Cardiotoxic and Cardioprotective Effects of Methylene Blue in the Animal Model of Cardiac Ischemia and Reperfusion.

Treatment of patients with myocardial ischemic diseases crucially involves cardiac reperfusion (CR). However, oxidative stress and tissue lesions caused by CR may also lead to lethal complications, such as arrythmias and vasoplegic syndrome (VS). Although methylene blue (MB) has long been used to treat VS due to cardiac ischemia and reperfusion (CIR) and/or surgery because of its vascular effects, MB's effects on the heart are unclear.

Use of etomidate in endotracheal intubations in the emergency room during the COVID-19 pandemic: a randomized clinical trial.

Purpose: Shock, cardiovascular problems, and respiratory failure constitute the main causes of death in patients cared in medical emergency rooms. Patients commonly require orotracheal intubation (OTI), a fact that has been intensified by diseases that generate important and fatal hemodynamic and respiratory problems in the affected patient.

Methods: Although etomidate (ETO) is a highly used anesthetic for OTI, its use remains controversial in several scenarios.

Forty years of a Postgraduate Program in Cardiology at a Brazilian public university: indicators of its graduates.

Purpose: To evaluate the profile of graduates of the Postgraduate Program (PGP) in Cardiology of a public federal university, according to sociodemographic factors and professional trajectory.

Methods: The variables were collected from databases from the observed institution and digital platforms. The analysis of differences between the various levels of degrees was carried out in three cohorts: the entire historical series (graduates from 1978-2021), the first 20 years (1978-1997) and the second 20 years (1998-2018).

Cardiotoxic Effects Produced by Omeprazole and Methylene Blue in an Animal Model of Cardiac Ischemia and Reperfusion and Potential Implications for the Pharmacological Strategy for Vasoplegic Syndrome.

Defined as systemic hypotension caused by intense vasodilation due to the loss of systemic vascular resistance, vasoplegic syndrome (VS) is associated with elevated morbidity and mortality in humans. Although vasopressors such as norepinephrine and vasopressin are the first-choice drugs for VS treatment, several other drugs such as methylene blue (MB) can be used as adjuvant therapy including rescue therapy. To develop new pharmacological strategies to reduce the risk of VS, we investigated the effects of treatments with MB (2 mg/kg/IV), omeprazole (OME, 10 mg/kg/IV), and their combination in an animal model of cardiac ischemia-reperfusion (CIR).

Effects of Calendula officinalis extract on liver histopathology, lipid profile, and oxidative stress in rats submitted to a diet rich in cholesterol and carbohydrates.

Purpose: To evaluate the modulatory properties of Calendula officinalis L. (Asteraceae) (C. officinalis) extract on cafeteria diet-fed rats.

Role of cardiac β-adrenergic and A-adenosine receptors in severe arrhythmias related to Parkinson's disease.

Aims: Although reduced life expectancy in Parkinson's Disease (PD) patients has been related to severe cardiac arrhythmias due to autonomic dysfunctions, its molecular mechanisms remain unclear. To investigate the role of cardiac β-Adrenergic (βAR) and A-Adenosine (AR) receptors in these dysfunctions, the pharmacological effects of stimulation of cardiac βAR (isoproterenol, ISO), in the absence and presence of cardiac βAR (atenolol, AT) or AR (1,3-dipropyl-8-cyclopentyl xanthine, DPCPX) blockade, on the arrhythmias induced by Ischemia/Reperfusion (CIR) in an animal PD model were studied.

Methods: PD was produced by dopaminergic lesions (confirmed by immunohistochemistry analysis) caused by the injection of 6-hydroxydopamine (6-OHDA, 6 μg) in rat striatum.

Pharmacological Modulation by Low Molecular Weight Heparin of Purinergic Signaling in Cardiac Cells Prevents Arrhythmia and Lethality Induced by Myocardial Infarction.

Background: Although several studies suggest that heparins prevent arrhythmias caused by acute myocardial infarction (AMI), the molecular mechanisms involved remain unclear. To investigate the involvement of pharmacological modulation of adenosine (ADO) signaling in cardiac cells by a low-molecular weight heparin (enoxaparin; ENOX) used in AMI therapy, the effects of ENOX on the incidences of ventricular arrhythmias (VA), atrioventricular block (AVB), and lethality (LET) induced by cardiac ischemia and reperfusion (CIR) were evaluated, with or without ADO signaling blockers.

Methods: To induce CIR, adult male Wistar rats were anesthetized and subjected to CIR.

Risk of Cardiac Lesion with Chronic and Acute Use of Loperamide-An Integrative Review.

Loperamide is a synthetic opioid commonly used as an antidiarrheal due to its activation of u-opioid receptors in the myenteric plexus. In therapeutic doses, it inhibits peristalsis and has anti-secretory and anti-motility effects, until metabolized by intestinal and hepatic CYP3A4 and CYP2C8 into inactive metabolites. Furthermore, loperamide also inhibits L-type voltage-gated calcium (Ca) channels, increases action potential duration, and can induce arrhythmias and even cardiotoxicity, particularly when taken in extremely high doses.

Cardioprotection stimulated by resveratrol and grape products prevents lethal cardiac arrhythmias in an animal model of ischemia and reperfusion.

Purpose: To evaluate the preventive cardioprotective effects of resveratrol and grape products, such as grape juice and red wine, in animal model of cardiac ischemia and reperfusion.

Methods: Male Wistar rats orally pretreated for 21-days with resveratrol and grape products were anesthetized and placed on mechanical ventilation to surgically induce cardiac ischemia and reperfusion by obstruction (ischemia) followed by liberation (reperfusion) of blood circulation in left descending coronary artery. These rats were submitted to the electrocardiogram (ECG) analysis to evaluate the effects of pretreatment with resveratrol and grape products on the incidence of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) resulting from cardiac ischemia and reperfusion.

Cardioprotective effects of pharmacological blockade of the mitochondrial calcium uniporter on myocardial ischemia-reperfusion injury.

Purpose: To evaluate whether the attenuation of mitochondrial Ca2+ overload produced by pharmacological blockade of mitochondrial Ca2+ uniporter (MCU) protects the myocardium against injuries caused by cardiac ischemia and reperfusion (CIR).

Methods: CIR was induced in adult male Wistar rats (300-350 g) by occlusion of the left anterior descendent coronary artery (10 min), followed by reperfusion (120 min). Rats were treated with different doses of MCU blocker ruthenium red (RuR), administered 5 min before ischemia or reperfusion.

Recent Advances in Pharmacological and Non-Pharmacological Strategies of Cardioprotection.

Ischemic heart diseases (IHD) are the leading cause of death worldwide. Although the principal form of treatment of IHD is myocardial reperfusion, the recovery of coronary blood flow after ischemia can cause severe and fatal cardiac dysfunctions, mainly due to the abrupt entry of oxygen and ionic deregulation in cardiac cells. The ability of these cells to protect themselves against injury including ischemia and reperfusion (I/R), has been termed "cardioprotection".

Sudden unexpected death in Parkinson's disease: why is drinking water important?

Parkinson's disease (PD) is one of the most common age-related neurodegenerative disorders. Several studies over the last few years have shown that PD is accompanied by high rates of premature death compared with healthy controls. Death in PD patients is usually caused by determinant factors such as pneumonia, and cerebrovascular and cardiovascular diseases.

Pharmacological modulation of b-adrenoceptors as a new cardioprotective strategy for therapy of myocardial dysfunction induced by ischemia and reperfusion.

Purpose: To evaluate the cardioprotective response of the pharmacological modulation of β-adrenergic receptors (β-AR) in animal model of cardiac ischemia and reperfusion (CIR), in spontaneously hypertensive (SHR) and normotensive (NWR) rats.

Methods: CIR was induced by the occlusion of left anterior descendent coronary artery (10 min) and reperfusion (75 min). The SHR was treated with β-AR antagonist atenolol (AT, 10 mg/kg, IV) 5 min before CIR, and NWR were treated with β-AR agonist isoproterenol (ISO, 0.

Cardioprotective effect of preconditioning is more efficient than postconditioning in rats submitted to cardiac ischemia and reperfusion1.

Purpose: To investigate the cardioprotective effects of ischemic preconditioning (preIC) and postconditioning (postIC) in animal model of cardiac ischemia/reperfusion.

Methods: Adult rats were submitted to protocol of cardiac ischemia/reperfusion (I/R) and randomized into three experimental groups: cardiac I/R (n=33), preCI + cardiac I/R (n=7) and postCI + cardiac I/R (n=8). After this I/R protocol, the incidence of ventricular arrhythmia (VA), atrioventricular block (AVB) and lethality (LET) was evaluated using the electrocardiogram (ECG) analysis.

Cardioprotective effect of lipstatin derivative orlistat on normotensive rats submitted to cardiac ischemia and reperfusion.

Purpose: To evaluate in vivo animal model of cardiac ischemia/reperfusion the cardioprotective activity of pancreatic lipase inhibitor of the orlistat.

Methods: Adult male Wistar rats were anesthetized, placed on mechanical ventilation and underwent surgery to induce cardiac I/R by obstructing left descending coronary artery followed by reperfusion to evaluation of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) with pancreatic lipase inhibitor orlistat (ORL). At the end of reperfusion, blood samples were collected for determination of triglycerides (TG), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), lactate dehydrogenase (LDH), creatine kinase (CK), and creatine kinase-MB (CK-MB).

Heparin Oligosaccharides Have Antiarrhythmic Effect by Accelerating the Sodium-Calcium Exchanger.

Blockage of the Na/Ca exchanger (NCX) is used to determine the role of NCX in arrhythmogenesis. Trisulfated heparin disaccharide (TD) and Low Molecular Weight Heparins (LMWHs) can directly interact with the NCX and accelerate its activity. In this work, we investigated the antiarrhythmic effect of heparin oligosaccharides related to the NCX activity.

Effect of atenolol pre-treatment in heart damage in a model of intestinal ischemia-reperfusion.

Purpose: To investigate the effects of atenolol in inflammatory mediator and oxidative stress in a myocardial injury by intestinal ischemia/reperfusion in rat model.

Methods: Adult Wistar male rats were randomly (n=8), anesthetized and divided in: Sham: submitted to operation only; group SS+IR: intravenous saline infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); group AT+IR: intravenous atenolol infusion (2 mg/kg) following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); and group AT+I+AT+R: intravenous atenolol infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and in the time 45 minutes other atenolol doses were administrated and the artery was open for 120 minutes (reperfusion), all animals were submitted to muscular relaxation for mechanical ventilation. In the end of experiment the animals were euthanized and the hearts tissue were morphology analyzed by histology and malondialdehyde by ELISA, and the plasma were analyzed for tumor necrosis factor-alpha by ELISA.

Challenges for the pharmacological treatment of neurological and psychiatric disorders: Implications of the Ca(2+)/cAMP intracellular signalling interaction.

In 2013, we discovered that the entitled "calcium paradox" phenomenon, which means a paradoxical sympathetic hyperactivity produced by l-type Ca(2+) channel blockers (CCBs), used in antihypertensive therapy, is due to interaction between the intracellular signalling pathways mediated by Ca(2+) and cAMP (Ca(2+)/cAMP interaction). In 2015, we proposed that the pharmacological manipulation of this interaction could be a new therapeutic strategy for increasing neurotransmission in psychiatric disorders, and producing neuroprotection in the neurodegenerative diseases. Besides the paradoxical sympathetic hyperactivity produced by CCBs, several clinical studies have been demonstrating pleiotropic effects of CCBs, including neuroprotective effects.

Would calcium or potassium channels be responsible for cardiac arrest produced by adenosine and ATP in the right atria of Wistar rats?

Autonomic nerves release ATP, which is processed into adenosine in the synaptic cleft. Adenosine and ATP exert a negative chronotropic effect in the heart. This study aims to evaluate adenosine and P2 receptors and cellular signalling in cardiac arrest produced by purines in the heart.

Pharmacological implications of the Ca(2+)/cAMP signaling interaction: from risk for antihypertensive therapy to potential beneficial for neurological and psychiatric disorders.

In this review, we discussed pharmacological implications of the Ca(2+)/cAMP signaling interaction in the antihypertensive and neurological/psychiatric disorders therapies. Since 1975, several clinical studies have reported that acute and chronic administration of L-type voltage-activated Ca(2+) channels (VACCs) blockers, such as nifedipine, produces reduction in peripheral vascular resistance and arterial pressure associated with an increase in plasma noradrenaline levels and heart rate, typical of sympathetic hyperactivity. Despite this sympathetic hyperactivity has been initially attributed to adjust reflex of arterial pressure, the cellular and molecular mechanisms involved in this apparent sympathomimetic effect of the L-type VACCs blockers remained unclear for decades.

Could α1-adrenoceptors and androgen receptors be modified by sexual maturation and testosterone in the rat testicular capsule?

Aims: Testicular capsule contractile dysfunctions are recognized to contribute to male infertility, but the influence of sexual maturation and exogenous testosterone on the expression and function of androgen receptor and α1-adrenoceptors on rat testicular capsule is unclear. Here, these two biological parameters were evaluated on testicular capsule from sexually immature and young adult rats treated or not with exogenous testosterone.

Main Methods: Male Wistar rats (45- and 60-day-old) were assigned into groups: control (saline 0.

Chronic treatment with red wine modulates the purinergic neurotransmission and decreases blood pressure in hypertensive SHR and diabetic-STZ rats.

It is known that red wine has cardioprotective properties. However, its influence is unknown about purinergic system. Therefore, we study the influence of the treatment with red wine or ethanol in purinergic neurotransmission.