Cardio-Pulmonary and Cerebral Dysfunctions
Over the last 10 years, our research team has mainly explored the following topics:
- identification of the predictive risk factors of cardiopulmonary complications after major surgery (cohort studies);
- implementation of peri-operative organ protective strategies (e.g., beta-blockers, epidural analgesia) and early treatment of acute lung oedema shortly after lung resection;
- circulatory adaptive mechanisms to acute hypoxia, myocardial ischemia, anaemia and surgical stress;
- pharmacological interactions between anaesthetic agents and methylene blue or neural blockade of the sympathetic nervous system (potentiation of general anaesthesia).
Cardio-pulmonary and cerebral dysfunctions have been thoroughly investigated by invasive hemodynamic monitoring, blood gas analysis (oxygenation indices, PaO2/FIO2), quantification of tissue biomarkers (Troponin-I, SP100), ECG and simplified EEG recordings as well as echocardiography and transcranial Doppler.
For the first time, we have demonstrated that moderate acute normovolemic hemodilution (ANH, hematocrit down to 27%) was well tolerated in patients with 3-vessels coronary disease and in those with severe aortic valvular stenosis : cardiac index increases by 20-25% as a result of facilitated venous return owing to lower blood viscosity whereas left ventricular afterload remains unchanged. Subsequently, we demonstrated in two RCTs including high-risk cardiac patients that moderate ANH was associated with less severe myocardial injuries, fewer arrhythmias as well as lower requirement for inotropes and vasopressor support. Likewise, we confirmed these beneficial effects of ANH in a rat model of transient coronary artery occlusion as evidence by smaller myocardial infarct size (-40%), better survival (83% vs 42% at 48 h). Interestingly, besides the improved rheological conditions, a delayed release of erythropoietine (EPO, 6-18h after ANH) might have contributed to these cardioprotective effects.
Experimental studies have unveiled the mechanisms of EPO-induced neuro- and cardio-protection involving different pathways (proliferation and differenciation of progenitor erythroid cells, inhibition of caspase activation, activation of JAK-2 kinase, activation of phosphatidyl-inositol-3 kinase and Akt phosporylation.
The infusion of Glucose-Insuline-Potassium (GIK) is another promising perioperative strategy to minimize myocardial ischemia-reperfusion injuries by acting at different key intra-cellular targets (activation of phospatidylinositol 3-kinase, hyperpolarisation of cardiomyocytes, increased glycogen content, utilization of glucides instead of FFA for energetic substrate synthesis, upregulation of the endothelial L-Arginine-NO pathway). In 3 clinical RCTs, we will investigate the potential cardioprotective effects of beta-adrenergic blockers (emergency surgery), EPO and GIK solution (aortic valvular replacement, coronary artery bypass surgery). Neurocognitive disorders and nosocomial infections will also be evaluated in studies involving the administration EPO and GIK.