Search Results (12)

Background: The perfusion of viscera, kidney, and spinal cord represents one of the main concerns during open repair (OR) of Thoraco-Abdominal Aortic Aneurisms (TAAAs). Passive shunting (PS) has been historically used for intraoperative distal aortic perfusion but has been progressively replaced almost entirely by partial left-sided heart or total cardiopulmonary bypass with extra-corporeal circulation (ECC). Despite several advantages of these methods, PS still has potential in mitigating some drawbacks of long extracorporeal circuits connected with centrifugal or roller pumps, such as the need for cardiac and great vessels cannulation, priming and large intravascular fluid volume shifts, high heparin dose, immunosuppressive effects, and systemic inflammatory response syndrome. Methods: This study prospectively analyzed data of a cohort of patients who underwent TAAA OR using a PS in a single institution. Outcomes of interest were mortality, rate of mesenteric, renal and spinal cord ischemia, cardiac complications, and intraoperative hemodynamic stability achieved in this setting. Our institutional bundle and a comprehensive literature review about the different configurations and applicability of PS for TAAA OR is also reported. The search was performed based on three databases (PubMed, EMBASE, and Cochrane Library) by two independent reviewers (LS and AA) from inception to 31 December 2023, and the reported clinical results (visceral, renal, and spinal cord complications and mortality) using PS during TAAAs OR were analyzed. Results: Between March 2021 and December 2023, 51 TAAA repairs were performed and eleven patients (n = 8, 73% male; mean age 67 years, range 63–79) were operated using a PS for a total of one (9%) type I, one (9%) type II, two (18%) type III, five (45%) type IV, and two (18%) type V TAAA. In our early experience, PS was indicated for limited staff resources during the COVID-19 pandemic to treat five non-deferable cases. The sixth and seventh patients were selected for PS as they already had a functioning axillo-bifemoral bypass that was used for this purpose. For the most recent cases, PS was chosen as the primary perfusion method according to a score based on clinical and anatomical factors with ECC as a bailout strategy. Selective renal perfusion with cold (4 °C) Custodiol solution was the method of choice for renal protection in all cases while antegrade perfusion of the coeliac trunk and the superior mesenteric artery was assured by PS through a loop graft (8–10mm) proximally anastomosed to the axillary artery (10 patients, 90.9%) or the descending thoracic aorta (one patient, 9%) and distally anastomosed to the infrarenal aorta (3), common iliac (3), or femoral vessels (5). In-hospital mortality was 9% as one patient died on the 10th postoperative day from mesenteric ischemia following hemodynamic instability; permanent spinal cord ischemia rate was 0% and the rate of AKI stage 3 was 9% (one patient). Bailout shifting to ECC was never required. No cardiac complications, nor a significant increase in serum CK-MB were reported in any patient. No prolonged severe intraoperative hypotension episodes (Mean Arterial Pressure < 50 mmHg) were assessed using the Software Acumen Analytics (Edwards LifeSciences, Irvine CA, USA). No peri-operative coagulopathy nor major bleeding was reported. Conclusions: Our experience showed satisfactory outcomes with the use of PS in specifically selected cases. Current data indicate that PS may represent an alternative to ECC techniques during TAAAs OR in high volume centers where assisted extracorporeal circulation could eventually be applied as a bailout strategy. However, due to the small sample size of this and previously published series, more data are needed to clearly define the potential role of such approach during TAAA OR. Full article

Brain injury and cerebral inflammation are frequent complications following cardiopulmonary bypass (CPB) resulting in neurocognitive dysfunction, encephalopathy, or stroke. We compared cerebral inflammation induced by del Nido and histidine-tryptophan-α-ketoglutarate (HTK) cardioplegia in a porcine model. Pigs underwent 90 min cardiac arrest using HTK (n = 9) or Jonosteril^®-based del Nido cardioplegia (n = 9), followed by a 120 min reperfusion. Brain biopsies were collected and analyzed for the mRNA and protein expression of hypoxia-inducible factor-1α (HIF-1α) and cytokines. HTK induced a decrease in blood sodium, chloride, and calcium concentration (cross-clamp aorta: p_sodium < 0.01, p_chloride < 0.01, p_calcium < 0.01; 90 min ischemia: p_sodium < 0.01, p_chloride < 0.01, p_calcium = 0.03) compared to the more stable physiological electrolyte concentrations during del Nido cardioplegia. Hyponatremia and hypochloremia persisted after a 120 min reperfusion in the HTK group (p_sodium < 0.01, p_chloride = 0.04). Compared to del Nido, a higher mRNA expression of the proinflammatory cytokine IL-1β was detected in the frontal cortex (HTK: ∆Ct 6.5 ± 1.7; del Nido: ∆Ct 8.8 ± 1.5, p = 0.01) and the brain stem (HTK: ∆Ct 5.7 ± 1.5; del Nido: ∆Ct 7.5 ± 1.6, p = 0.02) of the HTK group. In conclusion, we showed comparability of HTK and del Nido for cerebral inflammation except for IL-1β expression. Based on our study results, we conclude that del Nido cardioplegia is a suitable and safe alternative to the conventional HTK solution. Full article

Introduction: This systematic review aims to analyze the current literature regarding 30-day mortality and postoperative acute kidney disease (AKI) in complex abdominal aortic aneurysms (cAAAs), which included juxtarenal aortic aneurysm (JAA), suprarenal aortic aneurysm (SRAA), and type IV thoracoabdominal aortic aneurysm (TAAA) open surgery (OS), to evaluate the impact of renal perfusion on AKI and to try to define which is the best way to perform it. Methods: A literature search in PubMed and Cochrane Library was performed, and articles published from January 1986 to January 2024 reporting on JAA, SRAA, and TAAA type IV open surgery management were identified. Multicenter studies, single-center series, and case series with ≥10 patients were considered eligible. Comparisons of outcomes of patients who underwent OS for complex abdominal aortic aneurysms (cAAAs) with or without perfusion of the renal arteries were analyzed when available. The titles, abstracts, and full texts were evaluated by two authors independently. The primary outcomes included AKI and 30-day mortality rates. The new-onset dialysis rate was considered a secondary outcome. Results: A total of 295 articles were evaluated, and 21 were included, totaling 5708 patients treated for cAAAs with OS. The male patients totaled 4094 (71.7%), with a mean age of 70.35 ± 8.01 and a mean renal ischemia time of 32.14 ± 12.89 min. Data were collected and analyzed, at first in the entire cohort and then divided into two groups (no perfusion of the renal arteries—group A vs. selective perfusion—group B), with 2516 patients (44.08%) who underwent cAAAs OS without perfusion of the renal arteries and 3192 patients (55.92%) with perfusion. In group B, four types of renal perfusion were reported. Among the 21 studies included, 10 reported on selective renal perfusion in cAAA OS, with several types of fluids described: (1) “enriched” Ringer’s solution, (2) “Custodiol” (Istidine-tryptophan-ketoglutarate or Custodiol HTKsolution), (3) other cold (4 °C) solutions (i.e., several combinations of 4 °C isotonic heparinized balanced salt solution containing mannitol, sodium bicarbonate, and methylprednisolone), and (4) warm blood. Thirty-day mortality for patients in group A was 4.25% (107/2516) vs. 4.29% (137/3192) in group B. The reported incidence of AKI and new onset of dialysis was, respectively, 22.14% (557/2516) and 5.45% (137/2516) for group A and 22.49% (718/3192) and 4.32% (138/3192) for group B. A total of 579 patients presented with chronic kidney disease (CKD) at admission across all studies, which included 350 (13.91%) in group A vs. 229 (7.17%) in group B. Acute kidney injury, 30-day mortality, and new-onset dialysis rate were reported in four subgroups: (1) In the “Ringer” group, 30-day mortality was 2.52% (3/113), AKI affected 27.73% (33/119) of patients, and the new-onset dialysis rate was 2.52% (3/113). (2) In the “Custodiol” group, 30-day mortality was 3.70% (3/81), AKI affected 20.17% (24/81) of patients, and the new-onset dialysis rate was 2.46% (2/81). (3) In the “cold solutions” group (i.e., NaCl and mannitol), 30-day mortality was 4.38% (130/2966), AKI affected 21.81% (647/2966) of patients, and the new-onset dialysis rate was 4.48% (133/2966). (4) In the “Warm blood” group, 30-day mortality was 3.85% (1/26), AKI affected 53.84% (14/26) of patients, and the new-onset dialysis rate was 0% (0/26). Conclusions: This systematic review highlights the lack of standard definitions for AKI, CKD, and the type of renal perfusion. Despite similar results in terms of AKI and 30-day mortality, renal perfusion seems to be protective of the new-onset hemodialysis rate. Moreover, Custodiol appears to have lower rates of AKI and hemodialysis than the other perfusion types. A prospective randomized controlled trial to perform further subgroup analysis and research the various types of renal perfusion may be necessary to identify possible benefits. Full article

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. Full article

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. Full article

Uterus transplantation (UTx) is the only treatment method for women with absolute uterine infertility. Currently, the number of grafts retrieved from deceased donors is increasing; hence, prolonged cold ischemia time is inevitable. Thus, this study was designed to assess the effect of the novel relaxin (RLN)- or erythropoietin (EPO)-supplemented Custodiol-N (HTK-N) solutions in an experimental uterus static cold storage (SCS) model. A total of 15 Sprague Dawley rats were used. Uterus horns were randomly assigned into three groups (n = 10/group). SCS was performed by keeping samples at 4 °C in HTK-N solution without or with different additives: 10 IU/mL EPO or 20 nM RLN. Tissue samples were taken after 8 and 24 h of preservation. Uterine tissue histology, and biochemical and immunohistochemical markers were analyzed. No significant differences in SCS-induced tissue damage were observed between groups after 8 h of preservation. Uterine tissue histology, MDA, SOD levels and the TUNEL-positive cell number showed severe damage in HTK-N without additives after 24 h of preservation. This damage was significantly attenuated by adding RLN to the preservation solution. EPO showed no favorable effect. Our study shows that RLN as an additive to an HTK-N solution can serve as an effective uterine tissue preservative in the uterus SCS setting. Full article

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/dt_max and dp/dt_min 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. Full article

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. Full article

The race for an ideal cardioplegic solution has remained enthusiastic since the beginning of the modern cardiac surgery era. The Bretschneider solution, belonging to the “intracellular cardioplegic” group, is safe and practical in myocardial protection during ischemic time. Over time, some particular concerns have arisen regarding the effects on cardiac metabolism and postoperative myocardial functioning. This paper reviews the most important standpoints in terms of theoretical and practical analyses. Full article

Objective. Ischemia-reperfusion injury (IRI) is inevitable after kidney transplantation (KT), impairing outcomes. Relaxin-2 (RLX) is a promising insulin-related peptide hormone that protects against renal IRI in rodents, although large animal models are needed before RLX can be tested in a human setting. Methods. In this blinded, randomized, and placebo-controlled experimental study kidneys from 19 donor pigs were retrieved after perfusion with Custodiol^® ± RLX (5 or 20 nmol/L) and underwent static cold storage (SCS) for 24 and 48 h, respectively. Subsequently, KT was performed after unilateral right nephrectomy. Study outcomes included markers for kidney function, oxidative stress, lipid peroxidation, and endothelial cell damage. PCR analysis for oxidative stress and apoptosis-related gene panels as well as immunohistochemistry were performed. Results. RLX upregulated SOD2 and NFKB expression to 135% (p = 0.042) and 125% (p = 0.019), respectively, while RIPK1 expression was downregulated to 82% (p = 0.016) of corresponding controls. Further RLX significantly downregulated RIPK1 and MLKL expression and decreased the number of Caspase 3- and MPO-positive cells in grafts after SCS. Conclusions. RLX supplemented Custodiol^® significantly decreased IRI via both antioxidant and anti-apoptotic mechanisms. Clinical trials are warranted to implement synthetic human RLX as a novel additive to preservation solutions against IRI. Full article

Uterus transplantation (UTx) is the first and only available treatment for women with absolute uterine factor infertility. However, clinical application is limited by the lack of organs, ischemia/reperfusion injury, as well as immunosuppression after UTx. Several different preservation solutions are used in experimental and clinical UTx, including Custodiol^® solution. Recently, the novel Custodiol-N solution was developed with superior results in organ preservation. However, the solution was not tested yet in UTx. Therefore, the aims of this study were to evaluate the effect of Custodiol-N in uterus prolonged cold preservation time (8 and 24 h), compared to Custodiol^® solution. Uterus tissue samples were obtained from adult Sprague Dawley rats (n = 10/group). Cold ischemic injury was estimated by histology, including immunohistochemistry, and biochemical tissue analyses. After 8 h of cold ischemia, higher percentage of tissue edema, necrosis signs and myeloperoxidase expression, as well as lower superoxide dismutase activity were found in Custodiol^® compared to Custodiol-N (p < 0.05). These differences were more pronounced after 24 h of cold preservation time (p < 0.05). This study demonstrated that Custodiol-N protects uterus grafts from cold ischemic injury better than standard Custodiol^® most likely via inhibition of oxidative stress and tissue edema. It seems that iron chelators in the composition of Custodiol-N play an important protective role against cold ischemia. Full article

The effects of cold storage using Custodiol^® (Histidine-Tryptophan-Ketoglutarate, HTK) or isotonic saline solution on mitochondrial function in hearts (left and rights ventricles) and various blood vessels of pigs were investigated. Hearts, saphenous veins, internal-mammary-arteries and aortas of male landrace pigs were harvested and exposed to cold ischemia in either saline or Custodiol-HTK solution. Mitochondrial function was measured in situ in permeabilized fibers by high-resolution respirometry. Mitochondrial respiratory capacities (maximal respiration rates) were similar in the right and left ventricle in controls and after 14 h of cold storage were significantly better preserved in Custodiol-HTK than in saline solution. Mitochondrial respiration rates in various blood vessels including aorta, arteries and veins were less than 5% of myocardium rates. In contrast to the pig heart, in some blood vessels, like veins, mitochondrial function remained stable even after 24 h of cold ischemia. HTK-Custodiol protection of mitochondrial function after prolonged cold ischemia was observed in the myocardium but not in blood vessels. HTK-Custodiol solution thus offers significant protection of myocardial mitochondria against cold ischemic injury and can be used as efficient preservation solution in organ transplantation but probably has no benefit for blood vessels preservation. Analysis of mitochondrial function can be used as a valuable approach for the assessment of cold ischemic injury in various tissues including pig heart and various blood vessels. Full article