A gas that gives rotten eggs their distinctive odour could one day form the basis of new cardiovascular therapies. Research has indicated that a new compound, called AP39, which generates minute quantities of the gas hydrogen sulfide inside cells, could be beneficial in cases of high blood pressure and diseases of the blood vessels that occur with ageing and diabetes.
In such conditions, the body’s own levels of hydrogen sulfide are depleted, thought to be consumed by oxidants in the tissues and blood. Now, in laboratory tests, studies led by University of Exeter Medical School, in collaboration with the Slovak Academy of Sciences, found that replenishing these levels through tiny doses of AP39 yielded significant benefits.
The work, supported by the Slovak Research and Development Agency and published in the Nitric Oxide Journal special edition on hydrogen sulfide, found that administration of AP39 to animals with high blood pressure significantly lowered heart rate, blood pressure and blood vessel stiffness.
Professor Matt Whiteman, of the University of Exeter Medical School, who led the study, said: “This research significantly adds to our growing body of evidence that hydrogen sulfide could hold the key to new and effective therapies in humans. We are still at an early stage, but so far the key to success appears to be getting hydrogen sulfide delivered to the right place inside cells and mimicking the way the body naturally produces this gas. The mechanism may be through blocking a calcium channel on the heart that regulates heartbeat, slowing it down. Clinically used drugs which also block this channel have similar effects, but more than 10 fold higher doses are required.”
The research team is now investigating the effects of AP39 in other models of heart and blood vessel disease, such as cardiac arrest and heart attacks.
Hydrogen sulfide (H2 S) is a colorless, flammable gas that has strong odor of rotten eggs. H2 S poisoning is a rarity, mainly observed in industrial settings. However, the deliberate mixture of household chemicals to create hydrogen sulfide is increasingly used as means of committing suicide, and these cases pose a potential risk for first responders. Emergency physicians must be aware of the presentation and management of hydrogen sulfide poisoning because rapid identification and treatment is essential for recovery.
Significant hydrogen sulfide poisoning usually occurs by inhalation. Local irritant effects, along with arrest of cellular respiration, may follow. Hydrogen sulfide forms a complex bond to the ferric moiety causing inhibition of mitochondrial cytochrome oxidase (iron-containing protein), thereby arresting aerobic metabolism in an effect similar to cyanide toxicity. Very high lipid solubility allows it to penetrate easily through biologic membranes.
As a cellular poison, hydrogen sulfide affects all organs, particularly the CNS and pulmonary system. The spectrum of illness depends on the concentration and duration of exposure, with concentration being more important than duration. High concentrations (>700 ppm or >975 mg/m3) have the potential to cause sudden death, theoretically due to hydrogen sulfide?s effect on the brainstem respiratory center.
The paper can be accessed online here: http://www.sciencedirect.com/science/article/pii/S1089860314005199
Hydrogen sulfide (H2S, CAS# 7783-06-4) is an extremely hazardous, toxic compound. It is a colourless, flammable gas that can be identified in relatively low concentrations, by a characteristic rotten egg odor. The gas occurs naturally in coal pits, sulfur springs, gas wells, and as a product of decaying sulfur-containing organic matter, particularly under low oxygen conditions. It is therefore commonly encountered in places such as sewers, sewage treatment plants (H2S is often called sewer gas), manure stockpiles, mines, hot springs, and the holds of fishing ships. Industrial sources of hydrogen sulfide include petroleum and natural gas extraction and refining, pulp and paper manufacturing, rayon textile production, leather tanning, chemical manufacturing and waste disposal.
Hydrogen sulfide has a very low odor threshold, with its smell being easily perceptible at concentrations well below 1 part per million (ppm) in air. The odor increases as the gas becomes more concentrated, with the strong rotten egg smell recognisable up to 30 ppm. Above this level, the gas is reported to have a sickeningly sweet odor up to around 100 ppm. However, at concentrations above 100 ppm, a person’s ability to detect the gas is affected by rapid temporary paralysis of the olfactory nerves in the nose, leading to a loss of the sense of smell. This means that the gas can be present at dangerously high concentrations, with no perceivable odor. Prolonged exposure to lower concentrations can also result in similar effects of olfactory fatigue. This unusual property of hydrogen sulfide makes it extremely dangerous to rely totally on the sense of smell to warn of the presence of the gas.
University of Exeter
Nitric Oxide: Biology and Chemistry