Background: The current goal of treatment after acute ischemic stroke is the increase of cerebral blood flow (CBF) in ischemic brain tissue. Intra-aortic balloon pump (IABP) counterpulsation in the setting of cardiogenic shock is able to reduce left ventricular afterload and increase coronary blood flow. The effects of an IABP on CBF have not been sufficiently examined. We hypothesize that the use of an IABP especially enhances cerebral blood flow in patients with pre-existing heart failure. Methods: In this pilot study, 36 subjects were examined to investigate the effect of an IABP on middle cerebral artery (MCA) transcranial Doppler (TCD) flow velocity change and relative CBF augmentation by determining velocity time integral changes (ΔVTI) in a constant caliber of the MCA compared to a baseline measurement without an IABP. Subjects were divided into two groups according to their left ventricular ejection fraction (LVEF): Group 1 LVEF >30% and Group 2 LVEF ≤30%. Results: Both groups showed an increase in CBF using an IABP. Patients with a LVEF ≤30% showed a significantly higher increase of ΔVTI in the MCA under IABP augmentation compared to patients with a LVEF >30% (20.9% ± 3.9% Group 2 vs.10.5% ± 2.2% Group 1, p<0,05). The mean arterial pressure (MAP) increased only marginally in both groups under IABP augmentation. Conclusions: IABP improves cerebral blood flow, particularly in patients with pre-existing heart failure and highly impaired LVEF. Hence, an IABP might be a treatment option to improve cerebral perfusion in selected patients with cerebral misperfusion and simultaneously existing severe heart failure.

Im Rahmen der vorliegenden Dissertation wurde die prognostische Relevanz von Angiopoietin-2 (Ang-2) und Fibroblast Growth Factor 23 (FGF-23) als Prädiktor der 30-Tages sowie Ein-Jahres Mortalität bei Patienten im infarktbedingten kardiogenen Schock (CS) untersucht und dargestellt. Das betrachtete Patientenkollektiv dieser Substudie rekrutierte sich dabei aus den 218, im Rahmen der IABP- SHOCK II Studie in Leipzig eingeschlossenen Patienten. Nach Hospitalisierung und Randomisierung in den jeweiligen Therapiearm (IABP, Nicht-IABP) erfolgte eine prospektiv geplante Blutentnahme an den Tagen eins bis drei. Zur laborchemischen Bestimmung der Serum-, beziehungsweise Plasma Proteinkonzentration mittels ELISA von Ang-2 standen 189, für das Phosphathormon FGF-23 182 Blutproben zur Verfügung. Die 30-Tages Mortalität der untersuchten Substudien-Kohorte betrug 40%, die Ein-Jahres Mortalität 57%. Die vorliegende Arbeit bestätigt Ang-2 als einen starken und unabhängigen negativen Prädiktor des Kurz- und Langzeitverlaufs bei Patienten im CS auf Grund eines akuten Myokardinfarks. Weiterhin zeigt die Auswertung, dass die prognostische Relevanz des betrachteten Biomarkers im zeitlichen Verlauf signifikant zunimmt und verschiedene klinische Parameter wie beispielsweise eine akut eingeschränkte Nierenfunktion oder Blutungskomplikationen unabhängig mit erhöhten Ang-2 Konzentrationen assoziiert sind. Somit sind im infarktbedingten CS hohe Werte von Ang-2 unabhängig mit einem schlechteren klinischen Verlauf des Patienten, sowie dem Reperfusionserfolg und weiteren Komplikationen assoziiert. Patienten der Substudien-Kohorte im infarktbedingten CS waren durch signifikant erhöhte Konzentrationen von FGF-23 charakterisiert. Weiterhin zeigte sich, dass diese signifikant erhöhten Werte unabhängig mit einer deutlich schlechteren Prognose der 30-Tages und Ein-Jahres Mortalität verbunden sind. Diese Assoziation konnte jedoch ausschließlich bei Patienten mit eingeschränkter Nierenfunktion nachgewiesen werden.

INTRODUCTION : L’utilisation de la circulation extracorporelle durant la chirurgie cardiaque est associée à des problèmes pulmonaires chez certains patients. L’utilisation d’une pression pulsatile induite par un ballon intra-aortique (BIA) pourrait diminuer la dysfonction endothéliale et la survenue de tels événements. MATÉRIEL ET MÉTHODE : 12 porcs Landrace-Yorkshire ont subi une circulation extracorporelle et ont été divisés en deux groupes et 4 porcs ont servi de contrôles sans CEC. Le premier groupe (n=6) a bénéficié d’un flot pulsatile créé par un BIA en mode interne à 80 battements par minute durant les 90 minutes de l’opération alors que le second groupe (n=6) a subi une CEC standard. Après 60 minutes de reperfusion suivant la CEC, les valeurs hémodynamiques ont été évaluées dont les pressions artérielles, les pressions pulmonaires, l’index cardiaque et la concentration de glucose et de lactate. Les artères pulmonaires sont ensuite montées en chambre d’organe pour évaluer la fonction endothéliale. RÉSULTATS : Les porcs avec pression pulsatile ont tendance à produire moins de lactate sanguin après 60 minutes de reperfusion. Les autres valeurs hémodynamiques sont semblables. Finalement, la relaxation à la bradykinine est significativement meilleure dans le groupe pression pulsatile alors que la relaxation à l’acétylcholine n’est pas significativement différente. CONCLUSION : Ces résultats démontrent que la perfusion pulsatile produite par un BIA protège l’endothélium pulmonaire lors d'une CEC. Cet effet pourrait être dû à une augmentation du flot bronchique qui diminuerait l’ischémie pulmonaire ou à une diminution de la libération de cytokines et de bradykinine qui réduirait les dommages de reperfusion. / INTRODUCTION : Cardiopulmonary bypass (CPB) during cardiac surgery leads to postoperative pulmonary complications. The use of pulsatile pressure with an intra-aortic balloon pump (IABP) could preserve the endothelial function and decrease the occurence of pulmonary problems. MATERIAL AND METHODS : Twelve Landrace-Yorkshire swine were divided into two groups, one group (n=6) received pulsatile perfusion under CPB from an IABP in an internal mode at 80 beats per minute (bpm) and the other (n=6) had a standard CPB of 90 minutes. A third group (n=4) has been used as controls without CPB. The two first groups underwent aortic clamping for 80 minutes with administration of intermittent blood cardioplegia. After 60 minutes of reperfusion following of bypass, swine were sacrificed and pulmonary arteries were harvested. Haemodynamic values were calculated including pulmonary arterial pressures (PAP), mean arterial pressures (mAP), lactate production, blood glucose and cardiac index. Pulmonary arteries were placed in organ chambers and vascular reactivity studies were performed. RESULTS : There was a trend towards lower lactate production with use of pulsatile perfusion after 60 minutes of reperfusion. All other hemodynamics were not significally different in both groups. Relaxation to bradykinin was greater in pulsatile group while relaxation to acetylcholine did not differ. CONCLUSION : IABP induced pulsatile pressure protect the pulmonary endothelium during CPB. This could be explained by an increase in blood flow through the bronchial arteries or by a decreased release of cytokines or bradykinin which could reduce reperfusion damage.

Intraaortic balloon counterpulsation (IABP) is the most widely used mechanical support in the assistance of a failing heart.1 Despite extensive research in this field no experimental or clinical studies have been undertaken to evaluate the most effective manner to wean IABP.2 The research reported in this thesis examines early recognition of cardiac decompensation and the management of IABP weaning. Conducted in three phases, the aim of this research programme was to determine the best manner by which to wean IABP. Phase 1 utilised a comparative descriptive design to examine IABP practice at a single cardiothoracic tertiary referral hospital. The majority of data collection was prospective, however, the required sample size saw inclusion of some retrospective data. This single centre data were than compared with an international registry to contrast IABP management and outcome. Phase 2 utilised a questionnaire survey to audit all Australasian intensive care units. Survey results were combined and statistically analysed to describe Australasian IABP management, weaning and outcome. Phase 3 utilised a quasi-experimental, one-group, posttest-only design to clinically validate a tool designed to monitor a patient's cardiac function - the 'cardiac decompensation tool'. Phase 1 saw data collected for 669 IABP insertions over an 11 year period at a single Australian hospital. This cohort was compared against the 38,606 patient dataset of The Benchmark Counterpulsation Outcomes Registry. Australian IABP practice saw later application of the device in a higher acuity patient. Australian practice demonstrated a prejudice toward intraoperative use (34.2% versus 16.6%; p=< 0.0001) and an aversion to catheter laboratory support (10.6% versus 19%; p=< 0.0001). Australian mortality while slightly higher, remained comparable (22% versus 20.8%; p=ns). Phase 2 response rate was 60%. The most common Australasian method of IABP support withdrawal was ratio reduction only (61%). Units with a documented weaning policy were less likely to require balloon reinsertion or pharmacologic escalation following IABP removal (p=0.06). Indicators most likely to demonstrate a patient's readiness for IABP weaning were blood pressure (92%), heart rate (76%) and wedge pressure (59%). Phase 3 revealed cardiac decompensation tool scores to increase immediately prior to a treatment escalation (p=0.022) and decrease immediately following this escalation in therapy (p=0.0096). There was also some indication of decreasing scores prior to treatment minimisation (p=0.005). Tool scores demonstrated a corresponding treatment fluctuation up to three hours prior to the treatment intervention. With Phase 1 and 2 revealing many aspects of IABP practice to vary, the need for some direction regarding weaning is evident. Timely recognition of cardiac decompensation during IABP weaning allows an opportunity for the earlier escalation of treatment and consequent provision of increased cardiac support. Application of the Phase 3 cardiac decompensation tool can only assist in ensuring the best manner by which to support IABP weaning.