Suspended Animation by Nutchanok Vongswat

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SUSPENDED ANIMA THE SLOWING DOW PROCESS BY EXTER MEANS WITHOUT TERMINATION.”

ATION IS WN OF LIFE RNAL

SLO W I N

LIFE

When people typically think of suspended animation and life extension, they often get confused between suspended animation and the idea of cryonics. + In cryonics, a person is literally frozen using liquid nitrogen. The person technically dead. The cryonics proponents believe that, as technology develops, a frozen person cold be reanimated, or brought back to life. Some people have chosen to have their bodies frozen at the moment of death using cryonics with the idea that, decades or centuries from now, they could be reanimated and the cause of their death can be treated. I would say this is science fiction, expect that the freezing part has already happened, what hasnâ&#x20AC;&#x2122;t happened is that whole reviving and treating part in the future.

\\ THIS IS NOT CRYONICS

Suspended animation is the process of slowing metabolism and other activity associated with living through external means (such as applying cold) without causing death. This idea has led to all sorts of science fiction applications of suspended animation, the most common example is putting the idea of putting astronauts in suspended animation during space flights of incredibly long duration.

\\ INTRODUCTION

Suspended animation is an entirely different thing. Doctors are looking into the possibilities of placing a person in a state of suspended animation during certain surgical procedures to, in essence, buy time to fix things. Not only that, but there are also other ways to achieve suspened animation than simply making a body cold (such as hydrogen sulfide gas in the correct dosage which suspends that need for oxygen in the body). There has been researches in which animals were reanimated after being in a â&#x20AC;&#x153;technically deadâ&#x20AC;? state for three hours. This line of research is funded by the National Institutes of Health and other scientific organizations. +If suspended animation can be developed for use in trauma and other severe situations, it would have the potential to increase the survival rate from these procedures, thereby extending life. This line of research could have a variety of helpful applications, including sustaining the function of organs of critically ill people, Ichinose said. It may also be possible to use the finding for patients undergoing surgery. +This would be an advance, because anesthesia usually causes blood pressure to drop. Currently hypothermia is the only proven way to decrease metabolic rate and confer some protection when blood flow to the organs is impaired or purposely reduced. However, hypothermia has some adverse effects, including depressing cardiovascular functions and blood clotting. If we can figure out how hydrogen sulfide reduces metabolic rate without depressing myocardial function, we may be able to reduce metabolism and protect organs without using hypothermia.

\\ EXTENDING LIFE

> H E A R T R AT E DECREASED

> B R E AT H I N G R AT E DECREASED

CORE BODY T E M P E R AT U R E DECREASED

ACTIVITY LEVEL DECREASED

BLOOD PRESSURE NORMAL

SUSPENDED ANIMATION COULD CONVERT NEAR CERTAIN DEATH TO 90% SURVIVAL.

R E D U C E D I N M E TA B O L I C R AT E

Colorless

Gas

-76째F

213 K

BOILING P O I N T -60째C

-116째F

191 K

MELTING P O I N T -82째C

Flammable

Poisonous

CHEMICAL P R O P E R T I E S Acidic

PHYSICAL PROPERTIES

KEY INGREDIENT: HYDROGEN SULPHIDE

+ NAME

MOLECULAR FORMULA

HYDROGEN SULPHIDE

H2S

MOLECULAR MASS

34.08g mol^-1

DENSITY

0.001363g cm^-3

CAS NO.

UNIT

7783-06-4

YY9FVM7NSN

92.1째

Hydrogen sulfide is the chemical compound with the formula H2S. It is a colorless, very poisonous, flammable gas with the characteristic foul odor of rotten eggs at concentrations up to 100 parts per million. It often results from the bacterial breakdown of organic matter in the absence of oxygen, such as in swamps and sewers. It also occurs in volcanic gases, natural gas, and some well waters. The human body produces small amounts of H2 S and uses it as a signaling molecule. +Hydrogen sulfide is slightly heavier than air; a mixture of H2S and air is explosive. Hydrogen sulfide and oxygen burn with a blue flame to form sulfur dioxide (SO2) and water. In general, hydrogen sulfide acts as a reducing agent.

H2S

H2S H2S

HYDROGEN SULPHIDE IS ALSO PRODUCED BY SOME CELLS OF THE HUMAN BODY IN SMALL AMOUNTS AND HAS A NUMBER OFBIOLOGICAL SIGNALLING FUNCTIONS

\\ PRODUCTION

\\ OCCURRENCE

\\ TOXICITY

\\ FUNCTION IN THE BODY

Hydrogen sulfide is most commonly obtained by its separation from sour gas, which is natural gas with high content of H 2S. It can also be produced by reacting hydrogen gas with molten elemental sulfur at about 450Â°C. Hydrocarbons can replace hydrogen in this process. +Sulfate-reducing bacteria generate usable energy under low-oxygen conditions by using sulfates to oxidize organic compounds or hydrogen; this produces hydrogen sulfide as a waste product. +The standard lab prepartion is to gently heat ferrous sulfide (FeS) with a strong acid in a Kipp generator. FeS + 2HCl > FeCl 2 + H 2S. A less well-known and more convenient alternative is to react aluminium sulfide with water: 6 H 2O + Al 2S3 > 3H 2S + 2Al(OH)3 +This gas is also produced by heating sulfur with solid organic compounds and by reducing sulfurated organic compounds with hydrogen. Hydrogen sulfide is also a by product of some reactions and caution should be taken when production is likely as exposure can be fatal. Small amounts of hydrogen sulfide occur in crude petroleum, but natural gas can contain up to 90%. Volcanoes and some hot springs (as well as cold springs) emit some H 2S, where it probably arises via the hydrolysis of sulfide minerals. For example, MS + H 2O > MO + H 2S. +About 10% of total global emissions of H 2S is due to human activity. By far the largest industrial route to H 2S occurs in petroleum refineries: The hydrodesulfurization process liberates sulfur from petroleum by the action of hydrogen. The resulting H 2S is converted to elemental sulfur by partial combustion via the Claus process, which is a major source of elemental sulfur. Other anthropogenic sources of hydrogen sulfide include coke ovens, paper mills (using the sulfate method), and tanneries. H 2S arises from virtually anywhere where elemental sulfur comes in contact with organic material, especially at high temperatures. +Hydrogen sulfide can be present naturally in well water. In such cases, ozone is often used for its removal; an alternative method uses a filter with manganese dioxide. Both methods oxidize sulfides to much less toxic sulfates. Hydrogen sulfide is considered a broad-spectrum poison, meaning that it can poison several different systems in the body, although the nervous system is the most affected. The toxicity of H2S is comparable with that of hydrogen cyanide. It forms a complex bond with iron in the mitochondrial cytochrome enzymes, thus preventing cellular respiration. +Since hydrogen sulfide occurs naturally in the body, the environment and the gut, enzymes exist in the body capable of detoxifying it by oxidation to (harmless) sulfate. Hence, low levels of hydrogen sulfide may be tolerated indefinitely. At some threshold level, believed to average around 300â&#x20AC;&#x201C;350 ppm, the oxidative enzymes become overwhelmed. Many personal safety gas detectors, such as those used by utility, sewage and petrochemical workers, are set to alarm at as low as 5 to 10 ppm and to go into high alarm at 15 ppm. +An interesting diagnostic clue of extreme poisoning by H2S is the discoloration of copper coins in the pockets of the victim. Treatment involves immediate inhalation of amyl nitrite, injections of sodium nitrite, inhalation of pure oxygen, administration of bronchodilators to overcome eventual bronchospasm, and in some cases hyperbaric oxygen therapy (HBO). HBO therapy has anecdotal support and remains controversial. +Exposure to lower concentrations can result in eye irritation, a sore throat and cough, nausea, shortness of breath, and fluid in the lungs. These effects are believed to be due to the fact that hydrogen sulfide combines with alkali present in moist surface tissues to form sodium sulfide, a caustic. These symptoms usually go away in a few weeks. Long-term, low-level exposure may result in fatigue, loss of appetite, headaches, irritability, poor memory, and dizziness. Chronic exposure to low level H 2S (around 2 ppm) has been implicated in increased miscarriage and reproductive health issues among Russian and Finnish wood pulp workers, but the reports have not been replicated. Hydrogen sulfide is produced in small amounts by some cells of the mammalian body and has a number of biological signaling functions. (Only two other such gases are currently known: nitric oxide (NO) and carbon monoxide (CO)). The gas is produced from cysteine by the enzymes cystathionine beta-synthase and cystathionine gammalase. It acts as a relaxant of smooth muscle and as a vasodilator and is also active in the brain, where it increases the response of the NMDA receptor and facilitates long term potentiation, which is involved in the formation of memory. Eventually the gas is converted to sulfite in the mitochondria by thiosulfate reductase, and the sulfite is further oxidized to thiosulfate and sulfate by sulfite oxidase. The sulfates are excreted in the urine. +Due to its effects similar to nitric oxide, hydrogen sulfide is nrecognized as potentially protecting against cardiovascular disease. The cardioprotective role effect of garlic is caused by catabolism of the polysulfide group in allcin to H 2S, a reaction that could depend on reduction mediated by glutathione. +Though both nitric oxide and hydrogen sulfide have been shown to relax blood vessels, their mechanisms of action are different: while NO activates the enzyme guanylyl cyclase, H 2S activates ATP-sensitive potassium channel in smooth muscle cells. Researchers are not clear how the vessel-relaxing responsibilities are shared between nitric oxide and hydrogen sulfide. However, there exists some evidence to suggest that nitric oxide does most of the vessel relaxing work in large vessels and hydrogen sulfide is responsible for similar action in smaller blood vessels.

LOW DOSES OF HYDROGEN SULPHIDE, THE SEWER GAS, CAN SAFELY SLOW DOWN BOTH METABOLISM AND SOME CARDIOVASCULAR FUNCTION, PRODUCING A SUSPENDED ANIMATION LIKE STATE THAT INCLUDE A SUBSTANTIAL DECREASE IN HEART RATE WITHOUT A DROP IN BLOOD PRESSURE.

10 20 30 40 50

H 2 S INDUCES A SUSPENDED ANIMATION LIKE STATE IN MICE

00 60

+ Previous investigations into the effects of low-dose hydrogen sulfide showed that the gas could lower body temperature and metabolic rate and also improved survival of mice whose oxygen supply had been restricted. But since hypothermia itself cuts metabolic needs, it was unclear whether the reduced body temperature was responsible for the other observed effects. The current study was designed to investigate both that question and the effects of hydrogen sulfide inhalation on the cardiovascular system. +The researchers measured factors such as heart rate, blood pressure, body temperature, respiration and physical activity in normal mice exposed to low-dose (80 ppm) hydrogen sulfide for several hours. They analyzed cardiac function with electrocardiograms and echocardiography and measured blood gas levels. While some mice were studied at room temperature, others were kept in a warm environment about 98ยบ F to prevent their body temperatures from dropping. 70 80

THE MICE WERE PUT IN A CHAMBER FILLED WITH AIR LACED WITH 80 PA R T S P E R MILLION OF HYDROGEN SULPHIDE

MICE

Death isNâ&#x20AC;&#x2122;T caused by oxygen deprivation itself, but by a chain of damaging chemical reactions that are triggered by sharply dropping oxygen levels. Recent research has shown that hydrogen sulphide can induce a suspended animation like state where hydrogen sulfide takes the place of oxygen, preventing those deadly reactions from taking place. As a result, no chain reaction, no cell death. This suggests the possibility of inducing suspended animation-like states for medical applications in the future to prevent tissue damage; death in stroke or heart attack victims; preserve transplantable organs for longer; buy time for human trauma patients.

HYDROGEN SULPHIDE + OXYGEN > > >

WHAT WOULD HAPPEN? W E A L L N E E D O X Y G E N T O L I V E. I F Y O U DONâ&#x20AC;&#x2122;T GET IT FOR A FEW MINUTES YOU DIE. BUT SOMETHING ELSE IS GOING ON I N S I D E T H I S R AT. H E I S N â&#x20AC;&#x2122; T D E A D .

H2S + O2 = SUSPENDED ANIMATION

> > > > > > > > > >

> > > > > > > >

Hydrogen sulfide binds with iron in cytochrome enzymes, disrupting a critical step in a process called oxidative phosphorylation, in which oxygen is burned to produce energy in the form of a substance called ATP. By blocking oxygen from binding to the iron, hydrogen sulfide stops cellular respiration and energy production completely. When energy production is inhibited, body temperature and metabolic rate are severely reduced. Enzymes exist in the body that can detoxify hydrogen sulfide by oxidation to (harmless) sulfate. As a result, low levels of sulfide may be tolerated indefinitely. +When the oxygen levels are too low for respiration but high enough to allow metabolic activity, damage occurs because the cells continue to struggle to live. Under these conditions, seizures, cell death, coma and finally death can occur. However, decreasing the oxygen levels significantly stops all metabolic activity and the animals enter the state of suspended animation.

THE EXPERIMENT

Many organisms respond to changes in environmental conditions by entering into a suspended animation–like state in which a decrease in metabolic rate (MR) is followed by a reduction in core body temperature (CBT). Regulated induction of a hypometabolic state is hypothesized to have great medical benefit for a variety of conditions, including ischemia and reperfusion injury, pyrexia, and other trauma. Suspended animation–like states may also be useful for creating beneficial hypothermia in surgical situations and for improving organ preservation

\\ THE EXPERIMENT

> > >

CORE BODY T E M P E R AT U R E ( ° C )

TIME (HOURS)

> > >

2:00

04:00

06:00 END OF EXPOSURE

C O N T R O L AT M O S P H E R E

A M B I E N T T E M P E R AT U R E

CARBON DIOXIDE PRODUCTION

OXYGEN CONSUMPTION

-5 MINUTES

+5 MINUTES

+6 MINUTES

+1 HOUR RECOVERY

08:00

Inhibiting oxidative phosphorylation reversibly induces the states of profound hypometabolism in several model organisms. Because hydrogen sulfide (H2S) is a specific, potent, and reversible inhibitor of complex IV (cytochrome c oxidase), the terminal enzyme complex in the electron transport chain, we hypothesized that it could reduce MR and CBT in mammals. +When mice were exposed to 80 ppm of H2 S, their oxygen (O2) consumption dropped by 50% and their carbon dioxide (CO2) output dropped by 60% within the first 5 minutes. If left in this environment for 6 hours, their MR dropped by 90%. The MR of control mice, as judged from O2 consumption and CO2 output increases. This drop in MR was followed by a drop in CBT to 2°C above ambient temperature. The average CBT of these mice reached a minimum of 15°C in an ambient temperature of 13°C. At this minimum CBT, both CO2 output and O2 consumption was 10% of normal, and the breathing rate of the mice decreased from 120 breaths per minute (BPM) to less than 10 BPM. After 6 hours of exposure to H 2 S, the mice were returned to room air and temperature, and their MR and CBT returned to normal +Exposing mice to varying concentrations of H2 S revealed a linear relationship between the concentration of H2S and CBT. CBT dropped faster and reached lower temperatures as concentrations of H2 S increased from 0 to 80 ppm, suggesting that the effects of H2S are concentration-dependent. However, this MR reduction is not dependent on ambient temperature. +Because H2S can be toxic in high doses, we conducted behavioral and functional tests, selected from the SHIRPA protocol, to assay for H2S induced damage. No behavioral or functional differences in the mice were detected after exposure to 80 ppm of H2S for 6 hours. In the absence of H2S, no effect on CBT was observed. In addition, others report no long-term health effects with these H2S concentrations. +The sequential drop in MR and CBT observed in mice exposed to 80 ppm of H2S is similar to that observed when animals initiate hibernation, daily torpor, or estivation. On-demand induction of a suspended animation–like state could provide insight into the mechanisms that govern natural states of reduced metabolism. Lowering metabolic demand in this way could be used to reduce physiological damage resulting from trauma and might improve outcomes after surgery.

\\ THE EXPERIMENT

CORE BODY TEMPERATURE (째C) >>> 55

H2S CONCENTRATION (ppm)

>>>

THEIR BREATHING RATE FELL FROM 120 BREATHS PER MINUTE TO ONLY 25 BREATHS PER MINUTE.

80°

> > >

70°

60°

50°

40° 37° > >

30° > > >

20° H E A R T R AT E >

B R E AT H I N G R AT E >

T E M P E R AT U R E

11°

10°

00°

100 HPM >

ASTONISHING DROP THEIR METABOLIC RATE DROPPED BY 90% B R E AT H I N G

100 > 040 HPM

120 > 25 BPM

T E M P E R AT U R E

040 HPM

CORE BODY TEMPERATURE

37°C >

H E A R T R AT E

HEART RATE

11°C

37°C > 11°C

120 BPM >

025 BPM

100 R E G U L A R H E A R T B E AT PER MINUTE

040 H E A R T B E AT A F T E R H2 S I S I N D U C E D

BREATHING RATE

The mice stopped moving and appeared to lose consciousness within minutes of breathing the air and H2 S mixture. The animals’ heart rate dropped nearly 50 percent, from 100 beats per minute to 040 beats per minute during hydrogen sulfide administration, but there was no significant change in blood pressure or the strength of the heart beat. While respiration rate also decreased from 120 breaths to 25 breaths per minute, there were no changes in blood oxygen levels, suggesting that vital organs were not at risk of oxygen starvation. +During exposure their metabolic rates dropped by an astonishing 90%, and their core body temperatures fell from 37°C to as low as 11°C. +The mice kept at room temperature had the same drop in body temperature seen in earlier studies, but those in the warm environment maintained normal core body temperatures. The same metabolic and cardiovascular changes were seen in both groups, indicating that they did not depend on the reduced body temperature, and analyzing the timing of those changes showed that metabolic reduction actually began before body temperature dropped. +The mice were kept in this condition for six hours. When they were revived, they were tested to see if suspended animation had any effects on their behavior or their brain function. It did not, and all the mice were perfectly normal.

THE MICE WERE KEPT IN THIS CONDITION FOR SIX HOURS. WHEN THEY WERE REVIVED, THEY WERE TESTED TO SEE IF SUSPENDED ANIMATION HAD ANY EFFECTS

SIX HOURS. AFTER THE MICE RETURNED BREATHING FRESH NORMAL AIR, THEY QUICKLY RETURNED TO NORMAL.

STOKES

CANCER THERAPY

ORGANS P R E S E R VAT I O N

T R A U M A PAT I E N T S

H E A R T AT TA C K

FUTURE

Squirrels, bears, snakes and many other animals hibernate naturally, some more deeply than others. Humans have been known to hibernate by accident. A Norwegian skier was rescued in 1999 after being submerged in icy water for more than an hour. She had no heartbeat and her core body temperature was 57°F (normal is 98.6). She recovered. Canadian toddler Erika Nordby wandered outside at night and nearly froze to death in 2001. She wore only a diaper and T-shirt. It was minus 11°F (-24 Celsius). When found, her heart had stopped beating for two hours and her body temperature was 61°F. She suffered severe frostbite but required no amputations and otherwise recovered. +“Understanding the connections between random instances of seemingly miraculous, unexplained survival in so called clinically dead humans and our ability to in-duce - and reverse - metabolic quiescence in model organisms could have dramatic implications for medical care,” Roth said. “In the end I suspect there will be clinical benefits and it will change the way medicine is practiced, because we will, in short, be able to buy patients time.”

EXTENDS LIFE

I+In extreme doses, the hydrogen sulfide is thought to bind to cells in place of oxygen to shut down the organism’s metabolism. Upon breathing normal air again, the mice “quickly regained normal function and metabolic activity with no long-term negative effects,” the researchers report. They plan on to test the technique on larger mammals next. Doctors are looking into the possibilities of placing a person in a state of suspended animation during certain surgical procedures to buy time to fix things. +There are also other ways to achieve suspended animation than simply making a body cold (such as hydrogen sulfide gas in the correct dosage which suspends that need for oxygen in the body). There has been research in which animals were revived after being in a “technically dead” state for three hours. This line of research is funded by the National Institutes of Health and other scientific organizations. If suspended animation can be developed for use in trauma and other situations, it would have the potential to increase the survival rate from these procedures, and hence extending life.

A GAS PROVEN DEADLY IN CHEMICAL WEAPONS COULD ONE DAY BE USED TO PUT PEOPLE INTO LIFE-SAVING SUSPENDED ANIMATION.

Already there are companies that will gladly freeze the dead in hopes some way of curing and reviving them might develop in the future. The field is called cryonics. So far, no one has been brought back. The trick with the mice did not require any freezing. Instead, the rodents breathed air laced with hydrogen sulfide, a chemical produced naturally in the bodies of humans and other animals. Within minutes, the mice stopped moving and soon their cell functions approached total inactivity. +Humans use hydrogen sulfide to “buffer our metabolic flexibility,” Roth explained. “It’s what allows our core temperature to stay at 98.6 degrees, regardless of whether we’re in Alaska or Tahiti.” This line of research could have a variety of helpful applications, including sustaining the function of organs of critically ill people, Ichinose said. It may also be possible to use the finding for patients undergoing surgery. This would be an advance, because anesthesia usually causes blood pressure to drop as well. +“Currently, hypothermia is the only proven way to decrease metabolic rate and confer some protection when blood flow to the o-r gans is impaired or intentionally reduced, such

SURGERY PATIENTS

as during reduced, such as during complex cardiac surgery,” Ichinose said. “However, hypothermia has some adverse effects, including depressing cardiovascular functions and blood clotting. If we can figure out how hydrogen sulfide reduces metabolic rate without depressing myocardial function, we may be able to reduce metabolism and protect organs without using hypothermia.” +One caveat to this research so far is that hydrogen sulfide might produce this result in mice and other naturally hibernating species much more readily than other species, including humans, Ichinose said. The researchers intend to extend the study to bigger animals, such as sheep and pigs to see if they have the same cardiac and hemodynamic reaction. “If the same thing happens in those species that would be much more interesting,” Ichinose said. +Reduced levels of oxygen supply specifically, can be a major cause of cellularand tissue damage in donor organs and in the bodies of individuals that have suffered severe blood loss or blood flow obstruction in such cases as heart attacks or strokes. In cases such as these, restoring an adequate oxygen supply is not always easy.

+In addition, exposure to hydrogen sulfide may improve cancer treatment by allowing patients to tolerate higher radiation doses without damaging healthy cells. Cancer cells aren’t dependent on oxygen to grow and are therefore more resistant to radiation than surrounding healthy cells, which need oxygen to live. Roth hypothesizes that temporarily reducing oxygen consumption in healthy cells could make them a less-vulnerable target for radiation and chemotherapy and thus spare normal tissue during high-dose cancer therapy. +This work could also be used to put astronauts in suspended animation on long space flights thereby decreasing the need for food and oxygen. +It is difficult to overstate the impact these techniques could have on health care, particularly in the treatment of patients with severe injuries. Be they from car crashes, falls, exposure, or work-related incidents, accidents are the fifth-leading cause of death in America and the number one killer of people under age 44, resulting in more than 49,000 deaths a year.

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COLOPHON DESIGNER

Nutchanok Vongswat CLASS

INSTRUCTOR

SEMESTER

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Spring 2011

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