Hypotensive hemorrhage increases calcium uptake capacity and Bcl-XL content of liver mitochondria.
We tested the hypothesis that the response of mitochondrial uptake of calcium and content of Bcl proteins to reversible hemorrhagic shock increases the vulnerability for hepatocellular death. Pentobarbital-anesthetized rats were bled to a mean arterial pressure of 30 to 40 mmHg for 1 h. A subset was then resuscitated (isotonic sodium chloride solution, three times shed volume). Liver mitochondria were isolated at the end of hemorrhage and 1.5 h after the onset of resuscitation. Resuscitation accelerated mitochondrial respiration in the presence of adenosine diphosphate (state 3) above control (P<0.01). The respiratory control ratio ([RCR] state 3/state 4) was calculated using the respiratory rate in the presence of carboxyatractyloside (state 4). The RCR was depressed at the end of hemorrhage and recovered completely in response to resuscitation (P<0.05). The mitochondrial capacity for calcium uptake increased at the end of hemorrhage and remained greater than control (P<0.01) after resuscitation when plasma ornithine carbamoyltransferase (an index of hepatocellular injury) was greater than control (P<0.05). At this time, the capacity for calcium uptake was correlated with plasma ornithine carbamoyltransferase (r=0.819, P<0.01). Mitochondrial content of Bcl-xL, an antiapoptotic protein, was increased at the end of hemorrhage (P<0.03) with no further change after resuscitation and no change in mitochondrial Bak, a proapoptotic protein. Thus, mitochondrial mechanisms are triggered early during reversible hypovolemia that may limit the intensity of intracellular calcium signaling and its potential to cause cellular injury and death.
Carlson
Drew E
DE
Program in Trauma and Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. dcarlson@umm.edu
Nguyen
Phuong X
PX
Soane
Lucian
L
Fiedler
Suzelle M
SM
Fiskum
Gary
G
Chiu
William C
WC
Scalea
Thomas M
TM
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D006470:Hemorrhage / Q000378:metabolism* / Q000473:pathology; D007022:Hypotension / Q000378:metabolism* / Q000473:pathology; D020896:Hypovolemia / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D051020:bcl-X Protein / Q000378:metabolism*
C494813:Bcl2l1 protein, rat; D051020:bcl-X Protein; D002118:Calcium