Summary
Background
Hypothermic ischemia in open heart surgery and cardiopulmonary bypass involve a postischemic in-flammatory reaction caused by an activation of leukocytes and endothelia with the systemic release of cytokines and adhesion molecules. The present study addresses the question, if an amelioration of postischemic endothelial activation in the heart could be achieved by means of cardioplegic protection or ischemic preconditioning. In a randomized prospective study patients underwent a normothermic preconditioning procedure either followed by crystalloid or blood cardioplegia during coronary bypass surgery.
Methods
Patients (n=28) were included and randomized in the study according to defined criteria: Group A received St. Thomas cardioplegia, group B cold blood cardioplegia. Ischemic precon-ditioning was performed twice at normothermia under a cardiopulmonary bypass (CPB) for 5 min followed by 10 min of reperfusion before coronary aortic bypass graft (CABG) using St. Thomas (group C) or blood cardioplegia (group D) hypothermic protection. In coronary sinus blood and arterial blood myocardial (creatine-kinase myoglobin [CK-MB]) and endothelial activation (endothelin, IL-6, IL-8, sE-selectin, soluble vascular adhesion molecule-1 [sVCAM-1], soluble intercellular adhesion molecule-1 [sICAM-1]) parameters were investigated 1, 3, 6, 9, 12, and 24 h after coronary reperfusion.
Results
1) Parameters of myocardial injury (CK-MB, myoglobin) revealed increased levels at 1 h and 9 to 12 h after CABG. Levels at 12 h were lower in group B and D as compared to A and C. 2) Cytokines (IL-6, IL-8) showed increased levels 3 h after reperfusion with no difference between study groups. 3) Soluble adhesion molecules (E-selectin, VCAM-1, ICAM-1) were found increased in all groups 6 to 12 h after reperfusion. Lower levels were present in group D for E-selectin and VCAM-1.
Conclusions
The results indicate a sequence of cytokine and adhesion molecule release as a potential pathomechanism of myocardial reperfusion injury. Gradual decrease in the release of endothelial adhesion molecules in late myocardial injury was noted for blood cardioplegia and ischemic preconditioning. Amelioration of endothelial activation by means of preconditioning and blood cardioplegia may improve heart muscle recovery in open heart surgery with borderline ischemia time and organ dysfunction.
Zusammenfassung
Grundlagen
Hypotherme Organischämie in offener Herzchirurgie und bei extrakorporaler Zirkulation erzeugt eine postischemische Entzündungsreaktion, die durch eine Aktivierung von Leukozyten und Endothel mit Freisetzung von Zytokinen und Adhäsionsmolekülen vermittelt wird. Die hier vorgestellte Studie verfolgte die Frage, ob eine Reduction einer postischämischen Endothelaktivierung über Kardioplegie-Protektion oder ischämische Präkonditionierung erreichbar ist. In einer randomisierten prospektiven Studie wurden Patienten mit koronarer Bypassoperation ischämisch präkonditioniert gefolgt durch krystalloide oder Kaltblut-Kardioplegie. 28 Patienten wurden eingeschlossen und in 4 Untersuchungsgruppen randomisiert: Gruppe A erhielt St. Thomas-Kardioplegie, Gruppe B Blutkardioplegie (Kontrollen). Gruppe C (St. Thomas) und Gruppe D (Blutkardioplegie) erhielten vorher unter Normothermie eine ischämische Präkonditionierung von 2x 5 min gefolgt durch 10 min Reperfusion. Im Koronarsinusblut und arteriellem Blut wurden folgende Parameter untersucht: Creatinkinase-Myoglobin (CK-MB), endothelin, IL-6, ILB, sE-Selektin, sP-Selektin, Soluble vascular adhesion molecule-1 [sVCAM-1], Soluble intercellular adhesion molecule-1 [sICAM-1]), 1, 3, 6, 9, 12 und 24 h nach koronarer Reperfusion.
Ergebnisse
I. Parameter des Myokardschadens (CK-MB. Myoglobin) zeigten erhöhte Werte nach 1 und 9 bis 12 h nach ACB. Die Werte der Gruppen B und D waren nach 12 h niedriger als bei den Gruppen A und C. 2. Zytokine (IL-6, IL-8) zeigten erhöhte Werte 3 h nach Reperfusion ohne Differenz zwischen den Studiengruppen. 3. Lösliche Adhäsionsmoleküle (E-Selektin, VCAM-1, ICAM-1) zeigten in allen Gruppen nach 6 bis 12 h eine erhöhte Freisetzung. Niedrige Werte nach 12 h fanden sich insbesondere für E-Selektin und VCAM-1 in der Gruppe D.
Schlußfolgerungen
Die Resultate zeigen eine Sequenz einer Zytokin-und Adhäsionsmolekülfreisetzung als potentiellem Pathomechanismus des myokardialen Reperfusionsschadens. Eine graduelle Reduktion der Endothelaktivierung durch Präkonditionierung oder Blutkardioplegieprotektion könnte die Erholung des Herzmuskels in der Koronarchirurgie bei grenzwertiger Ventrikelfunktion verbessern.
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Steinhoff, G., Karck, M., Cremer, J. et al. Influence of ischemic preconditioning and blood cardioplegia protection on postischemic endothelial activation in coronary bypass surgery. Acta Chir Austriaca 28, 354–358 (1996). https://doi.org/10.1007/BF02616286
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DOI: https://doi.org/10.1007/BF02616286
Key-words
- Cytokines
- soluble adhesion molecules
- reperfusion injury
- coronary bypass surgery
- ischemic preconditioning
- blood cardioplegia