Effect of Dicumarol on Blood Vascular Integrity in the Rabbit
Results of experiments in rabbits in which the disappearance of Evans Blue labeled plasma proteins was used as a measure of vascular integrity, indicate that Dicumarol does increase the rate of loss of plasma proteins from the blood stream. This action does not occur immediately after the introduction of Dicumarol into the blood stream but requires a latent period of between 90 and 180 minutes. During this time there may actually be a decreased rate of loss from the blood.
The degree of increase in the dye disappearance rate, although not directly correlated with the degree of hypoprothrombinemia, can be roughly correlated with the extent and severity of internal hemorrhage. These results tend to confirm the idea that vascular fragility, usually considered independent of vascular permeability, may in this instance be the preliminary manifestation of Dicumarol hemorrhagic diathesis.
In experiments where the effect of Dicumarol on exchange of protein between plasma and the peritoneal cavity was measured, it has been found that the presence of vitamin K1 in the blood in sufficient amount to completely block the hypoprothrombinemic action will also block the tendency toward increased protein exchange. Also, if Dicumarol is introduced into the peritoneal cavity rather than directly into the blood stream, the increase in transperitoneal protein exchange rate appears to be fairly proportional to the degree of hypoprothrombinemia.
It is concluded that although the possibility of several independent actions of Dicumarol exists, one effecting vascular permeability and another inhibiting the elaboration of coagulation factors, it is more likely that the changes seen in vascular integrity are related to the effects of the drug on the coagulation mechanism by way of vitamin K inhibition.
- Received March 16, 1960.
- © 1960 American Heart Association, Inc.