Effects of a combined drug regimen on tumour necrosis factor and plasma kallikrein activity in experimental endotoxaemia.
OBJECTIVE
To clarify the relationship between changes in haemodynamics, liberation of tumour necrosis factor and generation of plasma kallikrein, and to see if treatment with a combination of drugs was successful in preventing activation of tumour necrosis factor and plasma kallikrein in experimental endotoxic shock.


METHODS
Controlled study.


METHODS
22 juvenile pigs.


METHODS
15 animals received 0.01 mg/kg endotoxin infusion, the rest being given the same volume of saline. 10 received no treatment, and 5 were given a combination of methylprednisolone, naloxone, ketanserin, promethazine, C1 esterase inhibitor, antithrombin III and aprotinin.


METHODS
Assessment of the liberation of tumour necrosis factor, generation of plasma kallikrein, and haemodynamic and cellular effects of endotoxaemia.


RESULTS
There was a linear statistical relationship between decreases in cardiac output and increases in packed cell volume, and between increases in packed cell volume and plasma kallikrein activity. The combination treatment totally blocked all the effects of the infusion of endotoxin.


CONCLUSIONS
Endotoxin affects several mediators, but combination treatment can prevent some of these effects.
Naess
F
F
Department of Surgery, Ullevål Hospital, University of Oslo, Norway.
Waage
A
A
Roeise
O
O
Stadaas
J O
JO
Aasen
A O
AO
D000818:Animals; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004927:Escherichia coli Infections / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D007610:Kallikreins / Q000378:metabolism*; D007650:Ketanserin / Q000494:pharmacology / Q000627:therapeutic use; D008775:Methylprednisolone / Q000494:pharmacology / Q000627:therapeutic use; D009270:Naloxone / Q000494:pharmacology / Q000627:therapeutic use; D011398:Promethazine / Q000494:pharmacology / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D011480:Protease Inhibitors; D014409:Tumor Necrosis Factor-alpha; D009270:Naloxone; D007650:Ketanserin; D007610:Kallikreins; D011398:Promethazine; D008775:Methylprednisolone