Drugs as Possible Triggers of Takotsubo Cardiomyopathy- Update 2022: Systematic Review.

BACKGROUND: A list of drugs that can induce takotsubo cardiomyopathy (TCM) was published in 2011 and 2016. The aim of the present review was to update this list. METHODS: Similar to the 2011 and 2016 reviews, from April 2015 to May 2022 case reports of druginduced TCM were identified by a comprehensive search in Medline/PubMed database. The search terms were: takotsubo cardiomyopathy, tako-tsubo cardiomyopathy, stress cardiomyopathy, transientleft- ventricular ballooning syndrome, apical ballooning syndrome, ampulla cardiomyopathy OR broken heart syndrome; together with "iatrogenic", "induced by" OR "drug-induced". Registers published in English or Spanish, in humans, and with full texts were retrieved. Articles that recognized any drug associated with the development of TCM were selected. RESULTS: Overall, 184 manuscripts were identified by the search. A total of 39 articles were included after an exhaustive revision. Eighteen drugs as possible triggers of TCM were identified in the current update. Of them, 3 (16.7%) have been previously identified, and 15 (83.3%) are different from the previous reports. Thus, the list of drugs as possible triggers of TCM updated in 2022 includes 72 drugs. CONCLUSION: There are new case reports that link drugs with the development of TCM. The current list is principally made up of drugs that generate sympathetic overstimulation. However, some of the listed drugs do not have a clear link with sympathetic activation.

Physiological Sympathetic Activation Reduces Systemic Inflammation: Role of Baroreflex and Chemoreflex.

Baroreflex and chemoreflex act through the autonomic nervous system, which is involved with the neural regulation of inflammation. The present study reports the effects of reflex physiological sympathetic activation in endotoxemic rats using bilateral carotid occlusion (BCO), a physiological approach involving the baroreflex and chemoreflex mechanisms and the influence of the baroreceptors and peripheral chemoreceptors in the cardiovascular and systemic inflammatory responses. After lipopolysaccharide (LPS) administration, the arterial pressure was recorded during 360 min in unanesthetized rats, and serial blood samples were collected to analyze the plasma cytokine levels. BCO elicited the reflex activation of the sympathetic nervous system, providing the following outcomes: (I) increased the power of the low-frequency band in the spectrum of the systolic arterial pressure during the BCO period; (II) reduced the levels of pro-inflammatory cytokines in plasma, including the tumor necrosis factor (TNF) and the interleukin (IL)-1ß; (III) increased the plasma levels of anti-inflammatory cytokine IL-10, 90 min after LPS administration. Moreover, selective baroreceptor or chemoreceptor denervation deactivated mechanosensitive and chemical sensors, respectively, and decreased the release of the LPS-induced cytokine but did not alter the BCO modulatory effects. These results show, for the first time, that physiological reflex activation of the sympathetic circuit decreases the inflammatory response in endotoxemic rats and suggest a novel function for the baroreceptors as immunosensors during the systemic inflammation.

Carotid body Thermoreceptors, sympathetic neural activation, and cardiometabolic disease

The carotid body (CB) is the main peripheral chemoreceptor that senses the arterial PO2, PCO2 and pH. In response to hypoxemia, hypercapnia and acidosis, carotid chemosensory discharge elicits reflex respiratory, autonomic and cardiovascular adjustments. The classical construct considers the CB as the main peripheral oxygen sensor, triggering reflex physiological responses to acute hypoxemia and facilitating the ventilatory acclimation to chronic hypoxemia at high altitude. However, a growing body of experimental evidence supports the novel concept that an abnormally enhanced CB chemosensory input to the brainstem contributes to overactivation of the sympathetic nervous system, and consequent pathology. Indeed, the CB has been implicated in several diseases associated with increases in central sympathetic outflow. These include hypertension, heart failure, sleep apnea, chronic obstructive pulmonary disease and metabolic syndrome. Indeed, ablation of the CB has been proposed for the treatment of severe and resistant hypertension in humans. In this review, we will analyze and discuss new evidence supporting an important role for the CB chemoreceptor in the progression of autonomic and cardiorespiratory alterations induced by heart failure, obstructive sleep apnea, chronic obstructive pulmonary disease and metabolic syndrome.