HTK vs. HTK-N for Coronary Endothelial Protection during Hypothermic, Oxygenated Perfusion of Hearts Donated after Circulatory Death.

Protection of the coronary arteries during donor heart maintenance is pivotal to improve results and prevent the development of coronary allograft vasculopathy. The effect of hypothermic, oxygenated perfusion (HOP) with the traditional HTK and the novel HTK-N solution on the coronary microvasculature of donation-after-circulatory-death (DCD) hearts is known. However, the effect on the coronary macrovasculature is unknown. Thus, we maintained porcine DCD hearts by HOP with HTK or HTK-N for 4 h, followed by transplantation-equivalent reperfusion with blood for 2 h. Then, we removed the left anterior descending coronary artery (LAD) and compared the endothelial-dependent and -independent vasomotor function of both groups using bradykinin and sodium-nitroprusside (SNP). We also determined the transcriptome of LAD samples using microarrays. The endothelial-dependent relaxation was significantly better after HOP with HTK-N. The endothelial-independent relaxation was comparable between both groups. In total, 257 genes were expressed higher, and 668 genes were expressed lower in the HTK-N group. Upregulated genes/pathways were involved in endothelial and vascular smooth muscle cell preservation and heart development. Downregulated genes were related to ischemia/reperfusion injury, oxidative stress, mitochondrion organization, and immune reaction. The novel HTK-N solution preserves the endothelial function of DCD heart coronary arteries more effectively than traditional HTK.

One-shot cardioplegia for minimally invasive mitral valve repair-a comparison of del Nido and Bretschneider Histidine-Tryptophan-Ketoglutarate solutions.

BACKGROUND: Minimally invasive procedures are demanding in terms of cardioprotection. In many leading centres Bretschneider HTK solution is used for mitral valve surgery. The study was designed to provide comparison of the del Nido and Bretschneider HTK protocol. METHODS: Patients who underwent minimally invasive mitral valve repair for primary mitral regurgitation and received single delivery of either del Nido (Group 1) or Bretschneider HTK cardioplegia (Group 2) were matched on basis of age, gender and length of the cross-clamp time. The groups were compared in terms of major adverse cardiac and cerebrovascular events (death, myocardial infarction, stroke), high sensitivity troponin T (hs-TnT) and creatine kinase- MB isoenzyme (CK-MB) release at 12 h and 24 h following the surgery, incidence of low cardiac output syndrome (LCOS), postoperative arrhythmia, transfusions and postoperative renal function. RESULTS: Case control matching selected 38 pairs of patients. None of patients died, nor suffered from myocardial infarction or stroke. Troponin values did not differ at 12 h (median: 281.0 pg/mL vs 313.0 pg/mL; p = .38) and 24 h (median: 261.0 pg/mL vs 299.0 pg/mL; p = .54), as well as CK-MB at 12 h (median: 25.0 ng/mL vs 29.0 ng/mL; p = .31) and 24 h (median: 11.0 ng/mL versus 9.6 ng/mL; p = .46). Difference in occurrence of LCOS was insignificant (2 vs 7; 5.2% vs 18.4%; p =.15). No difference was shown in incidence of postoperative arrhythmia, transfusions and renal function. CONCLUSIONS: Del Nido cardioplegia can be used safely as an alternative for Bretschneider HTK for minimally invasive mitral valve surgery.

Comparison of Bretschneider HTK cardioplegia solution and blood cardioplegia in terms of postoperative results in patients who underwent isolated supracoronary ascending aortic replacement.

INTRODUCTION: Cardiac arrest with cardioplegia is the most common and reliable method of myocardial protection in cardiac surgery, but there is no definite consensus on the use of different types of cardioplegia. Two of the commonly used types of cardioplegia are Bretschneider histidine-tryptophan-ketoglutarate solution (Custodiol) and conventional blood cardioplegia. In this study, Custodiol solution and conventional blood cardioplegia used in patients with type A aortic dissection who underwent supracoronary ascending aortic replacement were aimed to be compared in terms of postoperative results. METHODS: 70 patients with type A aortic dissection who underwent supracoronary ascending aortic replacement in our clinic between January 2011 - October 2020 were included. Patients were divided into two groups, blood cardioplegia group (n = 48) and Custodiol group (n = 22) and they were compared regarding preoperative, perioperative and postoperative variables. RESULTS: There was no significant difference between cardiopulmonary bypass time and cross-clamp time (p = 0.17 and p = 0.16, respectively). Mechanical ventilator weaning time, intensive care unit stay and hospital stay were shorter in Custodiol group (p = 0.04,p = 0.03 and p = 0.05, respectively). While inotropic support need was higher in the blood cardioplegia group (p = 0.001), there was no significant difference in terms of mortality, arrhythmia, neurological complications and renal complications. CONCLUSIONS: Our results show that Custodiol cardioplegia solution may be superior to blood cardioplegia in reducing mechanical ventilation weaning period, intensive care and hospital stay, and reducing the use of inotropic agents in patients with type A aortic dissection undergoing supracoronary ascending aorta replacement.

Improving Diastolic and Microvascular Function in Heart Transplantation with Donation after Circulatory Death.

The impact of the machine perfusion of donation after circulatory death (DCD) hearts with the novel Custodiol-N solution on diastolic and coronary microvascular dysfunction is unknown. Porcine DCD-hearts were maintained four hours by perfusion with normothermic blood (DCD-B), hypothermic Custodiol (DCD-C), or Custodiol-N (DCD-CN), followed by one hour of reperfusion with fresh blood, including microvascular and contractile evaluation. In another group (DCD group), one hour of reperfusion, including microvascular and contractile evaluation, was performed without a previous maintenance period (all groups N = 5). We measured diastolic function with a balloon catheter and microvascular perfusion by Laser-Doppler-Technology, resulting in Laser-Doppler-Perfusion (LDP). We performed immunohistochemical staining and gene expression analysis. The developed pressure was improved in DCD-C and DCD-CN. The diastolic pressure decrement (DCD-C: -1093 ± 97 mmHg/s; DCD-CN: -1703 ± 329 mmHg/s; DCD-B: -690 ± 97 mmHg/s; p < 0.05) and relative LDP (DCD-CN: 1.42 ± 0.12; DCD-C: 1.11 ± 0.13; DCD-B: 1.22 ± 0.27) were improved only in DCD-CN. In DCD-CN, the expression of eNOS increased, and ICAM and VCAM decreased. Only in DCD-B compared to DCD, the pathways involved in complement and coagulation cascades, focal adhesion, fluid shear stress, and the IL-6 and IL-17 pathways were upregulated. In conclusion, machine perfusion with Custodiol-N improves diastolic and microvascular function and preserves the microvascular endothelium of porcine DCD-hearts.

Beneficial Effects of RNS60 in Cardiac Ischemic Injury.

RNS60 is a physically modified saline solution hypothesized to contain oxygen nanobubbles. It has been reported to reduce ischemia/reperfusion injury in a pig model of acute myocardial infarction. We investigated the effects of RNS60 during cardiac hypoxia in mice and as an additive to cardioplegic solution in rat hearts. ApoE-/-LDLr-/- mice were treated by intravenous injection of RNS60 or saline as a control while monitoring the ECG and post-hypoxic serum release of troponin T and creatine kinase activity. Hearts infused with Custodiol containing 10% RNS60 or saline as the control were subjected to 4 h of 4 °C preservation, followed by an assessment of myocardial metabolites, purine release, and mechanical function. RNS60 attenuated changes in the ECG STU area during hypoxia, while the troponin T concentration and creatine kinase activity were significantly higher in the serum of the controls. During reperfusion after 4 h of cold ischemia, the Custodiol/RNS60-treated hearts had about 30% lower LVEDP and better dp/dtmax and dp/dtmin together with a decreased release of purine catabolites vs. the controls. The myocardial ATP, total adenine nucleotides, and phosphocreatine concentrations were higher in the RNS60-treated hearts. This study indicates that RNS60 enhances cardioprotection in experimental myocardial hypoxia and under conditions of cardioplegic arrest. Improved cardiac energetics are involved in the protective effect, but complete elucidation of the mechanism requires further study.

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.

The effect of Del Nido versus custodiol cardioplegia on clinical outcomes and troponin-I changes among pediatrics with tetralogy of fallot undergoing cardiopulmonary bypass.

BACKGROUND: Myocardial protection during operations with cardiopulmonary bypass (CPB) and aortic cross clamping is vital. For this purpose, Del Nido (DN) and Custodiol cardioplegia (CC) solutions are used for single-dose cardioplegia in cardiac surgical procedures with CPB. Present study aimed to compare the effects of DN and CC on peri-operative clinical outcomes in pediatrics with Tetralogy of Fallot (TF) undergoing cardiopulmonary bypass. METHODS: Present randomized clinical trial was performed in two trial groups with parallel design. One group received DN and another group received CC. We assessed circulatory Troponin-I (cTnI) and coronary sinus lactate level as primary outcomes. Secondary outcomes were ventilation time, electrolytes levels, pump time, cross-clamp time and other clinical parameters. RESULTS: Duration of CPB and cross-clamp were the same in both groups. There were no significant differences in hemodynamic parameters, left ventricular ejection fraction after the surgery and discharge time between the two trial groups. Ventilation time (8.5 vs. 18; p = 0.001), ICU stay, Troponin-I in ICU admission and Coronary sinus lactate level (p = 0.001) were significantly higher among patients of Custodiol group compared to other trial group. Electrolytes Na, Cl and K levels, during CPB, were significantly less in Custodiol group. CONCLUSION: When used for inducing cardiac arrest during CPB, DN solution offers better maintenance of the electrolyte balance during CPB, and is associated with less circulatory cTnI and coronary sinus lactate level compared with the CC.

Improvement of Left Ventricular Graft Function Using an Iron-Chelator-Supplemented Bretschneider Solution in a Canine Model of Orthotopic Heart Transplantation.

Demand for organs is increasing while the number of donors remains constant. Nevertheless, not all organs are utilized due to the limited time window for heart transplantation (HTX). Therefore, we aimed to evaluate whether an iron-chelator-supplemented Bretschneider solution could protect the graft in a clinically relevant canine model of HTX with prolonged ischemic storage. HTX was performed in foxhounds. The ischemic time was standardized to 4 h, 8 h, 12 h or 16 h, depending on the experimental group. Left ventricular (LV) and vascular function were measured. Additionally, the myocardial high energy phosphate and iron content and the in-vitro myocyte force were evaluated. Iron chelator supplementation proved superior at a routine preservation time of 4 h, as well as for prolonged times of 8 h and longer. The supplementation groups recovered quickly compared to their controls. The LV function was preserved and coronary blood flow increased. This was also confirmed by in vitro myocyte force and vasorelaxation experiments. Additionally, the biochemical results showed significantly higher adenosine triphosphate content in the supplementation groups. The iron chelator LK614 played an important role in this mechanism by reducing the chelatable iron content. This study shows that an iron-chelator-supplemented Bretschneider solution effectively prevents myocardial/endothelial damage during short- as well as long-term conservation.

St. Thomas and del Nido cardioplegia are superior to Custodiol cardioplegia in a rat model of donor heart.

OBJECTIVES: Cardiac transplantation is an effective treatment for advanced heart disease and protection of the donor organ is directly associated with post-transplantation outcomes. Cardioplegic strategies intend to protect the donor heart against ischemic injury during transplantation procedures. In our study, the effects of three different cardioplegia solutions were evaluated in a rat heart donor model in terms of cellular base. Design. Cardioplegia solutions as St. Thomas, del Nido or Custodiol were administered to male Wistar albino rats until cardiac arrest. Arrested hearts were excised and incubated in cold cardioplegia solutions for 4 h. Organ bath experiments were performed using the right ventricular free wall strips of the heart tissues. ATP, sialic acid, TNF-α levels and MMP-9 activities were measured in heart tissues. Incubation media were also used to measure TNF-α and troponin-I levels following organ baths experiments. Results. Custodiol administration led to reduced myocardial contraction (p < .05), decreased ATP levels (p < .001) and increased both TNF-α levels (p < .05), and MMP-9 activity (p < .05). Additionally, troponin-I and TNF-α levels in media were significantly increased (p < .05), TNF-α levels were positively correlated with MMP-9 activities (r = .93, p = .007) and negatively correlated with ATP levels (r = -.91, p = .01) in the Custodiol group. Also, MMP-9 activities were negatively correlated with ATP levels (r = -.90, p = .01) Conclusion. Custodiol cardioplegia cannot prevent functional and cellular damage in donor heart tissue. St. Thomas or del Nido cardioplegia could result in superior functional and biochemical improvement during transplantation procedures. In this respect, these cardioplegic solutions may be more advantageous as cellular and functional.

Use of the new preservation solution Custodiol-MP for ex vivo reconditioning of kidney grafts.

Organ shortage and the increasing use of extended criteria donor grafts for transplantation drives efforts for more efficient organ preservation strategies from simple cold storage toward dynamic organ reconditioning. The choice of a suitable preservation solution is of high relevance in different organ preservation or reconditioning situations. Custodiol-MP is a new machine perfusion solution giving the opportunity to add colloids according to organ requirements. The present study aimed to compare new Custodiol-MP with clinically established Belzer MPS solution. Porcine kidneys were ischemically predamaged and cold stored for 20 hours. Ex vivo machine reconditioning was performed either with Custodiol-MP (n = 6) or with Belzer MPS solution (n = 6) for 90 minutes with controlled oxygenated rewarming up to 20°C. Kidney function was evaluated using an established ex vivo reperfusion model. In this experimental setting, differences between both types of perfusion solutions could not be observed. Machine perfusion with Custodiol-MP resulted in higher creatinine clearance (7.4 ± 8.6 mL/min vs. 2.8 ± 2.5 mL/min) and less TNC perfusate levels (0.22 ± 0.25 ng/mL vs. 0.09 ± 0.08 ng/mL), although differences did not reach significance. For short-term kidney perfusion Custodiol-MP is safe and applicable. Particularly, the unique feature of flexible colloid supplementation makes the solution attractive in specific experimental and clinical settings.

Acute isotonic hyponatremia after single dose histidine-tryptophan-ketoglutarate cardioplegia: an observational study.

INTRODUCTION: Histidine-tryptophan-ketoglutarate cardioplegia is used for prolonged myocardial protection in complex cardiac surgery. Administration leads to acute hyponatremia in a majority of patients, because of its low sodium concentration (15 mmol/L). However, histidine-tryptophan-ketoglutarate solution's osmolality is slightly hypertonic (310 mOsm/kg). Hypothesized was that acute isotonic hyponatremia will be induced, which does not need to be corrected with hypertonic saline. METHODS: Cardiac surgery patients who received histidine-tryptophan-ketoglutarate cardioplegia were included in this prospective single center study. Serial blood samples were taken from each patient at five different time points: after induction of anesthesia (T1) and 10 minutes (T2), 6 hours (T3), 12 hours (T4), and 18 hours (T5) after administration of histidine-tryptophan-ketoglutarate cardioplegia, respectively. Blood samples were analyzed for sodium concentration, osmolality, and acid-base balance. RESULTS: Twenty-five patients were included. Median blood sodium levels decreased from 140 [138-141] at T1 to 128 [125-130] mmol/L at T2 (p < 0.001). At T3, T4, and T5, median blood sodium concentrations were 136 [134-138], 139 [137-140], and 140 [137-142] mmol/L, respectively. Median osmolality was 289 [286-293] at T1 and increased to 296 [291-299] mOsm/kg (p < 0.001) at T2. At T3, T4, and T5, osmolality was 298 [292-302], 298 [294-304], and 300 [297-306] mOsm/kg, respectively. Median pH decreased from 7.38 [7.36-7.40] at T1 to 7.30 [7.27-7.32] at T2 (p < 0.001). CONCLUSION: Administration of histidine-tryptophan-ketoglutarate cardioplegia during cardiac surgery leads to acute moderate to severe isotonic hyponatremia, which resolves spontaneously in the first 18 hours perioperatively. Correction with hypertonic saline is not necessary.

Impact of Custodiol-N cardioplegia on acute kidney injury after cardiopulmonary bypass.

Myocardial protection during cardiopulmonary bypass (CPB) can be achieved using cardioplegic solutions. Although, acute kidney injury (AKI) is a common complication following CPB, the effects of cardioplegic solutions on AKI have rarely been investigated. Within this study, the effects of the cardioplegic solutions histidine-tryptophan-ketoglutarate (HTK; Custodiol) and HTK-N (Custodiol-N) on AKI in a large animal model were compared. Therefore, Landrace pigs underwent median sternotomy, CPB at 34°C, 90 minutes of cardiac arrest and 120 minutes of reperfusion. Animals were randomized for single-shot cardioplegia with either HTK (n = 10) or HTK-N (n = 10). Renal biopsies and sera were analyzed to determine AKI biomarkers and apoptosis. Compared to HTK, HTK-N induced a decreased extent of proximal tubule swelling (48.3 ± 1.6 µm vs 52.3 ± 1.1 µm, P = .05) and decreased cytochrome c release (0.26 ± 0.04 vs 0.46 ± 0.08, P = .04) without reaching statistical significance due to Bonferroni correction. Comparing baseline and postreperfusion levels, the hemoglobin (Hb) and blood calcium levels were lower in HTK-N (Hbbaseline : 6.0 ± 0.6 mmol/L, Hbreperfusion : 6.2 ± 0.7 mmol/L, P = .12; Ca2+baseline : 1.36 ± 0.05 mmol/L, Ca2+reperfusion : 1.28 ± 0.05 mmol/L, P = .16) compared to the HTK group (Hbbaseline : 5.9 ± 0.4 mmol/L, Hbreperfusion : 4.7 ± 0.8 mmol/L, P < .01; Ca2+baseline : 1.34 ± 0.07 mmol/L, Ca2+reperfusion : 1.24 ± 0.06 mmol/L, P < .01). The present study showed that HTK-N could positively affect the kidney during CPB. Hb and calcium levels were stabilized. A statistical trend was found showing that AKI-related proximal tubule swelling and cytochrome c release were diminished.

Safety of Custodiol cardioplegia: a cohort study in patients undergoing cardiac surgery with elongated aortic cross-clamp time.

BACKGROUND/OBJECTIVES: The increasing complexity of patients undergoing cardiac surgery requires extended myocardial ischaemic periods. Cardiac surgeons demand a cardioplegic solution with prolonged myocardial protection. Therefore, we introduced Custodiol in our centre in 2011. The aim of this study was to investigate the safety and efficacy of Custodiol compared with the standard method of cardioplegia. METHODS: Between 2011 and 2016, 188 adult patients who underwent mitral valve surgery combined with coronary artery bypass grafting were included in this retrospective study. In 113 patients, Custodiol cardioplegia was used to achieve cardiac arrest, while St. Thomas Hospital solution was used in 75 patients. The primary endpoint of the study was the degree myocardial damage which was estimated by the measurement of creatine kinase-myocardial band on the first postoperative day. A linear regression analysis was performed to compare the aortic cross-clamp time with the postoperative myocardial damage in both groups. RESULTS: The extracorporeal circulation time and aortic cross-clamp were significantly longer in the Custodiol group than in the St. Thomas group: 125.6 ± 32.5 minutes versus 93.1 ± 27.7 minutes (p < 0.001), respectively. However, there was no significant difference between the two groups regarding the postoperative levels of creatine kinase-myocardial band (96 (70-140) U/L vs. 86 (69-120) U/L, respectively; p = 0.321). There was no significant differences between the two groups regarding the 30-day mortality (6.1% vs. 5.5%, respectively; p = 1.000) or 120-day mortality (9.6% vs. 11.0%, respectively; p = 0.806). CONCLUSION: Our findings demonstrate that Custodiol is a safe method of myocardial protection for patients who underwent mitral valve surgery with coronary artery bypass grafting in our hospital. Further investigations extended to more cardiac surgery populations are needed to confirm clinical benefits of Custodiol cardioplegia.

Effectiveness of Bokeria-Boldyrev ACH Solution in Surgerical Treatment of Adult Patients with Obstructive Hypertrophic Cardiomyopathy.

The study examined effectiveness of pharmaco-cold cardioplegia employing solutions of enhanced buffer capacity during surgery of obstructive hypertrophic cardiomyopathy in adult patients (N=51) operated during 2013-2018. In group 1 (N=28), the cardioplegia was performed with HTK (Custodiol) solution, whereas in group 2 (N=23), it was carried out with Bokeria-Boldyrev ACH solution. The mean, minimum, and maximum ages in group 1 were 46, 21, and 64 years, respectively; in group 2 - 42, 14, and 70 years, respectively. In both groups, the patients were subjected to myoectomy of exit pathway in the left ventricle according to Bokeria-Morrow operation and annuloplasty of tricuspid valve accompanied by reconstructive surgery (or replacement) of mitral valve. Atrial fibrillation (if any) was suppressed with cryoablation (-60°Ð¡) of the openings of the right and left pulmonary veins. The surgery was carried out in hypothermic mode at 28°C. The significant intergroup differences were observed in the asystole latent period after the onset of antegrade or retrograde injection of cardioplegic solution. In group 1, the asystole latent periods determined after antegrade or retrograde injection were 53±7 or 170±30 sec, respectively; in group 2 - 32±6 and 97±11 sec (p<0.0001), respectively. The mean times of aortic cross-clumping in groups 1 and 2 were 66±8 and 64±6 min, respectively; the electromechanical action of the heart restored after aortic unclamping in 35±7 and 30±6 sec, respectively. The biochemical and clinical data revealed no significant intergroup differences. Overall, novel Bokeria-Boldyrev ACH cardioplegic solution secured effective protection of the myocardium against intraoperative ischemia in adult patients with obstructive hypertrophic cardiomyopathy and significantly decreased the asystole latent period.

Arterial Switch Operation and Plasma Biomarkers: Analysis and Correlation with Early Postoperative Outcomes.

The aims of our study were to describe plasma brain natriuretic peptide (BNP), Troponin I (TnI), and Cystatin C (Cys-C) concentration kinetics in the postoperative period after arterial switch operation in neonate, and to test the correlation between the plasma biomarkers and early clinical outcomes. We prospectively enrolled 29 neonates who underwent ASO. All patients received Custodiol cardioplegia. Blood samples were collected preoperatively (one day before) and in the ICU immediately after admission, and then 6, 12, 24, and 48 h after surgery. TnI peak (mean 17.23 ± 7.0 ng/mL) occurred between the arrival in the ICU and the 6th hour, then we had a constant decrease. TnI had a good correlation with the inotropic support time (r = 0.560, p = 0.0015) and ICU time (r = 0.407, p = 0.028), less than with ventilation and Hospital stay (r = 0.37, p = 0.0451 and r = 0.385, p = 0.0404). BNP peak (mean 4773.79 ± 2724.52 ng/L) was in the preoperative time with a constant decrease after the operation and it had no significant correlations with clinical outcomes. The CyS-C had the highest preoperative values, which decreased during the operating phase, and then constantly increased upon arrival to the ICU with a peak at 48 h (mean 1.76 ± 0.35 mg/L). CyS-C peak had a good correlation with a plasmatic creatinine peak (r = 0.579, p = 0.0009) but not with other clinical outcomes. Our study demonstrated significant correlations between the Tnl peak and early clinical outcomes in neonates undergoing arterial switch operation. Other plasma biomarkers such as the BNP and CyS-C had no direct correlation.

Kidney transplantation after oxygenated machine perfusion preservation with Custodiol-N solution.

Custodiol-N, a new preservation solution, has been shown particularly suitable for hypothermic machine perfusion preservation (HMP) in isolated porcine kidneys. These preliminary results should be confirmed in an actual transplant model in vivo. Kidney function after 21 h of HMP was studied in an autotransplant model using Landrace pigs (25-30 kg; n = 6 per group). Perfusion was performed with oxygenated perfusate, using either Custodiol-N solution including 50 g/l dextran 40 (CND) or kidney perfusion solution 1 (KPS-1) as gold standard. Viability of the grafts was followed for 1 week after bilateral nephrectomy in the recipient pigs. HMP with CND resulted in less acute tubular injury, evaluated by levels of fatty acid-binding protein and better clearance function during the first 24 h after Tx than with KPS-1 (P < 0.05, resp.). Serum creatinine tended to be lower in the CND group during the whole observation period. Histological tissue scores one week after Tx were similar in both groups. Expression of endothelin-1 as well as of Toll-like receptor 4 15 min after reperfusion was lower in the CND group (P < 0.05), suggesting less endothelial stress response. The data provide first in vivo evidence for the suitability of Custodiol-N as an effective perfusate for renal machine perfusion.

Perfusion techniques for minimally invasive valve procedures.

In this paper, we present, in detail, the simplified perfusion technique that we have adopted since January 2009 and that we have utilized in 200 cases for cardiac minimally invasive valvular procedures that were performed through a right lateral mini-thoracotomy in the 3(rd)-4(th) intercostal space. Cardiopulmonary bypass was achieved by means of the direct cannulation of the ascending aorta and the insertion of a percutaneous venous cannula in the femoral vein. A flexible aortic cross-clamp was applied through the skin incision and cardioplegic arrest was obtained with the antegrade delivery of a crystalloid solution. Gravity drainage was enhanced by vacuum-assisted aspiration. There were no technical complications related to this perfusion technique that we have adopted in minimally invasive surgical procedures.

Use of autologous platelet-rich plasma for skin graft preservation: an experimental comparative study.

OBJECTIVE: In this experimental study, we aimed to determine whether platelet-rich plasma (PRP) is a suitable preservative for dermo-epidermal grafts. An additional objective was to investigate how long grafts can be stored without biological degradation. METHODS: We compared pig skin graft preservation using PRP versus saline solution and crystalloid Custodiol®, which is used for hypothermic preservation of organs for transplantation. Grafts (10 × 10 mm) were placed on gauze impregnated with one of the tested solutions, and stored for 3, 7, 11, and 15 days at a constant temperature of 4°C. We evaluated a total of 240 pig skin samples: 120 by histopathology and 120 by fluorescence optical microscopy. RESULTS: Overall, Custodiol® solution appeared to be the best medium for preservation of dermo-epidermal grafts, with beneficial properties manifested on days 7 and 11. Although we expected PRP to be a better preservative than saline, this was not confirmed by our results, as we found no significant difference between these two media. In fact, by day 3, the histopathological results were better with standard saline solution than with PRP. On day 15, with each tested solution, some samples showed histological changes that are incompatible with graft viability. CONCLUSION: Overall, Custodiol® appears to be the best medium for dermo-epidermal graft preservation. Moreover, the present findings suggest a maximum graft storage time of 11 days in all of the tested solutions. We do not recommend using grafts stored for 15 days, due to isolated signs of graft biodegradation with all solutions.

Comparison of modified Del Nido and Custodiol® cardioplegia in minimally invasive mitral valve surgery.

OBJECTIVES: In this study, we evaluated if modified Del Nido cardioplegia delivers comparable cardiac protection in comparison to Custodiol® in patients undergoing isolated minimally invasive mitral valve repair. METHODS: From January 2018 to October 2021, all patients undergoing non-emergent isolated minimally invasive mitral valve repair were included in this study. The cardioplegia was chosen at the surgeons' discretion. The primary end points of this study were peak postoperative cardiac enzyme levels. Secondary end points were in-hospital mortality, hospital stay, occurrence of cardiac arrhythmias, pacemaker implantations, postoperative lactate and sodium levels and postoperative incidence of renal failure requiring dialysis. RESULTS: A total of 355 patients were included in this study. The mean age of patients was 57. After propensity score matching, a total of 156 pairs were identified. There was no difference in cross-clamp time between both groups. Postoperative creatine kinase levels were higher in patients receiving Custodiol on the 1st and 2nd postoperative days. Creatine kinase isoenzyme MB levels were higher in patients receiving Custodiol on the 2nd postoperative day (0.5 ± 0.2 vs 0.4 ± 0.1 µmol/l s; P < 0.001). Postoperative Troponin T concentrations were similar between both groups. Maximum lactate concentrations were higher in patients receiving Custodiol on the day of surgery (2.4 ± 1.9 vs 2.0 ± 1.1 mmol/l; P = 0.04). The overall hospital stay was longer in patients receiving Del Nido cardioplegia (10.6 ± 3.2 vs 8 ± 4.1 days; P < 0.01). CONCLUSIONS: Modified Del Nido cardioplegia based on Ionosteril® solution offers equivalent protection compared to Custodiol for isolated minimally invasive mitral valve repair.

Myocardial protection: comparing histological effects of single-dose cardioplegic solutions-study protocol for a secondary analysis of the CARDIOPLEGIA trial.

Background: Myocardial protection is crucial for successful cardiac surgery, as it prevents heart muscle damage that can occur during the procedure. Prolonged hypoxia without proper protection can lead to adenosine triphosphate consumption, microvilli loss, blister formation, and edema. Custodiol, del Nido, and modified del Nido are single-dose cardioplegic solutions with proven safety and significance in modern surgery. While each has been independently assessed for patient outcomes, limited research directly compares them. This study aims to compare their myocardial protection using histological analysis. Methods: In a double-blind clinical trial, at least 90 patients will be randomly assigned to receive one of the three cardioplegic solutions. Myocardial biopsies will be collected before cardiopulmonary bypass and 15 minutes after reperfusion. The surgical, anesthetic and perfusion techniques will be the same for all patients, following the Institution's standard protocols. Discussion: The ideal cardioplegic solution does not exist, and its selection remains challenging for surgeons. In modern surgical practice, understanding the behavior of these solutions and the ischemic tissue damage caused during induced cardiac arrest allows for safer surgical procedures. The results of this clinical trial can help in understanding the behavior of cardioplegic solutions and their tissue effects. Thus, by selecting the best cardioplegic solution, ischemic damage can be minimized, enhancing the effectiveness of this essential technique in cardiac procedures. The study may aid in implementing clinical protocols in several institutions, aiming to choose the solution with a superior myocardial protection profile, increasing safety, and reducing expenses. Trial Registration: Brazilian Clinical Trials Registry (ReBEC, http://ensaiosclinicos.gov.br/): RBR-997tqhh. Registered: January 26th, 2022.