Indigo Carmine Hemodynamic Studies to Treat Vasoplegia Induced by Compound 48/80 in a Swine Model of Anaphylaxis.

Introduction: There are many reasons to believe that the nitric oxide/guanosine 3'5' - cyclic monophosphate (or NO/cGMP) pathway on vasoplegic states is underestimated. To study indigo carmine (IC) as an alternative to methylene blue was the investigation rationale.

Methods: The IC (3mg/kg intravenous infusion) study protocol included five experimental groups; 1) Control group - saline was injected at 0 and 10 minutes; 2) IC group - IC was injected at 0 and saline at 10 minutes; 3) compound 48/80 (C48/80) group - C48/80 was injected at 0 minute and saline at 10 minutes; 4) C48/80 + IC group - C48/80 was injected at 0 minute and IC at 10 minutes; and 5) IC + C48/80 group - IC was injected at 0 minute and C48/80 at 10 minutes.

Effect of Diterpene Manool on the Arterial Blood Pressure and Vascular Reactivity in Normotensive and Hypertensive Rats.

Background: Many studies have shown that the diterpenoid classes exert a significant effect on the cardiovascular system. Diterpenes, in particular, are among the main compound links to cardiovascular properties such as vasorelaxant, inotropic, diuretic and hypotensive activity. While the manool vasorelaxation mechanism is visible, its effect on blood pressure (BP) is still unknown.

In vitro evidence that endothelium-dependent vasodilatation induced by clozapine is mediated by an ATP-sensitive potassium channel.

Background: There is a definite association between antipsychotic drugs and arterial hypertension. However, endothelium functions are scarcely considered. This investigation was carried out to study the mechanisms involved in clozapine endothelium-dependent vascular reactivity.

Why Methylene Blue Have to Be Always Present in the Stocking of Emergency Antidotes.

Evidence-based review of the existing literature ultimately recommends stocking of Methylene Blue (MB) as an emergency antidote in the United States. The same is reported around the world in Japan, Greece, Italy and Canada. The observation that MB is always present as the main antidote required in emergency and critical care units calls for a revisit on its effects on the NO/cGMP system to reemphasize its multisystem actions.

Effect of rosmarinic acid on the arterial blood pressure in normotensive and hypertensive rats: Role of ACE.

Background: In recent years, it has been demonstrated the inhibitory effect of some plant species on the angiotensin-converting enzyme and rosmarinic acid is a prominent constituent of these species.

Hypothesis/purpose: This study was carried out to verify the effect of rosmarinic acid on blood pressure through inhibitory activity on angiotensin-converting enzyme in rats.

Study Design: The arterial hypertension was promoted using 2-kidneys 1-clip model in rats.

The Left Atrial Appendage Revised.

Nonvalvular atrial fibrillation is associated with a 4- to 5-fold strokes increase and may be responsible for 15% to 20% of all strokes in the elderly. In this scenario, the left atrial appendage thrombus would be the associated with 90% of cases. The use of anticoagulants, percutaneous devices, and the left atrial appendage surgical exclusion is still an open discussion.

The Diterpene Sclareol Vascular Effect in Normotensive and Hypertensive Rats.

Background:: The diterpene Sclareol has antimicrobial action, cytotoxic and cytostatic effects and anti-tumor activities. However, researches on the cardiovascular system are scarce.

Objective:: This study was designed to investigate the mechanisms involved in the Sclareol cardiovascular effect in normotensive and hypertensive rats.

Methylene Blue to Treat Protamine-induced Anaphylaxis Reactions. An Experimental Study in Pigs.

Objective: To examine if methylene blue (MB) can counteract or prevent protamine (P) cardiovascular effects.

Methods: The protocol included five heparinized pig groups: Group Sham -without any drug; Group MB - MB 3 mg/kg infusion; Group P - protamine; Group P/MB - MB after protamine; Group MB/P - MB before protamine. Nitric oxide levels were obtained by the nitric oxide/ozone chemiluminescence method, performed using the Nitric Oxide Analizer 280i (Sievers, Boulder, CO, USA).

In vitro reactivity ("organ chamber") of guinea pig tracheal rings-methodology considerations.

The present text was motivated by the difficulties faced by our postgraduate students when using airways studies protocols and will take into consideration the three mechanisms of relaxation: (I) guanosine 3,5-cyclic monophosphate (cGMP)/NO-dependent; (II) adenosine 3,5-cyclic monophosphate (cAMP)/PGI2-dependent, and (III) hyperpolarization-dependent. Tracheal rings are studied in an organ bath containing a gassed physiological salt solution, usually at a temperature of 37 °C. An agent or procedure that causes contraction [acetylcholine (Ach) or metacholine] of the smooth muscle is needed before study airway dilator drugs.

Effects of methylene blue in acute lung injury induced by oleic acid in rats.

Background: In acute lung injury (ALI), rupture of the alveolar-capillary barrier determines the protein-rich fluid influx into alveolar spaces. Previous studies have reported that methylene blue (MB) attenuates such injuries. This investigation was carried out to study the MB effects in pulmonary capillary permeability.

High conductance potassium channels activation by acid exposure in rat aorta is endothelium-dependent.

Background: We investigated, previously, the mechanism by which extracellular acidification promotes relaxation in rat thoracic aorta. These studies suggested that extracellular acidosis promotes vasodilation mediated by NO, KATP and SKCa, and maybe other K(+) channels in isolated rat thoracic aorta. This study was carried out to investigate the paxilline-mediated hyperpolarization induced by acid exposure.

In vitro effects of extracellular hypercapnic acidification on the reactivity of rat aorta: Rat aorta vasodilation during hypercapnic acidification.

Unlabelled: The mechanisms by which pH influences vascular tone are not entirely understood, but evidence suggests that the endothelium is involved. Here, we aimed to study the in vitro vascular responses induced by extracellular hypercapnic acidification (HA), as well as the endothelium-dependent mechanisms that are involved in the responses. We bubbled a mixture of CO (40%)/O (60%) in an organ bath; we constructed a pH-response curve (pH range 7.

Presentation of an experimental method to induce in vitro ("organ chambers") respiratory acidosis and its effect on vascular reactivity.

Purpose: To create in vitro a model to generate acidosis by CO2 bubbling "organ chambers", which would be useful for researchers that aim to study the effects of acid-base disturbs on the endothelium-dependent vascular reactivity.

Methods: Eighteen male Wistar rats (230-280 g) were housed, before the experiments, under standard laboratory conditions (12h light/dark cycle at 21°C), with free access to food and water. The protocol for promoting in vitro respiratory acidosis was carried out by bubbling increased concentrations of CO2.

In vitro effects of the organophosphorus pesticide malathion on the reactivity of rat aorta.

Background And Purpose: There is a remarkable paucity of studies analyzing the role of the endothelium-derived relaxing factors on the vascular effects of organophosphates. This study was carried out to evaluate the vascular effects of malathion and the role of nitric oxide (NO) and prostacyclin (PGI2).

Methods: Vascular reactivity measuring isometric forces in vitro ('organ chambers') and flow cytometry (cells loaded with DAF-FM DA) were used.

Guanylate cyclase inhibition by methylene blue in circulatory shock caused by acute necrotizing pancreatitis: a word of caution based on a porcine model.

Objective: To study the therapeutic application of guanylate cyclase inhibition by methylene blue in an experimental model of acute pancreatitis in pigs.

Methods: acute necrotizing pancreatitis was induced in anesthetized pigs by the retrograde infusion of 1 ml/kg of 5% sodium taurocholate and 8 U/kg enterokinase in the pancreatic duct. Three groups were studied (n = 5): control (C), pancreatitis (AP), and MB bolus followed by pancreatitis (MB+P).

Metabolic acidosis treatment as part of a strategy to curb inflammation.

Abnormalities in systemic acid-base balance may induce significant changes in the immune response, and they may play a significant role in the development or maintenance of immune dysfunction. Different forms of acidosis (metabolic and respiratory) and even different types of metabolic acidosis (hyperchloremic and lactic) may produce different effects on immune function. If alkalization has, or not, some effect on inflammation control is still a matter of speculation.

Curbing inflammation in the ischemic heart disease.

A modern concept considers acute coronary syndrome as an autoinflammatory disorder. From the onset to the healing stage, an endless inflammation has been presented with complex, multiple cross-talk mechanisms at the molecular, cellular, and organ levels. Inflammatory response following acute myocardial infarction has been well documented since the 1940s and 1950s, including increased erythrocyte sedimentation rate, the C-reactive protein analysis, and the determination of serum complement.

The effect of extracellular pH changes on intracellular pH and nitric oxide concentration in endothelial and smooth muscle cells from rat aorta.

Aims: It has been known for more than a century that pH changes can alter vascular tone. However, there is no consensus about the effects of pH changes on vascular response. In this study, we investigated the effects of extracellular pH (pHo) changes on intracellular pH (pHi) and intracellular nitric oxide concentration ([NO]i) in freshly isolated endothelial cells and cross sections from rat aorta.

The lignan (-)-cubebin inhibits vascular contraction and induces relaxation via nitric oxide activation in isolated rat aorta.

Cubebin, the most abundant lignan in Piper cubeba, has been described as having several effects as trypanocidal, antimycobacterial, antispasmodic, antimicrobial, anti-inflammatory, and analgesic. This study investigated the vasorelaxant effect produced by (-)-cubebin in isolated rat aortic rings pre-contracted with phenylephrine (Phe), and the possible mechanism involved in this event was evaluated. Endothelium-dependent relaxation was evoked by acetylcholine and (-)-cubebin in intact aortic rings, while endothelium-independent vasorelaxation was elicited by sodium nitroprusside and (-)-cubebin in denuded rings.

Is rosmarinic acid underestimated as an experimental cardiovascular drug?

Purpose: The rationale of the present review is to analize the activity of Rosmarinus officinalis in the the cardiovascular system

Methods: A MEDLINE database search (from January 1970 to December 2011) using only rosmarinic acid as searched term.

Results: The references search revealed 509 references about rosmarinic acid in 40 years (the first reference is from 1970). There is a powerful prevalence of antioxidant and cancer studies.

Cardiovascular therapeutics targets on the NO-sGC-cGMP signaling pathway: a critical overview.

In a brief overview, in NO-sGC-cGMP signaling in a blood vessel, l-arginine is converted in the endothelium monolayer by the endothelial nitric oxide synthase (eNOS) to NO which diffuses into both the vessel lumen and the vessel wall, thereby activating soluble guanylate cyclase (sGC). Heme-dependent sGC stimulators and hem-independent sGC activators increase the cellular cGMP concentration via the direct activation of sGC, which results in both vasorelaxation and inhibition of platelet aggregation. Studies of the 90's definitively established the role of endothelium in all cardiovascular diseases, which were associated with endothelial dysfunction by impaired release of endothelium-derived relaxing factors with consequent risk of spasm and thrombosis.

Guanylate cyclase inhibition by methylene blue as an option in the treatment of vasoplegia after a severe burn. A medical hypothesis.

Today it is known that severe burns can be accompanied by the phenomenon of vasoplegic syndrome (VS), which is manifested by persistent and diffuse vasodilation, hypotension and low vascular resistance, resulting in circulatory and respiratory failure. The decrease in systemic vascular resistance observed in VS is associated with excessive production of nitric oxide (NO). In the last 2 decades, studies have reported promising results from the administration of an NO competitor, methylene blue (MB), which is an inhibitor of the soluble guanylate cyclase (sGC), in the treatment of refractory cases of vasoplegia.

The protective effect of cilostazol on isolated rabbit femoral arteries under conditions of ischemia and reperfusion: the role of the nitric oxide pathway.

Objectives: The clinical significance of ischemia/reperfusion of the lower extremities demands further investigation to enable the development of more effective therapeutic alternatives. This study investigated the changes in the vascular reactivity of the rabbit femoral artery and nitric oxide metabolites under partial ischemia/ reperfusion conditions following cilostazol administration.

Methods: Ischemia was induced using infrarenal aortic clamping.

Nitric oxide synthase in heart and thoracic aorta after liver ischemia and reperfusion injury: an experimental study in rats.

Objectives: We tested the effects of liver reperfusion in the immunohistochemical expression of nitric oxide synthase on the thoracic aorta and the heart.

Materials And Methods: We randomized 24 male Wistar rats into 3 groups: (1) control; (2) R2 group, with 60 minutes of partial (70%) liver ischemia and 2 hours of global liver reperfusion; (3) and R6 group, with 60 minutes of partial liver ischemia and 6 hours of global liver reperfusion.

Results: In the heart, there was little, diffuse immunohistochemical endothelial staining; immunohistochemical inducible nitric oxide synthase staining was expressed in the adventitia layer of intramyocardial vessels in both cases, with a time-dependent but not statistically significant increase.