Mechanism of liposoluble drugs and general anaesthetic's membrane action: action of difluorodichloromethane (FC 12) on different types of cardiac fibres isolated from sheep hearts

Lessard, Yvon; Paulet, G

doi:10.1093/cvr/19.8.465

Cited by 9 publications

(7 citation statements)

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“…By means of conventional in vitro microelectrode techniques using Purkinje fiber, atrial and ventricular preparations from sheep heart, Lessard and Paulet demonstrated regional heterogeneity of effects of FC-12 at concentrations ranging from 0.3 to 1.3 mmol/L. While action potential amplitude, upstroke, and conduction velocity were generally reduced, presumably due to sodium channel inhibition, ventricular action potential duration and effective refractory period were prolonged, presumably by inhibition of repolarizing potassium channels, whereas the respective parameters were shortened in Purkinje fibers (Lessard and Paulet, 1985). Furthermore, the spontaneous firing frequency of unstimulated Purkinje fibers was enhanced, suggesting increased automaticity (Lessard and Paulet, 1985) that was potentiated by a high concentration of adrenaline (Lessard and Paulet, 1986).…”

Section: Action Potentials Conduction and Intercellular Couplingmentioning

confidence: 96%

“…While action potential amplitude, upstroke, and conduction velocity were generally reduced, presumably due to sodium channel inhibition, ventricular action potential duration and effective refractory period were prolonged, presumably by inhibition of repolarizing potassium channels, whereas the respective parameters were shortened in Purkinje fibers (Lessard and Paulet, 1985). Furthermore, the spontaneous firing frequency of unstimulated Purkinje fibers was enhanced, suggesting increased automaticity (Lessard and Paulet, 1985) that was potentiated by a high concentration of adrenaline (Lessard and Paulet, 1986). Hence, reduced overall conduction velocity, shortened refractory period, and increased automaticity of Purkinje fibers, together with enhanced regional heterogeneity, act in unison to create a situation of electrical instability favoring extrasystoles and re-entry arrhythmias.…”

Section: Action Potentials Conduction and Intercellular Couplingmentioning

confidence: 99%

“…Cardiac sodium channels are probably also targeted by halocarbons, e.g., dichlorodifluoromethane (FC-12; Lessard et al, 1980;Lessard and Paulet, 1985). Investigations using in vivo and in vitro electrophysiological techniques demonstrated that FC-12 decreased the action potential amplitude in atrial and ventricular myocardium of anesthetized rats (Lessard et al, 1980) and in various ex vivo preparations from sheep heart, i.e., Purkinje fiber, and atrial and ventricular myocardium (Lessard and Paulet, 1985).…”

Section: Cardiac Sodium Channelsmentioning

confidence: 99%

“…Investigations using in vivo and in vitro electrophysiological techniques demonstrated that FC-12 decreased the action potential amplitude in atrial and ventricular myocardium of anesthetized rats (Lessard et al, 1980) and in various ex vivo preparations from sheep heart, i.e., Purkinje fiber, and atrial and ventricular myocardium (Lessard and Paulet, 1985). The cardiac cellular parameter action potential amplitude as measured in the former study is highly unlikely to be influenced by the central nervous system (CNS) depression occurring at the FC-12 concentrations used (compare Table 4).…”

Section: Cardiac Sodium Channelsmentioning

confidence: 99%

“…Follow-up investigations using in vivo and in vitro electrophysiological techniques yielded results in support of this interpretation. FC-12 shortened the duration of action potentials in atrial and ventricular myocardium of anesthetized rats (Lessard et al, 1980) and in ex vivo Purkinje fiber preparations from sheep heart (Lessard and Paulet, 1985).…”

Section: Cardiac Calcium Channels Intracellular Calcium Homeostasismentioning

confidence: 99%

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Mechanisms Involved in Cardiac Sensitization by Volatile Anesthetics: General Applicability to Halogenated Hydrocarbons?

Himmel

2008

Critical Reviews in Toxicology

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An increased sensitivity of the heart to catecholamines or cardiac sensitization is a recognized risk during acute human exposure to halogenated hydrocarbons used as solvents, foam-blowing or fire-extinguishing agents, refrigerants, and aerosol propellants. Although cardiac sensitization to such "industrial" halocarbons can result in serious arrhythmia and death, research into its mechanistic basis has been limited, whereas the literature on volatile anesthetics (e.g., halothane, chloroform) is comparably extensive. A review of the literature on halocarbons and related volatile anesthetics was conducted. The available experimental evidence suggests that volatile anesthetics at physiologically relevant concentrations interact predominantly with the main repolarizing cardiac potassium channels hERG and I Ks , as well as with calcium and sodium channels at slightly higher concentrations. On the level of the heart, inhibition of these ion channels is prone to alter both action potential shape (triangulation) and electrical impulse conduction, which may facilitate arrhythmogenesis by volatile anesthetics per se and is potentiated by catecholamines. Action potential triangulation by regionally heterogeneous inhibition of calcium and potassium channels will facilitate catecholamine-induced afterdepolarizations, triggered activity, and enhanced automaticity. Inhibition of cardiac sodium channels will reduce conduction velocity and alter refractory period; this is potentiated by catecholamines and promotes reentry arrhythmias. Other cardiac and/or neuronal mechanisms might also contribute to arrhythmogenesis. The few scattered in vitro data available for halocarbons (e.g., FC-12, halon 1301, trichloroethylene) suggest inhibition of cardiac sodium (conduction), calcium and potassium channels (triangulation), extraneuronal catecholamine reuptake, and various neuronal ion channels. Therefore, it is hypothesized that halocarbons promote cardiac sensitization by similar mechanisms as volatile anesthetics. Experimental approaches for further investigation of these sensitization mechanisms by selected halocarbons are suggested.

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Section: Action Potentials Conduction and Intercellular Couplingmentioning

confidence: 96%

Section: Action Potentials Conduction and Intercellular Couplingmentioning

confidence: 99%

Section: Cardiac Sodium Channelsmentioning

confidence: 99%

Section: Cardiac Sodium Channelsmentioning

confidence: 99%

Section: Cardiac Calcium Channels Intracellular Calcium Homeostasismentioning

confidence: 99%

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Mechanisms Involved in Cardiac Sensitization by Volatile Anesthetics: General Applicability to Halogenated Hydrocarbons?

Himmel

2008

Critical Reviews in Toxicology

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Organic Chlorofluoro Hydrocarbons

Gadagbui,

Onyema

2023

Patty's Toxicology

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This chapter is about organic chlorofluoro hydrocarbons, which are fully or partly halogenated hydrocarbons that contain carbon (C), hydrogen (H), chlorine (Cl), and fluorine (F). In the early 1930s, chlorofluorocarbons (CFCs) were introduced in the 1930s as “safe” replacements for refrigerants such as sulfur dioxide, ammonia, carbon tetrachloride, and chloroform. The list was later expanded during World War II to include their use to produce insecticide aerosols to protect the troops in tropical areas against malaria and other insect‐borne diseases. Current usages include foam blowing, precision cleaning, and propellants for medicinal, cosmetic, and general‐purpose aerosols, air conditioning, and refrigeration. The expanded use of these CFCs has resulted in their emissions into the atmosphere. The CFCs have low chemical reactivity, long atmospheric lifetime, and are globally distributed. However, since they are ozone‐depleting and are also powerful greenhouse gases (GHGs), development was initiated to replace them with comparatively less ozone‐depleting and less greenhouse‐warming hydrochlorofluorocarbons (HCFCs). Subsequently, hydrofluorocarbons (HFCs) were developed that were both less ozone‐depleting and less GHGs accumulating. Both CFCs and HCFCs are controlled under the Montreal Protocol. The widespread use concerns about their environmental and human health effects of these substances have been extensively reviewed. This chapter updates information on the health effects of some of the major and minor CFCs, HCFCs, and HFCs, their global emissions estimates, the discrepancies, if any, between the major reporting regions and the global atmospheric emissions values, and the likely sources of the gap between the atmospheric measurements and the reported emissions.

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Organic Chlorofluoro Hydrocarbons

Rusch¹

2001

Patty's Toxicology

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The chlorofluorocarbons (CFCs) were introduced in the 1930s as “safe” replacements for refrigerants such as sulfur dioxide, ammonia, carbon tetrachloride, and chloroform. In World War II, they were used to produce insecticide aerosols to protect the troops in tropical areas against malaria and other insectborne diseases. During the next 40–50 years, the number and type of applications expanded to include foam blowing, precision cleaning, and propellants for medicinal, cosmetic, and general‐purpose aerosols, air conditioning, and refrigeration. These uses eventually resulted in emission of the CFCs into the atmosphere. Because of their low chemical reactivity, they typically have long atmospheric residence times, and as a consequence, they are distributed globally. In 1974 Molina and Rowland hypothesized that, once the CFCs reach the stratosphere, they will undergo breakdown to release chlorine atoms. The chlorine atoms could then react with the stratospheric ozone breaking it down into oxygen. Since the stratospheric ozone absorbed much of the sun's ultraviolet β radiation (UVB), decreased ozone levels would lead to increases in ground‐level UVB. This could affect crop growth and lead to increases in cataracts and nonmelanoma skin cancers. Following reports of a marked drop in column ozone over Antarctica (the “ozone hole”) during the Antarctic winter, in 1987 most of the nations of the world drafted and signed an agreement calling for the phaseout of CFCs. This agreement is known as the Montreal Protocol . Development was initiated on two types of “in‐kind” replacements. The first were the hydrochlorofluorocarbons (HCFCs) and the second were the hydrofluorocarbons (HFCs). Both contain hydrogen and are susceptible to attack by hydroxyl radicals present in the atmosphere. Therefore, they have a shorter atmospheric lifetime and either are not transported to the stratosphere or are transported there only in small amounts. The HCFCs contain chlorine and are still capable of causing ozone depletion, although, since their atmospheric lifetimes are short, their ozone‐depleting potential (ODP) is lower than those associated with the CFCs. The HFCs do not contain chlorine (or bromine, also associated with ozone depletion). They, therefore, do not cause ozone depletion. A ranking scale has been developed using CFC11 as the reference compound, with an assigned value of 1. These values are also presented. A second concern, regarding both CFCs and their replacements, is that they are greenhouse warming gases. They, along with other substances such as carbon dioxide, trap the sun's infrared radiation and convert it to heat. However, they are also good insulating materials, and frequently their use as foam blowing agents in refrigeration equipment can lead to considerable energy savings, reducing carbon dioxide emissions. The greenhouse warming potentials (GWPs) for many of the CFCs, HCFCs, and HFCs are given. Many methods have been developed for atmospheric monitoring of these substances. Because of their widespread use and concerns about their environmental effects and health effects, several reviews have been written on these materials. From the reviews as well as the data presented later in this chapter, it can be seen that many of these chemicals are not highly toxic. Some, in fact, do not show significant signs of toxicity at air exposure levels up to a few percent or even over 5 or 10%. The most typical response seen following overexposure is CNS depression related to the anesthetic properties of many of these chemicals. Also, some have caused hepatotoxicity and occasionally reproductive effects. Each compound is discussed individually. They have been divided into three general areas: chlorofluorocarbons, hydrochlorofluorocarbons, and hydrofluorocarbons.

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Mechanism of liposoluble drugs and general anaesthetic's membrane action: action of difluorodichloromethane (FC 12) on different types of cardiac fibres isolated from sheep hearts

Cited by 9 publications

References 0 publications

Mechanisms Involved in Cardiac Sensitization by Volatile Anesthetics: General Applicability to Halogenated Hydrocarbons?

Mechanisms Involved in Cardiac Sensitization by Volatile Anesthetics: General Applicability to Halogenated Hydrocarbons?

Organic Chlorofluoro Hydrocarbons

Organic Chlorofluoro Hydrocarbons

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