Studies on the effect of human lys-plasminogen in a rat model of global cerebral ischemia.
Human lys-plasminogen and the corresponding formulation buffer were tested in a rat model of global cerebral ischemia (clamping of both carotid arteries, withdrawal of 5 ml blood for 30 min). The two main parameters, tested in different experimental set-ups, were 1. brain edema (water content) 23.5 h after reperfusion and 2. assessment of neurological deficits 24, 48 and 72 h after reperfusion. In some groups of animals of the first set-up, brains were examined histologically for microvascular fibrin deposits. In a separate group of animals the fibrinolytic plasma activity of rats treated with 500 CU/kg lys-plasminogen was studied. Concerning brain water content lys-plasminogen completely antagonized the formation of brain edema when given with 500 caseolytic Units (CU)/kg i.v. with blood reperfusion and was still effective when given 30 min later. 200 CU/kg i.v. given with blood reperfusion as well as 500 CU/kg i.v. given 60 min after blood reperfusion proved ineffective. In none of the brains investigated microvascular fibrin deposits were found. In experiments with assessment of neurological deficits, animals treated with 500 CU/kg lys-plasminogen i.v. showed almost no disabilities (like sham operated animals) when compared to ischemic (positive) controls which were rather severely handicapped. The formulation buffer of lys-plasminogen, tested in an equivalent volume, was without any effect in both set-ups. No fibrinolytic activity was found in plasma samples of rats up to 240 min after treatment with 500 CU/kg lys-plasminogen i.v. It is concluded from these experiments that human lys-plasminogen has a protective effect in rats against the sequelae of global cerebral ischemia which is not related to the well-known fibrinolytic potential but might be a separate quality.
Auer
W
W
Research Laboratories, Immuno AG, Vienna, Austria.
Muchitsch
E M
EM
Philapitsch
A
A
Pichler
L
L
Schwarz
H P
HP
D000818:Animals; D001834:Body Water / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D001929:Brain Edema / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002339:Carotid Arteries / Q000502:physiology; D005337:Fibrin / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000097:blood; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000627:therapeutic use*; D010958:Plasminogen / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology
D005343:Fibrinolytic Agents; D010446:Peptide Fragments; C018998:lysyl-plasminogen; D005337:Fibrin; D010958:Plasminogen