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.

Custodiol HTK Versus Plegisol: in-Vitro Comparison With The Use of Immature (H9C2) and Mature (HCM) Cardiomyocytes Cultures

Background: Although cardioplegia is used since the ‘70s of the last century, debate on cardioprotection during cardio-surgical procedures is still actual. The selection of a particular method depends mainly on the preferences and experience of a specific center or even surgeon. Crystalloid cardioplegia is an aqueous ion solution similar to intracellular (Custodiol HTK) or extracellular (Plegisol) fluid. Numerous publications compare different types of cardioplegic solutions, but only a few used cultured cells in laboratory conditions. Methods: In this study, the authors compare two crystalloid solutions using an in-vitro model simulating cardioplegic arrest. The efficacy of myocardial protection during ischemia was investigated with susceptible indicators like the appearance of the deleterious effect of reactive oxygen species and oxidative stress markers. Incubated human cardiomyocytes and rat cardiomyoblasts H9C2 in cardioplegia for 4h were examined for expression of oxidative stress markers (MnSOD, iNOS, HSP27), cardioplegic solutions cytotoxicity, and peroxidation damage of the cell’s lipids and proteins. All tests were performed after 0.5h, 1h, 2h, and 4h in identical physical and biological conditions, which is difficult to achieve in clinical trials. Results: The tests performed on matured cells of human cardiomyocytes showed the superiority of Custodiol HTK. Differences between solutions on immature cells H9C2 were not relevant. Both Plegisol and Custodiol HTK produced a similar expression of MnSOD and iNOS. There was no significant advantage of Custodiol over Plegisol in the cytotoxicity test. However, Custodiol induced a higher level of lipid peroxidation. Conclusions: Considering proceeded examinations on cultured cardiomyocytes, Custodiol HTK appears to be safer than Plegisol.

Cardioplegia between Evolution and Revolution: From Depolarized to Polarized Cardiac Arrest in Adult Cardiac Surgery

Despite current advances in perioperative care, intraoperative myocardial protection during cardiac surgery has not kept the same pace. High potassium cardioplegic solutions were introduced in the 1950s, and in the early 1960s they were soon recognized as harmful. Since that time, surgeons have minimized many of the adverse effects by lowering the temperature of the heart, lowering K+ concentration, reducing contact K+ time, changing the vehicle from a crystalloid solution to whole-blood, adding many pharmacological protectants and modifying reperfusion conditions. Despite these attempts, high potassium remains a suboptimalway to arrest the heart. We briefly review the historical advances and failures of finding alternatives to high potassium, the drawbacks of a prolonged depolarized membrane, altered Ca2+ intracellular circuits and heterogeneity in atrial-ventricular K+ repolarization during reanimation. Many of these untoward effects may be alleviated by a polarized membrane, and we will discuss the basic science and clinical experience from a number of institutions trialling different alternatives, and our institution with a non-depolarizing adenosine, lidocaine and magnesium (ALM) cardioplegia. The future of polarized arrest is an exciting one and may play an important role in treating the next generation of patients who are older, and sicker with multiple comorbidities and require more complex operations with prolonged cross-clamping times.

Comparison of troponin 1 level among the patients who underwent coronary artery bypass grafting with and without adenosine as an adjunct to blood cardioplegia

Background: Cellular injury is not avoidable with current cardioplegic solutions. No method of cardioplegia has been shown to completely protect the myocardium against cellular injury. The objective of the study is to evaluate the safety and efficacy of adenosine as an adjunct to blood cardioplegia during CABG.Methods: A retrospective study at GMCT, Thiruvananthapuram in CABG patients for 3 years from January 1, 2016, to December 31, 2019, between the age of 40 and 70 years. Patients with other chronic diseases and pre-operative echo showing EF less than 40% were excluded. The study variables were level of troponin I intra and postoperative period, time taken for cardiac standstill, number of days in ventilator, ICU and on inotropic supports. Also, postoperative lactate levels, changes in RWMA and EF.Results: Of the total 75 subjects, 40 got adenosine while 35 didn’t. The mean post op EF for those who got adenosine is 55.30 and without is 56.46. The mean time of cardiac stand still with adenosine is 12.88 sec and without is 16.51 sec. The mean post op troponin I level in those who got adenosine is 6.43 and without is 12.94.Conclusions: Decreased level of troponin I and inotropic requirement suggests that an optimal myocardial protection. Adenosine usage helps in early extubation but doesn’t alter the number of days in ICU. Adenosine is safe, gives more rapid cardiac arrest but it will not alter the post op left ventricular function.

Relevance and Recommendations for the Application of Cardioplegic Solutions in Cardiopulmonary Bypass Surgery in Pigs

Cardioplegic solutions play a major role in cardiac surgery due to the fact that they create a silent operating field and protect the myocardium against ischemia and reperfusion injury. For studies on cardioplegic solutions, it is important to compare their effects and to have a valid platform for preclinical testing of new cardioplegic solutions and their additives. Due to the strong anatomical and physiological cardiovascular similarities between pigs and humans, porcine models are suitable for investigating the effects of cardioplegic solutions. This review provides an overview of the results of the application of cardioplegic solutions in adult or pediatric pig models over the past 25 years. The advantages, disadvantages, limitations, and refinement strategies of these models are discussed.

PHARMACEUTICAL MARKET OF CARDIOPLEGIC DRUGS AND FEATURES OF THEIR APPLICATION IN RUSSIA

Relevance. Surgical treatment of cardiovascular diseases with the use of artificial blood circulation is associated with the need to protect the myocardium. Various cardioplegic solutions are widely used in cardiac surgery to stop and protect the heart. Currently, a significant number of mixtures of drug solutions are used in "open" heart surgery. However, not all of them have been officially registered as cardioplegic solutions and not all have the appropriate indications in the instructions for medical use of the drug, which jeopardizes the safety and quality of medical care for patients. Goal. To study the pharmaceutical market of registered drugs for cardioplegia and to estimate the share of heart operations with the connection of artificial circulation performed without the use of officially registraited drugs for cardioplegia. Materials and methods. The following methods were used in the work: content analysis, statistical, marketing, graphic. The main information sources were: the State Register of Medicines; statistical indicators of surgical interventions in cardiac surgery, information on public procurement of medicines, instructions for the medical use of medicines, regulatory documents. Results. This study presents the results of a marketing analysis of the pharmaceutical market of drugs officially registered for cardioplegia. Three medicines have been registraited in Russia, which, in accordance with the instructions for use, can be used during surgical interventions in the quality of cardioplegic solutions. According to the ATC classification, all of them belong to the subgroup of the fifth level B05XA16 "Cardioplegic solutions". For the period 2018-2020. the volumes of purchases of cardioplegic solutions for the needs of medical organizations have been established and the volumes of drugs for surgical intervention in cardiac surgery during operations on the "open" heart have been determined. The comparison of morbidity rates and the estimated number of surgical interventions of the cardiac surgery service based on the data of public procurement of drugs for cardioplegia, revealed a discrepancy between the volumes of purchased cardioplegic solutions and the care provided. The data analysis shows that at least 23 thousand cardiac surgeries in Russia are performed annually without the use of registraited medicines for cardioplegia. Conclusion. When performing surgical interventions on an "open" heart with the connection of artificial blood circulation, it is necessary to use cardioplegic solutions that have an official indication in the instructions for medical use, in order to ensure the safety of patients and to perform medical interventions of appropriate quality.

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.