Relationship between tissue hypoxia and apoptosis: a preliminary observational study.
OBJECTIVE
This observational study examined the relationship between tissue hypoxia (PO2 of 30mmHg and 15mmHg) and the development of dysoxia and apoptosis.


METHODS
28 Sprague-Dawley rats were studied in three groups. Group 1 had no interventions (controls; n=6). Graded hypoxia was induced in Group 2 (n =13) and Group 3 (n =9) to achieve a subcutaneous PO2 of < 30mmHg (20 minutes) followed by < 15mmHg (20 minutes). In addition, Group 3 received reoxygenation to baseline after hypoxia. Ileal and cutaneous tissues were assessed for apoptosis (by histology, TUNEL and immunohistochemistry for caspase-3) and dysoxia (tissue lactate concentration and energy charge).


RESULTS
An interstitial PO2 < 30mmHg led to statistically significant elevations in skin and gut lactate concentrations from baseline (mean +/-SD: skin, 0.2+/-0.07 to 0.6 +/-0.3mmol/ kg wet weight, P < 0.01; gut, 1 +/-0.7 to 6 +/-4mmol/kg wet weight, P<0.05). With hypoxia, there was an increase in apoptosis scores in the gut villi from baseline in the experimental arms (17% +/-21% to 53% +/-58%, P<0.05 in Group 2; 9% +/-5% to 27%+/-12%, P < 0.05 in Group 3). There was no significant increase in skin apoptosis. No significant correlation was noted between gut lactate concentrations and gut apoptosis (r= -0.28).


CONCLUSIONS
In this pilot study, reductions in PO2 to <30mmHg were associated with significant dysoxic changes in the gut and skin. No clear tissue PO2 threshold for the initiation of apoptosis was identified. Further studies with refinements to the experimental model may allow more precise identification of PO2 thresholds that are critical for the development of apoptosis.
Venkatesh
Bala
B
Department of Intensive Care, Princess Alexandra Hospital, Brisbane, QLD, Australia. bala_venkatesh@health.qld.gov.au
Gobe
Glenda
G
Morgan
T John
TJ
Beindorf
Andrea
A
Hall
Jonathon
J
Jones
Mark
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004195:Disease Models, Animal; D000860:Hypoxia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D007773:Lactates / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism / Q000473:pathology
D007773:Lactates; D010100:Oxygen