A Cardioplegic Solution with an Understanding of a Cardiochannelopathy

Cardiac surgeries have been improved by accompanying developing cardioplegia solutions. However, the cardioplegia application presents an ongoing challenge with a view of a sufficiently restored cardiac function. In this review, we focus on the cardioplegia-induced mechanism and summarize the findings of studies undertaken to improve cardioprotective strategies. Currently, and somewhat surprisingly, relatively little is known about cardiac electrolyte regulation through channel physiology. We hope that an improved understanding of the electrolyte transport through ion channels/transporters and modulations of water channel aquaporins will provide an insight into cardiac channel physiology and a channel-based cardiac pathology of a cardiochannelopathy.

Nanocarriers Loaded with Oxygen to Improve the Protection of the Heart to be Transplanted

: In the case of serious cardiovascular diseases, such as refractory heart failure, heart transplantation is the only possible intervention. Currently, the modes of organ transport in hypothermic cardioplegic solution do not allow the implantation of the heart beyond 4-5 hours from the explant. The heart being an organ with a greater consumption of oxygen and high metabolism than the brain, its transport in hypothermic cardioplegic solutions presents critical issues in terms of time and conservation. An ambitious goal of many researchers and clinicians is to minimize the hypoxia of the explanted heart and extend the permanence time in cardioplegic solution without damage from hypoxia. Adequately oxygenating the explanted organs may extend the usability time of the explanted organ. This challenge has been pursued for years with approaches that are often expensive, risky, and/or difficult to use. We propose to consider oxygenated nanocarriers realizing oxygen for a long time. In this way, it will also be possible to use organs from distant countries with respect to the recipient, thus exceeding the canonical 4-5 hours tolerated up to now. In addition to the lack of oxygen, the transplanted organ can undergo the accumulation of catabolites due to the lack of perfusion during transport. Therefore, nanocarriers can also be perfused in adequate solution during organ transportation. A better oxygenation improving the postoperative recovery of the transplanted heart will improve the recipient's quality of life.

Comparison between Custodiol, del Nido and modified del Nido in the myocardial protection - Cardioplegia Trial: a study protocol for a randomised, double-blind clinical trial

IntroductionMyocardial protection is essential for successful cardiac surgery, and the search for an ideal cardioplegic solution has continued since its beginning. In this context, Custodiol, del Nido and modified del Nido are single-dose cardioplegic solutions with good safety profiles and great relevance in modern surgical practice. While these solutions have all been evaluated for their impact on patient outcomes independently, limited research exists comparing them directly. Thus, the present study aims to examine the effects of these cardioplegic solutions on myocardial protection and clinical outcomes in adult patients undergoing elective cardiac surgery. The assessment of the increase in myocardial injury biomarkers in patients submitted to all treatment methods may be considered a major strength of our study.Methods and analysisThis is a clinical trial study protocol that will compare myocardial protection and clinical outcomes among three patient groups based on which cardioplegic solution was used. Patients will be randomised to receive del Nido (n=30), modified del Nido (n=30) or Custodiol (n=30). Myocardial injury biomarkers will be measured at the baseline and 2 hours, 12 hours and 24 hours after the cardiopulmonary bypass. Clinical outcomes will be assessed during the trans operative period and the intensive care unit stay, in addition to other haematological parameters.Ethics and disseminationThis protocol and its related documents were approved by the Research Ethics Committee of the Hospital Nossa Senhora da Conceição, Brazil, registered under no. 4.029.545. The findings of this study will be published in a peer-reviewed journal in the related field.Trial registration numberRBR-7g5s66.

In search of optimal cardioplegia for minimally invasive valve surgery

Cardioplegic solutions are used in cardiac surgery to achieve controlled cardiac arrest during operations, making surgery safer. Cardioplegia can either be blood or crystalloid based, with perceived pros and cons of each type. Whilst it is known that cardioplegia causes cardiac arrest, there is debate over which cardioplegic solution provides the highest degree of myocardial protection during arrest. Myocardial damage is measured post-operatively by biomarkers such as serum TnT, TnI or CK-MB. It is known that the outcomes of minimally invasive valve surgery are comparable to full sternotomy valve operations. Despite there being a wide diversity in use of different cardioplegic solutions across the world, this comprehensive literature review found no superiority of one cardioplegic solution over the other for myocardial protection during minimally invasive valve procedures.

Celsior® crystalloid cardioplegia versus standard hyperkalemic normothermic blood cardioplegia: Analysis of myocardial protection in elective mitral valve repair

Introduction: With the increase and refinement of video assisted mitral valve surgery, cristalloïd cardioplegia started regaining popularity. The aim of our study was to evaluate the effectiveness of Celsior®, a crystalloid cardioplegic solution, on myocardial protection in elective surgical mitral valve repair in comparison to blood based hyperkalemic cardioplegia. Methods: In this observational retrospective study, all consecutive elective isolated surgical mitral valve repair where Celsior® or normothermic hyperkalemic blood cardioplegia were used were included. Primary endpoint was any sign of myocardial protection failure (troponin levels, need for inotropic or mechanical support, rhythm disturbances, mortality). Secondary endpoint was Celsior® safety (allergic reactions, bleeding, organ toxicities). Results: From January 2009 to August 2016, 382 patients underwent elective isolated mitral valve repair in whom normothermic hyperkalemic blood cardioplegia ( n = 181) or Celsior® ( n = 201) were used. There were no statistically significant differences in baseline characteristics including Euroscore 2. Peak troponin (pg/ml) release and 30-days mortality were not statistically different. Need for cardioversion was significantly more frequent in the Celsior® group (47% vs 13%, p < 0.001). There was no statistical difference in post-operative atrial fibrillation, permanent pacemaker implantation, reoperation for bleeding, transfusion, acute kidney injury, haemoglobin at discharge or length of stay. No allergic reaction to Celsior® occurred. Conclusion: Effective myocardial protection was achieved with the Celsior® cardioplegic solution with no unexpected toxicity. Celsior® may be an efficacious and safe cardioprotective strategy in mitral valve repair.

Donor heart preservation with hypoxic-conditioned medium-derived from bone marrow mesenchymal stem cells improves cardiac function in a heart transplantation model

Background In heart transplantation, donor hearts inevitably suffer from ischemia/reperfusion (I/R) injury, which leads to primary graft dysfunction and affects patients’ survival rate. Bone marrow mesenchymal stem cells (BMSCs) have been reported to attenuate myocardial I/R injury via their paracrine effects, which can be enhanced by hypoxic preconditioning. We hypothesized that the donor heart preservation with hypoxic conditioned medium (CdM) derived from BMSCs would improve post-transplant graft function. Methods Normoxic or hypoxic CdM were isolated from rat BMSCs cultured under normoxic (20% O2) or hypoxic (1% O2) condition. Donor hearts were explanted; stored in cardioplegic solution supplemented with either a medium (vehicle), normoxic CdM (N-CdM), or hypoxic CdM (H-CdM); and then heterotopically transplanted. Antibody arrays were performed to compare the differences between hypoxic and normoxic CdM. Results After heart transplantation, the donor heart preservation with normoxic CdM was associated with a shorter time to return of spontaneous contraction and left ventricular systolic diameter, lower histopathological scores, higher ejection fraction, and fractional shortening of the transplanted hearts. The cardioprotective effects may be associated with the inhibition of apoptosis and inflammation, as reflected by less TUNEL-positive cells and lower levels of plasma proinflammatory cytokines (interleukin-1β, interleukin-6, tumor necrosis factor-α) and cardiac troponin I in the N-CdM group compared with the vehicle group. These therapeutic effects can be further enhanced by hypoxic preconditioning. Antibody arrays revealed that nine proteins were significantly increased in hypoxic CdM compared with normoxic CdM. Furthermore, compared with vehicle and N-CdM groups, the protein levels of PI3K and p-Akt/Akt ratio in the transplanted hearts significantly increased in the H-CdM group. However, no significant difference was found in the phosphorylation of Smad2 and Smad3 for the donor hearts among the three groups. Conclusions Our results indicate that the cardioplegic solution-enriched with hypoxic CdM can be a novel and promising preservation solution for donor hearts.

Myocardial Protection by Retrograde Application of HTK Solution Compare with Cold Blood Cardioplegic Solution during Heart Valve Surgery

Objective: Cardioplegic solution is one important principle for adequate myocardial protection in cardiac surgery. Bretschneider’s histidine-tryptophan-ketoglutarate (HTK) solution is an intracellular solution while blood cardioplegia solution is an extracellular solution. Both have been used to preserve the myocardium. The present study compared between the two cardioplegic solutions for incidence of ventricular fibrillation after aortic clamp removal in double valve replacement (DVR) and tricuspid annuloplasty (TVA) to assess the effectiveness for myocardial protection. Materials and Methods: A retrospective study was conducted among patients who underwent DVR with TVA operations between January 1, 2013 and June 30, 2017 and divided in two groups at Queen Sirikit Heart Center of the Northeast. The medical records were searched for detailed demographics, preoperative status, operative technique, and post-operative hospital course. Results: Thirty-six patients were included in the present study, 18 patients received HTK solution, the others received blood cardioplegia. The demographic data presented no statistical difference between the two groups. Incidence of ventricular fibrillation after aortic clamp removal occurred in 10 patients (55.6%) in the HTK group, which was more than the cold blood group [five patients (27.78%)]. Cardiopulmonary bypass (CPB) and aortic cross clamp time in the cold blood group was significantly longer than in the HTK group (p<0.001). The peak of Trop-T and CK-MB within six hours after surgery tended to be downward after 24 hours and was not related to perioperative myocardial ischemia in the HTK group. No statistically difference was observed in postoperative outcome, ICU stay, or hospital stay. Conclusion: The use of HTK solution has no significant different outcome compared to conventional cold blood cardioplegia via retrograde route in DVR with TVA operation. There was no significantly different incidence of ventricular fibrillation and there was no evidence of postoperative myocardial infarction. CPB and aortic cross clamp time in the HTK group were shorter than in the cold blood cardioplegia significantly. Keywords: Cardioplegia, HTK, Custodiol, Ventricular fibrillation

Donor heart preservation with hypoxic conditioned medium derived from bone marrow mesenchymal stem cell improves cardiac function in a heart transplantation model

Background: In heart transplantation, donor hearts inevitably suffer from ischemia/reperfusion (I/R) injury, which leads to primary graft dysfunction and affects patients’ survival rate. Bone marrow mesenchymal stem cells (BMSCs) have been reported to attenuate myocardial I/R injury via their paracrine effects, which can be enhanced by hypoxic preconditioning. We hypothesized that the donor heart preservation with hypoxic conditioned medium (CdM) derived from BMSCs would improve post-transplant graft function. Methods: Normoxic or hypoxic CdM were isolated from rat BMSCs cultured under normoxic (20% O2) or hypoxic (1% O2) condition. Donor hearts were explanted, stored in cardioplegic solution supplemented with either a medium (Vehicle), normoxic CdM (N-CdM), or hypoxic CdM (H-CdM), and then heterotopically transplanted. Antibody arrays were performed to compare the differences between hypoxic and normoxic CdM.Results: After heart transplantation, the donor heart preservation with normoxic CdM was associated with a shorter time to return of spontaneous contraction and left ventricular systolic diameter, lower histopathological scores, higher ejection fraction, and fractional shortening of transplanted hearts. The cardioprotective effects may be associated with the inhibition of apoptosis and inflammation, as reflected by less TUNEL-positive cells and lower levels of plasma proinflammatory cytokines (Interleukin-1β, Interleukin-6, tumor necrosis factor-α) and cardiac troponin I in the N-CdM group compared with the vehicle group. These therapeutic effects can be further enhanced by hypoxic preconditioning. Antibody arrays revealed that nine proteins were significantly increased in hypoxic CdM compared with normoxic CdM. Furthermore, compared with vehicle and N-CdM groups, the protein levels of PI3K and p‐Akt/Akt ratio in the transplanted hearts significantly increased in the H-CdM group. However, no significant difference was found in the phosphorylation of Smad2 and Smad3 for the donor hearts among the three groups. Conclusions: Our results indicate that the cardioplegic solution-enriched with hypoxic CdM can be a novel and promising preservation solution for donor hearts.

Donor Heart Preservation with Hypoxic Conditioned Medium Derived from Bone Marrow Mesenchymal Stem cell improves Cardiac Function in a Heart Transplantation Model

Background: In heart transplantation, donor hearts inevitably suffer from ischemia/reperfusion (I/R) injury, which leads to primary graft dysfunction and affects patients’ survival rate. Bone marrow mesenchymal stem cells (BMSCs) have been reported to attenuate myocardial I/R injury via their paracrine effects, which can be enhanced by hypoxic preconditioning. We hypothesized that the donor heart preservation with hypoxic conditioned medium derived from BMSCs (CM-BMSCs) would improve post-transplant graft function. Methods: Normoxic CM and hypoxic CM were isolated from rat BMSCs cultured under normoxic (20% O2) or hypoxic (1% O2) condition. Donor hearts were explanted, stored in cardioplegic solution supplemented with either a medium (Vehicle), normoxic CM (N-CM), or hypoxic CM (H-CM), and then heterotopically transplanted. Antibody arrays were performed to compare the differences between hypoxic CM and normoxic CM.Results: After heart transplantation, the donor heart preservation with normoxic CM was associated with shorter re-beating time, histopathological scores, and left ventricular systolic diameter, higher ejection fraction, and fractional shortening of transplanted hearts. These protective effects may be associated with the inhibition of apoptosis and inflammation, as reflected by less TUNEL-positive cells and lower levels of serum proinflammatory cytokines (Interleukin-1β, Interleukin-6, tumor necrosis factor-α) and cardiac troponin I in the N-CM group compared with the vehicle group. These therapeutic effects can be further enhanced by hypoxic preconditioning. Antibody arrays revealed that nine proteins were significantly increased in hypoxic CM compared with normoxic CM. Furthermore, compared with vehicle and N-CM groups, the protein levels of PI3K and p‐Akt/Akt ratio in the transplanted hearts significantly increased in the H-CM group. Conclusions: Our results indicate that cardioplegic solution-enriched with hypoxic CM-BMSCs can be a novel and promising preservation solution for donor hearts.