Hydrogen Sulfide Donors: Cardiovascular SYstem

In epicardial vessels there is not enough resistance to blood flow in healthy heart. Due to the presence of atherosclerotic plaques in the arteries or vessels, blood flow is slow down, but autoregulation process can pay off to a certain degree. Autorgulation is the process of myocardial vessel dilation in response to diminish supply of oxygen. By autoregulation process, there are rapid changes in blood flow to heart because of increase in demand. Adenosine which is potent vasodilator, are the key mediators that are involved in myocardial perfusion. Other mediators are nitric oxide (NO), prostaglandins (PGE2), carbon dioxide (CO2) and hydrogen ions. Obstruction as result of atherosclerosis can be fixed to coronary blood flow, or dynamics as with coronary

Several animal studies suggested that inhalation of formaldehyde and acetaldehyde has a negative consequence on the cardiovascular system, either directly or indirectly. Specifically, these studies showed that formaldehyde exposure altered the heart rate [PMID: 3735804], blood pressure [PMID: 418528], cardiac contractility [PMID: 2342227], cardiac oxidative stress and platelet count (PMID: 24040369). Formaldehyde inhalation also induced bradycardia in animals [PMID: 3735804], and this effect was found to be mediated by a sympathetic nerve activity (PMID: 3735804). Additionally, subacute and subchronic inhalation of formaldehyde was associated with cardiac oxidative stress, and consequently a cardic cells damage (PMID: 16716041). With regards to platelets, it was shown that the total platelet count significantly increased in mice exposed to formaldehyde gas for 2 weeks ( PMID: 24040369 ); the potential negative consequence of this effect should be considered in the context of the importance of platelets in maintaining hemostasis, and their role in thrombotic disorders. As for acetaldehyde, elevated blood pressure and heart rate were reported in animals following inhalation of variable doses, which could be due to its sympathomimetic effect (PMID: 5071036, PMID: 5681176). It is noteworthy that while the source(s) of formaldehyde and acetaldehyde in these studies were not from e-cigarette vapors, the concentrations used are

It inhibits Na+K+ ATPase active transport raising cytosolic Na+ concentrtion and leading to the increasement of Ca2+ concentration in the sarcoplasmic reticulum by the reversival exchange of Na+ and Ca2+ in the myocardial cell. This increase in the contraction of the heart (32) and improve cardiac outpur , left ventricualr ejection fraction, stroke volume, pulmonary capilary wedge pressure and exercise tolerance (33). Secondly, digoxin produce vagus activation showing negavite chronotropic action in SA node and negative dromotropic action in AV node. This lead to a shift in automatic balance by dominating the positive iontropic action of the drugs digoxin (33). In this way digoxin is cosinder as a only available inotropic drug which increase cardiac output and decreae pulmoary capillary wedge preure with our increasing heart rate and without decreasing blood pressure

Nitric oxide (NO) acts as a messenger molecule produced by the NO synthase (NOS) isoforms neuronal NOS (nNOS, or NOS1), inducible NOS (iNOS, or NOS2), and endothelial NOS (eNOS, or NOS3). NO has been involved in relaxing smooth muscle, inhibiting smooth muscle cell migration and proliferation, and decreasing platelet adherence and aggregation. NO also inhibits vascular inflammation [1].

As well as this, Nox2 affects the level of HIF-2a, which is responsible for anti-oxidative activity, and decreases it that lead to increased oxidative responses and neuronal

Mitochondrial play a crucial role in energy transduction of myocardium. Cellular and mitochondria metabolism observed in the course of hyperglycemia is associated with excessive production of reactive oxygen species (ROS). Among other factors involve in ROS production, is intracellular concentration of glucose secreted by the pancreatic β cells. Glucose play a key role in the mitochondrial-dependent oxidative reaction thus involvement of insulin resistance contribute to the influx of calcium ion Ca2+, generating excessive ROS. Therefore, mitochondrial radical ROS production in response to hyperglycemia is associated with Ca2+ concentration linked to cardiac mitochondrial dysfunction.

Each carotid artery was palpated one at the time and rated 2+ equal bilaterally with smooth contour. There was no presence of JVD. Auscultation at angle of jaw, midcervical area, and base of the neck, no presence of bruits. Precordium, no heaves visible. Heart auscultated with a diaphragm of the stethoscope. Regular rhythmic S2 and S1 sound heard at aortic, pulmonic, erb’s point, and tricuspid, no presence of murmur or splitting. Apical pulse listened for one full minute at 5th intercostal space in the left midclavicular line, rated 84, loud with regular rhythmic. History of hypertension. Client denied history of coronary arteries disease. Labs Na/138, K/3.9, Cl/10.2, Calcium/8.8, CO2/27.4, Anion gap/12.5; CBC with PLT no differential, RBC/3.54, HGB/10.5, HCT 30.8, PLT/275. Currently taking metoprolol (50 mg tabs PO BID) to manage heart rate. Diltiazem 120 mg PO daily for hypertension. Lovenox 40 mg subcutaneous every 24 hours to prevent deep vein thrombosis.

Vasopressin (Antidiuretic hormone) also is oxidized by the oxygen released from erythrocytes. Vasopressin plays a role in circulatory homeostasis and serum osmolality. Oxytocin and vasopressin are oxidized with formation of dityrosine [77]. Its oxidation and depletion cause vasodilatory shock - a syndrome with high mortality [78-81]. Low expression levels of Angiotensin II and ACE (angiotensin converting enxyme) are valuable in predicting the mortality of patients

Mitochondrial integrity is principal to efficient energy procedures and cardiac cell survival in response to diverse set of stressors, such as ischemia and various genotoxic parameters, such as infectious and immunological agents. The mitochondria are one of the major sources of adenine triphosphate, or ATP, via the electron transport chain/oxidative phosphorylation system and also provide a myriad service to the cell, such as pyruvate oxidation, the Krebs cycle, and amino acid, fatty acid, and steroid metabolism (3,4). The myocardium is a highly oxidative tissue, producing > 90% of its energy from mitochondrial respiration (5,6). However, at least 90% of the heart`s oxidative capacity is utilized during exercise, thus allowing for considerable

Both eNOS and nNOS are known to be constitutive although iNOS can be inducible. eNOS role in cardiovascular system has been extensively studied and has been shown to be essential in the protection against initiation and progression of cardiovascular diseases. Chemical inhibition or ablation of eNOS induces vasoconstriction, hypertension, and chronical aneurism. eNOS is accountable for modulation of blood pressure and vascular tone. It also inhibits the platelet aggression and leukocyte adhesion.

The research was done by Sabry M. El-Bahr at the Department of Biochemistry, Faculty of Veterinary Medicine, P.O. Box 22758, Alexandria University, Egypt. The overall purpose of this experiment was to study the causes of oxidative stress that is caused by free radical. It is known that the free radicals and the Reactive Oxygen Species (ROS) are used interchangeably. ROS can damage DNA, biomembrane lipids, proteins and other macromolecules. The primary source of ROS is the leakage of electron from the respiratory chain during the reduction of molecular oxygen to water generating superoxide anion. The classification of ROS includes oxygen centered radicals and oxygen centered non- radicals. Moreover,

C-Reactive Protein acts on eNOS or endothelial nitric oxide synthase, which is responsible for vasodilation, inhibition of smooth muscle, the degradation of LDL as well as the inhibition of platelet adhesion and aggregation which are essential components for a normally functioning cardiovascular system. Due to the inhibition of eNOS, vasoconstriction of the vessels can then occur leading to elevated blood pressure levels within the body.

Nitric oxide (NO) is synthesized from the amino acid L-arginine (precursor of NO) by the with the concomitant production of L-citrulline, and the enzyme which catalyses its synthesis is called ‘Endothelial Nitric Oxide Synthase’ (eNOS). The catalysis of this reaction requires a number of essential cofactors such as calmodulin (CaM), tetrahydrobiopterin (H4B), flavin mononucleotide, FAD, and NADPH (.Ingrid, B. Rudy 2003).

Hydrogen sulfide (H2S) is the latest molecule added to the gasotransmitter group after nitric oxide (NO) and carbon monoxide (CO). Great attention has been given to H2S in the last few years with regards to its production, metabolism, physiological functions and clearance. H2S constitutes a sound example of science’s evolution based on research and development; since H2S has been named as a toxic gas since its discovery in 1713, and only in the late 80’s of the past century scientist and researchers were capable to determine quantities of endogenous H2S in animals brain [1-3]. Yet recent; number of fundamental investigations were able to illustrate the physiochemical properties of the H2S as a reducing agent and nucleophile, which affords its ability to scavenge reactive oxygen species (ROS). Another essential field of research addressed cytoprotective properties of H2S based on its antithrombotic, anti-inflammatory, and anti-proliferative actions, in addition to ion channels regulatory processes, and ultimately, its usefulness as a potential treatment for several cardiovascular disorders through H2S releasing substances, formally named H2S donors [6]. The most studied H2S donors in cardiovascular field is Sodium hydrosulfide (NaHS), while Sodium sulfide (Na2S), is another H2S donor has been implicated more in anti-inflammatory and anti-oxidants research field. Similar to (NO); H2S in mammalians produced endogenously by endothelial cells to respond of various

Current drugs designed for the treatment of systolic HF act to block the neurohumoral response by inhibition of the RASS, adrenergic block and aldosterone antagonism, however non are focused on improving the contractile function of the heart (McMurray, 2010). In theory improving the contractile function of the heart would reduce the neurohumoral activation and improve or stabilise the decline in cardiac function. Previous attempts to increase cardiac function by using inotropes, such as β-adrenergic receptor agonists and phosphodiesterase inhibitors, which work by activating secondary messenger pathways that increase intracellular calcium, have been unsuccessful. In clinical trials they have resulted in arrhythmias, increased heart rate and oxygen consumption and have increased mortality (Cohn et al., 1998; Cuffe et al., 2002; Packer et al., 1991; Petersen and Felker, 2008).