- Email: [email protected]
BLOOD LOSS ASSOCIATED WITH ADMINISTRATION OF LOW MOLECULAR WEIGHT DEXTRAN
Jm OlüWmal cfr
VOLUME 48 DECEMBER 1964 NUMBER 6
Thoracic and Cardiovascular Surgery
Original
Communications
BLOOD LOSS ASSOCIATED W I T H A D M I N I S T R A T I O N OF LOW MOLECULAR W E I G H T D E X T R A N Antonio A. Garzon, M.D. (by invitation), (by invitation), Karl E. Karbon,
Lawrence H. Fink, B.A.
Gerald W. Sbaftan, M.D.
(by invitation),
M.D., Ph.D., Brooklyn, N.
and
Y.
L
ow molecular weight dextran (LMD) has been used extensively for the treat■J ment of shock and for hemodilution in pump oxygenators. 9 · 12 The beneficial effects which occur are ascribed to improved capillary blood flow.6'7 Thei'e have been reports of increased bleeding during operation when low molecular weight dextran has been employed, but this experience has not been uniform. 5 ' 16 Most of the reports in which bleeding has been evaluated were concerned with openheart surgerv and controls have been difficult to establish. MATERIALS AXD METHODS
Dogs were anesthetized with intravenous pentobarbital sodium and the femoral artery and vein were cannulated. Five parallel incisions down to the fascia, 5 cm. long and 2 cm. apart, were made on one flank (Fig. 1). The dura tion of bleeding and weighed blood loss were determined. After the bleeding of this control period had ceased, the dogs were rapidly bled through the femoral artery cut-down. The volume of blood withdrawn was calculated to be osmotically equivalent to the subsequent infusion, the volume of which was always 30 ml. per kilogram of body weight. One of the control series had no withdrawal From The Department of Surgery, State University of New York Downstate Medical Center, Brooklyn, N. Y. This investigation was supported in part by U. S. Public Health Service Kesearch Grant HE-01011 from the National Heart Institute. Read at the Forty-fourth Annual Meeting of The American Association for Thoracic Surgery, Montreal, Canada, April 27, 28, and 29, 1964. 873
874
GARZON ET AL.
J. Thoracic ami Cardiovas. Surg.
of blood and no infusion, with only the second group of five incisions being made after an appropriate time lapse. Blood pressure was monitored during the experiment. After rapid withdrawal of the appropriate volume of blood, the dogs were quickly infused intravenously either with 30 ml./Kg. 0.9 per cent saline, 30 ml./Kg. autologous ACD blood, 10 m l / K g . LMD* + 20 m l / K g . saline, 20 ml./Kg. LMD + 10 ml./Kg. saline, or 30 ml./Kg. LMD.
Fig:. 1.—Five parallel incisions were made in one flank before bleeding· and infusion and a similar set of five incisions made in the other flank 15 min. after infusion of test solution.
Fifteen minutes after the infusion was completed, five identical parallel incisions were made on the other flank. The duration of bleeding and weighed blood loss were determined. Blood was drawn for coagulation studies before withdrawal of blood and 15 min., 60 min., and 240 min. after infusion of the test solution. The following coagulation tests were performed: clotting time (3-tube Lee-White 11 ), clot retraction, 13 platelet count,10 prothrombin activity," prothrombin consump tion,18 fibrinogen,15 euglobulin clot lysis,4 and whole clot lysis.17 Four experiments were done in each group. The bleeding duration, blood loss, and coagulation factors are reported as the average per cent of control for each of the 4 animals. Each individual value was compared with the control *10% Rheomacrodex in saline (Pharmacia Laboratories. Rochester, Minn.). One gram LMD in 10 nil. saline, which has an average osmolarity of 339 mOsm. per kilogram, plasma being 28.5 mOsm. per kilogram.
Vol. 48, No. 6 December, 1964
BLOOD LOSS ASSOCIATED W I T H LMD
875
value for that animal and the average per cent of normal was calculated for each group :
Σ^ο (2 control value
experimental value
xlOO
) _
average % of control.
RESULTS
Coagulation Studies.—Whole clot lysis was never observed. Clot retraction was graded as "good" in more than 90 per cent of determinations. Clotting time was transiently shorter in all groups, except in those animals receiving normal saline (Fig. 2). The platelet count diminished transiently in CLOTTING TIME AFTER L.M.D. INFUSION
60-
^
50
Q.
- 0
o----.©
No infusion 3 0 ml/Kg
Saline
3 0 m l / K g Autologous
Blood
D
□
I0ml/Kg L M D + 20ml/Kg
X
X
O
O
2 0 m l / K g L M D. + I 0 m l / K g 3 0 m l / K g L.M.D
15
Soline Saline
60
POST-INFUSION TIME (min.) Fig. 2.—Clotting time represented as average per cent of control time before bleeding and infusion. Less than 100% indicates coagulation faster than control. The point above 100% is the result of one isolated clotting time of 225% of control.
0 *
10-
20-
30-
40-
so-
βο-
70-
80-
90-
\fcx
».
\\
\
1
1
1
/
240
□ ■■ —■-—O No infusion O— - - - O 3 0 m l / K g Soline X-.--.X 30 ml/Kg Autologous Blood Q D I0ml/Kg L.M.D. + 20ml/Kg Saline X ^ ^ _ X 20ml/Kg L.M.D. + I0ml/Kg Saline O O 30ml/Kg L.M.D.
#
m
^f ^^τ0*^
// .^X^^X
-^"C^
^V ^V ^ L ^^r
/
/
POST-INFUSION TIME (min.)
\
*0*'
\A\A
^ /
/
/
C£
u
o
O
20
30-
130
15
60
□ ■ ■ ■ ■ ■ ■ D N o infusion 0 » ~ — « O 30 ml/Kg. Saline X - - — — - X 30ml/Kg Autologous Blood Q ^ ^ ^ — Q 10 ml/Kg L. M.D. + 20ml/Kg Saline X X 20ml/Kg L.M.D. + I0ml/Kg Saline O Q 3 0 m l / K g L.M.D.
PROTHROMBIN ACTIVITY AFTER L.M.D. INFUSION
Fig. 3.
POST-INFUSION TIME (min.) Fig. 4. Fig. 3.- -Platelet count represented as average per cent of control count before bleeding and infusion. Fig. 4.- -Prothrombin activity represented as average per cent of control activity before bleeding and infusion.
LU CL.
u C£
LU
<£.
o 1—
LL.
z O u
t—
o
—1
100-
110-
120-
PLATELET COUNT AFTER L.M.D. INFUSION
IS
60
No infusion 3 0 m l / K g Saline 3 0 m l / K g Autotogous Blood 10 ml/Kg 'L.M.D. + 20ml/Kg Saline 20ml/KgL.MD+I0ml/Kg Saline 30ml/Kg L.M.D.
POST-INFUSION TIME (min.)
■ CJ -O "X •Q -X -O
240
DC
u
o u
2
I—
O
60
POST-INFUSION TIME (min.)
IS
No infusion 30 ml/Kg. Saline 30ml/Kg Autologous Blood 10 ml/Kg L.M.D. + 20ml/Kg Saline 20ml/Kg L.M.D. + I0ml/Kg Saline 30ml/Kg L.M.D.
FIBRINOGEN AFTER L.M.D. INFUSION
240
Fig. 5. Fig. 6. Fig. 5.—Euglobulin clot lysis represented as average per cent of control lysis time before bleeding and infusion. Less than 100% indi cates shorter lysis time and greater plasmin activity. Fig. 6.—Fibrinogen concentration in plasma represented as average per cent of control flbrinogen concentration before bleeding and infusion.
20-
XΘXΘ-
oo-
EUGLOBULIN CLOT LYSIS AFTER L.M.D. INFUSION
oo
ö
F
»
>-3
ö
>
M
Ω
o
CO CO
>
O CO CO
W F O O Ö
GARZON E T AL.
878
J . Thoracic and Cardiovas. Surg.
BLEEDING TIME AFTER L.M.D. INFUSION
30ml/Kg SALINE
30ml/Kg AUTOLOGOUS BLOOD
47%
lOml/Kç L.M.D. + 20ml/Kg SALINE
I 115%
PERCENT OF CONTROL Fig. 7.—Duration of bleeding from test incisions represented as average per cent of bleeding time of control incisions. Values below 100% indicate that bleeding stopped in a shorter time than control.
BLOOD LOSS AFTER L.M.D. INFUSION
30ml/Kg SALINE
30ml/Kg AUTOLOGOUS BLOOD
36%
0
100
200
300
400
500
600
PERCENT OF CONTROL
Fig. 8.—Weighed blood loss from test incisions represented as average per cent of loss from control incisions. Values below 100% indicate blood loss less than the control.
Vol.48, No. 6 December, 1964
BLOOD LOSS ASSOCIATED W I T H LMD
«7Q
all animals. In the groups infused with LMD, the decrease appears to be a bit more pronounced (Pig. 3). The prothrombin activity (Fig. 4) and euglobulin clot lysis (Fig. 5) also appear to have been transiently affected in those animals receiving LMD. There was a drop in concentration of plasma fibrinogen in the group of animals that received normal saline, probably due to hemodilution. However the hypofibrinogenemia in the group receiving LMD was greater, and it remained depressed at 4 hours in the group receiving 30 ml./Kg. LMD (Fig. 6). Blood Loss.—The average duration of bleeding after infusion did not exceed that of the control in any group except those in which the infusion contained LMD (Fig. 7). With 10 ml./Kg. LMD, the increase was insignificant. After 20 ml./Kg. LMD, the increase was to 562 per cent of control, and after 30 ml./Kg. LMD the increase was to 507 per cent of control. The average weighed blood loss after infusion also did not exceed the loss from the control incisions unless LMD had been infused (Fig. 8). After 10 ml./Kg. LMD the blood loss was 285 per cent of control, after 20 ml./Kg. LMD it was 560 per cent of control, and after 30 ml./Kg. it was 4,380 per cent of control. DISCUSSION
The platelet count and fibrinogen concentration decreased more than an ticipated as a consequence of hemodilution. However, the coagulation factors were not depressed to the extent that might be expected to result in inadequate hemostasis, except for isolated values. 1 Gelin8 reported a mild and transient prolongation of bleeding time and a slight fall in the platelet count in normal individuals receiving 1,000 ml. of 10 per cent Rheomacrodex (100 grams LMD). Bergentz 3 did not find significant changes in coagulation factors after adminis tration of 1 to 1.5 Gm./Kg. LMD to dogs. Arterial hypotension occurred after withdrawal of 30 ml./Kg. of blood, but the blood pressure returned to almost the pre-bleeding value soon after the infu sion. The arterial pressure levels were similar in all the groups. Perhaps a logical explanation of the increased blood loss associated with LMD is augmen tation of the blood flow through small vessels, especially capillaries. LMD re duces intravascular aggregation of blood cells, increases the fluidity of blood, and improves the capillary flow. Although changes in the rheological properties of the blood after addition of LMD are not well understood, the primary effect of LMD is to decrease blood viscosity.7 This decreased viscosity is very important at the capillary level where flow velocity is slow as it allows much better small vessel perfusion.2 Better perfusion is, in our opinion, probably responsible for increased bleeding time and blood loss with LMD. We recognize there is some species specificity in the action of LMD. Never theless, increased blood loss may occur when more than one gram per kilogram body weight of LMD is used during operation.
GARZON E T AL.
880
J. Thoracic and Cardiovas. Surg.
CONCLUSIONS
1. Intravenously administered low molecular weight dextran in saline in excess of one gram per kilogram of body weight produces markedly increased blood loss in dogs. 2. Alterations of the coagulation mechanism appear to be inadequate to explain the bleeding. The authors wish to acknowledge gratefully the valuable technical assistance of Hedda Ribolow, Bernard Lerner, and Stanley Lichtenstein. REFERENCES
1. Aggeler, P . M. : Survival of Transfused Clotting Factors ire Bleeding in the Surgical Patient, 1964, New York Academy of Sciences. 2. Bayliss, L. E. : The Rheology of Blood in Handbook of Physiology, W. F . Hamilton, Edi tor, Baltimore, 1962, The Williams & Wilkins Co., Vol. I, Sect. 2, Chapt. 8. 3. Bergentz, S. E., Eiken, O., and Nilsson, I. M. : The Effect of Dextran of Various Molecu lar Weight on the Coagulation in Dogs, Thromb. Diath. Haemorrh. 6: 15, 1961. 4. Buckell, M.: The Effect of Citrate in the Euglobuline Clot Lysis, J . Clin. P a t h . 11: 403, 1958. 5. Breckenridge, J . M., and Walker, W. F . : Blood-Loss in Open-Heart Surgery With LowMolecular-Weight Dextran, Lancet 1: 1190, 1963. 6. Gelin, L. E . : Disturbance of the Flow Properties of Blood and I t s Counteraction in Surgery, Acta chir. scandinav. 122: 287, 1961. 7. Gelin, L. E., and Ingelman, B . : Rheomacrodex—A New Dextran Solution for Rheological Treatment of Impaired Capillary Flow, Acta chir. scandinav. 122: 294, 1961. 8. Gelin, L. E., Korsan-Bengtsen, K. Ygge, J., and Zederfeldt, B . : Influence of Low Viscous Dextran on the Hemostatie Mechanism, Acta chir. scandinav. 122: 324, 1961. 9. Hepp, S. A., Roe, B. B., Wright, R. R., and Gardner, R. E . : Amelioration of the Pul monary Post-perfusion Syndrome With Hemodilution and Low Molecular Weight Dextran, Surgery 54: 232, 1963. 10. Kracke, R. R., and Parker, F . P . : Textbook of Clinical Pathology, Baltimore, 1940, William Wood & Company. 11. Lee, R. I., and White, P . D . : A Clinical Study of the Coagulation Time of Blood, Am. J . M. Se. 145: 495, 1913. 12. Long, D. M., Jr., Sanchez, L., Varco, R. L., and Lillehei, C. W. : The Use of Low Molecu lar Weight Dextran and Serum Albumin as Plasma Expanders in Extracorporeal Circulation, Surgery 50: 12, 1961. 13. MacFarlane, R. G. : A Simple Method for Measuring Clot Retraction, Lancet 1: 1199,1939. 14. Quick, A. J . : The Physiology and Pathology of Hemostasis, Philadelphia, 1951, Lea & Febiger. 15. Ratnoff, O. D., and Menzie, C. : A New Method for the Determination of Fibrinogen in Small Samples of Plasma, J . Lab. & Clin. Med. 37: 316, 1951. 16. Smith, B., Omari, A., Melrose, D. G., and Bentall, H. H. : Blood Loss After Extracorporeal Circulation, S. Forum 14: 271-273, 1963. 17. Stefanini, M., and Dameshek, W. : The Hemorrhagic Disorders, New York, 1955, Grune & Stratton, Inc. 18. Sussman, L. N., Cohen, I . B., and Gittler, R. : Clinical Application of Simplified Serum Prothrombin Consumption Test, J . A. M. A. 156: 702, 1954. (For Discussion, see page 902)
VOLUME 48 DECEMBER 1964 NUMBER 6
Thoracic and Cardiovascular Surgery
Original
Communications
BLOOD LOSS ASSOCIATED W I T H A D M I N I S T R A T I O N OF LOW MOLECULAR W E I G H T D E X T R A N Antonio A. Garzon, M.D. (by invitation), (by invitation), Karl E. Karbon,
Lawrence H. Fink, B.A.
Gerald W. Sbaftan, M.D.
(by invitation),
M.D., Ph.D., Brooklyn, N.
and
Y.
L
ow molecular weight dextran (LMD) has been used extensively for the treat■J ment of shock and for hemodilution in pump oxygenators. 9 · 12 The beneficial effects which occur are ascribed to improved capillary blood flow.6'7 Thei'e have been reports of increased bleeding during operation when low molecular weight dextran has been employed, but this experience has not been uniform. 5 ' 16 Most of the reports in which bleeding has been evaluated were concerned with openheart surgerv and controls have been difficult to establish. MATERIALS AXD METHODS
Dogs were anesthetized with intravenous pentobarbital sodium and the femoral artery and vein were cannulated. Five parallel incisions down to the fascia, 5 cm. long and 2 cm. apart, were made on one flank (Fig. 1). The dura tion of bleeding and weighed blood loss were determined. After the bleeding of this control period had ceased, the dogs were rapidly bled through the femoral artery cut-down. The volume of blood withdrawn was calculated to be osmotically equivalent to the subsequent infusion, the volume of which was always 30 ml. per kilogram of body weight. One of the control series had no withdrawal From The Department of Surgery, State University of New York Downstate Medical Center, Brooklyn, N. Y. This investigation was supported in part by U. S. Public Health Service Kesearch Grant HE-01011 from the National Heart Institute. Read at the Forty-fourth Annual Meeting of The American Association for Thoracic Surgery, Montreal, Canada, April 27, 28, and 29, 1964. 873
874
GARZON ET AL.
J. Thoracic ami Cardiovas. Surg.
of blood and no infusion, with only the second group of five incisions being made after an appropriate time lapse. Blood pressure was monitored during the experiment. After rapid withdrawal of the appropriate volume of blood, the dogs were quickly infused intravenously either with 30 ml./Kg. 0.9 per cent saline, 30 ml./Kg. autologous ACD blood, 10 m l / K g . LMD* + 20 m l / K g . saline, 20 ml./Kg. LMD + 10 ml./Kg. saline, or 30 ml./Kg. LMD.
Fig:. 1.—Five parallel incisions were made in one flank before bleeding· and infusion and a similar set of five incisions made in the other flank 15 min. after infusion of test solution.
Fifteen minutes after the infusion was completed, five identical parallel incisions were made on the other flank. The duration of bleeding and weighed blood loss were determined. Blood was drawn for coagulation studies before withdrawal of blood and 15 min., 60 min., and 240 min. after infusion of the test solution. The following coagulation tests were performed: clotting time (3-tube Lee-White 11 ), clot retraction, 13 platelet count,10 prothrombin activity," prothrombin consump tion,18 fibrinogen,15 euglobulin clot lysis,4 and whole clot lysis.17 Four experiments were done in each group. The bleeding duration, blood loss, and coagulation factors are reported as the average per cent of control for each of the 4 animals. Each individual value was compared with the control *10% Rheomacrodex in saline (Pharmacia Laboratories. Rochester, Minn.). One gram LMD in 10 nil. saline, which has an average osmolarity of 339 mOsm. per kilogram, plasma being 28.5 mOsm. per kilogram.
Vol. 48, No. 6 December, 1964
BLOOD LOSS ASSOCIATED W I T H LMD
875
value for that animal and the average per cent of normal was calculated for each group :
Σ^ο (2 control value
experimental value
xlOO
) _
average % of control.
RESULTS
Coagulation Studies.—Whole clot lysis was never observed. Clot retraction was graded as "good" in more than 90 per cent of determinations. Clotting time was transiently shorter in all groups, except in those animals receiving normal saline (Fig. 2). The platelet count diminished transiently in CLOTTING TIME AFTER L.M.D. INFUSION
60-
^
50
Q.
- 0
o----.©
No infusion 3 0 ml/Kg
Saline
3 0 m l / K g Autologous
Blood
D
□
I0ml/Kg L M D + 20ml/Kg
X
X
O
O
2 0 m l / K g L M D. + I 0 m l / K g 3 0 m l / K g L.M.D
15
Soline Saline
60
POST-INFUSION TIME (min.) Fig. 2.—Clotting time represented as average per cent of control time before bleeding and infusion. Less than 100% indicates coagulation faster than control. The point above 100% is the result of one isolated clotting time of 225% of control.
0 *
10-
20-
30-
40-
so-
βο-
70-
80-
90-
\fcx
».
\\
\
1
1
1
/
240
□ ■■ —■-—O No infusion O— - - - O 3 0 m l / K g Soline X-.--.X 30 ml/Kg Autologous Blood Q D I0ml/Kg L.M.D. + 20ml/Kg Saline X ^ ^ _ X 20ml/Kg L.M.D. + I0ml/Kg Saline O O 30ml/Kg L.M.D.
#
m
^f ^^τ0*^
// .^X^^X
-^"C^
^V ^V ^ L ^^r
/
/
POST-INFUSION TIME (min.)
\
*0*'
\A\A
^ /
/
/
C£
u
o
O
20
30-
130
15
60
□ ■ ■ ■ ■ ■ ■ D N o infusion 0 » ~ — « O 30 ml/Kg. Saline X - - — — - X 30ml/Kg Autologous Blood Q ^ ^ ^ — Q 10 ml/Kg L. M.D. + 20ml/Kg Saline X X 20ml/Kg L.M.D. + I0ml/Kg Saline O Q 3 0 m l / K g L.M.D.
PROTHROMBIN ACTIVITY AFTER L.M.D. INFUSION
Fig. 3.
POST-INFUSION TIME (min.) Fig. 4. Fig. 3.- -Platelet count represented as average per cent of control count before bleeding and infusion. Fig. 4.- -Prothrombin activity represented as average per cent of control activity before bleeding and infusion.
LU CL.
u C£
LU
<£.
o 1—
LL.
z O u
t—
o
—1
100-
110-
120-
PLATELET COUNT AFTER L.M.D. INFUSION
IS
60
No infusion 3 0 m l / K g Saline 3 0 m l / K g Autotogous Blood 10 ml/Kg 'L.M.D. + 20ml/Kg Saline 20ml/KgL.MD+I0ml/Kg Saline 30ml/Kg L.M.D.
POST-INFUSION TIME (min.)
■ CJ -O "X •Q -X -O
240
DC
u
o u
2
I—
O
60
POST-INFUSION TIME (min.)
IS
No infusion 30 ml/Kg. Saline 30ml/Kg Autologous Blood 10 ml/Kg L.M.D. + 20ml/Kg Saline 20ml/Kg L.M.D. + I0ml/Kg Saline 30ml/Kg L.M.D.
FIBRINOGEN AFTER L.M.D. INFUSION
240
Fig. 5. Fig. 6. Fig. 5.—Euglobulin clot lysis represented as average per cent of control lysis time before bleeding and infusion. Less than 100% indi cates shorter lysis time and greater plasmin activity. Fig. 6.—Fibrinogen concentration in plasma represented as average per cent of control flbrinogen concentration before bleeding and infusion.
20-
XΘXΘ-
oo-
EUGLOBULIN CLOT LYSIS AFTER L.M.D. INFUSION
oo
ö
F
»
>-3
ö
>
M
Ω
o
CO CO
>
O CO CO
W F O O Ö
GARZON E T AL.
878
J . Thoracic and Cardiovas. Surg.
BLEEDING TIME AFTER L.M.D. INFUSION
30ml/Kg SALINE
30ml/Kg AUTOLOGOUS BLOOD
47%
lOml/Kç L.M.D. + 20ml/Kg SALINE
I 115%
PERCENT OF CONTROL Fig. 7.—Duration of bleeding from test incisions represented as average per cent of bleeding time of control incisions. Values below 100% indicate that bleeding stopped in a shorter time than control.
BLOOD LOSS AFTER L.M.D. INFUSION
30ml/Kg SALINE
30ml/Kg AUTOLOGOUS BLOOD
36%
0
100
200
300
400
500
600
PERCENT OF CONTROL
Fig. 8.—Weighed blood loss from test incisions represented as average per cent of loss from control incisions. Values below 100% indicate blood loss less than the control.
Vol.48, No. 6 December, 1964
BLOOD LOSS ASSOCIATED W I T H LMD
«7Q
all animals. In the groups infused with LMD, the decrease appears to be a bit more pronounced (Pig. 3). The prothrombin activity (Fig. 4) and euglobulin clot lysis (Fig. 5) also appear to have been transiently affected in those animals receiving LMD. There was a drop in concentration of plasma fibrinogen in the group of animals that received normal saline, probably due to hemodilution. However the hypofibrinogenemia in the group receiving LMD was greater, and it remained depressed at 4 hours in the group receiving 30 ml./Kg. LMD (Fig. 6). Blood Loss.—The average duration of bleeding after infusion did not exceed that of the control in any group except those in which the infusion contained LMD (Fig. 7). With 10 ml./Kg. LMD, the increase was insignificant. After 20 ml./Kg. LMD, the increase was to 562 per cent of control, and after 30 ml./Kg. LMD the increase was to 507 per cent of control. The average weighed blood loss after infusion also did not exceed the loss from the control incisions unless LMD had been infused (Fig. 8). After 10 ml./Kg. LMD the blood loss was 285 per cent of control, after 20 ml./Kg. LMD it was 560 per cent of control, and after 30 ml./Kg. it was 4,380 per cent of control. DISCUSSION
The platelet count and fibrinogen concentration decreased more than an ticipated as a consequence of hemodilution. However, the coagulation factors were not depressed to the extent that might be expected to result in inadequate hemostasis, except for isolated values. 1 Gelin8 reported a mild and transient prolongation of bleeding time and a slight fall in the platelet count in normal individuals receiving 1,000 ml. of 10 per cent Rheomacrodex (100 grams LMD). Bergentz 3 did not find significant changes in coagulation factors after adminis tration of 1 to 1.5 Gm./Kg. LMD to dogs. Arterial hypotension occurred after withdrawal of 30 ml./Kg. of blood, but the blood pressure returned to almost the pre-bleeding value soon after the infu sion. The arterial pressure levels were similar in all the groups. Perhaps a logical explanation of the increased blood loss associated with LMD is augmen tation of the blood flow through small vessels, especially capillaries. LMD re duces intravascular aggregation of blood cells, increases the fluidity of blood, and improves the capillary flow. Although changes in the rheological properties of the blood after addition of LMD are not well understood, the primary effect of LMD is to decrease blood viscosity.7 This decreased viscosity is very important at the capillary level where flow velocity is slow as it allows much better small vessel perfusion.2 Better perfusion is, in our opinion, probably responsible for increased bleeding time and blood loss with LMD. We recognize there is some species specificity in the action of LMD. Never theless, increased blood loss may occur when more than one gram per kilogram body weight of LMD is used during operation.
GARZON E T AL.
880
J. Thoracic and Cardiovas. Surg.
CONCLUSIONS
1. Intravenously administered low molecular weight dextran in saline in excess of one gram per kilogram of body weight produces markedly increased blood loss in dogs. 2. Alterations of the coagulation mechanism appear to be inadequate to explain the bleeding. The authors wish to acknowledge gratefully the valuable technical assistance of Hedda Ribolow, Bernard Lerner, and Stanley Lichtenstein. REFERENCES
1. Aggeler, P . M. : Survival of Transfused Clotting Factors ire Bleeding in the Surgical Patient, 1964, New York Academy of Sciences. 2. Bayliss, L. E. : The Rheology of Blood in Handbook of Physiology, W. F . Hamilton, Edi tor, Baltimore, 1962, The Williams & Wilkins Co., Vol. I, Sect. 2, Chapt. 8. 3. Bergentz, S. E., Eiken, O., and Nilsson, I. M. : The Effect of Dextran of Various Molecu lar Weight on the Coagulation in Dogs, Thromb. Diath. Haemorrh. 6: 15, 1961. 4. Buckell, M.: The Effect of Citrate in the Euglobuline Clot Lysis, J . Clin. P a t h . 11: 403, 1958. 5. Breckenridge, J . M., and Walker, W. F . : Blood-Loss in Open-Heart Surgery With LowMolecular-Weight Dextran, Lancet 1: 1190, 1963. 6. Gelin, L. E . : Disturbance of the Flow Properties of Blood and I t s Counteraction in Surgery, Acta chir. scandinav. 122: 287, 1961. 7. Gelin, L. E., and Ingelman, B . : Rheomacrodex—A New Dextran Solution for Rheological Treatment of Impaired Capillary Flow, Acta chir. scandinav. 122: 294, 1961. 8. Gelin, L. E., Korsan-Bengtsen, K. Ygge, J., and Zederfeldt, B . : Influence of Low Viscous Dextran on the Hemostatie Mechanism, Acta chir. scandinav. 122: 324, 1961. 9. Hepp, S. A., Roe, B. B., Wright, R. R., and Gardner, R. E . : Amelioration of the Pul monary Post-perfusion Syndrome With Hemodilution and Low Molecular Weight Dextran, Surgery 54: 232, 1963. 10. Kracke, R. R., and Parker, F . P . : Textbook of Clinical Pathology, Baltimore, 1940, William Wood & Company. 11. Lee, R. I., and White, P . D . : A Clinical Study of the Coagulation Time of Blood, Am. J . M. Se. 145: 495, 1913. 12. Long, D. M., Jr., Sanchez, L., Varco, R. L., and Lillehei, C. W. : The Use of Low Molecu lar Weight Dextran and Serum Albumin as Plasma Expanders in Extracorporeal Circulation, Surgery 50: 12, 1961. 13. MacFarlane, R. G. : A Simple Method for Measuring Clot Retraction, Lancet 1: 1199,1939. 14. Quick, A. J . : The Physiology and Pathology of Hemostasis, Philadelphia, 1951, Lea & Febiger. 15. Ratnoff, O. D., and Menzie, C. : A New Method for the Determination of Fibrinogen in Small Samples of Plasma, J . Lab. & Clin. Med. 37: 316, 1951. 16. Smith, B., Omari, A., Melrose, D. G., and Bentall, H. H. : Blood Loss After Extracorporeal Circulation, S. Forum 14: 271-273, 1963. 17. Stefanini, M., and Dameshek, W. : The Hemorrhagic Disorders, New York, 1955, Grune & Stratton, Inc. 18. Sussman, L. N., Cohen, I . B., and Gittler, R. : Clinical Application of Simplified Serum Prothrombin Consumption Test, J . A. M. A. 156: 702, 1954. (For Discussion, see page 902)