Increased myocardial matrix metalloproteinases in hypoxic newborn pigs during resuscitation: effects of oxygen and carbon dioxide.
BACKGROUND
Perinatal asphyxia is associated with cardiac dysfunction, and it is important to prevent further tissue injury during resuscitation. There is increasing evidence that myocardial matrix metalloproteinases (MMPs) are involved in myocardial hypoxaemia-reoxygenation injury.


OBJECTIVE
To assess MMPs and antioxidant capacity in newborn pigs after global ischaemia and subsequent resuscitation with ambient air or 100% O(2) at different PaCO(2)-levels.


METHODS
Newborn pigs (12-36 h of age) were resuscitated for 30 min by ventilation with 21% or 100% O(2) at different PaCO(2) levels after a hypoxic insult, and thereafter observed for 150 min. In myocardial tissue extracts, MMPs were analyzed by gelatin zymography and broad matrix-degrading capacity (total MMP). Total endogenous antioxidant capacity in myocardial tissue extracts was measured by the oxygen radical absorbance capacity (ORAC) assay.


RESULTS
Matrix metalloproteinase-2 more than doubled from baseline values (P < 0.001), and was higher in piglets resuscitated with 100% O(2) than with ambient air (P = 0.012). The ORAC value was considerably decreased (P < 0.001). In piglets with elevated PaCO(2), total MMP-activity in the right ventricle was more increased than in the left ventricle (P = 0.008). In the left ventricle, total MMPactivity was higher in the piglets with low PaCO(2) than in the piglets with elevated PaCO(2) (P = 0.013).


CONCLUSIONS
In hypoxaemia-reoxygenation injury the MMP-2 level was highly increased and was most elevated in the piglets resuscitated with 100% O(2). Antioxidant capacity was considerably decreased. Assessed by total MMP-activity, elevated PaCO(2) during resuscitation might protect the left ventricle, and probably increase right ventricle injury of the myocardium.
Borke
W B
WB
Rikshospitalet University Hospital, Oslo, Norway. w.b.borke@klinmed.uio.no
Munkeby
B H
BH
Halvorsen
B
B
Bjornland
K
K
Tunheim
S H
SH
Borge
G I A
GI
Thaulow
E
E
Saugstad
O D
OD
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism; D002245:Carbon Dioxide / Q000097:blood*; D000860:Hypoxia / Q000201:enzymology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology*; D010100:Oxygen / Q000502:physiology*; D012151:Resuscitation; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013552:Swine
D000975:Antioxidants; D002245:Carbon Dioxide; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D010100:Oxygen