Feasibility and Effects of PICSO in Patients with Ischemia and Cardiogenic Shock

Mortality in conservatively treated patients with cardigenic shock is high. Although early reopening of the infarctet coronary vessel may be life-saving in individual patients, mortality in unselected patients including older patients with multivessel disease still remains markedly above 50%. Retrograde perfusion techniques via the coronary sinus have been shown to improve myocardial ischemia in the setting of acute coronary occlusion and have been found to ameliorate reperfusion damage after achievement of antegrade reflow. These favourable results have been confirmed by preliminary intraoperative studies using pressure controlled intermittent coronary sinus occlusion (PICSO). The purpose of the present study is to examine the feasibility and effects of PICSO in ICU-patients with severe myocardial ischemia and cardiogenic shock. 40 sedated and mechanically ventilated patients with myocardial ischemia will undergo treatment with PICSO in addition to standard treatment for cardiogenic shock. A specially designed coronary sinus balloon catheter will be introduced through a central venous access and will be connected to the external PICSO device. According to the integrated closed-loop feed back algorithm pressure controlled inflation and deflation of the coronary sinus balloon will be performed in order to improve retrograde perfusion of the ischemic myocardium and to enhance washout of ischemia-induced toxic metabolites. The effects of treatment with PICSO will be evaluated by serial hemodynamic (Swan Ganz catheter), echocardiographic (global systolic and diastolic function, regional wall motion analysis) and serologic (cardiac enzymes, lactate, cytokines, fibrinolytic/antifibrinolytic proteins, endothelial cell markers) measurements. In addition survival of PICSO-treated patients will be compared to survival in a matched historical group of patients with cardiogenic-shock.

Myocardial infarction remains a major killer in spite of advances in interventional cardiology. PICSO (an interventional method reducing the perfusion deficit during the development of myocardial infarction via the coronary venous system and to induce washout of toxic metabolites) has proven in experiments and early clinical trials to salvage myocardium and to reduce reperfusion injury. This method was developed in Vienna and evaluated from concept to clinics. The aim of the current project was to develop a clinical useable PICSO system and to evaluate the effects of this perfusion technique as well as the pathophysiologic background in a large animal model with acute coronary artery occlusion and to validate the ability of PICSO in patients with acute coronary syndromes and hemodynamic instability. In a first step the available literature was screened on different retroperfusion techniques to evaluate the potential of PICSO against the other known coronary sinus interventions. As a result a meta-analysis of all papers published in peer reviewed journals substantiated the salvage potential of this method (results will be published in JCTVS 2004). In parallel the PICSO system was developed. The pump system was developed by a grant from the BMVIT by ARCS Medizintechnik and catheters by a contract manufacturer CMI Dresden. After completion, the system was tested in an animal model simulating acute myocardial infarction. The robustness of the catheter and pump system was evaluated and the system is feasible to be used in clinical series. In these experiments the therapeutic range and the timing of intermittent coronary sinus occlusions as stimulus for myocardial salvage was evaluated and volume shifts within the myocardium were tested in relation to the pressure increase in the coronary venous circulation. The amount of collateral circulation towards the deprived myocardium was improved substantially by this method, corroborating earlier observations on myocardial salvage especially in border zones. Gene expression pattern were also evaluated as consequence of the PICSO treatment in ischemic areas and there is some evidence that this method may also up regulate cytoprotective genes as well as genes involved in the regeneration process. These results have to be substantiated in future experiments to verify the hypothesis that shear stress on venous endothelium may result in changes in the regeneration of the heart. This would lead to a new insight on regeneration and restoration of function of the jeopardized heart since in theory the enhancement of autochthonic repair mechanisms without the additional use of homologous stem cells should result in the healing of the failing heart. This would have great clinical impact, since it could be used in patients with severe heart failure with no other alternative than heart transplantation as bridge to recovery. All necessary requirements for a clinical use of PICSO in acute coronary syndromes are met and a clinical series as proof of principle is in preparation in cooperation with the Department of Cardiology of the Medical University of Vienna.