Jochen Pöling

Tissue injury initiates a complex, multicellular programme whose outcome i.e. functional repair or irreversible fibrosis, is determined by the coordinated activity of the stroma-vascular compartment (SVC). This network of resident fibroblasts, vascular mural cells, endothelial cells and immune populations acts as a gatekeeper of tissue integrity. Following ischaemia, trauma, or mechanical damage, extracellular danger signals are sensed by pattern-recognition receptors and transduced into cell type-specific metabolic and mechanical responses. An initial inflammatory wave clears cellular debris, after which endothelial sprouting and matrix deposition proceed toward scar maturation; a collagen-rich structure whose geometry ultimately governs future perfusion. Epigenetic reprogramming and metabolic rewiring enforce each of these transitions while simultaneously imprinting a memory that skews subsequent responses in the context of ageing, diabetes, chronic inflammation or clonal haematopoiesis. Targeting the SVC, rather than the parenchyma alone, now underpins therapeutic strategies spanning precision senolytics, engineered stromal cell grafts, and biomechanically instructive scaffolds.

Objectives: The “German Registry for Acute Aortic Dissection Type A” (GERAADA) long-term follow-up firstly investigates the neurologic outcomes over a 16-year timeframe and secondly determines whether acute Stanford type A aortic dissection (ATAAD) patients are at risk for secondary neurologic complications. Methods: Thirty-three centres provided follow-up data of 2686 individuals. Of those, 814 provided long-term data regarding their neurological status and incidence of stroke. Multivariable regression analysis was used to identify risk factors of both postoperative and secondary neurologic deficits. Subgroup analyses of patients operated in hypothermic circulatory arrest with or without selective antegrade cerebral perfusion was performed to assess further influencing factors. Results: Four hundred and fifteen (15%) out of the 2686 patients experienced postoperatively a new-onset neurologic deficit while being hospitalized. Age, renal malperfusion, dissected supra-aortic vessels, extracorporeal circulation time, and re-exploration were independent risk factors (all P < .05) for worse neurological outcomes while hemiarch replacement seemed to have a protective effect (OR = 0.68; P = .008). Neither cerebral protection strategy nor temperature management showed significant differences between the groups regarding neurological outcome. Out of the 814 follow-up patients, 188 (23%) experienced secondary neurologic deficits after initial treatment for ATAAD within a median follow-up of 10.2 years. Long-term risk factors were a persistent cerebral malperfusion and late reoperation. No association between perioperative neurologic damage and operative techniques on long-term neurologic outcomes could be found. Conclusions: Surgery for ATAAD is associated with frequent early neurologic complications that can be predicted by perioperative factors. Open treatment of the aortic arch shows a positive effect on neurological outcome. Further, every fourth follow-upped patients suffered from secondary neurological damage highlighting the importance of a close surveillance.

Background: The purpose of this study was to validate myocardial microdialysis measurements in patients after myocardial infarction with or without associated postoperative functional recovery in order to develop a highly sensitive tool for real-time in vivo detection of microcellular disorder during cardiac operations. Methods: In 20 patients undergoing coronary artery bypass grafting, microdialysis catheters were implanted into scar or hibernating segments detected by means of magnetic resonance imaging, and into a vital area of the right ventricle (control). Myocardial glucose, lactate and pyruvate were analyzed perioperatively. Myocardial ethanol washout was measured as a sign of recovered local blood flow. Results: After surgical revascularization, improvement of wall motion was found in all hibernating segments compared to the scar segments paralleling an increased glucose delivery to the tissue and increased myocardial tissue flow. The myocardial glucose/lactate ratio and pyruvate also showed significantly higher values. Microdialytic measurements of the viable segments were comparable with those of the right ventricle. Conclusions: Our results indicate that microdialysis measurements parallel magnetic resonance imaging findings in patients with revascularization of chronic ischemic myocardium with dyskinetic segments. The metabolism of those segments is characterized by a significantly increased tissue flow, an increased utilization of glucose and a better oxidative nutrition.

Introduction: Myocardial dysfunction necessitating inotropic support is a typical complication after on-pump cardiac surgery. This prospective, randomized pilot study analyzes the metabolic and renal effects of the inotropes adrenaline and milrinone in patients needing inotropic support after coronary artery bypass grafting (CABG). Methods: During an 18-month period, 251 patients were screened for low cardiac output upon intensive care unit (ICU) admission after elective, isolated CABG surgery. Patients presenting with a cardiac index (CI) of less than 2.2 liters/minute per square meter upon ICU admission – despite adequate mean arterial (titrated with noradrenaline or sodium nitroprusside) and filling pressures – were randomly assigned to 14-hour treatment with adrenaline (n = 7) or milrinone (n = 11) to achieve a CI of greater than 3.0 liters/minute per square meter. Twenty patients not needing inotropes served as controls. Hemodynamics, plasma lactate, pyruvate, glucose, acid-base status, insulin requirements, the urinary excretion of alpha-1-microglobuline, and creatinine clearance were determined during the treatment period, and cystatin-C levels were determined up to 48 hours after surgery (follow-up period). Results: After two to four hours after ICU admission, the target CI was achieved in both intervention groups and maintained during the observation period. Plasma lactate, pyruvate, the lactate/pyruvate ratio, plasma glucose, and insulin doses were higher (p < 0.05) in the adrenaline-treated patients than during milrinone or control conditions. The urinary excretion of alpha-1-microglobuline was higher in the adrenaline than in the control group 6 to 14 hours after admission (p < 0.05). No between-group differences were observed in creatinine clearance, whereas plasma cystatin-C levels were significantly higher in the adrenaline than in the milrinone or the control group after 48 hours (p < 0.05). Conclusion: This suggests that the use of adrenaline for the treatment of postoperative myocardial dysfunction – in contrast to treatment with the PDE-III inhibitor milrinone – is associated with unwarranted metabolic and renal effects. Clinical trials registration: ClinicalTrials.gov NCT00446017.

Background: Post-operative ischemia after coronary artery bypass grafting (CABG) is well described but effective intervention requires immediate diagnosis. One possible way of increasing efficacy of peri-operative myocardial monitoring is using the microdialysis technique. Methods: In 30 patients undergoing routine CABG, a microdialysis catheter was inserted in the left heart in an area of abnormal ventricular contraction. A second catheter was placed in normal tissue of the right ventricle. Microdialysis measurements were performed at time intervals before, during and 24 h after cardiopulmonary bypass (CPB) and retrospectively compared with standard clinical monitoring and clinical course. Results: During CPB, both ventricles showed signs of poor tissue oxygenation. Glycerol was significantly higher in the left myocardium (146 ± 67 vs. 72 ± 36 μmol/l) and the glucose/lactate ratio (GLR), as a marker of nutritional disorder of the right ventricle (41 ± 15% vs. 67 ± 17%, P < 0.05), had significantly better values at this time point. Myocardial lactate concentrations were significantly higher in the dyskinetic segments (2.82 ± 0.81 vs. 1.5 ± 0.81 μM). During this period, no abnormal clinical standard monitoring results were observed. Post-operative significantly increased lactate/pyruvate ratios of three patients were clinically associated with peri-operative myocardial infarction (108 ± 67 vs. 38 ± 9, P < 0.05). The lactate/pyruvate ratio started rising before any other standard monitoring tools showed abnormal values. Conclusions: Peri-operative microdialytic measurements of parameters related to ischemia can be safely performed in a clinical setting, resulting in faster and more reliable detection of ongoing or new ischemia.

Objectives. Microdialysis allows the in vivo biochemical analysis of interstitial fluids. Our aim was to reveal in vivo reliable data of the myocardium during open beating heart surgery. Design. In ten patients undergoing routine beating coronary artery bypass grafting a microdialysis catheter was inserted into the left ventricle. Measurements were performed up to 45 min after anastomosis. Data were retrospectively compared with standard on-pump procedures. Results. The myocardial lactate remained stable during anastomosis, followed by a significant decrease of lactate after revascularisation. Myocardial glucose levels showed a slight decrease, followed by a significant increase after revascularisation. Myocardial purines showed a slight increase during anastomosis, followed by a sharp decrease during reperfusion period. Conclusions. In contrast to on-pump procedures myocardial lactate and purines showed less increasing trend during the ischemic period, while myocardial glucose remained stable as a sign of preserved tissue blood flow. Myocardial microdialysis showed different values compared to the elective on-pump CABG and previous animal studies. This technique allows bedside monitoring of biochemical changes, suggesting its possible role as a clinical monitoring tool.

Background: For the first time, microdialysis was used to investigate in vivo and online the myocardial metabolism during and after cardiac surgery in patients treated with two different methods of myocardial protection. Methods: Thirty patients underwent standard CABG with one of two different methods of myocardial protection. The patients were randomised to receive either cold blood (COLD group) or warm modified Calafiore cardioplegia (WARM group). Microdialysis probes were implanted into the myocardium of left ventricular apical region of the heart. Cardioplegia was given antegrade only. Microdialysis measurements were performed at time intervals before, during and 24 h after cardiopulmonary bypass and analysed for glucose, lactate, pyruvate and glycerol. Results: Myocardial lactate concentrations were significantly higher in the WARM group compared with that of the COLD group, while serum lactate was comparable. Glycerol was significantly higher at the end of the clamping time in the WARM group. At the same time the glucose–lactate ratio as a marker of nutritional disorder had significantly lower levels in the WARM group. The cumulative CK-MB release over 24 h was significantly higher in those hearts protected with warm blood. Conclusions: The oxidative stress measured was significantly higher in patients undergoing CABG using modified Calafiore cardioplegia, whereas the cold cardioplegia minimised the effects of aortic clamping. The results indicate that cold cardioplegia offers superior protection of the heart, in terms of more rapid normalisation of myocardial metabolism. In elective myocardial revascularisation, intermittent antegrade warm blood cardioplegia is a comparable safe method of myocardial protection. However, in patients referring to a long clamping time, advantages of cold cardioplegia for myocardial revascularisation may be magnified.