is the myocardial protection, but it also substitutes the great volumes of fluid that characterize the use of crystalloid cardioplegia(AU)

Development and Evaluation of a New Apparatus for Continuous Perfusion of Isolated Perfused Pig Heart

To develop a better model of isolated perfused heart, a new apparatus of "coronary artery cannula- fixed-in-aortic tube" was developed for continuous normothermic perfusion and compared to the Casalis apparatus with cold ischemia. Eight mongrel pigs with the body weight of 18 to 24 kg were divided half into two groups.All the continuous perfusion experimental hearts resumed a spontaneous heart beat and stabilized earlier than the control hearts without the need of defibrillator or pacemaker, indicating no reperfusion injury on the heart. All the experimental hearts did not show fibrillation nor stopped beating during the entire experiment, whereas the control hearts fibrillated. Two control hearts stopped beating, and only one of the two survived with the help of pacemaker.The coronary systolic, diastolic, and mean pressures were more stable with low variation in the experimental hearts than the cold ischemic control hearts. The experimental hearts consumed more oxygen than the control hearts, indicating more cardiac output.According to these results, the continuous normothermic perfusion method by the new cannula, even though with a short-period of hypothermic perfusion, provided better myocardial protection than the cold ischemia.

Volatile cardioplegia: fast normothermic cardiac arrest induction and recovery with halothane in isolated rat hearts

To study the effect of halothane as a cardioplegic agent, ten Wistar rats were anesthetized by ether inhalation and their hearts were perfused in a Langgendorff system with Krebs-Henseleit solution (36 graus Celsius; 90 cm H2O pressure). After a 15-min period for stabilization the control values for heart rate, force (T), dT/dt and coronary flow were recorded and a halothane-enriched solution (same temperature and pressure) was perfused until cardiac arrest was obtained. The same Krebs-Henseleit solution was reperfused again and the parameters studied were recorded after 1,3,5,10,20 and 30 min. Cardiac arrest occurred in all hearts during the first two min of perfusion with halothanebubbled solution. One minute after reperfusion without halothane, the following parameters reported in terms of control values were obtained: 90.5 percent of control heart rate (266.9 + 43.4 to 231.5 + 71.0 bpm), 20.2 percent of the force (1.83 + 0.28 to 0.37 + 0.25 g), 19.8 percent of dT/dt (46.0 + 7.0 to 9.3 + 6.0 g/s) and 90.8 percent of coronary flow (9.9 + 1.5 to 9.4 + 1.5 ml/min). After 3 min of perfusion they changed to 99.0 percent heart rate (261.0 + 48.2), 98.9 percent force (1.81 + 0.33), 98.6 dT/dt (45.0 + 8.2) and 94.8 percent coronary flow (9.3 + 1.4). At 5 min 100.8 percent (267.0 + 40.6) heart rate, 105.0 percent (1.92 + 0.29) force and 104.4 percent (48.2 + 7.2) dT/dt were recorded and maintained without significant differences (P>0.01) until the end of the experiment. These data demonstrate that volatile cardioplegia with halothane is an effective technique for fast induction of and prompt recovery from normothermic cardiac arrest of the rat heart.

Estudio comparativo de tres soluciones cardiopléjicas en pacientes sometidos a cirugía cardíaca / Comparative study of three cardioplegic solutions in patients submitted to cardiac surgery

Veinte pacientes operadores de cirugía de by pass aortocoronario fueron divididos en grupo I (n=7), que recibió como protección miocárdica una solución cardiopléjica standard; grupo II (n=6), que recibió una solución cardiopléjica conteniendo manitol; y grupo III (n=7) que recibió solución cardiopléjica con deferoxamina. Se tomaron biopsias de miocardio, previo al período isquémico (muestras A o preisquémicas) y a los 10 minutos de la reperfusión (muestras B o de reperfusión) las cuales fueron procesadas para quimioluminiscencia para detectar actividad de radicales libres y para microscopía electrónica con el objeto de evaluar lesión miocárdica a nivel de ultraestructura. Se observó que en el grupo I se producía un significativo aumento de los valores de quimioluminiscencia en las muestras B y ésto se asociaba con la presencia de áreas con franco edema mitocondrial. En los grupos II y III no había diferencia significativa entre las muestras A y B. Los resultados sugieren que durante la reperfusión se produce un daño miocárdico que en parte es causado por la citotoxicidad de los radicales libres del oxígeno. Se concluye además que la deferoxamina y más el manitol reducen las lesiones de reperfusión y que su mecanismo de acción sería por la capacidad antioxidante que poseen ambas sustancias