suspended animation

RESUME

> > T H E S T U D Y O F S U S P E N D E D A N I M A T I O N

100

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AL

L R

IGH

T R

ES

ER

VE

D

NO

PA

RT

OF

TH

IS B

OO

K M

AY

BE

US

ED

OR

RE

PR

O-

DU

CE

D I

N A

NY

FO

RM

OR

BY

AN

Y E

LE

CT

RO

NIC

OR

M

EC

HA

NIC

AL

M

EA

NS

, IN

CL

UD

ING

IN

FO

RM

AT

ION

S

TO

RA

GE

A

ND

R

ET

RIE

VA

L

SY

ST

EM

S,

WIT

H-

OU

T P

ER

MIS

SIO

N I

N W

RIT

ING

FR

OM

TH

E C

OP

Y-

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HT

OW

NE

RS

, E

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EP

T B

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PR

INT

ED

IN

US

A

SUSPENDED ANIMATION IS THE SLOWING DOWN OF LIFE PROCESS BY EXTERNAL MEANS WITHOUT TERMINATION.”

“

SUSPENDED ANIMATION IS THE SLOWING DOWN OF LIFE PROCESS BY EXTERNAL MEANS WITHOUT TERMINATION.”

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+

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+

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+

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SLO W I N G

LIFE

> > > > > > > > > >

> > >

\\

IN

TR

OD

UC

TIO

N

Sus

pen

ded

an

imat

ion

is

the

pro

cess

of

slow

ing

met

abol

ism

and

oth

er a

ctiv

ity

asso

ciat

ed w

ith

liv-

ing

thro

ugh

exte

rnal

mea

ns (

such

as

appl

ying

col

d)

wit

hout

cau

sing

dea

th. T

his

idea

has

led

to a

ll so

rts

of s

cien

ce f

icti

on a

pplic

atio

ns o

f su

spen

ded

anim

a-ti

on,

the

mos

t co

mm

on e

xam

ple

is p

utti

ng t

he i

dea

of p

utti

ng a

stro

naut

s in

sus

pend

ed a

nim

atio

n du

r-in

g sp

ace

flig

hts

of in

cred

ibly

long

dur

atio

n.

>

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TH

IS I

S N

OT

CR

YO

NIC

S

Whe

n pe

ople

typ

ical

ly t

hink

of

susp

ende

d an

imat

ion

and

life

exte

nsio

n, t

hey

ofte

n ge

t co

nfus

ed b

etw

een

susp

ende

d an

imat

ion

and

the

idea

of

cryo

nics

. +

In c

ryon

ics,

a p

erso

n is

lite

rally

fro

zen

usin

g liq

uid

nitr

ogen

. The

per

son

tech

nica

lly d

ead.

The

cry

onic

s pr

opon

ents

bel

ieve

tha

t, a

s te

chno

logy

dev

elop

s, a

fr

ozen

per

son

cold

be

rean

imat

ed, o

r br

ough

t ba

ck

to li

fe. S

ome

peop

le h

ave

chos

en t

o ha

ve t

heir

bod

ies

froz

en a

t th

e m

omen

t of

dea

th u

sing

cry

onic

s w

ith

the

idea

tha

t, d

ecad

es o

r ce

ntur

ies

from

now

, the

y co

uld

be r

eani

mat

ed a

nd t

he c

ause

of

thei

r de

ath

can

be t

reat

ed. I

wou

ld s

ay t

his

is s

cien

ce f

icti

on,

expe

ct t

hat

the

free

zing

par

t ha

s al

read

y ha

ppen

ed,

wha

t ha

sn’t

hap

pene

d is

tha

t w

hole

rev

ivin

g a

nd

trea

ting

par

t in

the

fut

ure.

\\

EX

TE

ND

ING

LIF

E

Sus

pend

ed a

nim

atio

n is

an

enti

rely

dif

fere

nt t

hing

. D

octo

rs a

re lo

okin

g in

to t

he p

ossi

bilit

ies

of p

laci

ng

a pe

rson

in a

sta

te o

f su

spen

ded

anim

atio

n du

ring

ce

rtai

n su

rgic

al p

roce

dure

s to

, in

esse

nce,

buy

tim

e to

fix

thi

ngs.

Not

onl

y th

at, b

ut t

here

are

als

o ot

her

way

s to

ach

ieve

sus

pene

d an

imat

ion

than

sim

ply

mak

ing

a bo

dy c

old

(suc

h as

hyd

roge

n su

lfid

e ga

s in

th

e co

rrec

t do

sag

e w

hich

sus

pend

s th

at n

eed

for

oxyg

en in

the

bod

y). T

here

has

bee

n re

sear

ches

in

whi

ch a

nim

als

wer

e re

anim

ated

aft

er b

eing

in

a “t

echn

ical

ly d

ead”

sta

te f

or t

hree

hou

rs. T

his

line

of

rese

arch

is f

unde

d by

the

Nat

iona

l Ins

titu

tes

of H

ealt

h an

d ot

her

scie

ntif

ic o

rgan

izat

ions

.

+

If s

uspe

nded

an

imat

ion

can

be d

evel

oped

for

use

in

trau

ma

and

othe

r se

vere

sit

uati

ons,

it

wou

ld h

ave

the

pote

n-ti

al

to

incr

ease

th

e su

rviv

al

rate

fr

om

thes

e pr

oced

ures

, th

ereb

y ex

tend

ing

lif

e. T

his

line

of

rese

arch

cou

ld h

ave

a va

riet

y of

hel

pful

app

lica-

tion

s, i

nclu

ding

su

stai

ning

th

e fu

ncti

on o

f or

gans

of

cri

tica

lly i

ll pe

ople

, Ic

hino

se s

aid.

It

may

als

o be

po

ssib

le t

o us

e th

e fi

ndin

g fo

r pa

tien

ts u

nder

goin

g su

rger

y.

+

This

wou

ld b

e an

adv

ance

, be

caus

e an

esth

esia

usu

ally

cau

ses

bloo

d pr

essu

re t

o dr

op.

Cur

rent

ly h

ypot

herm

ia i

s th

e on

ly p

rove

n w

ay t

o de

crea

se m

etab

olic

rat

e an

d co

nfer

som

e pr

otec

-ti

on w

hen

bloo

d fl

ow t

o th

e or

gans

is

impa

ired

or

purp

osel

y re

duce

d. H

owev

er, h

ypot

herm

ia h

as s

ome

adve

rse

effe

cts,

incl

udin

g de

pres

sing

car

diov

ascu

-la

r fu

ncti

ons

and

bloo

d cl

otti

ng. I

f w

e ca

n fi

gure

out

ho

w h

ydro

gen

sulf

ide

redu

ces

met

abol

ic r

ate

wit

h-ou

t de

pres

sing

myo

card

ial f

unct

ion,

we

may

be

able

to

red

uce

met

abol

ism

and

pro

tect

org

ans

wit

hout

us

ing

hypo

ther

mia

.

H E A R T R A T E D E C R E A S E D

B R E A T H I N G R A T E

D E C R E A S E D

C O R E B O D Y T E M P E R A T U R E

D E C R E A S E D

A C T I V I T Y L E V E L

D E C R E A S E D

B L O O D P R E S S U R E

N O R M A L

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R E D U C E D I N M E T A B O L I C R A T E

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

PH

YS

ICA

L P

RO

PE

RT

IES

ME

LT

ING

P

OIN

T

CH

EM

ICA

L P

RO

PE

RT

IES

BO

ILIN

G

PO

INT

Ga

s

Ac

idic

-82

°C

-60

°C

Co

lor

les

s

Po

iso

no

us

Fla

mm

ab

le

19

1 K

21

3 K

-11

6°

F

-76

°F

N A M E

HYDROGEN SULPHIDE

D E N S I T Y

C A S N O . U N I T

7783-06-4 YY9FVM7NSN

S

H H

M O L E C U L A R F O R M U L A M O L E C U L A R M A S S

34.08g mol^-1

92.1°0.001363g cm^-3

KEY INGREDIENT: HYDROGEN SULPHIDE

Hydrogen sulfide is the chemical compound with the formula H S. It is a color-less, 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 H S and uses it as a signaling molecule. +Hydrogen sulfide is slightly heavier than air; a mixture of H S and air is explosive. Hydrogen sulfide and oxygen burn with a blue flame to form sulfur dioxide (SO ) and water. In general, hydrogen sulfide acts as a reducing agent.

2

2

2

2

H S

H S2

2

+

+

+

+

+

+

+

+

HY

DR

OG

EN

S

ULP

HID

E IS

ALS

O

PR

OD

UC

ED

B

Y S

OM

E

CE

LLS

OF

T

HE

HU

MA

N

BO

DY

IN

S

MA

LL

AM

OU

NT

S

AN

D H

AS

A

NU

MB

ER

O

FB

IOLO

GIC

AL

SIG

NA

LLIN

G

FU

NC

TIO

NS

H S2 H S2 H S2

Hydrogen sulfide is most commonly obtained by its separation from sour gas, which is natural gas with high content of H S. It can also be produced by reacting hydrogen gas with molten elemental sulfur at about 450°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 + H S. A less well-known and more convenient alternative is to react aluminium sulfide with water: 6 H O + Al S > 3H S + 2Al(OH) +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 S, where it probably arises via the hydrolysis of sulfide minerals. For example, MS + H O > MO + H S. +About 10% of total global emissions of H S is due to human activity. By far the largest industrial route to H S occurs in petroleum refineries: The hydrodesulfurization process liberates sulfur from petroleum by the action of hydrogen. The resulting H S 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 S arises from vir- tually 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 H S 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 300–350 ppm, the oxidative enzymes become overwhelmed. Many personal safety gas detectors, such as those used by utility, sewage and petroche- mical 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 H S 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 S (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 S, a reac- tion 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 S 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.

\ \ P R O D U C T I O N

\ \ T O X I C I T Y

\ \ O C C U R R E N C E

\ \ F U N C T I O N I N T H E B O D Y

22 2

22

2

2

2

2

2

2

2

2 2 23 3

2 2

2

LOW

DO

SE

S O

F H

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ULP

HID

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TH

E S

EW

ER

GA

S,

CA

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ELY

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OW

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ETA

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ND

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NC

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N,

PR

OD

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US

PEN

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MA

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STA

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HA

T IN

CLU

DE

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UB

STA

NTI

AL

DEC

REA

SE

IN H

EAR

T R

ATE

WIT

HO

UT

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P IN

BLO

OD

PR

ESS

UR

E.

H

S I

ND

UC

ES

A

SU

SP

EN

DE

D A

NIM

AT

ION

LI

KE

STA

TE

IN

MIC

E

2

+ + + + + + + +

MICE

0 0 1 0 2 0 3 0 4 0 5 0 6 0

+ + + + + + + +

MICE

Pre

viou

s in

vest

igat

ions

int

o th

e ef

fect

s of

low

-dos

e hy

drog

en s

ulfi

de s

how

ed

that

the

gas

cou

ld l

ower

bod

y te

mpe

ratu

re a

nd m

etab

olic

rat

e an

d al

so i

m-

prov

ed s

urvi

val

of m

ice

who

se o

xyge

n su

pply

had

bee

n re

stri

cted

. But

sin

ce

hypo

ther

mia

its

elf

cuts

met

abol

ic n

eeds

, it

was

unc

lear

whe

ther

the

red

uced

bo

dy t

empe

ratu

re w

as r

espo

nsib

le f

or t

he o

ther

obs

erve

d ef

fect

s. T

he c

urre

nt

stud

y w

as d

esig

ned

to i

nves

tig

ate

both

tha

t qu

esti

on a

nd t

he e

ffec

ts o

f hy

drog

en s

ulfid

e in

hala

tion

on

the

card

iova

scul

ar s

yste

m.

+Th

e re

sear

cher

s m

easu

red

fact

ors

such

as

hear

t ra

te,

bloo

d pr

essu

re,

body

tem

pera

ture

, re

spir

atio

n an

d ph

ysic

al a

ctiv

ity

in n

orm

al m

ice

expo

sed

to lo

w-d

ose

(80

ppm

) hy

drog

en s

ulfi

de f

or s

ever

al h

ours

. The

y an

alyz

ed c

ardi

ac f

unct

ion

wit

h el

ectr

o-ca

rdio

gram

s an

d ec

hoca

rdio

grap

hy a

nd m

easu

red

bloo

d ga

s le

vels

. Whi

le s

ome

mic

e w

ere

stud

ied

at r

oom

tem

pera

ture

, oth

ers

wer

e ke

pt in

a w

arm

env

iron

men

t ab

out

98º

F to

pre

vent

the

ir b

ody

tem

pera

ture

s fr

om d

ropp

ing.

T H E M I C E W E R E P U T I N

A C H A M B E R F I L L E D W I T H

A I R L A C E D W I T H 8 0

P A R T S P E R M I L L I O N O F

H Y D R O G E N S U L P H I D E

7 0 8 0

Dea

th i

sN

’T c

au

sed

by

ox

ygen

de-

p

riv

ati

on

its

elf,

bu

t b

y a

ch

ain

of

da

ma

gin

g c

hem

ica

l r

eac

tio

ns

th

at

ar

e tr

igg

ered

by

sh

ar

ply

dr

op

pin

g

ox

yg

en

le

ve

ls.

Re

ce

nt

re

se

ar

ch

h

as

sh

ow

n t

hat

hyd

ro

gen

su

lph

ide

ca

n i

nd

uc

e a

su

sp

end

ed a

nim

ati

on

li

ke s

tate

wh

ere

hyd

ro

gen

su

lfid

e ta

kes

th

e p

lac

e o

f o

xyg

en, p

rev

en-

tin

g t

ho

se

dea

dly

rea

cti

on

s f

ro

m

tak

ing

pla

ce.

As

a r

esu

lt,

no

ch

ain

r

eac

tio

n,

no

cel

l d

eath

. Th

is s

ug

- g

es

ts

th

e p

os

sib

ilit

y o

f in

du

cin

g

su

sp

en

de

d a

nim

at

ion

-lik

e s

tat

es

fo

r m

edic

al

ap

pli

ca

tio

ns

in t

he

fu-

tu

re

to

pr

ev

en

t t

iss

ue

da

ma

ge

; d

eath

in

str

ok

e o

r h

ear

t a

tta

ck

vic

tim

s;

pr

eser

ve

tra

ns

pla

nta

ble

o

rg

an

s f

or

lo

ng

er;

bu

y ti

me

for

h

um

an

tr

au

ma

pa

tien

ts.

HYDROGEN SULPHIDE+ OXYGENW H A T W O U L D H A P P E N ?

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.

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 D O N ’ T G E T I T F O R A F E W M I N U T E S Y O U D I E . B U T S O M E T H I N G E L S E I S G O I N G O N I N S I D E T H I S R AT. H E I S N ’ T D E A D .

H2S + O2 = SUSPENDED ANIMATION

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TH

E E

XP

ER

IME

NT

Man

y or

gani

sms

resp

ond

to c

hang

es in

env

iron

men

tal c

on-

diti

ons

by e

nter

ing

into

a s

uspe

nded

ani

mat

ion–

like

stat

e in

w

hich

a d

ecre

ase

in m

etab

olic

rat

e (M

R)

is f

ollo

wed

by

a re

duct

ion

in c

ore

body

tem

pera

ture

(C

BT)

. Reg

ulat

ed in

- du

ctio

n of

a h

ypom

etab

olic

sta

te i

s hy

poth

esiz

ed t

o ha

ve

grea

t m

edic

al b

enef

it f

or a

var

iety

of

cond

itio

ns,

incl

udin

g is

chem

ia a

nd r

eper

fusi

on in

jury

, pyr

exia

, and

oth

er t

raum

a.

Sus

pend

ed a

nim

atio

n–lik

e st

ates

may

als

o be

use

ful

for

crea

ting

ben

efic

ial h

ypot

herm

ia in

sur

gic

al s

itua

tion

s an

d fo

r im

prov

ing

orga

n pr

eser

vati

on

2 : 0 0 0 4 : 0 0 0 6 : 0 0

TH

E

EX

PE

RI-

ME

NT

E N D O F E X P O S U R E

C O R E B O D Y T E M P E R A T U R E ( ° C )

> > >

> > >

T I M E ( H O U R S )

4 0

3 5

2 0

1 5

1 0

0 5

0 0

\\

TH

E E

XP

ER

IME

NT

0 8 : 0 0

- 5 M I N U T E S

+ 5 M I N U T E S

+ 6 M I N U T E S

+ 1 H O U R R E C O V E R Y

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

C A R B O N D I O X I D E P R O D U C T I O N

O X Y G E N C O N S U M P T I O N

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

Inhi

biti

ng o

xida

tive

pho

spho

ryla

tion

rev

ersi

bly

indu

ces

the

stat

es o

f pr

ofou

nd h

ypom

etab

olis

m in

sev

eral

mod

el o

rgan

-is

ms.

Bec

ause

hyd

roge

n su

lfid

e (H

2S) i

s a

spec

ific

, pot

ent,

an

d re

vers

ible

inhi

bito

r of

com

plex

IV

(cy

toch

rom

e c

oxi-

dase

), t

he t

erm

inal

enz

yme

com

plex

in t

he e

lect

ron

tran

s-po

rt c

hain

, we

hypo

thes

ized

tha

t it

cou

ld r

educ

e M

R a

nd C

BT

in m

amm

als.

+

Whe

n m

ice

wer

e ex

pose

d to

80

ppm

of

H S

, th

eir

oxyg

en (

O2)

con

sum

ptio

n dr

oppe

d by

50%

and

th

eir

carb

on d

ioxi

de (

CO

2) o

utpu

t dr

oppe

d by

60%

wit

hin

the

firs

t 5

min

utes

. If

left

in

this

env

iron

men

t fo

r 6

hour

s,

thei

r M

R d

ropp

ed b

y 90

%. T

he M

R o

f co

ntro

l mic

e, a

s ju

dged

fr

om O

2 co

nsum

ptio

n an

d C

O2

outp

ut in

crea

ses.

Thi

s dr

op

in M

R w

as f

ollo

wed

by

a dr

op i

n C

BT

to 2

°C a

bove

am

bien

t te

mpe

ratu

re.

The

aver

age

CB

T of

the

se m

ice

reac

hed

a m

inim

um o

f 15

°C i

n an

am

bien

t te

mpe

ratu

re o

f 13

°C.

At

this

min

imum

CB

T, b

oth

CO

ou

tput

and

O

cons

umpt

ion

was

10%

of

norm

al,

and

the

brea

thin

g ra

te o

f th

e m

ice

de-

crea

sed

from

120

bre

aths

per

min

ute

(BP

M)

to l

ess

than

10

BP

M. A

fter

6 h

ours

of

expo

sure

to

H

S, t

he m

ice

wer

e re

turn

ed t

o ro

om a

ir a

nd t

empe

ratu

re, a

nd t

heir

MR

and

CB

T re

turn

ed t

o no

rmal

+

Expo

sing

mic

e to

var

ying

con

cen-

tr

atio

ns o

f H

S

rev

eale

d a

linea

r re

lati

onsh

ip b

etw

een

the

conc

entr

atio

n of

H

S a

nd C

BT.

CB

T dr

oppe

d fa

ster

and

re

ache

d lo

wer

tem

pera

ture

s as

con

cent

rati

ons

of H

S

in-

crea

sed

from

0 t

o 80

ppm

, sug

gest

ing

that

the

eff

ects

of

H S

are

con

cent

rati

on-d

epen

dent

. How

ever

, thi

s M

R r

educ

-ti

on is

not

dep

ende

nt o

n am

bien

t tem

pera

ture

.

+B

ecau

se

H S

can

be

toxi

c in

hig

h do

ses,

we

cond

ucte

d be

havi

oral

and

fu

ncti

onal

test

s, s

elec

ted

from

the

SH

IRPA

pro

toco

l, to

ass

ay

for

H S

ind

uced

dam

age.

No

beha

vior

al o

r fu

ncti

onal

dif

-fe

renc

es i

n th

e m

ice

wer

e de

tect

ed a

fter

exp

osur

e to

80

ppm

of

H S

for

6 h

ours

. In

the

abse

nce

of H

S, n

o ef

fect

on

CB

T w

as o

bser

ved.

In a

ddit

ion,

oth

ers

repo

rt n

o lo

ng-t

erm

he

alth

eff

ects

wit

h th

ese

H S

con

cent

rati

ons.

+

The

se-

quen

tial

dro

p in

MR

and

CB

T ob

serv

ed in

mic

e ex

pose

d to

80

ppm

of

H S

is s

imila

r to

tha

t ob

serv

ed w

hen

anim

als

init

iate

hi

bern

atio

n, d

aily

tor

por,

or

esti

vati

on. O

n-de

man

d in

duct

ion

of a

sus

pend

ed a

nim

atio

n–lik

e st

ate

coul

d pr

ovid

e in

sig

ht

into

the

mec

hani

sms

that

gov

ern

natu

ral s

tate

s of

red

uced

m

etab

olis

m. L

ower

ing

met

abol

ic d

eman

d in

thi

s w

ay c

ould

be

used

to

redu

ce p

hysi

olog

ical

dam

age

resu

ltin

g fr

om t

raum

a an

d m

ight

impr

ove

outc

omes

aft

er s

urge

ry.

2

22

2

22

2

2

2

2

2

2

2

2

3 02 01 00 0

0 5

1 0

1 5

2 0

2 5

3 0

3 5

4 0

4 5

5 0

5 5

H 2 S C O N C E N T R A T I O N ( p p m )

C O R E B O D Y T E M P E R A T U R E ( ° C )

> > >

>>

>

8 06 0 7 05 0

>>

>>

>>

>

>>

>

>

>

>>

>>

>>

>>

TH

EIR

BR

EA

TH

ING

RA

TE

FE

LL F

RO

M 1

20

BR

EA

TH

S

PE

R M

INU

TE

TO

ON

LY 2

5 B

RE

AT

HS

PE

R M

INU

TE

.

H E A R T R A T E


T E M P E R A T U R E

80°

60°

50°

40°

30°

20°

10°1 1 °

37°

00°

70°

80°

60°

50°

40°

30°

20°

10°1 1 °

00°

The mice stopped moving and appeared to lose conscious-ness within minutes of breathing the air and H S mixture. The animals’ heart rate dropped nearly 50 percent, from 100 beats per minute to 040 beats per minute during hy-drogen 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.

2

ASTO- NISHING DROP

RESULT

T H E I R M E T A B O L I C R A T E D R O P P E D B Y 9 0 %

H E A R T R A T E B R E A T H I N G T E M P E R A T U R E

1 0 0 > 0 4 0 H P M 1 2 0 > 2 5 B P M 3 7 ° C > 1 1 ° C

70°

>>

100

040

R E G U L A R H E A R T B E A T P E R M I N U T E

H E A R T B E A T A F T E R H S I S I N D U C E D2

H E A R T R A T E


C O R E B O D Y T E M P E R A T U R E

1 0 0 H P M>>

> 1 2 0 B P M

3 7 ° C

0 4 0 H P M

0 2 5 B P M

1 1 ° C

TH

E M

ICE

WE

RE

KE

PT

IN T

HIS

CO

ND

ITIO

N F

OR

S

IX H

OU

RS

. WH

EN

TH

EY

W

ER

E R

EV

IVE

D, T

HE

Y

WE

RE

TE

ST

ED

TO

SE

E

IF S

US

PE

ND

ED

AN

IMA

-T

ION

HA

D A

NY

EF

FE

CT

S

SIX

HO

UR

S. A

FT

ER

T

HE

MIC

E R

ET

UR

NE

D

BR

EA

TH

ING

FR

ES

H

NO

RM

AL

AIR

, TH

EY

Q

UIC

KLY

RE

TU

RN

ED

T

O N

OR

MA

L.

FUTURE

O R G A N S P R E S E R V A T I O N

S T O K E S

C A N C E R T H E R A P Y

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

H E A R T A T T A C K

Squ

irre

ls,

bear

s, s

nake

s an

d m

any

othe

r an

i-

mal

s hi

bern

ate

natu

rally

, so

me

mor

e de

eply

th

an o

ther

s. H

uman

s ha

ve b

een

know

n to

hi-

be

rnat

e by

acc

iden

t. A

Nor

weg

ian

skie

r w

as

resc

ued

in 1

999

afte

r be

ing

subm

erge

d in

icy

w

ater

for

mor

e th

an a

n ho

ur. S

he h

ad n

o he

art-

be

at a

nd h

er c

ore

body

tem

pera

ture

was

57°

F (n

orm

al is

98.

6). S

he r

ecov

ered

. Can

adia

n to

d-

dler

Eri

ka N

ordb

y w

ande

red

outs

ide

at n

ight

and

ne

arly

fro

ze t

o de

ath

in 2

00

1. S

he w

ore

only

a

diap

er a

nd T

-shi

rt. I

t w

as m

inus

11

°F (

-24

Cel

sius

). W

hen

foun

d, h

er h

eart

had

sto

pped

be

atin

g fo

r tw

o ho

urs

and

her

body

tem

pera

-tu

re w

as 6

1°F.

She

suf

fere

d se

vere

fro

stbi

te

but

requ

ired

no

ampu

tati

ons

and

othe

rwis

e re

cove

red.

+“U

nder

stan

ding

the

con

nec-

ti

ons

betw

een

rand

om i

nsta

nces

of

seem

ingl

y m

irac

ulou

s, u

nexp

lain

ed s

urvi

val

in s

o ca

lled

clin

ical

ly d

ead

hum

ans

and

our

abili

ty to

in-d

uce

- an

d re

vers

e -

met

abol

ic q

uies

cenc

e in

mod

el

orga

nism

s co

uld

have

dra

mat

ic i

mpl

icat

ions

fo

r m

edic

al

care

,” R

oth

said

. “I

n th

e en

d I

susp

ect

ther

e w

ill b

e cl

inic

al b

enef

its

and

it

will

cha

nge

the

way

med

icin

e is

pra

ctic

ed,

beca

use

we

will

, in

sh

ort,

be

able

to

bu

y pa

tien

ts t

ime.

”

I+In

ext

rem

e do

ses,

the

hyd

rog

en s

ulfi

de i

s th

ough

t to

bin

d to

cel

ls i

n pl

ace

of o

xyge

n to

sh

ut d

own

the

orga

nism

’s m

etab

olis

m.

Upo

n br

eath

ing

norm

al a

ir a

gain

, th

e m

ice

“qui

ckly

re

gain

ed n

orm

al f

unct

ion

and

met

abol

ic a

cti-

vi

ty w

ith

no l

ong-

term

neg

ativ

e ef

fect

s,”

the

rese

arch

ers

repo

rt. T

hey

plan

on

to t

est

the

tech

niqu

e on

la

rger

m

amm

als

next

. D

oc-

tors

are

loo

king

int

o th

e po

ssib

iliti

es o

f pl

ac-

ing

a pe

rson

in

a st

ate

of s

uspe

nded

ani

ma-

tion

du

ring

ce

rtai

n su

rgic

al

proc

edur

es

to

buy

tim

e to

fix

thin

gs.

+Th

ere

are

also

oth

er

way

s to

ach

ieve

sus

pend

ed a

nim

atio

n th

an

sim

ply

mak

ing

a bo

dy c

old

(suc

h as

hyd

roge

n su

lfid

e g

as i

n th

e co

rrec

t do

sag

e w

hich

sus

-pe

nds

that

nee

d fo

r ox

ygen

in t

he b

ody)

. The

re

has

been

res

earc

h in

whi

ch a

nim

als

wer

e re

-vi

ved

afte

r be

ing

in a

“te

chni

cally

dea

d” s

tate

fo

r th

ree

hour

s. T

his

line

of r

esea

rch

is f

unde

d by

the

Nat

iona

l In

stit

utes

of

Hea

lth

and

othe

r sc

ient

ific

org

aniz

atio

ns. I

f sus

pend

ed a

nim

atio

n ca

n be

dev

elop

ed fo

r us

e in

trau

ma

and

othe

r si

- tu

atio

ns, i

t w

ould

hav

e th

e po

tent

ial t

o in

crea

se

the

surv

ival

rat

e fr

om t

hese

pro

cedu

res,

and

he

nce

exte

ndin

g lif

e.

A G

AS

PR

OV

EN

DE

AD

LY I

N

CH

EM

ICA

L W

EA

PO

NS

CO

ULD

O

NE

DA

Y B

E U

SE

D T

O P

UT

P

EO

PLE

IN

TO

LIF

E-S

AV

ING

S

US

PE

ND

ED

AN

IMA

TIO

N.

EX

TE

ND

S L

IFE

Alr

eady

the

re a

re c

ompa

nies

tha

t w

ill g

ladl

y fr

eeze

the

dea

d in

hop

es s

ome

way

of

curi

ng

and

revi

ving

the

m m

ight

dev

elop

in t

he f

utur

e.

The

fiel

d is

cal

led

cryo

nics

. So

far,

no o

ne h

as

been

bro

ught

bac

k. T

he t

rick

wit

h th

e m

ice

did

not

requ

ire

any

free

zing

. In

stea

d, t

he r

oden

ts

brea

thed

air

lac

ed w

ith

hydr

ogen

sul

fide

, a

chem

ical

pro

duce

d na

tura

lly i

n th

e bo

dies

of

hum

ans

and

othe

r an

imal

s. W

ithi

n m

inut

es,

the

mic

e st

oppe

d m

ovin

g an

d so

on t

heir

cel

l fun

c-ti

ons

appr

oach

ed t

otal

inac

tivi

ty.

+H

uman

s us

e hy

drog

en s

ulfi

de t

o “b

uffe

r ou

r m

etab

olic

fl

exib

ility

,” R

oth

expl

aine

d. “

It’s

wha

t al

low

s ou

r co

re t

empe

ratu

re t

o st

ay a

t 98

.6 d

egre

es, r

e-

gar

dles

s of

whe

ther

we’

re in

Ala

ska

or T

ahit

i.”

This

lin

e of

res

earc

h co

uld

have

a v

arie

ty o

f he

lpfu

l ap

plic

atio

ns,

incl

udin

g su

stai

ning

the

fu

ncti

on o

f or

gans

of

crit

ical

ly i

ll pe

ople

, Ich

i-no

se s

aid.

It m

ay a

lso

be p

ossi

ble

to u

se t

he

find

ing

for

pati

ents

und

ergo

ing

surg

ery.

Thi

s w

ould

be

an a

dvan

ce, b

ecau

se a

nest

hesi

a us

- ua

lly c

ause

s bl

ood

pres

sure

to

drop

as

wel

l. +

“Cur

rent

ly,

hypo

ther

mia

is

the

only

pro

ven

way

to

decr

ease

met

abol

ic r

ate

and

conf

er

som

e pr

otec

tion

whe

n bl

ood

flow

to

the

o-r

gans

is im

pair

ed o

r in

tent

iona

lly r

educ

ed, s

uch

as d

urin

g r

educ

ed,

such

as

duri

ng c

ompl

ex

car

diac

sur

gery

,” Ic

hino

se s

aid.

“How

ever

, hyp

o-

ther

mia

has

som

e ad

vers

e ef

fect

s, i

nclu

ding

de

pres

sing

car

diov

ascu

lar

func

tion

s an

d bl

ood

clot

ting

. If

we

can

fig

ure

out

how

hyd

rog

en

sulf

ide

red

uces

met

abol

ic r

ate

wit

hout

de-

pr

essi

ng m

yoca

rdia

l fu

ncti

on, w

e m

ay b

e ab

le

to r

educ

e m

etab

olis

m a

nd p

rote

ct o

rgan

s w

ith-

ou

t us

ing

hypo

ther

mia

.”

+One

cav

eat

to t

his

rese

arch

so

far

is t

hat

hydr

ogen

sul

fide

mig

ht

prod

uce

this

res

ult

in m

ice

and

othe

r na

tura

lly

hibe

rnat

ing

spec

ies

muc

h m

ore

read

ily t

han

othe

r sp

ecie

s, in

clud

ing

hum

ans,

Ichi

nose

sai

d.

The

rese

arch

ers

inte

nd t

o ex

tend

the

stu

dy t

o bi

gger

ani

mal

s, s

uch

as s

heep

and

pig

s to

see

if

they

hav

e th

e sa

me

card

iac

and

hem

odyn

amic

re

acti

on. “

If t

he s

ame

thin

g h

appe

ns in

tho

se

spec

ies

that

wou

ld b

e m

uch

mor

e in

tere

st-

ing,

” Ic

hino

se s

aid.

+

Red

uced

leve

ls o

f ox

y-

gen

supp

ly s

pec

ific

ally

, can

be

a m

ajor

cau

se

of c

ellu

lara

nd t

issu

e da

mag

e in

don

or o

rgan

s an

d in

the

bod

ies

of i

ndiv

idua

ls t

hat

have

suf

- fe

red

seve

re

bloo

d lo

ss

or

bloo

d fl

ow

ob-

stru

ctio

n in

suc

h ca

ses

as h

eart

att

acks

or

stro

kes.

In c

ases

suc

h as

the

se, r

esto

ring

an

adeq

uate

oxy

gen

supp

ly is

not

alw

ays

easy

.

+In

add

itio

n, e

xpos

ure

to h

ydro

gen

sulf

ide

may

im

prov

e ca

ncer

tre

atm

ent

by a

llow

ing

pati

ents

to

tol

erat

e hi

gher

rad

iati

on d

oses

wit

hout

da-

m

agin

g he

alth

y ce

lls. C

ance

r ce

lls a

ren’

t dep

en-

dent

on

oxyg

en t

o g

row

and

are

the

refo

re

mor

e re

sist

ant

to r

adia

tion

tha

n su

rrou

ndin

g he

alth

y ce

lls,

whi

ch n

eed

oxyg

en t

o liv

e. R

oth

hypo

thes

izes

tha

t te

mpo

rari

ly r

educ

ing

oxyg

en

cons

umpt

ion

in h

ealt

hy c

ells

cou

ld m

ake

them

a

less

-vul

nera

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targ

et f

or r

adia

tion

and

che

- m

othe

rapy

and

thu

s sp

are

norm

al t

issu

e du

r-in

g hi

gh-d

ose

canc

er t

hera

py.

+Th

is w

ork

coul

d al

so b

e us

ed t

o pu

t as

tron

auts

in

sus-

pend

ed a

nim

atio

n on

long

spa

ce f

light

s th

ereb

y de

crea

sing

the

nee

d fo

r fo

od a

nd o

xyge

n.

+

It i

s di

ffic

ult

to o

vers

tate

the

im

pact

the

se

tech

niqu

es c

ould

hav

e on

hea

lth

care

, par

ticu

-la

rly

in t

he t

reat

men

t of

pat

ient

s w

ith

seve

re

inju

ries

. Be

they

fro

m c

ar c

rash

es, f

alls

, exp

o-su

re, o

r w

ork-

rela

ted

inci

dent

s, a

ccid

ents

are

th

e fi

fth-

lead

ing

caus

e of

dea

th in

Am

eric

a an

d th

e nu

mbe

r on

e ki

ller

of p

eopl

e un

der

age

44,

resu

ltin

g in

mor

e th

an 4

9,00

0 de

aths

a y

ear.

A G

AS

PR

OV

EN

DE

AD

LY I

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CH

EM

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L W

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CO

ULD

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DA

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D T

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P

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IN

TO

LIF

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AV

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US

PE

ND

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AN

IMA

TIO

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SU

RG

ER

Y P

AT

IEN

TS

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

9 8 9 H O W A R D S T . S A N F R A N C I S C O , C A 9 4 1 0 5

7 9 N E W M O N T G O M E R Y S T . S A N F R A N C I S C O , C A 9 4 1 0 5

H E A D L I N E N U M B E R S B O D Y T E X T

C A P T I O N

Typography 4 Ariel Grey Spring 2011

Nutchanok Vongswat

Staple Matte Photo Supreme (Double Sided)

Epson Stylus Photo R1900

California Office Service

Academy Of Art University

United Serif CarbonBlender Pro Blender Pro

C L A S S I N S T R U C T O R S E M E S T E R

D E S I G N E R

COLO- PHON

P A P E R

P R I N T E R

B I N D E R

S C H O O L

T Y P E F A C E

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