Overactivation of the sympatho-
adrenergic system is an essential mechanism providing short-term adaptation to the stressful conditions of
critical illnesses. In the same way, the administration of exogenous
catecholamines is mandatory to support the failing circulation in acutely ill patients. In contrast to these short-term benefits, prolonged
adrenergic stress is detrimental to the cardiovascular system by initiating a series of adverse effects triggering significant
cardiotoxicity, whose pathophysiological mechanisms are complex and only partially elucidated. In addition to the development of myocardial
oxygen supply/demand imbalance induced by the sustained activation of
adrenergic receptors,
catecholamines can damage cardiomyocytes by fostering
mitochondrial dysfunction, via two main mechanisms. The first one is
calcium overload, consecutive to β-
adrenergic receptor-mediated activation of
protein kinase A and subsequent phosphorylation of multiple Ca(2+)-cycling
proteins. The second one is oxidative stress, primarily related to the transformation of
catecholamines into "aminochromes," which undergo redox cycling in mitochondria to generate copious amounts of
oxygen-derived
free radicals. In turn,
calcium overload and oxidative stress promote mitochondrial permeability transition and cardiomyocyte cell death, both via the apoptotic and necrotic pathways. Comparable mechanisms of myocardial toxicity, including marked oxidative stress and
mitochondrial dysfunction, have been reported with the use of
cocaine, a common
recreational drug with potent
sympathomimetic activity. The aim of the current review is to present in detail the pathophysiological processes underlying the development of
catecholamine and
cocaine-induced
cardiomyopathy, as such conditions may be frequently encountered in the clinical practice of cardiologists and ICU specialists.