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The vascular response of oral tissues to brief severe hemorrhage
Research The vascular responseof oral tissuesto brief severehemorrhage Jack G. Bishop, Ph.D., and Homer L. Dorman, Ph.D., Dallas, Texas DEPARTMENT
OF PHYSIOLOGY,
BAYLOR
UNIVERSITY
COLLEGE
OF DENTISTRY
T
he capillary circulation of animals and man is considerably larger than can be perfused with the normal cardiac output at usual blood pressures. This situation requires that capillaries be intermittently patent in order that a systemic blood pressure can be maintained at adequate levels. The capillary flow is therefore adjusted to that required by the individual demands of the tissue supplied by a particular vessel. Removal of a portion of the circulating blood through hemorrhage sets off a complex series of neurogenic and humoral events1 which are probably designed to compensate for the reduction in circulating volume and the resultant lowered cardiac output. Vasoconstriction in the skin is widely recognized as an immediate consequence of bleeding. Hemorrhage also evokes an immediate outpouring of catecholamine (primarily epinephrine) into the adrenal vein.2 Blanching of the gingiva has been observed clinically following hemorrhage, but there has been little documentation of the phenomenon. The object of this study was to determine the effect of hemorrhage upon the peripheral vascular resistance of the oral tissues. MATERIALS AND METHODS
Mongrel dogs that had large heads and were free of oral disease were selected. The right mandibular artery was exposed by means of an inframandibular incision, and this vessel was cannulated with No. 90 polyethylene tubing in such a manner that solutions (usually blood) could be perfused into the vascular bed of the oral tissues distal to the cannula. The polyethylene tubing was connected to a 10 cc. syringe that was mounted on a constant-flow perfusion apparatus.* The polyethylene tubing was fitted with a T tube so that a lateral Supported in part by United States Public Health Service Grant HE09049-12 by the Me&d Research Foundation of Texas from funds supplied by the Clayton annual grant. *Harvard Apparatus Company, Inc., Millis,,Mass.
and in part Foundation
547
548
O.S.,O.M.&O.P. October,1968
Bishop and Dorman
connection could be made to a Xtatham strain gauge. The injection pressure could then be measured during perfusion. The flow and pressure data were used to calculate the peripheral vascular resistance. The femoral artery was cannulated and fitted with a connection that allowed rapid hemorrhage of the animal and also allowed systemic blood pressure measurements to be made by means of a second Statham pressure transducer. The femoral vein was cannulated and fitted with a funnel for rapid transfusion of the animal’s blood. Heparin (3 mg. per kilogram) was used as the anticoagulant. Color photographs were made of the gingiva with a 35 mm. reflex camera fitted with a synchronized ring flash and a close-up extension tube. Blood volume measurements were made by the dye dilution technique,3 and hemorrhage was limited to 20 per cent of the calculated blood volume. Tooth transluminosity was monitored by means of a photoconductive device which could be cla.mped directly on the tooth. Changes in tooth optical density are related to blood-flow surges in the pulp tissue that occur with each heart beat.4
Table
I
A?&?Ml.l
lturfber
Blood
volme
(0.0.)
Femoral blocd
Yc&?lmlzller
Optical
Pm-f U.&n
pream.re
perfudm presswe
dfm&g p&e height (9m.)
rate (C.C./?nin.)
170/110 1lO)SO 17moo 150;115 190/152 14OJ105 163/110
140 130 125 145 160 135 170
8
3.88 3.88 3.88 3.88 3.88 3.88 3.88 3.88
Cmtrol ,?Pwmwr0mmts Average
PRU:
33
1
i
3 4 5 6 7
740 792 783 560 635 862 526
149
700 Aftw
7
8
hemorrhage SO
Average PRU: i
792 740
3 4
783 560
6" 7 Mean After
9" 8 :
55/30 @s/55
100
4
3.88
98/78 100/75
110 l"d8
5 6
3.88 3.88
862 635 5,26 -KG-
125/100 75/50 100/65 93/65
115 150 117
Ii 4
3.88 3.88 3.88
740 792 783
160/110 120/85 170/110
150 145 115
6 s"
3.88 3.88 3.88
635 560 862 526 700
165/120 14tqllO 175/135 165/95 157/109
158 145 ii:
7 i
4
retrmwfwakn 45
Average PRU:
% 6 7 Mean
175
7
3.88 3.88 3.88 3.88
Volume 26 Number 4
Vascular
response
to brief severe hemorrhage 549
Pig. 1. Left: A view of the oral mucous membrane and gingiva before hemorrhage. Right: The mucous membranes and gingivae of the same animal after hemorrhage, showing the intense blanching that occurs.
Volume 26 Number 4
Vascular response to brief severe hemorrhage 551
RESULTS
The control group of measurements showed that an average mandibular pressure of 129 mm. Hg. was required to perfuse the mandibular artery at a rate of 3.88 CC. per minute (Table I). These data were used to compute the prehemorrhage peripheral resistance of this vascular bed, and an average value of 33 was found. The same measurements and calculations were used following hemorrhage of the animal (to the extent of 20 per cent of its blood volume) and yielded a value of peripheral resistance of 30. Retransfusion raised the peripheral resistance to an average of 45. During the course of the hemorrhage, an intense blanching of the gingiva and mucous membranes of the mouth occurred (Fig. 1). Blanching and, presumably, vasoconstriction were not immediately reversed upon retransfusion but persisted fo’r as long as 2 hours after retransfusion. Retransfusion, however, was always very effective in restoring the systemic blood pressure. The systemic blood pressure measured from the femoral artery averaged 157/109 prior to hemorrhage. It dropped to 75/65 immediately after hemorrhage but returned to control values following retransfusion of the animal’s blood. Fig. 2 shows a typical recording of femoral blood pressure, perfusion pressure, and changes in tooth transluminosity. The optical density pulses which occur during each heart cycle are greatly reduced during the period of hemorrhagic hypotension but return toward normal as the systemic blood pressure is restored.
Fig. 3. Recording of the effects of hemorrhage on tooth transluminosity, femoral blood pressure, back pressure of the mandibular artery, and perfusion pressure in the mandibular artery. The mandibular back pressure (lower trace) resulta from anastomotic blood vessel connections (for example, the mandibular symphysis) . The tooth transluminosity (upper trace) represents blood-flow surges within the pulpal blood vessels. Both back pressure in the mandibular artery and the height of the transluminosity pulses are reduced coincidently with the fall in femoral pressure.
552
Bishop and Dorma%
O.S., O.M. & O.P. October, 1968
DISCUSSION
An obvious vasoconstriction of superficial vessels of the gingiva, mucous membranes, and pulp occurred immediately after bleeding and the gingiva and mucous membranes did not return to normal for some time following restoration of the animal’s blood volume and systemic blood pressure. The blood-flow pulses in the pulp promptly increased to normal as soon as the systemic blood pressure was restored. During the time that intense blanching of the gingiva and mucous membranes could be seen by visual inspection, the peripheral vascular resistance was found by direct measurement to be lowered. Decreased resistance to the flow of blood in the mandibula,r a,rtery in the face of constriction in some areas supplied by this vessel (for example, the gingiva) may be explained if we assume that other vessels open so that the runoff from the artery is increased. The occurrence of arteriovenous anastomoses has been reported in oral tissues involved in periodontosis5 a.nd have been shown to increase during development of experimental periodontal disease in dogs.6 A loss of neurogenic control may contribute to the reduction in total vascular resistance and influence the development of irreversibility in hemorrhagic shock in dogs.7 The anastomosesthat connect the branches of the mandibular artery to its venous drainage may fail to constrict in response to hemorrhage as much as those of the capillaries of the gingiva and mucosa. The apparent peripheral resistance decrease would then result from the increased flow of the blood out of the artery into the venous drainage which bypasses the capillary beds. A second explanation of the finding that vasoconstriction occurs following hemorrhage can be based upon the existence of artery-to-artery shunts. If increased artery-to-artery shunting of blood flow occurs, the resistance to “runoff” from the mandibular artery would decrease. The utility of this mechanism to survival of the organism could then be stated as follows: An intense vasoconstriction of the capillary beds supplied by the mandibular artery, together with a relaxation of the constrictor tone in the vessels that form artery-to-artery shunts, could allow a preferential shunting to favor other vesselsof the head (for example, the brain). SUMMARY
The peripheral resistance of the vascular bed supplied by the mandibular artery was measured before and after hemorrhage of 20 per cent of the blood volume. Blanching of the gingiva and oral mucosa was seen during the hemorrhage and for some time following restoration of the blood volume by retransfusion. The PRU of the mandibular vascula’r bed dropped slightly following hemorrhage and increased by about 25 per cent following retransfusion. The period immediately following hemorrhage was characterized by blanching (and presumably vasconstriction) in the oral mucosa while the peripheral resistance of the mandibular vascular bed was reduced. Increased artery-to-artery or arteryto-vein shunting is offered as a possible explanation. REFERENCES
1. Field, L. W., and Laverty, R.: Nervous the Rat, J. Physiol. 143: 213-225, 1958.
and Humoral
Response
to Acute
Blood
Loss in
Volume 26 Number 4
Vascular response
to brief
severe
hemorrhage
553
2. Walker, W. F., Zieli, M. S., Reutter, F. W., Shoemaker, W. C., Friend, D., and Moore, F. D.: Adrenal Medullary Secretion m Hemorrhagic Shock, Am. J. Physiol. 197: 773-780, 1959. 3. Hepler, 0. E.: Manual of Clinical Laboratory Methods, Spri@eld, Ill., 1960, Charles C Thomas, Publisher, pp. 46-47. 4. Upthegrove, D. D., Bishop, J. G., and Dorman, H. L.: A Method of Detection of Blood Flow in the Dental Pulp, J. D. Res. 45: 1115-1119, 1966. 5. Provenza D. W., Biddington, W. R., and Cheng, T. C.: Studies on the Etiology of Periododosis, ORAL Sm., ORAL MED. & ORAL PATH. 12: 676,1959. 6. Dorman, H. L., and Bishop, J. G.: Cha.ng@ in Vascula.r Resistance Following Induction of Chronic Unilateral Periodontitis in Dogs, J. D. Res. 41: 453-458, 1962. 7. Rothe, C. F., Love, J. R., a.nd Selkurt E. E.: Control of Total Vascular R&stance in Hemorrhagic Shock in Dogs, Circulation kes. 12: 667-675, 1963.
OF PHYSIOLOGY,
BAYLOR
UNIVERSITY
COLLEGE
OF DENTISTRY
T
he capillary circulation of animals and man is considerably larger than can be perfused with the normal cardiac output at usual blood pressures. This situation requires that capillaries be intermittently patent in order that a systemic blood pressure can be maintained at adequate levels. The capillary flow is therefore adjusted to that required by the individual demands of the tissue supplied by a particular vessel. Removal of a portion of the circulating blood through hemorrhage sets off a complex series of neurogenic and humoral events1 which are probably designed to compensate for the reduction in circulating volume and the resultant lowered cardiac output. Vasoconstriction in the skin is widely recognized as an immediate consequence of bleeding. Hemorrhage also evokes an immediate outpouring of catecholamine (primarily epinephrine) into the adrenal vein.2 Blanching of the gingiva has been observed clinically following hemorrhage, but there has been little documentation of the phenomenon. The object of this study was to determine the effect of hemorrhage upon the peripheral vascular resistance of the oral tissues. MATERIALS AND METHODS
Mongrel dogs that had large heads and were free of oral disease were selected. The right mandibular artery was exposed by means of an inframandibular incision, and this vessel was cannulated with No. 90 polyethylene tubing in such a manner that solutions (usually blood) could be perfused into the vascular bed of the oral tissues distal to the cannula. The polyethylene tubing was connected to a 10 cc. syringe that was mounted on a constant-flow perfusion apparatus.* The polyethylene tubing was fitted with a T tube so that a lateral Supported in part by United States Public Health Service Grant HE09049-12 by the Me&d Research Foundation of Texas from funds supplied by the Clayton annual grant. *Harvard Apparatus Company, Inc., Millis,,Mass.
and in part Foundation
547
548
O.S.,O.M.&O.P. October,1968
Bishop and Dorman
connection could be made to a Xtatham strain gauge. The injection pressure could then be measured during perfusion. The flow and pressure data were used to calculate the peripheral vascular resistance. The femoral artery was cannulated and fitted with a connection that allowed rapid hemorrhage of the animal and also allowed systemic blood pressure measurements to be made by means of a second Statham pressure transducer. The femoral vein was cannulated and fitted with a funnel for rapid transfusion of the animal’s blood. Heparin (3 mg. per kilogram) was used as the anticoagulant. Color photographs were made of the gingiva with a 35 mm. reflex camera fitted with a synchronized ring flash and a close-up extension tube. Blood volume measurements were made by the dye dilution technique,3 and hemorrhage was limited to 20 per cent of the calculated blood volume. Tooth transluminosity was monitored by means of a photoconductive device which could be cla.mped directly on the tooth. Changes in tooth optical density are related to blood-flow surges in the pulp tissue that occur with each heart beat.4
Table
I
A?&?Ml.l
lturfber
Blood
volme
(0.0.)
Femoral blocd
Yc&?lmlzller
Optical
Pm-f U.&n
pream.re
perfudm presswe
dfm&g p&e height (9m.)
rate (C.C./?nin.)
170/110 1lO)SO 17moo 150;115 190/152 14OJ105 163/110
140 130 125 145 160 135 170
8
3.88 3.88 3.88 3.88 3.88 3.88 3.88 3.88
Cmtrol ,?Pwmwr0mmts Average
PRU:
33
1
i
3 4 5 6 7
740 792 783 560 635 862 526
149
700 Aftw
7
8
hemorrhage SO
Average PRU: i
792 740
3 4
783 560
6" 7 Mean After
9" 8 :
55/30 @s/55
100
4
3.88
98/78 100/75
110 l"d8
5 6
3.88 3.88
862 635 5,26 -KG-
125/100 75/50 100/65 93/65
115 150 117
Ii 4
3.88 3.88 3.88
740 792 783
160/110 120/85 170/110
150 145 115
6 s"
3.88 3.88 3.88
635 560 862 526 700
165/120 14tqllO 175/135 165/95 157/109
158 145 ii:
7 i
4
retrmwfwakn 45
Average PRU:
% 6 7 Mean
175
7
3.88 3.88 3.88 3.88
Volume 26 Number 4
Vascular
response
to brief severe hemorrhage 549
Pig. 1. Left: A view of the oral mucous membrane and gingiva before hemorrhage. Right: The mucous membranes and gingivae of the same animal after hemorrhage, showing the intense blanching that occurs.
Volume 26 Number 4
Vascular response to brief severe hemorrhage 551
RESULTS
The control group of measurements showed that an average mandibular pressure of 129 mm. Hg. was required to perfuse the mandibular artery at a rate of 3.88 CC. per minute (Table I). These data were used to compute the prehemorrhage peripheral resistance of this vascular bed, and an average value of 33 was found. The same measurements and calculations were used following hemorrhage of the animal (to the extent of 20 per cent of its blood volume) and yielded a value of peripheral resistance of 30. Retransfusion raised the peripheral resistance to an average of 45. During the course of the hemorrhage, an intense blanching of the gingiva and mucous membranes of the mouth occurred (Fig. 1). Blanching and, presumably, vasoconstriction were not immediately reversed upon retransfusion but persisted fo’r as long as 2 hours after retransfusion. Retransfusion, however, was always very effective in restoring the systemic blood pressure. The systemic blood pressure measured from the femoral artery averaged 157/109 prior to hemorrhage. It dropped to 75/65 immediately after hemorrhage but returned to control values following retransfusion of the animal’s blood. Fig. 2 shows a typical recording of femoral blood pressure, perfusion pressure, and changes in tooth transluminosity. The optical density pulses which occur during each heart cycle are greatly reduced during the period of hemorrhagic hypotension but return toward normal as the systemic blood pressure is restored.
Fig. 3. Recording of the effects of hemorrhage on tooth transluminosity, femoral blood pressure, back pressure of the mandibular artery, and perfusion pressure in the mandibular artery. The mandibular back pressure (lower trace) resulta from anastomotic blood vessel connections (for example, the mandibular symphysis) . The tooth transluminosity (upper trace) represents blood-flow surges within the pulpal blood vessels. Both back pressure in the mandibular artery and the height of the transluminosity pulses are reduced coincidently with the fall in femoral pressure.
552
Bishop and Dorma%
O.S., O.M. & O.P. October, 1968
DISCUSSION
An obvious vasoconstriction of superficial vessels of the gingiva, mucous membranes, and pulp occurred immediately after bleeding and the gingiva and mucous membranes did not return to normal for some time following restoration of the animal’s blood volume and systemic blood pressure. The blood-flow pulses in the pulp promptly increased to normal as soon as the systemic blood pressure was restored. During the time that intense blanching of the gingiva and mucous membranes could be seen by visual inspection, the peripheral vascular resistance was found by direct measurement to be lowered. Decreased resistance to the flow of blood in the mandibula,r a,rtery in the face of constriction in some areas supplied by this vessel (for example, the gingiva) may be explained if we assume that other vessels open so that the runoff from the artery is increased. The occurrence of arteriovenous anastomoses has been reported in oral tissues involved in periodontosis5 a.nd have been shown to increase during development of experimental periodontal disease in dogs.6 A loss of neurogenic control may contribute to the reduction in total vascular resistance and influence the development of irreversibility in hemorrhagic shock in dogs.7 The anastomosesthat connect the branches of the mandibular artery to its venous drainage may fail to constrict in response to hemorrhage as much as those of the capillaries of the gingiva and mucosa. The apparent peripheral resistance decrease would then result from the increased flow of the blood out of the artery into the venous drainage which bypasses the capillary beds. A second explanation of the finding that vasoconstriction occurs following hemorrhage can be based upon the existence of artery-to-artery shunts. If increased artery-to-artery shunting of blood flow occurs, the resistance to “runoff” from the mandibular artery would decrease. The utility of this mechanism to survival of the organism could then be stated as follows: An intense vasoconstriction of the capillary beds supplied by the mandibular artery, together with a relaxation of the constrictor tone in the vessels that form artery-to-artery shunts, could allow a preferential shunting to favor other vesselsof the head (for example, the brain). SUMMARY
The peripheral resistance of the vascular bed supplied by the mandibular artery was measured before and after hemorrhage of 20 per cent of the blood volume. Blanching of the gingiva and oral mucosa was seen during the hemorrhage and for some time following restoration of the blood volume by retransfusion. The PRU of the mandibular vascula’r bed dropped slightly following hemorrhage and increased by about 25 per cent following retransfusion. The period immediately following hemorrhage was characterized by blanching (and presumably vasconstriction) in the oral mucosa while the peripheral resistance of the mandibular vascular bed was reduced. Increased artery-to-artery or arteryto-vein shunting is offered as a possible explanation. REFERENCES
1. Field, L. W., and Laverty, R.: Nervous the Rat, J. Physiol. 143: 213-225, 1958.
and Humoral
Response
to Acute
Blood
Loss in
Volume 26 Number 4
Vascular response
to brief
severe
hemorrhage
553
2. Walker, W. F., Zieli, M. S., Reutter, F. W., Shoemaker, W. C., Friend, D., and Moore, F. D.: Adrenal Medullary Secretion m Hemorrhagic Shock, Am. J. Physiol. 197: 773-780, 1959. 3. Hepler, 0. E.: Manual of Clinical Laboratory Methods, Spri@eld, Ill., 1960, Charles C Thomas, Publisher, pp. 46-47. 4. Upthegrove, D. D., Bishop, J. G., and Dorman, H. L.: A Method of Detection of Blood Flow in the Dental Pulp, J. D. Res. 45: 1115-1119, 1966. 5. Provenza D. W., Biddington, W. R., and Cheng, T. C.: Studies on the Etiology of Periododosis, ORAL Sm., ORAL MED. & ORAL PATH. 12: 676,1959. 6. Dorman, H. L., and Bishop, J. G.: Cha.ng@ in Vascula.r Resistance Following Induction of Chronic Unilateral Periodontitis in Dogs, J. D. Res. 41: 453-458, 1962. 7. Rothe, C. F., Love, J. R., a.nd Selkurt E. E.: Control of Total Vascular R&stance in Hemorrhagic Shock in Dogs, Circulation kes. 12: 667-675, 1963.