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.

Transcriptomic Changes in the Myocardium and Coronary Artery of Donation after Circulatory Death Hearts following Ex Vivo Machine Perfusion.

Donation after circulatory death (DCD) hearts are predominantly maintained by normothermic blood perfusion (NBP). Nevertheless, it was shown that hypothermic crystalloid perfusion (HCP) is superior to blood perfusion to recondition left ventricular (LV) contractility. However, transcriptomic changes in the myocardium and coronary artery in DCD hearts after HCP and NBP have not been investigated yet. In a pig model, DCD hearts were harvested and maintained for 4 h by NBP (DCD-BP group, N = 8) or HCP with oxygenated histidine-tryptophane-ketoglutarate (HTK) solution (DCD-HTK, N = 8) followed by reperfusion with fresh blood for 2 h. In the DCD group (N = 8), hearts underwent reperfusion immediately after procurement. In the control group (N = 7), no circulatory death was induced. We performed transcriptomics from LV myocardial and left anterior descending (LAD) samples using microarrays (25,470 genes). We applied the Boruta algorithm for variable selection to identify relevant genes. In the DCD-BP group, compared to DCD, six genes were regulated in the myocardium and 1915 genes were regulated in the LAD. In the DCD-HTK group, 259 genes were downregulated in the myocardium and 27 in the LAD; and 52 genes were upregulated in the myocardium and 765 in the LAD, compared to the DCD group. We identified seven genes of relevance for group identification: ITPRIP, G3BP1, ARRDC3, XPO6, NOP2, SPTSSA, and IL-6. NBP resulted in the upregulation of genes involved in mitochondrial calcium accumulation and ROS production, the reduction in microvascular endothelial sprouting, and inflammation. HCP resulted in the downregulation of genes involved in NF-κB-, STAT3-, and SASP-activation and inflammation.

First experience with the new extracorporeal membrane oxygenation system Colibrì.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is increasingly used for circulatory or pulmonary support not only in-hospital but also out-of-hospital. Small dimensions and a lightweight design are important, especially for out-of-hospital use but also for intra-hospital transportation of patients who require ECMO support. We share our first experience with the new Colibrì ECMO system. PATIENTS AND METHODS: From December 2022 to January 2023, we used the new Colibrì extracorporeal circulation (ECC) system in six patients with cardiac or pulmonary failure. RESULTS: The Colibrì system was used in-hospital in six patients with post-cardiac surgery low output syndrome, respiratory failure due to influenza or acute respiratory distress syndrome, cardiogenic shock, pulmonary embolism, and failed weaning from cardiopulmonary bypass. The system was implanted in venovenous (VV) and venoarterial (VA) fashion in 3 patients, respectively. In one patient, the configuration was switched from VA to VV after cardiac recovery. One patient received left-ventricular unloading using the IMPELLA®5.5. ECMO run time was 1 to 13 days. We did not notice any ECC system-associated complications. No ECMO system changes were required. CONCLUSION: Our case series concludes that the new Colibrì system is safe and effective for in-hospital ECMO indications. The small dimensions and lightweight design are very beneficial for the transportation of patients. It might be especially helpful for out-of-hospital situations.

Impact of Age on Endothelial Function of Saphenous Vein Grafts in Coronary Artery Bypass Grafting.

BACKGROUND: An intact and functionally preserved endothelial layer in the graft is crucial for myocardial perfusion and graft patency after coronary artery bypass grafting (CABG). We hypothesized that old age is a risk factor for decreased endothelial function of bypass grafts. Thus, we investigated the impact of age in patients treated with CABG on endothelial function in saphenous vein grafts. METHODS: We mounted the saphenous vein graft segments of CABG patients < 70 (n = 33) and ≥70 (n = 40) years of age in organ bath chambers and exposed them to potassium chloride (KCl) and phenylephrine (PE) to test the receptor-independent and -dependent contractility, followed by exposure to acetylcholine (ACh) and sodium nitroprusside (SNP) to test the endothelial-dependent and -independent relaxation. RESULTS: The maximal contraction induced by KCl (2.3 ± 1.8 vs. 1.8 ± 2 g) was stronger in patients ≥ 70 years of age. The relative contraction induced by PE in % of KCl (167 ± 64 vs. 163 ± 59%) was similar between groups. Patients aged < 70 years showed a higher endothelial-dependent relaxation induced by acetylcholine than patients ≥ 70 years (51 ± 27 vs. 42 ± 18%). The relaxation induced by SNP was similar between both groups. CONCLUSIONS: The endothelial function of saphenous vein bypass grafts decreases during aging. Thus, age should be considered when improving graft maintenance.

Sex-Specific Protection of Endothelial Function after Vascular Ischemia/Reperfusion Injury by the Senomorphic Agent Ruxolitinib.

Ischemia/reperfusion (I/R)-induced endothelial dysfunction occurs in various cardiovascular disorders. I/R injury is partially driven by the release of cytokines. Known for its use in senotherapy, the JAK inhibitor ruxolitinib is able to block the release of cytokines. We investigated the effect of ruxolitinib on the cytokine release and endothelial-dependent vasorelaxation in an in vitro model of I/R. Aortic segments of C57BL/6J mice (N = 12/group) were divided into three groups: control, in vitro I/R (I/R group), and in vitro I/R with ruxolitinib during ischemic incubation (I/R+Ruxo group). We determined cytokine expression. In organ bath chambers, we investigated the maximal endothelial-dependent relaxation to acetylcholine (RmaxACh) and maximal endothelial-independent relaxation to sodium-nitroprusside (RmaxSNP). RmaxACh was decreased in I/R compared to the control (83.6 ± 2.4 vs. 48.6 ± 3.4%; p < 0.05) and I/R+Ruxo (74.4 ± 2.6 vs. 48.6 ± 3.4%; p < 0.05). RmaxSNP was comparable between all groups. IL-10 was detectable only in I/R+Ruxo. CXCL5, CCL2, CCL3, CCL8, CCL11, ICAM-1, IL-1α, IL-7, TNF-α, and G-CSF were decreased or not detectable in I/R+Ruxo. In I/R+Ruxo, ICAM-1 was reduced in rings only from male mice. Treatment of the aorta from mice during in vitro ischemia with the senomorphic agent ruxolitinib reduces cytokine release and protects the endothelium from I/R-mediated dysfunction.

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.

Extracorporeal Membrane Oxygenation in Intoxication and Overdoses: A Systematic Review.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been increasingly applied over recent decades to treat severe cardiogenic shock and acute lung failure and cardiac arrest of various causes. Acute intoxication with therapeutic substances or other chemical substances can cause severe cardiogenic shock or even cardiac arrest. The purpose of this study was to conduct a qualitative systematic review of ECMO use in intoxication and poisoning. METHODS: We searched the PubMed, Medline, and Web of Science databases from January 1971 to December 2021 and selected appropriate studies according to our inclusion and exclusion criteria to evaluate the role of ECMO in intoxication and poisoning systematically. Survival at hospital discharge was examined to describe the outcome. RESULTS: The search resulted in 365 publications after removing duplicates. In total, 190 full-text articles were assessed for eligibility. A total of 145 articles from 1985 to 2021 were examined in our final qualitative analysis. A total of 539 (100%) patients were included (mean age: 30.9 ± 16.6 years), with a distribution of n = 64 (11.9%) cases with venovenous (vv) ECMO, n = 218 (40.4%) cases with venoarterial (va) ECMO, and n = 257 (47.7%) cases with cardiac arrest and extracorporeal cardiopulmonary resuscitation. Survival at hospital discharge was 61.0% for all patients, 68.8% for vaECMO, 75% for vvECMO, and 50.9% for extracorporeal cardiopulmonary resuscitation. CONCLUSION: When used and reported, ECMO seems to be a valid tool for adult and pediatric patients suffering intoxication from various pharmaceutical and nonpharmaceutical substances due to a high survival rate at hospital discharge.

Cytokine Adsorber Use during DCD Heart Perfusion Counteracts Coronary Microvascular Dysfunction.

Microvascular dysfunction (MVD) in cardiac allografts is associated with an impaired endothelial function in the coronary microvasculature. Ischemia/reperfusion injury (IRI) deteriorates endothelial function. Hearts donated after circulatory death (DCD) are exposed to warm ischemia before initiating ex vivo blood perfusion (BP). The impact of cytokine adsorption during BP to prevent MVD in DCD hearts is unknown. In a porcine DCD model, we assessed the microvascular function of hearts after BP with (DCD-BPCytoS, n = 5) or without (DCD-BP, n = 5) cytokine adsorption (CytoSorb®). Microvascular autoregulation was assessed by increasing the coronary perfusion pressure, while myocardial microcirculation was measured by Laser-Doppler-Perfusion (LDP). We analyzed the immunoreactivity of arteriolar oxidative stress markers nitrotyrosine and 4-hydroxy-2-nonenal (HNE), endothelial injury indicating cell adhesion molecules CD54, CD106 and CD31, and eNOS. We profiled the concentration of 13 cytokines in the perfusate. The expression of 84 genes was determined and analyzed using machine learning and decision trees. Non-DCD hearts served as a control for the gene expression analysis. Compared to DCD-BP, relative LDP was improved in the DCD-BPCytoS group (1.51 ± 0.17 vs. 1.08 ± 0.17). Several pro- and anti-inflammatory cytokines were reduced in the DCD-BPCytoS group. The expression of eNOS significantly increased, and the expression of nitrotyrosine, HNE, CD54, CD106, and CD31, markers of endothelial injury, majorly decreased in the DCD-BPCytoS group. Three genes allowed exact differentiation between groups; regulation of HIF1A enabled differentiation between perfusion (DCD-BP, DCD-BPCytoS) and non-perfusion groups. CAV1 allowed differentiation between BP and BPCytoS. The use of a cytokine adsorption device during BP counteracts preload-dependent MVD and preserves the microvascular endothelium by preventing oxidative stress and IRI of coronary arterioles of DCD hearts.

Prediction Model for Contractile Function of Circulatory Death Donor Hearts Based on Microvascular Flow Shifts During Ex Situ Hypothermic Cardioplegic Machine Perfusion.

Background Hearts procured from circulatory death donors (DCD) are predominantly maintained by machine perfusion (MP) with normothermic donor blood. Currently, DCD heart function is evaluated by lactate and visual inspection. We have shown that MP with the cardioplegic, crystalloid Custodiol-N solution is superior to blood perfusion to maintain porcine DCD hearts. However, no method has been developed yet to predict the contractility of DCD hearts after cardioplegic MP. We hypothesize that the shift of microvascular flow during continuous MP with a cardioplegic preservation solution predicts the contractility of DCD hearts. Methods and Results In a pig model, DCD hearts were harvested and maintained by MP with hypothermic, oxygenated Custodiol-N for 4 hours while myocardial microvascular flow was measured by Laser Doppler Flow (LDF) technology. Subsequently, hearts were perfused with blood for 2 hours, and left ventricular contractility was measured after 30 and 120 minutes. Various novel parameters which represent the LDF shift were computed. We used 2 combined LDF shift parameters to identify bivariate prediction models. Using the new prediction models based on LDF shifts, highest r2 for end-systolic pressure was 0.77 (P=0.027), for maximal slope of pressure increment was 0.73 (P=0.037), and for maximal slope of pressure decrement was 0.75 (P=0.032) after 30 minutes of reperfusion. After 120 minutes of reperfusion, highest r2 for end-systolic pressure was 0.81 (P=0.016), for maximal slope of pressure increment was 0.90 (P=0.004), and for maximal slope of pressure decrement was 0.58 (P=0.115). Identical prediction models were identified for maximal slope of pressure increment and for maximal slope of pressure decrement at both time points. Lactate remained constant and therefore was unsuitable for prediction. Conclusions Contractility of DCD hearts after continuous MP with a cardioplegic preservation solution can be predicted by the shift of LDF during MP.

[Biological mechanisms of aging in the cardiovascular system]. / Biologische Alterungsmechanismen im Herz-Kreislauf-System.

Cardiovascular diseases, which are at the end of a spectrum of degenerative processes, are one of the leading causes of death worldwide. A causal contribution to these and many other diseases is made by key biological aging mechanisms that have been summarized as the hallmarks of aging. These include accumulation of macromolecular damage, epigenetic changes, impaired proteostasis, telomere shortening, mitochondrial dysfunction, cellular senescence, inflammatory reactions, altered metabolism, impaired cellular communication and changes in the stem cell niche. In the cardiovascular system, oxidative and glycative stress are particularly important as sources of macromolecular damage. These induced insidious changes reduce the resilience and resistance of the heart and vessels to stress, ultimately leading to functional impairments and diseases. A possible novel approach, which does not aim at an intervention against the classical cardiovascular diseases but against the hallmarks of aging, and is termed geroscience, provides valuable concepts but still has to prove itself in the future.

A Systematic Review with Meta-Analysis Investigating the Impact of Targeted Perfusion Parameters during Extracorporeal Cardiopulmonary Resuscitation in Out-of-Hospital and Inhospital Cardiac Arrest.

Evidence regarding perfusion conditions during extracorporeal cardiopulmonary resuscitation (ECPR) is rare. Therefore, we investigated the impact of perfusion parameters on neurologic outcome and survival in patients with in- or out-of-hospital cardiac arrest (IHCA; OHCA) treated with ECPR. We performed a systematic review with meta-analysis. The focus was set on perfusion parameters and their impact on survival and a goal neurological outcome using the cerebral performance category score of 1-2. We conducted random- and mixed-effects meta-analyses and computed pooled estimates and 95% confidence intervals (CI). We included a total of n = 1,282 ECPR (100%) patients from 20 ECPR studies. The target values of flow and mean arterial pressure (MAP) were frequently available. We transferred flow and MAP target values to high, medium, and low categories. The meta-analysis could not demonstrate a single effect of flow or MAP on outcome variables. In a second mixed-effects model, the combined occurrence of targeted flow and MAP as medium and high showed a significant effect on survival (OHCA: 52%, 95% CI: 29%, 74%; IHCA: 60%, 95% CI: 35%, 85%) and on neurological outcomes (OHCA: 53%, 95% CI: 27%, 78%; IHCA: 62%, 95% CI: 38%, 86%). Random-effects analysis showed also that IHCA led to a significant 11% (p = 0.006; 95% CI: 3%, 18%) improvement in survival and 12% (p = .005; 95% CI: 4%, 21%) improvement in neurological outcomes compared to OHCA. A combination of medium flow and high MAP showed advantages in survival and for neurological outcomes. We also identified improved outcomes for IHCA.

Relationship of Laser-Doppler-Flow and coronary perfusion and a concise update on the importance of coronary microcirculation in donor heart machine perfusion.

BACKGROUND: Machine perfusion (MP) is a novel method for donor heart preservation. The coronary microvascular function is important for the transplantation outcome. However, current research on MP in heart transplantation focuses mainly on contractile function. OBJECTIVE: We aim to present the application of Laser-Doppler-Flowmetry to investigate coronary microvascular function during MP. Furthermore, we will discuss the importance of microcirculation monitoring for perfusion-associated studies in HTx research. METHODS: Porcine hearts were cardioplegically arrested and harvested (Control group, N = 4). In an ischemia group (N = 5), we induced global ischemia of the animal by the termination of mechanical ventilation before harvesting. All hearts were mounted on an MP system for blood perfusion. After 90 minutes, we evaluated the effect of coronary perfusion pressures from 20 to 100 mmHg while coronary laser-doppler-flow (LDF) was measured. RESULTS: Ischemic hearts showed a significantly decreased relative LDF compared to control hearts (1.07±0.06 vs. 1.47±0.15; p = 0.034). In the control group, the coronary flow was significantly lower at 100 mmHg of perfusion pressure than in the ischemia group (895±66 ml vs. 1112±32 ml; p = 0.016). CONCLUSIONS: Laser-Doppler-Flowmetry is able to reveal coronary microvascular dysfunction during machine perfusion of hearts and is therefore of substantial interest for perfusion-associated research in heart transplantation.

Reconditioning of circulatory death hearts by ex-vivo machine perfusion with a novel HTK-N preservation solution.

BACKGROUND: Warm ischemia followed by blood reperfusion is associated with reduced myocardial contractility. Circulatory death (CD) hearts are maintained by machine perfusion (MP) with blood. However, the impact of MP with histidine-tryptophane-ketoglutarate (HTK) or novel HTK-N solution on reconditioning of CD-heart contractility is unknown. METHODS: In a porcine model, native hearts were directly harvested (control), or CD was induced before harvesting, followed by left ventricular (LV) contractile assessment. In MP-groups, CD-hearts were maintained for 4 h by MP with blood (CD-B), cold oxygenated HTK (CD-HTK) or HTK-N (CD-HTK-N) before contractile evaluation (all groups n = 8). We performed immunohistochemistry of LV myocardial samples. We profiled myocardial expression of 84 oxidative stress-related genes and correlated the findings with myocardial contractility via a machine learning algorithm. RESULTS: HTK-N improved end-systolic pressure (ESP=172±10 vs 132±5 mmHg, p = 0.02) and maximal slope of pressure increment (dp/dtmax=2161±214 vs 1240±167 mmHg/s, p = 0.005) compared to CD, whereas CD-B failed to improve contractility. Dp/dtmax (2161±214 vs 1177±156, p = 0.08) and maximal rate of pressure decrement (dp/dtmin=-1501±228 vs -637±79, p = 0.005) were also superior in CD-HTK-N compared to CD-B. In CD-HTK-N, myocardial 4-hydroxynonenal (marker for oxidative stress; p<0.001), nitrotyrosine (marker for nitrosative stress; p = 0.004), poly(adenosine diphosphate-ribose)polymerase (marker for necrosis; p = 0.028) immunoreactivity and cell swelling (p = 0.008) were decreased compared to CD-B. Strong correlation of gene expression with ESP was identified for oxidative stress defense genes in CD-HTK-N. CONCLUSION: During harvesting procedure, MP with HTK-N reconditions CD-heart systolic and diastolic function by reducing oxidative and nitrosative stress and preventing cardiomyocytes from cell swelling and necrosis.

Impact of skeletonized harvesting of the internal thoracic artery on intrasternal microcirculation considering preparation quality.

OBJECTIVES: Previous studies have demonstrated the impact of internal thoracic artery (ITA) harvesting on microcirculation in parasternal tissues. However, the impact of skeletonized ITA harvesting on intrasternal microcirculation is unknown. Intraskeletal tissue perfusion has been proven to be crucial for deep wound healing. Furthermore, the impact of different levels of surgical preparation quality on intrasternal microcirculation has not been investigated yet. METHODS: Sternal microcirculation (sLDP) was monitored with a novel Laser Doppler Perfusion needle probe, while the ITA was skeletonized in a pig model. To mimic different levels of preparation quality, satellite veins were either coagulated or not during preparation. To show the effect of ideally avoiding any surgical manipulation on sLDP, the ITA was clipped in a third sham-harvested group. RESULTS: sLDP was reduced highly significant to 71 [standard deviation (SD): 9]% (P < 0.001) after skeletonized harvesting of the ITA. Coagulation of the satellite veins as a detrimental surgical factor resulted in a significantly stronger reduction of sLDP to 56 (SD: 11)% (P < 0.05) compared to sLDP with non-coagulated satellite veins. ITA clipping reduced sLDP highly significant to 71 (SD: 8)% (P < 0.001) in the sham-operated group. CONCLUSIONS: ITA harvesting markedly impairs microcirculation of the sternum but remains unavoidable when coronary artery bypass grafting should be performed. Nevertheless, excessive surgical damage and coagulation of satellite veins is avoidable and should be reduced to a minimum to minimize the risk of deep sternal wound healing complications.

Monitoring of perfusion quality and prediction of donor heart function during ex-vivo machine perfusion by myocardial microcirculation versus surrogate parameters.

Currently, lactate (Lac) is used to evaluate machine perfusion (MP) of hearts, donated after circulatory death (DCD). We hypothesize that monitoring of myocardial microcirculation (mLDP) by Laser-Doppler-Perfusion is superior to Lac to evaluate perfusion and predict contractility. In a pig model, DCD-hearts were perfused 4 hours followed by reperfusion and left ventricular contractility measurement. Lac and mLDP were measured every 30 min in successfully (N = 9) and unsuccessfully (N = 7) maintained hearts. Successfully maintained hearts showed decreasing Lac (5.6 to 2.8 mmol/L) and slightly downregulated (92%) mLDP. In unsuccessfully maintained hearts Lac first decreased (5.1 to 3.8 mmol/L) followed by increase and mLDP dropped to 39%. In a single-variable regression only mLDP showed a significant r² for systolic (0.514, p = 0.045) and diastolic (0.501, p = 0.049) parameters. The combination of mLDP and Lac (r2 = 0.876, p = 0.005) showed best results. mLDP seems to be superior to Lac to show perfusion disorders and predict DCD-heart contractility.

Ethical Decision Diagrams on Donation After Cardiocirculatory Death Heart Transplantation Considering Organ Preservation Techniques.

BACKGROUND: To overcome organ shortage, some centers accept hearts from cardiocirculatory determined death (DCD) donors for heart transplantation (HTx). DCD-HTx is attached with special ethical conflicts on the donor, family, and recipient side. Ethically motivated decisions also have to be made considering organ preservation techniques. However, ethical decision diagrams, which can be applied to find a final answer on the complex field of ethical questions, have not been developed yet. METHODS: In an interdisciplinary group of clinical ethicists, transplantation surgeons, transplantation researchers, and perfusionists, after review of relevant literature, we focused on crucial ethical aspects on DCD-HTx in general and separated ethical conflicts with regard to the individual perspective of the donor, family, and recipient. RESULTS: The leading aspect of discussion in the donor perspective mainly deals with the standoff period and with the definition of death. The perspective of recipients focuses on the wish to say farewell after the patient is deceased. In the recipient perspective ethical questions regarding organ procurement techniques occur. CONCLUSIONS: Ethical decision-making on DCD-HTx is complex, but it can be processed in a structured way by applying the decision diagrams that we have developed.

Machine perfusion of circulatory determined death hearts: A scoping review.

BACKGROUND: Ex vivo machine perfusion (EVMP) is reported to can successfully be applied for donor heart preservation. To respond to the organ shortage, some centres also accept hearts from marginal donors such as non-heart beating donors (NHBD) or hearts donated after cardiac death (DCD) for heart transplantation (HTx). Clinical as well as preclinical science on EVMP of DCD hearts seems to be promising but the ideal perfusion practice itself appears unclear. OBJECTIVES: In accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA), this systematic review scopes all EVMP techniques for human and animal DCD heart preservation and addresses three specific questions, which refer to (a) the perfusion solutions, (b) the perfusion parameters and respective target values and (c) if possible, a direct comparison between cold static storage (CSS) and EVMP. RESULTS: Search results predominantly consisted of animal studies. Either perfusion with a crystalloid or blood-based solution, each with cardioplegic or non-cardioplegic properties was used. Some perfusates were supplemented with specific pharmacological medication to block pathophysiological pathways, which are involved in ischemia/reperfusion injury or edema formation. Besides normothermic EVMP with oxygenated blood, a wide range of temperature was applied in all approaches, with the lowest temperature at 4 °C. Pressure controlled anterograde Langendorff perfusion was applied mostly. If investigated, crystalloid machine perfusion was presented superior to CSS. CONCLUSIONS: Only blood based EVMP was introduced into clinical practice. More research, clinical as well as preclinical, is needed to develop the ideal EVMP technique, in terms of blood or crystalloid perfusion.

Perfusion parameters and target values during extracorporeal cardiopulmonary resuscitation: a scoping review protocol.

INTRODUCTION: Extracorporeal cardiopulmonary resuscitation (eCPR) is increasingly applied in out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA) patients. Treatment results are promising, but the efficacy and safety of the procedure are still unclear. Currently, there are no recommended target perfusion parameters during eCPR, the lack of which could result in inadequate (re)perfusion. We aim to perform a scoping review to explore the current literature addressing target perfusion parameters, target values, corresponding survival rates and neurologic outcomes in OHCA and IHCA patients treated with eCPR. METHODS AND ANALYSIS: To identify relevant research, we will conduct searches in the electronic databases MEDLINE, EMBASE, Social Science Citation Index, Social Science Citation Index Expanded and the Cochrane library. We will also check references of relevant articles and perform a cited reference research (forward citation tracking).Two independent reviewers will screen titles and abstracts, check full texts for eligibility and perform data extraction. We will resolve dissent by consensus, moderated by a third reviewer. We will include observational and controlled studies addressing target perfusion parameters and outcomes such as survival rates and neurologic findings in OHCA and IHCA patients treated with eCPR. Data extraction tables will be set up, including study and patients' characteristics, aim of study, details on eCPR including target perfusion parameters and reported outcomes. We will summarise the data using tables and figures (ie, bubble plot) to present the research landscape and to describe potential clusters and/or gaps. ETHICS AND DISSEMINATION: An ethical approval is not needed. We intend to publish the scoping review in a peer-reviewed journal and present results on a scientific meeting.

Cutaneous microcirculation during operations with a cardiopulmonary bypass.

BACKGROUND: Cutaneous microcirculation (cMC) is influenced by many factors. In cardiac surgery, most operations are performed with a cardiopulmonary bypass (CPB) and cardiac arrest induced by cardioplegic solutions. OBJECTIVES: Aim of this study was to examine a correlation between cMC and hemodynamic parameters in patients undergoing heart surgery with two different cardioplegic solutions. METHODS: 20 patients were included and divided into Histidine-Tryptophane-α-Ketoglutarate solution- (HTK, n = 10) and blood cardioplegia- (BCP, n = 10) groups. With initiation of CPB, cMC was continuously monitored with Laser-Doppler-Perfusion (LDP) until termination of CPB. Additionally, we measured hemoglobin-concentration (HbC) with a Blood-Parameter-Monitoring-System. RESULTS: LDP pulsation was almost equal before and after CPB and decreased during aortic cross clamping. The following factors influenced LDP: central venous pressure (CVP), mean arterial pressure (MAP), total peripheral resistance (TPR) and flow of the heart-lung machine. We measured relative LDP and HbC (RLDP; RHbC). Five and 25 min after administration of cardioplegia, RLDP (1.22±0.8; 1.17±0.94) and RHbC (0.92±0.06; 0.96±0.09) in the HTK-group were lower than in the BCP-group: RLDP (1.58±1.11; 1.58±2.2) and RHbC (1.00±0.05; 0.99±0.13). HTK-patients with a body surface area (BSA) <2 m2 showed a lower RLDP (0.75±0.50), than patients over 2 m2 (RLDP = 1.64±0.97). CONCLUSIONS: The cMC is influenced by CPB. Cutaneous LDP monitoring is a non-invasive method, for estimating hemodynamics intraoperatively.

Cardiac frequency and cutaneous microcirculation during and after exercising in the view of physical condition.

INTRODUCTION: In the field of cardiovascular diseases an ergometer test is a common diagnostical method in which a change in microcirculation can be reached. In this paper cardiac frequency and cutaneous microcirculation during and after exercising will be compared with each other. MATERIALS AND METHODS: The cutaneous microcirculation of  6 healthy volunteers (2 females, 4 males) is measured. As an instrument the PeriFlux 5000 combined with a Laser-Doppler-Flow(LDF)-Probe (Perimed Instruments) is used. The cardiac frequency (CF) is measured by the POLAR T31 sensor and as an ergometer the ERGO-FIT ® 457 is used. RESULTS: The mean initial LDF (97,7±57,3 PU) decreases at the beginning (64,5±21,7 PU), increases during theexercise, reaches its maximum (247,8±82,1 PU) after the end of the exercise and drops to lower values (256,4±69,5 PU)after a few minutes. Contrasting to the LDF the mean initial CF (86±22/min) increases at the beginning (97±9/min),furthermore during the whole exercise (103±9/min) and then falls after having finished the exercise (96±3/min).Furthermore, during regeneration, one can see the CF decreasing towards its initial value, while LDF reaches its maximum. CONCLUSION: In further studies, realized with volunteers with well-known levels of physical condition, a directconnection between cutaneous microcirculation and physical condition might be found.