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1.
Allicin pharmacology: Common molecular mechanisms against neuroinflammation and cardiovascular diseases.
Mocayar Marón, FJ, Camargo, AB, Manucha, W
Life sciences. 2020;:117513
Abstract
According to investigations in phytomedicine and ethnopharmacology, the therapeutic properties of garlic (Allium sativum) have been described by ancestral cultures. Notwithstanding, it is of particular concern to elucidate the molecular mechanisms underlying this millenary empirical knowledge. Allicin (S-allyl prop-2-ene-1-sulfinothioate), a thioester of sulfenic acid, is one of the main bioactive compounds present in garlic, and it is responsible for the particular aroma of the spice. The pharmacological attributes of allicin integrate a broad spectrum of properties (e.g., anti-inflammatory, immunomodulatory, antibiotic, antifungal, antiparasitic, antioxidant, nephroprotective, neuroprotective, cardioprotective, and anti-tumoral activities, among others). The primary goal of the present article is to review and clarify the common molecular mechanisms by which allicin and its derivates molecules may perform its therapeutic effects on cardiovascular diseases and neuroinflammatory processes. The intricate interface connecting the cardiovascular and nervous systems suggests that the impairment of one organ could contribute to the dysfunction of the other. Allicin might target the cornerstone of the pathological processes underlying cardiovascular and neuroinflammatory disorders, like inflammation, renin-angiotensin-aldosterone system (RAAS) hyperactivation, oxidative stress, and mitochondrial dysfunction. Indeed, the current evidence suggests that allicin improves mitochondrial function by enhancing the expression of HSP70 and NRF2, decreasing RAAS activation, and promoting mitochondrial fusion processes. Finally, allicin represents an attractive therapeutic alternative targeting the complex interaction between cardiovascular and neuroinflammatory disorders.
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2.
Mitochondria in acute myocardial infarction and cardioprotection.
Ramachandra, CJA, Hernandez-Resendiz, S, Crespo-Avilan, GE, Lin, YH, Hausenloy, DJ
EBioMedicine. 2020;:102884
Abstract
Acute myocardial infarction (AMI) and the heart failure (HF) that often follows are among the leading causes of death and disability worldwide. As such, new treatments are needed to protect the myocardium against the damaging effects of the acute ischaemia and reperfusion injury (IRI) that occurs in AMI, in order to reduce myocardial infarct (MI) size, preserve cardiac function, and improve patient outcomes. In this regard, cardiac mitochondria play a dual role as arbiters of cell survival and death following AMI. Therefore, preventing mitochondrial dysfunction induced by acute myocardial IRI is an important therapeutic strategy for cardioprotection. In this article, we review the role of mitochondria as key determinants of acute myocardial IRI, and we highlight their roles as therapeutic targets for reducing MI size and preventing HF following AMI. In addition, we discuss the challenges in translating mitoprotective strategies into the clinical setting for improving outcomes in AMI patients.
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3.
Effects of short-term consumption of strawberry powder on select parameters of vascular health in adolescent males.
Holt, RR, Zuelch, ML, Charoenwoodhipong, P, Al-Dashti, YA, Hackman, RM, Keen, CL
Food & function. 2020;(1):32-44
Abstract
Cardiovascular disease is a leading cause of death in the United States and much of the developed world, costing billions of dollars in lost work time, lower productivity and high health care expenditures. Research on foods and bioactive food components that have cardioprotective benefits may provide new insights as to how modest changes in one's diet may result in a reduced risk of vascular disease. In intervention trials, the consumption of strawberries, either fresh or freeze-dried, has been reported to improve select markers of cardiovascular health, including improved lipid profiles, microvascular function, and platelet reactivity. Consistent with the above, epidemiological studies suggest beneficial effects of strawberries on vascular function. Preliminary studies on the effects of freeze-dried strawberry powder on vascular health are reviewed in the current paper.
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4.
Milrinone Use in Persistent Pulmonary Hypertension of the Newborn.
Qasim, A, Jain, SK
NeoReviews. 2020;(3):e165-e178
Abstract
Failure of the normal transition from in utero to ex utero physiology leads to "persistent" pulmonary hypertension of the newborn (PPHN). PPHN is frequently associated with low systemic blood pressure and low cardiac output because of increased right ventricular afterload and myocardial dysfunction. The general management of newborns with PPHN is geared toward maintenance of normothermia, normal serum electrolytes, normal intravascular volume, correction of acidosis, adequate sedation/analgesia, adequate ventilation and oxygenation with optimal lung recruitment, and avoidance of hyperoxia. Inotropic and vasoactive agents are commonly initiated early to increase cardiac output, maintain adequate systemic blood pressure, and enhance oxygen delivery to the tissue. Unfortunately, there is not much evidence on the choice, timing of initiation, dosing, monitoring, and titrating of vasoactive agents in this patient population. In this review, we will discuss the pathophysiology of PPHN and review the use of inotropic, lusitropic, and vasoactive agents in the management of PPHN, with particular attention to milrinone.
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5.
Cardiac Calcitropes, Myotropes, and Mitotropes: JACC Review Topic of the Week.
Psotka, MA, Gottlieb, SS, Francis, GS, Allen, LA, Teerlink, JR, Adams, KF, Rosano, GMC, Lancellotti, P
Journal of the American College of Cardiology. 2019;(18):2345-2353
Abstract
The term "inotrope" is familiar and intimately connected with pharmaceuticals clinically used for treatment of low cardiac output with cardiogenic shock. Traditional inotropic agents exert their effect by modulating calcium signaling in the myocardium. Their use is associated with poor long-term outcomes. Newer molecules in development intend to break from calcium mediation and the associated detrimental long-term effects by targeting distinct mechanisms of action to improve cardiac performance. Thus, "inotropy" does not sufficiently describe the range of potential novel pharmaceutical products. To enhance communication around and evaluation of current, emerging, and potential therapies, this review proposes a novel nuanced and holistic framework to categorize pharmacological agents that improve myocardial performance based on 3 myocardial mechanisms: calcitropes, which alter intracellular calcium concentrations; myotropes, which affect the molecular motor and scaffolding; and mitotropes, which influence energetics. Novel chemical entities can easily be incorporated into this structure, distinguishing themselves based on their mechanisms and clinical outcomes.
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6.
Inotropes and vasopressors use in cardiogenic shock: when, which and how much?
Levy, B, Buzon, J, Kimmoun, A
Current opinion in critical care. 2019;(4):384-390
Abstract
PURPOSE OF REVIEW Data and interventional trials regarding vasopressor and inotrope use during cardiogenic shock are scarce. Their use is limited by their side-effects and the lack of solid evidence regarding their effectiveness in improving outcomes. In this article, we review the current use of vasopressor and inotrope agents during cardiogenic shock. RECENT FINDINGS Two recent Cochrane analyses concluded that there was not sufficient evidence to prove that any one vasopressor or inotrope was superior to another in terms of mortality. A recent RCT and a meta-analysis on individual data suggested that norepinephrine may be preferred over epinephrine in patients with cardiogenic shock . For inotrope agents, when norepinephrine fails to restore perfusion, dobutamine represents the first-line agent. Levosimendan is a calcium sensitizer agent, which improves acute hemodynamics, albeit with uncertain effects on mortality. SUMMARY When blood pressure needs to be restored, norepinephrine is a reasonable first-line agent. Dobutamine is the first-line inotrope agent wheraes levosimendan can be used as a second-line agent or preferentially in patients previously treated with beta-blockers. Current information regarding comparative effective outcomes is nonetheless sparse and their use should be limited as a temporary bridge to recovery, mechanical circulatory support or heart transplantation.
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7.
New Applications of Oleanolic Acid and its Derivatives as Cardioprotective Agents: A Review of their Therapeutic Perspectives.
Sun, N, Li, D, Chen, X, Wu, P, Lu, YJ, Hou, N, Chen, WH, Wong, WL
Current pharmaceutical design. 2019;(35):3740-3750
Abstract
Oleanolic acid is an analogue of pentacyclic triterpenoids. It has been used as a hepatic drug for over 20 years in China. Currently, there are only five approved drugs derived from pentacyclic triterpenoids, including oleanolic acid (liver diseases), asiaticoside (wound healing), glycyrrhizinate (liver diseases), isoglycyrrhizinate (liver disease) and sodium aescinate (hydrocephalus). To understand more about the bioactivity and functional mechanisms of oleanolic acid, it can be developed as a potent therapeutic agent, in particular, for the prevention and treatment of heart diseases that are the leading cause of death for people worldwide. The primary aim of this mini-review is to summarize the new applications of oleanolic acid and its derivatives as cardioprotective agents reported in recent years and to highlight their therapeutic perspectives in cardiovascular diseases.
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8.
Cardiac contractility modulation: mechanisms of action in heart failure with reduced ejection fraction and beyond.
Tschöpe, C, Kherad, B, Klein, O, Lipp, A, Blaschke, F, Gutterman, D, Burkhoff, D, Hamdani, N, Spillmann, F, Van Linthout, S
European journal of heart failure. 2019;(1):14-22
Abstract
Heart failure (HF) is responsible for substantial morbidity and mortality and is increasing in prevalence. Although there has been remarkable progress in the treatment of HF with reduced ejection fraction (HFrEF), morbidity and mortality are still substantial. Cardiac contractility modulation (CCM) signals, consisting of biphasic high-voltage bipolar signals delivered to the right ventricular septum during the absolute refractory period, have been shown to improve symptoms, exercise tolerance and quality of life and reduce the rate of HF hospitalizations in patients with ejection fractions (EF) between 25% and 45%. CCM therapy is currently approved in the European Union, China, India, Australia and Brazil for use in symptomatic HFrEF patients with normal or slightly prolonged QRS duration. CCM is particularly beneficial in patients with baseline EF between 35% and 45%, which includes half the range of HF patients with mid-range EFs (HFmrEF). At the cellular level, CCM has been shown in HFrEF patients to improve calcium handling, to reverse the foetal myocyte gene programme associated with HF, and to facilitate reverse remodelling. This review highlights the preclinical and clinical literature related to CCM in HFrEF and HFmrEF and outlines the potential of CCM for HF with preserved EF, concluding that CCM may fill an important unmet need in the therapeutic approach to HF across the range of EFs.
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9.
Novel Pharmacotherapy for Hypertrophic Cardiomyopathy.
Wong, TC, Martinez, M
Cardiology clinics. 2019;(1):113-117
Abstract
Medical therapy for hypertrophic cardiomyopathy (HCM) has focused on minimizing the impact of symptoms due to left ventricular outflow tract obstruction and diastolic dysfunction. This article briefly discusses currently available therapy and focuses on both clinically available medications with novel applications for HCM as well as novel medications under development with specific indication for HCM. Finally, a brief summary of the current gaps and potential targets for pharmacotherapy is discussed.
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10.
NICORANDIL EFFICACY IN THE TREATMENT OF ISCHEMIC HEART DISEASE (REVIEW).
Gvishiani, M, Gabunia, L, Makharadze, T, Gongadze, N
Georgian medical news. 2018;(280-281):152-155
Abstract
Nicorandil is an antianginal agent with a dual mechanism of action. It belongs to ATP-senitive potassium channel openers which has the beneficial effect in angina pectoris, playing an significant role in the dilation of arteries, veins and coronary artery. It leads to the relaxation of vascular smooth muscle and causes vasodilatation of major epicardial vessels. This effect is crucial for reducing risks of further damage in cases when percutaneous coronary intervention (PCI) is necessary. Relevant new studies concluded that Nicorandil has antiarrhythmic and cardioprotective effects by improving reperfusion, ultimately leading to a reduction in microvascular damage caused by PCI. Furthermore, Nicorandil addition to the standard therapy of paitents with ischemic heart disease has demonstrated improved quality of life.