Macromolecules reduce abnormal microvascular permeability in rat limb ischemia-reperfusion injury.
We studied the effect of iv administration of biodegradable macromolecules on microvascular permeability after ischemia-reperfusion injury in a rat gastrocnemius model. After 2 h of tourniquet ischemia of the rats' hind limb, groups of animals were given iv lactated Ringer's solution (RL), serum albumin 5%, or varying MW fractions of biodegradable macromolecules of hydroxyethyl starch (HES), glycogen, and dextran. At the conclusion of the 24-h reperfusion period, the rat gastrocnemius muscles were collected. Water and K+ differences between the ischemic and control muscles were compared. Rats given a 100,000 to 300,000-dalton fraction of HES had significantly decreased water content (5.1 +/- 3.4%) when compared to rats receiving RL (8.3 +/- 2.2, p less than .01), less than 100,000 dalton HES (8.3 +/- 3.2, p less than .05), less than 300,000 glycogen (7.9 +/- 2.5, p less than .01), or dextran 150,000 (8.3 +/- 1.5, p less than .05). Rats given 100,000 to 300,000-dalton HES also had significantly higher ischemic muscle K+ content as compared to the nontourniquet control (difference 14.2 +/- 9.7 mEq/g) than rats receiving any of the other solutions (range 32.5 to 39.3) except the 300,000 to 1,000,000-dalton fraction of HES. Regression analysis comparison of K+ difference to the histologic evaluation of the muscles on the criteria of polymorphonuclear infiltration and interstitial edema (0, best; 3, worst) had a Pearson correlation coefficient of r = .73. Reduction of abnormally increased microvascular permeability may be accomplished by the iv use of appropriate sized biodegradable macromolecules.
Zikria
B A
BA
Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Subbarao
C
C
Oz
M C
MC
Shih
S T
ST
McLeod
P F
PF
Sachdev
R
R
Freeman
H P
HP
Hardy
M A
MA
D000818:Animals; D001834:Body Water / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects*; D003911:Dextrans / Q000494:pharmacology; D006003:Glycogen / Q000494:pharmacology; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology*; D007552:Isotonic Solutions / Q000494:pharmacology; D007866:Leg / Q000098:blood supply; D008297:Male; D011188:Potassium / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000503:physiopathology*; D000077325:Ringer's Lactate; D012709:Serum Albumin / Q000494:pharmacology; D013213:Starch / Q000031:analogs & derivatives*
D003911:Dextrans; D006895:Hydroxyethyl Starch Derivatives; D007552:Isotonic Solutions; D000077325:Ringer's Lactate; D012709:Serum Albumin; D013213:Starch; D006003:Glycogen; D011188:Potassium