The activity of the Laboratory of Cardiovascular Preclinical Research focuses on the study of the pathophysiology of cardiac arrest and myocardial infarction in experimental models. Cardiac dysfunction, neurological damage, and the associated systemic inflammatory response are explored with the support of in vivo imaging techniques (echocardiography and magnetic resonance imaging) and advanced histology and immunohistochemistry techniques.
The laboratory is also involved, in collaboration with the Laboratory of Clinical Research in Brain and Cardiovascular Injury, in randomized and multicentric clinical studies aimed at evaluating the efficacy of innovative therapeutic strategies to improve survival in patients with cardiac arrest or myocardial infarction.
CARDIAC ARREST AND CARDIOPULMONARY RESUSCITATION
In Europe, the annual incidence of out-of-hospital cardiac arrest ranges between 67 and 170 cases per 100,000 inhabitants. Unfortunately, despite prompt interventions, only about 8% of patients survive without significant neurological damage. In the field of cardiac arrest research, our laboratory is dedicated to studying the mechanisms of brain and heart damage following cardiac arrest and subsequent reperfusion. It has been widely demonstrated that noble gases possess cardioprotective and neuroprotective properties following ischemic events. Our studies have highlighted the neuroprotective effects of ventilation with a mixture of argon and oxygen in a medium-duration cardiac arrest experimental model in pigs. These data laid the foundation for the CPAr clinical trial, which is currently in phase 2. Additionally, we have conducted studies to explore the efficacy of different combinations of argon with other gases, including hydrogen, to optimize therapeutic strategies, demonstrating the neuroprotective effect of the mixture in a porcine model of cardiac arrest and cardiopulmonary resuscitation. New studies are currently underway to evaluate the cardioprotective effect of argon in a rat model of cardiac arrest and investigate its mechanisms of action, with particular attention to the effect of the noble gas on mitochondrial damage. Through a multidisciplinary and innovative approach, our laboratory is committed to translating this knowledge into advanced therapeutic strategies, aiming to improve prognosis and quality of life for patients affected by cardiac arrest.
MYOCARDIAL INFARCTION
Despite its reduction in incidence, acute myocardial infarction remains one of the leading causes of death globally, with high mortality and a significant risk of rehospitalization for heart failure. In this field, our studies aim to explore the damage mechanisms triggered by cardiac ischemia and to evaluate innovative therapeutic approaches. Among the damage mechanisms involved in the progression of post-infarction cardiac dysfunction, the kynurenine pathway, the main metabolic route of tryptophan, appears to play a key role. Previously published studies have shown that its genetic inhibition improves survival and reduces neuronal damage post-cardiac arrest. Currently, we are evaluating the impact of inhibiting the kynurenine pathway on post-infarction cardiac damage. Coronary artery disease underlies myocardial infarction and is characterized by the progressive growth of atherosclerotic plaque, which may remain asymptomatic but predispose to acute events. Despite the availability of pharmacological and surgical therapies, the cardiovascular risk in atherosclerotic patients remains high. The complement system, in particular the lectin pathway and ficolin-2, is involved in plaque vulnerability and the risk of adverse events. Our laboratory, in collaboration with the Laboratory of Stroke and Vascular Dysfunction, is engaged in a project aimed at developing a complex 3D in vitro model of atherosclerotic plaque. Additionally, we will further investigate the role of the complement system in plaque rupture and myocardial infarction, with the goal of developing new diagnostic and therapeutic tools for more effective secondary prevention of cardiovascular events.
CHARACTERIZATION OF CARDIAC DYSFUNCTION IN NON-CARDIOVASCULAR DISEASES
Our laboratory is exploring the role of the heart in diseases with a non-cardiac aetiology in collaboration with external research institutions and pharmaceutical companies. Even diseases seemingly unrelated to a cardiac cause, such as epilepsy, rare hereditary diseases, and certain forms of cancer, can involve the myocardium, contributing to the worsening of their progression. Through various studies, our objective is to identify and understand the cardiac dysfunction associated with these conditions, assessing its impact on disease progression. This research opens new perspectives for a more integrated and personalized medicine, placing the heart at the centre of scientific innovation.
International Consensus on Cardiopulmonary Resuscitation.
