Nifedipine and Impaired Oxygenation in Patients with Chronic Bronchitis and Cor Pulmonale (original) (raw)
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Acute Cardiovascular Effects of Dimethyl Sulfoxide
Annals of the New York Academy of Sciences, 1983
Dimethyl sulfoxide (DMSO] is a solvent that readily permeates living tissues and membranes. This capability appears related to DMSO's relatively polar nature, acceptance of hydrogen bonds, and compact structure which allow free interactions with water, proteins, carbohydrates, nucleic acids, ionic substances, and other biological constituents.' Known for its cutaneous absorption, DMSO has spawned a host of controversial claims regarding its efficacy in various clinical situations. Accepted as a tissue cryoprotectant and radioprotectant,' DMSO is reportedly also beneficial in central nervous system trauma and ischemia. Studies in extradural brain compression in rhesus monkeys, respiratory anoxia in rats, and spinal cord trauma in dogs suggest that DMSO may be more protective than steroids or barbiturates without altering neurological or cardiovascular f~n c t i o n .~.~ While adverse cardiovascular effects of barbiturates have required corrective inotropic support in some clinical DMSO cardiovascular effects are unclear. In vitro studies on mammalian have shown DMSO-induced depression of conduction and automaticity, but in vivo data on DMSO cardiovascular effects are lacking. In this study, the authors measured acute cardiovascular changes in barbiturate-anesthetized, normovolemic dogs receiving i.v. DMSO in doses of 2 g/kg, which were reported to have protective effects in cerebral i~c h e m i a .~.~
Toxicology Letters, 2000
The issue of dimethylsulfoxide (DMSO) neurotoxicity is an important one, given its wide use in experimental toxicology as a solvent for hydrophobic substances. We examined the effect of the intraperitoneal administration of different DMSO solutions (1.8-7.2%) on the peripheral nervous system of Wistar rats treated for 10 consecutive days and followed-up for an additional 45 days. DMSO administration induced a dose-dependent reduction in nerve conduction velocity, with complete recovery occurring in the follow-up. No structural changes were found in the sciatic nerve at 1.8% and 3.6% DMSO concentrations, suggesting that the mechanism of action of DMSO involves a functional impairment (i.e. conduction block) similar to that already described for this substance in isolated systems. However, when DMSO was administered at the 7.2% concentration, evident structural changes were observed in the sciatic nerve, with myelin disruption and uncompacted myelin lamelle. The neurophysiological and pathological changes observed in our study are severe enough to merit careful consideration in the course of experimental studies involving DMSO as a solvent for drugs which are under evaluation for their potential neurotoxicity.
Pharmacology of dimethyl sulfoxide in cardiac and CNS damage
Pharmacological Reports, 2009
The pharmacological effects of dimethyl sulfoxide (DMSO) administration include some desirable properties that may be useful in the treatment of medical disorders resulting in tissue injury and compromised organ systems.These properties include the reported effects of DMSO on impaired blood flow, suppression of cytotoxicity from excess glutamate release that may result in lethal NMDA-AMPA activation, restriction of cytotoxic Na + and Ca 2+ entry into damaged cells, blocking tissue factor (TF) from contributing to thrombosis, reduction of intracranial pressure, tissue edema, and inflammatory reactions, and inhibition of vascular smooth muscle cell migration and proliferation that can lead to atherosclerosis of the coronary, peripheral, and cerebral circulation. A review of the basic and clinical literature on the biological actions of DMSO in cardiac and central nervous system (CNS) damage or dysfunction indicates that this agent, alone or in combination with other synergistic molecules, has been reported to neutralize or attenuate pathological complications that harmed or can further harm these two organ systems. The effects of DMSO make it potentially useful in the treatment of medical disorders involving head and spinal cord injury, stroke, memory dysfunction, and ischemic heart disease.
Annals of the New York Academy of Sciences, 1983
Beginning with the studies published by Sams and colleagues' in 1966, there has been a growing list of effects of dimethyl sulfoxide (DMSO) on the myocardium. Many of the studies of cardiac effects of DMSO focused on its use in high (multimolar) concentrations to reduce freeze-thaw-induced injury to the heart, with the ultimate goal being long-term cryopreservation of human hearts for transplantation. Studies aimed at using DMSO for cryopreservation of other organs such as the kidney were also prevalent during the 1970s. Despite the fact that these organ cryopreservation studies invariably involved organ ischemia, albeit under extremely low temperatures, little consideration was given to evaluating the effects of DMSO under more common settings of global cardiac ischemia as occurs intraoperatively during some cardiothoracic surgical procedures, or in the context of regional ischemia that can precipitate infarction. Although there were two studies of the effects of DMSO on myocardial ischemia,2,3 the relative paucity of studies in more clinically relevant ischemic states may have been due to both an incomplete understanding of the processes contributing to ischemic injury, and a failure at the time to appreciate and apply new facts about the pharmacology of DMSO that had been elucidated in a variety of noncardiac and nonischemic settings, many of which overtly shared no obvious relationships with cardiac pathophysiology. This paper first briefly summarizes the major pharmacological effects of DMSO on the normal mammalian myocardium, considering their possible implications to human medicine and cardiac ischemic states in particular, but also suggesting that although these effects are intrinsically interesting and demonstrate the diverse actions of this drug, they may be of little utility in currently encountered clinical situations. Evidence will then be presented to support the concept that an important component of ischemic injury to the heart and possibly to other ischemic organs is generation of oxygen radicals, including the hydroxyl radical. A proposal will then be made that the hydroxyl radical-scavenging ability of DMSO, combined with its ability to permeate cells readily, may confer upon the drug a unique and important adjunctive role for preventing this aspect of cell death in some clinical settings of ischemia. EFFECTS OF DMSO ON THE MYOCARDIUM Because of the problems associated with interpreting the direct cardiac effects of any drug with peripheral vascular effects, most of the work describing the cardiac effects of DMSO has been conducted on isolated hearts or other 170
Dimethyl Sulfoxide Induces Hemolysis and Pulmonary Hypertension
PRILOZI
Vascular and lung injury are well established complications associated with hemolytic disorders, and hemolysis associated pulmonary hypertension (PH) has emerged as the most serious complication of sickle cell disease. The causal relationship between intravascular hemolysis and the development of PH is still under investigation. Previously we have shown that repetitive administration of hemolyzed autologous blood causes PH in rats. Dimethyl sulfoxide (DMSO), a widely used solvent and anti-inflammatory agent, induces hemolysis in vivo. We hypothesized that repetitive administration of DMSO would induce PH in rats. We also examined hemolysis-induced release of adenosine deaminase (ADA) and arginase from red blood cells, which may amplify hemolysis-mediated vascular injury. Acute administration of DMSO (1.5ml/30 min into the right atrium) induced intravascular hemolysis and pulmonary vasoconstriction. DMSO-induced increase in right ventricular peak systolic pressure (RVPSP) was associa...
Elucidation of dimethylsulfone metabolism in rat using a 35S radioisotope tracer method
Nutrition Research, 2002
The metabolism of dimethylsulfone was quantified for possible medical applications based on the hypothesis that the agent may be metabolized to yield methionine or its metabolites. The 35 S-labeled dimethylsulfone and methionine are orally administrated to rat. Over 80% of the administrated dimethylsulfone is metabolized in the rats tissues, and 59.7-79.1% of it is then excreted into the urine as 35 S-containing metabolites; 3.5-10.3% of the same remains incorporated in the tissues. The uptake of radioactivity, though different from the quantity of methionine in percentage at the retained site, is observed in the blood, spleen and hair, and over 80% of the administered [ 35 S] dimethylsulfone is excreted the same day. Meanwhile, the distribution of the 35 S concentrations of both agents in the rat system suggests that this compound had been metabolized to yield certain sulfur-containing compounds.
Molecules
Dimethylsulfoxide (DMSO) is an amphipathic molecule composed of a polar domain characterized by the sulfinyl and two nonpolar methyl groups, for this reason it is able to solubilize polar and nonpolar substances and transpose hydrophobic barriers. DMSO is widely used to solubilize drugs of therapeutic applications and studies indicated that 10% v/v concentration did not modify culture viability when used to treat human peripheral blood mononuclear cells (PBMC). However, some DMSO concentrations could influence lymphocyte activation and present anti-inflammatory effects. Therefore, the objective of this study was to evaluate the effect of DMSO on lymphocyte activation parameters. Cell viability analysis, proliferation, and cytokine production were performed on PBMC from six healthy subjects by flow cytometry. The results indicated that 2.5% v/v DMSO concentrations did not modify lymphocytes viability. DMSO at 1% and 2% v/v concentrations reduced the relative proliferation index of lymphocytes and at 5% and 10% v/v concentrations reduced the percentage of total lymphocytes, cluster of differentiation 4 + (CD4 +) T lymphocytes and CD8 + T lymphocytes interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2) producers. Thus, it was concluded that DMSO has an in vitro anti-inflammatory effect by reducing lymphocyte activation demonstrated with proliferation reduction and the decrease of cytokine production.