Editing Clinical death (section)

==Limits of reversal==

Most tissues and organs of the body can survive clinical death for considerable periods. Blood circulation can be stopped in the entire body below the heart for at least 30 minutes, with injury to the spinal cord being a limiting factor.<ref>{{cite journal
| last1 = Hazim J
| title = Effect of extended cross-clamp time during thoracoabdominal aortic aneurysm repair
| journal = The Annals of Thoracic Surgery
| volume = 66
| pages = 1204–08
| year = 1998
| publisher = The Society of Thoracic Surgeons
| doi = 10.1016/S0003-4975(98)00781-4
| pmid = 9800807
| first1 = HJ
| last2 = Winnerkvist
| first2 = A
| last3 = Miller Cc
| first3 = 3rd
| last4 = Iliopoulos
| first4 = DC
| last5 = Reardon
| first5 = MJ
| last6 = Espada
| first6 = R
| last7 = Baldwin
| first7 = JC
| issue = 4
| doi-access = free
}}</ref>  Detached limbs may be successfully reattached after 6 hours of no blood circulation at warm temperatures. Bone, tendon, and skin can survive as long as 8 to 12 hours.<ref>{{EMedicine|emerg|502|Replantation}}</ref>

The brain, however, appears to accumulate ischemic injury faster than any other organ. Without special treatment after circulation is restarted, full recovery of the brain after more than 3 minutes of clinical death at normal body temperature is rare.<ref>{{cite journal
| last1 = Safar P
| title = Cerebral resuscitation after cardiac arrest: a review
| journal = Circulation
| volume = 74
| pages = IV138–53
| year = 1986
| publisher = Lippincott Williams & Wilkins
| pmid=3536160
| first1 = P
| issue = 6 Pt 2
}}</ref><ref>{{cite journal
| last1 = Safar P
| title = Resuscitation from clinical death: pathophysiologic limits and therapeutic potentials
| journal = Critical Care Medicine
| volume = 16
| pages = 923–41
| year = 1988
| publisher = Lippincott Williams & Wilkins
| pmid=3048894
| doi = 10.1097/00003246-198810000-00003
| first1 = P
| issue = 10
| s2cid = 25384932
}}</ref>  Usually brain damage or later brain death results after longer intervals of clinical death even if the heart is restarted and blood circulation is successfully restored. Brain injury is therefore the chief limiting factor for recovery from clinical death.

Although loss of function is almost immediate, there is no specific duration of clinical death at which the non-functioning brain clearly dies. The most vulnerable cells in the brain, CA1 neurons of the [[hippocampus]], are fatally injured by as little as 10 minutes without oxygen.  However, the injured cells do not actually die until hours after resuscitation.<ref>{{cite journal
| last1 = Kirino T
| title = Delayed neuronal death
| journal = Neuropathology
| volume = 20
| pages = S95–97
| year = 2000
| pmid=11037198
| doi = 10.1046/j.1440-1789.2000.00306.x
| first1 = T| s2cid = 651613
}}</ref>  This delayed death can be prevented ''[[in vitro]]'' by a simple drug treatment even after 20 minutes without oxygen.<ref>{{cite journal
| last1 = Popovic R
| title = Anesthetics and mild hypothermia similarly prevent hippocampal neuron death in an in vitro model of cerebral ischemia
| journal = Anesthesiology
| volume = 92
| pages = 1343–49
| year = 2000
| publisher = Lippincott Williams & Wilkins
| pmid=10781280
| doi = 10.1097/00000542-200005000-00024
| first1 = R
| last2 = Liniger
| first2 = R
| last3 = Bickler
| first3 = PE
| issue = 5| s2cid = 18553131
| doi-access = free
}}</ref>  In other areas of the brain, viable human [[neurons]] have been recovered and grown in culture hours after clinical death.<ref>{{cite journal
| last1 = Kim SU
| title = Tissue culture of adult human neurons
| journal = Neuroscience Letters
| volume = 11
| pages = 137–41
| year = 1979
| publisher = Elsevier Scientific Publishers Ireland
| pmid=313541
| doi = 10.1016/0304-3940(79)90116-2
| first1 = SU
| last2 = Warren
| first2 = KG
| last3 = Kalia
| first3 = M
| issue = 2| s2cid = 42264136
|display-authors=etal}}</ref>  Brain failure after clinical death is now known to be due to a complex series of processes called [[reperfusion injury]] that occur ''after'' blood circulation has been restored, especially processes that interfere with blood circulation during the recovery period.<ref name="Crippen">{{cite web
| last = Crippen
| first = David
| title = Brain Failure and Brain Death: Introduction
| work = ACS Surgery Online, Critical Care, April 2005
| url= http://www.acssurgery.com/abstracts/acs/acs0812.htm
| access-date = 9 January 2007 |archive-url = https://web.archive.org/web/20071011024814/http://www.acssurgery.com/abstracts/acs/acs0812.htm <!-- Bot retrieved archive --> |archive-date = 11 October 2007}}</ref> Control of these processes is the subject of ongoing research.

In 1990, the laboratory of resuscitation pioneer [[Peter Safar]] discovered that reducing body temperature by three degrees Celsius after restarting blood circulation could double the time window of recovery from clinical death without brain damage from 5 minutes to 10 minutes. This [[induced hypothermia]] technique is beginning to be used in emergency medicine.<ref>{{cite journal
| last1 = Holzer M, Behringer W
| title = Therapeutic hypothermia after cardiac arrest
| journal = Current Opinion in Anesthesiology
| volume = 18
| pages = 163–68
| year = 2005
| publisher = Lippincott Williams & Wilkins
| pmid=16534333
| doi = 10.1097/01.aco.0000162835.33474.a9
| first1 = M
| last2 = Behringer
| first2 = W
| issue = 2
| s2cid = 6675084
}}</ref><ref>{{cite news
  | last = Davis
  | first = Robert
  | title = To treat cardiac arrest, doctors cool the body
  | newspaper = USA Today
  | date = 11 December 2006
  | url = https://www.usatoday.com/news/health/2006-12-10-body-cooling-cover_x.htm
  | access-date = 7 January 2007}}</ref>  The combination of mildly reducing body temperature, reducing blood cell concentration, and increasing blood pressure after resuscitation was found especially effective{{snd}}allowing for recovery of dogs after 12 minutes of clinical death at normal body temperature with practically no brain injury.<ref>{{cite journal
| last1 = Leonov Y
| title = Mild cerebral hypothermia during and after cardiac arrest improves neurologic outcome in dogs
| journal = Journal of Cerebral Blood Flow and Metabolism
| volume = 10
| pages = 57–70
| year = 1990
| publisher = Nature Pub. Group
| pmid=2298837
| first1 = Y
| last2 = Sterz
| first2 = F
| last3 = Safar
| first3 = P
| last4 = Radovsky
| first4 = A
| last5 = Oku
| first5 = K
| last6 = Tisherman
| first6 = S
| last7 = Stezoski
| first7 = SW
| issue = 1
| doi = 10.1038/jcbfm.1990.8
|display-authors=etal| doi-access = free
}}</ref><ref>{{cite journal
| last1 = Safar P
| title = Improved cerebral resuscitation from cardiac arrest in dogs with mild hypothermia plus blood flow promotion
| journal = Stroke
| volume = 27
| pages = 105–13
| year = 1996
| publisher = Lippincott Williams & Wilkins
| pmid=8553385
| first1 = P
| last2 = Xiao
| first2 = F
| last3 = Radovsky
| first3 = A
| last4 = Tanigawa
| first4 = K
| last5 = Ebmeyer
| first5 = U
| last6 = Bircher
| first6 = N
| last7 = Alexander
| first7 = H
| last8 = Stezoski
| first8 = SW
| issue = 1
| doi = 10.1161/01.STR.27.1.105
|display-authors=etal}}</ref>  The addition of a drug treatment protocol has been reported to allow recovery of dogs after 16 minutes of clinical death at normal body temperature with no lasting brain injury.<ref>{{cite journal
| last1 = Lemler J
| title = The arrest of biological time as a bridge to engineered negligible senescence
| journal = Annals of the New York Academy of Sciences
| volume = 1019
| issue = 1
| pages = 559–63
| year = 2004
| publisher = New York Academy of Sciences
| doi = 10.1196/annals.1297.104
| pmid = 15247086
| first1 = J
| last2 = Harris
| first2 = SB
| last3 = Platt
| first3 = C
| last4 = Huffman
| first4 = TM|display-authors=etal| bibcode = 2004NYASA1019..559L
| s2cid = 27635898
}}</ref>  Cooling treatment alone has permitted recovery after 17 minutes of clinical death at normal temperature, but with brain injury.<ref>{{cite journal
| last1 = Leonov Y
| title = Moderate hypothermia after cardiac arrest of 17 minutes in dogs. Effect on cerebral and cardiac outcome
| journal = Stroke
| volume = 21
| pages = 1600–06
| year = 1990
| publisher = Lippincott Williams & Wilkins
| pmid=2237954
| first1 = Y
| last2 = Sterz
| first2 = F
| last3 = Safar
| first3 = P
| last4 = Radovsky
| first4 = A
| issue = 11
| doi = 10.1161/01.STR.21.11.1600
|display-authors=etal| doi-access = free
}}</ref>

Under laboratory conditions at normal body temperature, the longest period of clinical death of a cat (after complete circulatory arrest) survived with eventual return of brain function is one hour.<ref>{{cite journal
| last1 = Hossmann KA
| title = Recovery of Neuronal Function after Prolonged Cerebral Ischemia
| journal = Science
| volume = 168
| pages = 375–76
| year = 1970
| publisher = American Association for the Advancement of Science
| doi =  10.1126/science.168.3929.375
| pmid = 4908037
| first1 = KA
| last2 = Sato
| first2 = K
| issue = 3929|display-authors=etal| bibcode = 1970Sci...168..375H
| s2cid = 39147135
}}</ref><ref>{{cite journal
| last1 = Hossmann KA
| title = Recovery of integrative central nervous function after one hour global cerebro-circulatory arrest in normothermic cat
| journal = Journal of the Neurological Sciences
| volume = 77
| pages = 305–20
| year = 1987
| publisher = Elsevier
| pmid=3819770
| doi = 10.1016/0022-510X(87)90130-4
| first1 = KA
| last2 = Schmidt-Kastner
| first2 = R
| last3 = Grosse Ophoff
| first3 = B
| issue = 2–3| s2cid = 11822788
|display-authors=etal}}</ref>