Sudden cardiac death (SCD) is an unexpected sudden death due to a heart condition, that occurs within one hour of symptoms onset. SCD is a leading cause of death in western countries, and is responsible for the majority of deaths from cardiovascular disease. Moreover, SCD accounts for mortality in approximately half of all coronary heart disease patients. Nevertheless, the recent advancements made in screening, prevention, treatment, and management of the underlying causes has decreased this number. In this article, we sought to review established and new modes of screening patients at risk for SCD, treatment and prevention of SCD, and the role of new technologies in the field. Further, we delineate the current epidemiologic trends and pathogenesis. In particular, we describe the advancement in molecular autopsy and genetic testing, the role of target temperature management, extracorporeal membrane oxygenation (ECMO), cardiopulmonary resuscitation (CPR), and transvenous and subcutaneous implantable cardioverter devices (ICDs).

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Rostromedial tegmental nucleus (RMTg) GABA neurons exert a primary inhibitory drive onto midbrain dopamine neurons and are excited by a variety of aversive stimuli. There is, however, little evidence that the RMTg-ventral tegmental area (VTA)-nucleus accumbens shell (Acb) circuit plays a role in the aversive consequences of alcohol withdrawal. This study was performed in adult male Long-Evans rats at 48-h withdrawal from chronic alcohol drinking in the intermittent schedule. These rats displayed clear anhedonia and depression-like behaviors, as measured with the sucrose preference, and forced swimming tests. These aberrant behaviors were accompanied by a substantial increase in cFos expression in the VTA-projecting RMTg neurons, identified by a combination of immunohistochemistry and retrograde-tracing techniques. Pharmacological or chemogenetic inhibition of RMTg neurons mitigated the anhedonia and depression-like behaviors. Ex vivo electrophysiological data showed that chemogenetic inactivation of RMTg neurons reduced GABA release and accelerated spontaneous firings of VTA dopamine neurons. Finally, using a functional hemispheric disconnection procedure, we demonstrated that inhibition of unilateral RMTg, when combined with activation of D1 and D2 dopamine receptors in the contralateral (but not ipsilateral) Acb, mitigated the anhedonia and depressionlike behaviors in alcohol-withdrawal rats. These data show that the integrity in the RMTg-VTA-Acb pathway in a single hemisphere is sufficient to elicit depression-like behavior during ethanol-withdrawal. Overall, the present results reveal that the RMTg-VTA-Acb pathway plays a crucial role in the depression-like behavior in animals undergoing alcohol withdrawal, further advocating the RMTg as a potential therapeutic target for alcoholism.

Propofol is a short-acting intravenous anesthetic agent suitable for induction and maintenance of general anesthesia as well as for procedural and intensive care unit sedation. As such it has become an unparalleled anesthetic agent of choice in many institutional and office practices. However, in addition to its idealistic properties as an anesthetic agent, there is accumulating evidence suggesting its potential for abuse. Clinical and experimental evidence has revealed that not only does propofol have the potential to be abused, but also that addiction to propofol shows a high mortality rate. Based on this evidence, different researchers have shown interest in determining the probability of propofol to be an addictive agent by comparing it with other drugs of abuse and depicting a functional similitude that involves the mesocorticolimbic pathway of addiction. In light of this, the Drug Enforcement Agency and the American Society of Anesthesiologists have put forth certain safety recommendations for the use of propofol. Despite this, the abuse potential of propofol has been challenged at different levels and therefore the preeminent focus will be to further validate the linkage from medicinal and occasional use of propofol to its addiction, as well as to explore the cellular and molecular targets involved in establishing this linkage, so as to curb the harm arising out of it. This review incorporates the clinical and biomolecular evidence supporting the abuse potential of propofol and brings forth the promising targets and the foreseeable mechanism causing the propofol addiction phenotypes, which can be called upon for future developments in this field.

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