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Effect of 50 per cent sodium diatrizoate (Hypaque) on blood flow in the internal carotid artery of man
Effect
of 50 per
on blood
flow
cent sodium in the
internal
diatrizoate carotid
(Hypaque) artery
of man
George T. T&all, M.D.* Joseph C. Greenfield, Jr., M.D. William Dillingham, B.A. J. Fletcher Lee, M.D. Durham, N. C.
C
onsiderable investigative work has been done in an effort to define the changes in circulatory dynamics which follow the intravascular administration of contrast media. Alterations in blood pressure, heart rate, and cerebral blood flow have been studied in various experimental animals.‘-” Also, changes have been noted in both the blood pressure and the pulse rate in man during cerebral angiography.12-I5 However, the response of the cerebral vessels to the intracarotid administration of contrast media is debated; some workers believe that vasospasm occurs,*.7J6 whereas others believe that vasodilatation is the principal change.6*gJ1f1’ To our knowledge, no quantitative measurements of either partial or total cerebral blood flow have been obtained after the injection of contrast media into the internal carotid artery of man. Therefore, a study of simultaneously determined flow and pressure in the internal carotid artery of man after the intracarotid administration of 50 per cent sodium diatrizoate (Hypaquet), a contrast agent currently in use in many clinics for cerebral angiography, should clarify this question. From
Method
and
case material
These studies were made in 10 male patients who were undergoing surgery on the carotid vessels in the neck so that a cancer-chemotherapy drug% could be infused directly into the internal carotid artery. Craniotomy and subtotal resection of a brain tumor had been performed from 10 to 14 days prior to the dissection in the neck in each subject. In 6 cases the tumor type was a glioblastoma multiforme (Patients 1, 2, 5-8, Table I); in 3 patients, an astrocytoma (Patients 3, 4, and 10, Table I); and in 1 patient, an oligodendroglioma (Patient 9, Table I). The surgical procedure on the neck was done using general anesthesia, consisting of a mixture of halothane (0.5 per cent), nitrous oxide (49.5 per cent), and oxygen (50 per cent). The common carotid and proximal portions of the external and internal carotid arteries were dissected free from surrounding tissue. A polyvinyl catheter (No. VX-044) was inserted into the superior thyroid artery and threaded down the vessel so that the tip of the catheter was just within the carotid bifurcation. The remaining branches of the
the Division of Neurosurgery and the Department of Medicine. Luke rnirersity Metical Veterans Administration Hospital, Durham. N. C. Received for publication April 13, 1964. *Address: Veterans Administration Hospital, Fulton St. and Erwin Rd., Durham, N. C. tManufactured by Winthrop Laboratories, New York, N.Y. Sin each case. S-112, a chloroethylthioacetamide was used in a dosage of 0.08 mg. per kilogram
21.5
Center,
and
of body
weigilt.
Daham
ipsilateral external carotid arter), were then ligated. The hinged probe of a KolinKado type of electromagnetic flo\vmeter (EMF) was placed about the common carotid artery approsimately 4 cm. prosima1 to the bifurcation.‘” A Crutchfield clamp* 13.a~ also placed about this vessel distal to the EMF probe. The stem of the Crutchfield clamp, polyvinyl catheter, and insulated leads to the EMF probe lvere brought out through the edges of the wound, which was closed in anatomic layers with silk sutures. Measurements of flow and pressure in the internal carotid artery xvere obtained in the alvake state in 9 patients 2 to 8 hours after the general anesthesia had been discontinued. The patients received no other medication prior to this procedure and \vere studied while the). were in the supine position. After the satisfactory recording of control flow and pressure, a rapid injection of 50 per cent sodium diatrizoate (3 to 10 C.C. in each patient, Table I) was given into the internal carotid artery through the polyvinyl catheter. Recordings of both flow and pressure aere obtained continuously for 60 seconds after this injection. In one patient (Patient 3, Table I), these measurelllents were made while the patient was still under general anesthesia. Blood tlow \s:as measured \vith a KolinKado t\:pe EMF. 1XThe zero flow reference was obtained by temporarilv occluding the artery with the Crutchkeld clamp. The EMF xvas calibrated after the procedure by passing knolvn quantities of physiologic saline through the probes in a given period of time. The calibration factor for the probes, i.e., flow per unit EMF signal, remained within a S.D. of ~5.4 per cent during the period of this study. Arterial pressure was measured with a Statham P23Db strain gauge connected to the polyvinyl catheter. Mean values of both pressure and Aow were obtained by electrical integration. In order to assess the physiologic state of the patients prior to the intracarotid administration of 50 per cent sodium diatrizoate, samples of blood were drawn from the brachial artery for measurement
of p(X)? and p&. These dcternlinations were done with an Instrumentation Laboratories meter, Model 113. The lumbar subarnchnoid space x’as entered \\rith an 18-gauge lunlbar puncture needle from 30 to 60 minutes after the intracarotid administration of 50 per cent sodium diatrizoate. The cerebrospinal fluid pressure was measured at this time with a Statham P23Db transducer connected directly to the needle. All recording of data leas carried out on a Sanborn Model 850 eightchannel direct-writing oscillograph. .%fter the studies had been completed, the cancer-chemotherapy, drug was infused through the pol\vinyI catheter, and the patients were then returned to the operating room for removal of the Crutchfield clamp, EMF probe, and the catheter. Standard statistical methods were used in analyzing data. The peripheral vascular resistance (p.v.r.) of the region supplied b,* the internal carotid artery was calculated as: Mean blood pressure, mm. Hg p.v.r. = -~-. Mean blood flow, C.C. min. Results
;\lthough the blood pressure and Now were measured continuously, only values obtained during the control state and at 5, 10, 20, 30, and 60 seconds after completion of the injection of 50 per cent sodium diatrizoate were analyzed. These data are summarized in Table I and illustrated in Fig. 1. The average control heart rate was 105 beats per minute. In 2 subjects (Patients 1 and 2, Table I), a period of asystole that lasted for 2 and 3 seconds, respectively, occurred shortly after the injection. Thus, the S-second data on these subjects were not included. The heart rate decreased at 5 and 10 seconds to a mean value of 96 and 88 beats per minute, respectively. These differences are significant (p < .05) from the control values. The heart rate returned to control levels at 20 seconds and remained constant. There was an increase in the flow of blood in the internal carotid artery after the injection of 50 per cent sodium diatrizoate in every case. The average value for control blood flow was 160 C.C. per
Efect
of sodium diatrizoate
minute (S.D. ~43). The average flow for the group increased at 5 (178 CC. per minute) and 10 seconds (217 C.C. per minute), reaching its greatest average value at 20 seconds (242 C.C. per minute, SD. k89). The difference from contro1 flow at 20 seconds is significant (p < .Ol). The average value for flow at 30 and 60 seconds was 221 and 193 C.C. per minute, respectively. The average control value for mean arterial pressure was 103 mm. Hg (S. D. h20). Although the pressure rose slightly at 10 and 20 seconds, the increase was not significant (p > .OS). The average value for control p.v.r. was 0.69 (S. D. hO.24). The p.v.r. decreased significantly (p < .05) at both 5 seconds [0.61 (S.D. ~0.19) ] and at 10 seconds [0.59 (S.D. hO.24) 1. At 20 seconds the p.v.r. fell significantly (p < .Ol) to 0.49 (S.D. &0.18), its lowest value. At 30 and 60 seconds the p.v.r. was 0.51 (SD. ~0.14) and 0.57 (S.D. &0.16), respectiveIy. Discussion
The control values for flow in a single internal carotid artery in these 10 patients ranged from 111 to 220 C.C. per minute, with an a.verage for the group of 160 C.C. per minute. These values are less than might be expected for normal subjects. However, these studies were carried out in a group of patients in whom craniotomy and partial resection of a brain tumor had been performed from 10 to 14 days prior to the study. The fact that the major part of the tumor and some normal brain tissue supplied by this internal carotid artery had been removed probably contributed to the seemingly low flow. Other factors were the slightly reduced values for pCOZ and the elevated pressure of the cerebrospinal fluid. The vascular responses which follow the injection of various contrast media into the carotid artery in experimental animals have been studied extensively by other investigators. K?tgstrom, Lindgren, and T6rne11gJ0obtained an increase in cerebral blood flow in dogs and cats after the injection of ‘contrast media into the internal carotid artery. The increase in blood flow after the injection of sodium diatrizoate never exceeded 100 per cent, and the
on blood $0~ in carotid artery
217
275r
0.
5 E”” s
1
30 x, 4o e0
Time (Seconds)
Fig. 1. Average values for blood flow, blood pressure, heart rate, and peripheral vascular resistance during the control state and after the injection of 50 per cent diatrizoate in 10 subjects. The small cross vertical bars represent the 4 standard errors.
duration of the effect lasted approximately 2 minutes. The results of the present study in man are consistent with these findings. The increase in blood flow in the internal carotid artery after the intracarotid injection of 50 per cent diatrizoate shown in this study would imply that the mechanism of the occasional adverse clinical reaction to arteriography is not due to a decrease in blood flow, but rather to some other cause. A transient decrease in blood pressure and heart rate after injection of contrast media into the circulatory system has been noted previously in man and experimental animals. In cats, Lindgren and Tornells reported a decrease in blood pressure and heart rate after the injection of sodium acetrizoate into the carotid artery. In carotid angiography with sodium acetrizoate, Gritz13 observed changes in blood pressure and heart rate in most of his patients. The changes usually consisted of a decrease in blood pressure of short duration, with an associated bradycardia and arrhythmia. Fischer, Eckstein, and
Perrett’j noted a decrease in blood pressure and bradycardia in patients who were underoing cerebral angiography with 60 per cent Renografin (methylglucamine salt of the diatrizoate compound) and 50 per cent sodium diatrizoate. In general, these responses were minor and brief. On the other hand, Smolik and NashI found no significant changes in blood pressure or heart rate in patients during carotid angiography carried out with 50 per cent sodium diatrizoate. In the present study,, a significant decrease in heart rate that lasted for approximately 20 seconds occurred after the intracarotid injection of 50 per cent sodium diatrizoate. There w;ere no significant or consistent changes in arterial pressure. An increase in the flow of blood to the brain after the administration of contrast media into its vascular bed is not a finding restricted to this organ. Increased flow to other organs after the administration of contrast agents has been reported by several investigators. Sakolq noted an in-
crease in femoral arterial flo\v in both dogs and man after the injection of contrast media, included among which were sodium acetrizoate, iodopyracet, and sodium diatrizoate. He believed that the increased flow resulted from a lowering of vascular resistance through vasodilatation. Lindgren and TBrnellr observed vasodilatation and an increase in blood flow in the skeletal muscle and intestine of cats after the injection of sodium acetrizoate and sodium diatrizoate into the vascular bed of these tissues. Although some workers have reported vasospasm,4n7**6 most investigators have found that the principal vascular reaction to an infusion of contrast medium is transient vasodilatation. In studies in cats, Schmidt6 observed vasodilatation in the pial arteries after the injection of contrast media into the carotid artery. He did not observe vasospasm at any time, even when high concentrations of the contrast media were used. In pathologic studies, Bloor, Wrenn, and Margolis” noted dilatation
Table I. E#ect of the intracarotid administration of 30 per cent sodium diatrizoate on mean Hood flow and intraaascular pressure in the internal carotid artery
-___-__--_-Cerebvospinal fluid pressure (wzwz. H20) 1.
45
a
2.
39
10
3.*
41
3
4.
38
8
5.
49
3
35.8
81.0
--
6.
32
8
38.0
78.0
276
7.
52
8
38.6
64.0
358
8.
72
8
38.0
69.0
19.5
9.
50
8
32.8
81.5
250
10.
36
8
36 8
75.0
3.58
*Values obtained I;: Flow, in cubic
during general anesthesia. centimeters wr minute.
32 3
59.0
---
37.0
78.5
----
24 0
P: Pressure.
200.0
--
--
260
in millimeters
of mercury.
Control / F P F P F P F P F P F P F P F P F P F P
111 106 207 88 137 149 205 85 13.5 108 154 88 220 128 113 96 198 92 117 88
--~~~145 149 205 82 144 88 154 88 294 140 161 104 186 88 135 85
132 106 423 64 150 152 2.55 90 148 108 176 96 308 160 161 108 2.50 112 165 88
204 111 467 88 175 141 238 90 172 112 190 96 290 128 178 96 281 92 22.5 100
204 111 449 102 17.5 141 238 87 197 104 176 84 248 120 1.58 98 229 92 135 90
104 311 90 163 141 230 87 172 104 154 88 234 120 133 96 213 96 128 90
Effect of sodium diatrizoate
of the parenchymal vessels of all caliber as an early change after cerebral angiography. Although the response of localized areas of the cerebral vasculature may vary, the findings of our study imply that the overall response of the cerebral blood vessels to the injection of contrast media is one of immediate vasodilatation. Since the p.v.r. decreased immediately after the injection and remained depressed throughout the observation period, no evidence for generalized vasospasm was found.
4.
5.
6.
7.
Summary
1. The effect of the intracarotid injection of 50 per cent sodium diatrizoate on flow in the internal carotid artery, intravascular pressure in the carotid artery, and heart rate has been determined in 10 patients. 2. The average control value of mean flow in these subjects was 160 C.C. per minute. After the injection of 50 per cent sodium diatrizoate there was an immediate increase in flow in the internal carotid artery which reached an average peak at 20 seconds of 242 C.C. per minute for the group, and which lasted throughout the observation period of 60 seconds. 3. There were no consistent or significant changes in arterial pressure. 4. The heart rate decreased significantly immediately after injection, but returned to normal in 20 seconds. 5. There was a significant decrease in peripheral resistance in the vascular bed of the injected internal carotid artery which began within 5 seconds, and which persisted throughout the observation period of 60 seconds. 6. These data show that the over-all vascular response after an intracarotid injection of 50 per cent sodium diatrizoate is that of vasodilatation. We Maxine
are indebted Mangum
to Mr. Ezra Hayes for their technical
and Mrs. assistance.
REFERENCES 1. Lindgren, P., and Torneli, G.: Blood circulation during and after peripheral arteriography, Acta radiol. 49:425, 1958. 2. Lindgren, P.: Carotid angiography with triiodobenzoic acid derivatives, Acta radiol. 51:353, 1959. 3. Lindner, D. W., Martin, F. A., Webster, J. E., and Gurdjian, E. S.: An evaluation of Hypaque
8.
9.
10.
11.
12.
13.
on
blood flow in carotid artery
219
sodium (WIN 8308-3) for cerebral angiography, Surg. Forum 7:553, 1956. Foltz, E. L., Thomas, L. B., and Ward, A. A.: The effects of intracarotid Diodrast, J. Neurosurg. 9:68, 1952. Linderen. - , P.. , and Tornell. G.: Blood oressure and heart rate responses in carotid angiography with sodium acetrizoate (Triurol). An experimental study in cats, Acta radiol. 50:160, 1958. Schmidt, H. W.: The behavior of the pial vessels during and after the intracarotid injection of roentgen contrast media, Acta radiol. 44:100, 1955. Ingvar, D. H., and Sijderberg, LT.: Cerebral vasomotor tone and EEG during injections of Umbradil, Acta radiol. 47:185, 1957. Soderberg, U., and Weckman, N.: Blood pressure changes in cerebral arteries during carotid angiography with Umbradil, Acta radiol. 50:317, 1958. K%gstrom, E., Lindgren, P., and Tornell, G.: Circulatory disturbances during cerebral angiography. An experimental evaluation of certain contrast media, Acta radiol. 54:3, 1960. Kagstrom, E., Lindgren, P., and Tiirnell, G.: Changes in cerebral circulation during carotid angiography with sodium acetrizoate (Triurol) and sodium diatrizoate (Hypaque). An experimental study, Acta radiol. 50:151, 1958. KQgstrom, E., and Lindgren, P.: Changes in intracranial pressure during carotid angiography. An experimental investigation in cats, Acta radiol. 54:379, 1960. Smolik, E. A., and Nash, F. P.: Experiences with Hypaque, a new contrast medium in ;;$ral angiography, Missouri Med. 53:99,
Greitz, T.: A radiologic study of the brain circulation by rapid serial angiography of the carotid artery, Acta radiol., Suppl. 140, 19.56, p:123. 14. Robb, G. P., and Steinberg, I.: Visualization of the chambers of the heart, the pulmonary circulation, and the great blood vessels in man. A practical method, Am. J. Roentgenol. 41:1, 1939. 15. Fischer, H. W., Eckstein, J. W., and Perrett, G.: Comparison of the cardiovascular effects of contrast media in cerebral angiography in man. 1. Neurosure. 19:943.1962. 16. Raynor, R. B., &rd Ross, G.: Arteriography and vasospasm. The effects of intracarotid contrast media on vasospasm, J. Neurosurg. 17:1055, 1960. 17. Bloor, B. M., Wrenn, F. R., Jr., and Margolis, G.: An experimental evaluation of certain contrast media used for cerebral angiography; electroencephalographic and histopathological correlations, J. Neurosurg. 8:.585, 1951. 18. Kolin, A., and Kado, R. T.: Miniaturization of the electromagnetic blood flow meter and its use for the recording of circulatory responses of conscious animals to sensory stimuli, Proc. National Acad. SC. 45:1312,1959. 19. Sako, Y.: Hemodynamic changes during arteriography, J.A.M.A. 183:253, 1963.
of 50 per
on blood
flow
cent sodium in the
internal
diatrizoate carotid
(Hypaque) artery
of man
George T. T&all, M.D.* Joseph C. Greenfield, Jr., M.D. William Dillingham, B.A. J. Fletcher Lee, M.D. Durham, N. C.
C
onsiderable investigative work has been done in an effort to define the changes in circulatory dynamics which follow the intravascular administration of contrast media. Alterations in blood pressure, heart rate, and cerebral blood flow have been studied in various experimental animals.‘-” Also, changes have been noted in both the blood pressure and the pulse rate in man during cerebral angiography.12-I5 However, the response of the cerebral vessels to the intracarotid administration of contrast media is debated; some workers believe that vasospasm occurs,*.7J6 whereas others believe that vasodilatation is the principal change.6*gJ1f1’ To our knowledge, no quantitative measurements of either partial or total cerebral blood flow have been obtained after the injection of contrast media into the internal carotid artery of man. Therefore, a study of simultaneously determined flow and pressure in the internal carotid artery of man after the intracarotid administration of 50 per cent sodium diatrizoate (Hypaquet), a contrast agent currently in use in many clinics for cerebral angiography, should clarify this question. From
Method
and
case material
These studies were made in 10 male patients who were undergoing surgery on the carotid vessels in the neck so that a cancer-chemotherapy drug% could be infused directly into the internal carotid artery. Craniotomy and subtotal resection of a brain tumor had been performed from 10 to 14 days prior to the dissection in the neck in each subject. In 6 cases the tumor type was a glioblastoma multiforme (Patients 1, 2, 5-8, Table I); in 3 patients, an astrocytoma (Patients 3, 4, and 10, Table I); and in 1 patient, an oligodendroglioma (Patient 9, Table I). The surgical procedure on the neck was done using general anesthesia, consisting of a mixture of halothane (0.5 per cent), nitrous oxide (49.5 per cent), and oxygen (50 per cent). The common carotid and proximal portions of the external and internal carotid arteries were dissected free from surrounding tissue. A polyvinyl catheter (No. VX-044) was inserted into the superior thyroid artery and threaded down the vessel so that the tip of the catheter was just within the carotid bifurcation. The remaining branches of the
the Division of Neurosurgery and the Department of Medicine. Luke rnirersity Metical Veterans Administration Hospital, Durham. N. C. Received for publication April 13, 1964. *Address: Veterans Administration Hospital, Fulton St. and Erwin Rd., Durham, N. C. tManufactured by Winthrop Laboratories, New York, N.Y. Sin each case. S-112, a chloroethylthioacetamide was used in a dosage of 0.08 mg. per kilogram
21.5
Center,
and
of body
weigilt.
Daham
ipsilateral external carotid arter), were then ligated. The hinged probe of a KolinKado type of electromagnetic flo\vmeter (EMF) was placed about the common carotid artery approsimately 4 cm. prosima1 to the bifurcation.‘” A Crutchfield clamp* 13.a~ also placed about this vessel distal to the EMF probe. The stem of the Crutchfield clamp, polyvinyl catheter, and insulated leads to the EMF probe lvere brought out through the edges of the wound, which was closed in anatomic layers with silk sutures. Measurements of flow and pressure in the internal carotid artery xvere obtained in the alvake state in 9 patients 2 to 8 hours after the general anesthesia had been discontinued. The patients received no other medication prior to this procedure and \vere studied while the). were in the supine position. After the satisfactory recording of control flow and pressure, a rapid injection of 50 per cent sodium diatrizoate (3 to 10 C.C. in each patient, Table I) was given into the internal carotid artery through the polyvinyl catheter. Recordings of both flow and pressure aere obtained continuously for 60 seconds after this injection. In one patient (Patient 3, Table I), these measurelllents were made while the patient was still under general anesthesia. Blood tlow \s:as measured \vith a KolinKado t\:pe EMF. 1XThe zero flow reference was obtained by temporarilv occluding the artery with the Crutchkeld clamp. The EMF xvas calibrated after the procedure by passing knolvn quantities of physiologic saline through the probes in a given period of time. The calibration factor for the probes, i.e., flow per unit EMF signal, remained within a S.D. of ~5.4 per cent during the period of this study. Arterial pressure was measured with a Statham P23Db strain gauge connected to the polyvinyl catheter. Mean values of both pressure and Aow were obtained by electrical integration. In order to assess the physiologic state of the patients prior to the intracarotid administration of 50 per cent sodium diatrizoate, samples of blood were drawn from the brachial artery for measurement
of p(X)? and p&. These dcternlinations were done with an Instrumentation Laboratories meter, Model 113. The lumbar subarnchnoid space x’as entered \\rith an 18-gauge lunlbar puncture needle from 30 to 60 minutes after the intracarotid administration of 50 per cent sodium diatrizoate. The cerebrospinal fluid pressure was measured at this time with a Statham P23Db transducer connected directly to the needle. All recording of data leas carried out on a Sanborn Model 850 eightchannel direct-writing oscillograph. .%fter the studies had been completed, the cancer-chemotherapy, drug was infused through the pol\vinyI catheter, and the patients were then returned to the operating room for removal of the Crutchfield clamp, EMF probe, and the catheter. Standard statistical methods were used in analyzing data. The peripheral vascular resistance (p.v.r.) of the region supplied b,* the internal carotid artery was calculated as: Mean blood pressure, mm. Hg p.v.r. = -~-. Mean blood flow, C.C. min. Results
;\lthough the blood pressure and Now were measured continuously, only values obtained during the control state and at 5, 10, 20, 30, and 60 seconds after completion of the injection of 50 per cent sodium diatrizoate were analyzed. These data are summarized in Table I and illustrated in Fig. 1. The average control heart rate was 105 beats per minute. In 2 subjects (Patients 1 and 2, Table I), a period of asystole that lasted for 2 and 3 seconds, respectively, occurred shortly after the injection. Thus, the S-second data on these subjects were not included. The heart rate decreased at 5 and 10 seconds to a mean value of 96 and 88 beats per minute, respectively. These differences are significant (p < .05) from the control values. The heart rate returned to control levels at 20 seconds and remained constant. There was an increase in the flow of blood in the internal carotid artery after the injection of 50 per cent sodium diatrizoate in every case. The average value for control blood flow was 160 C.C. per
Efect
of sodium diatrizoate
minute (S.D. ~43). The average flow for the group increased at 5 (178 CC. per minute) and 10 seconds (217 C.C. per minute), reaching its greatest average value at 20 seconds (242 C.C. per minute, SD. k89). The difference from contro1 flow at 20 seconds is significant (p < .Ol). The average value for flow at 30 and 60 seconds was 221 and 193 C.C. per minute, respectively. The average control value for mean arterial pressure was 103 mm. Hg (S. D. h20). Although the pressure rose slightly at 10 and 20 seconds, the increase was not significant (p > .OS). The average value for control p.v.r. was 0.69 (S. D. hO.24). The p.v.r. decreased significantly (p < .05) at both 5 seconds [0.61 (S.D. ~0.19) ] and at 10 seconds [0.59 (S.D. hO.24) 1. At 20 seconds the p.v.r. fell significantly (p < .Ol) to 0.49 (S.D. &0.18), its lowest value. At 30 and 60 seconds the p.v.r. was 0.51 (SD. ~0.14) and 0.57 (S.D. &0.16), respectiveIy. Discussion
The control values for flow in a single internal carotid artery in these 10 patients ranged from 111 to 220 C.C. per minute, with an a.verage for the group of 160 C.C. per minute. These values are less than might be expected for normal subjects. However, these studies were carried out in a group of patients in whom craniotomy and partial resection of a brain tumor had been performed from 10 to 14 days prior to the study. The fact that the major part of the tumor and some normal brain tissue supplied by this internal carotid artery had been removed probably contributed to the seemingly low flow. Other factors were the slightly reduced values for pCOZ and the elevated pressure of the cerebrospinal fluid. The vascular responses which follow the injection of various contrast media into the carotid artery in experimental animals have been studied extensively by other investigators. K?tgstrom, Lindgren, and T6rne11gJ0obtained an increase in cerebral blood flow in dogs and cats after the injection of ‘contrast media into the internal carotid artery. The increase in blood flow after the injection of sodium diatrizoate never exceeded 100 per cent, and the
on blood $0~ in carotid artery
217
275r
0.
5 E”” s
1
30 x, 4o e0
Time (Seconds)
Fig. 1. Average values for blood flow, blood pressure, heart rate, and peripheral vascular resistance during the control state and after the injection of 50 per cent diatrizoate in 10 subjects. The small cross vertical bars represent the 4 standard errors.
duration of the effect lasted approximately 2 minutes. The results of the present study in man are consistent with these findings. The increase in blood flow in the internal carotid artery after the intracarotid injection of 50 per cent diatrizoate shown in this study would imply that the mechanism of the occasional adverse clinical reaction to arteriography is not due to a decrease in blood flow, but rather to some other cause. A transient decrease in blood pressure and heart rate after injection of contrast media into the circulatory system has been noted previously in man and experimental animals. In cats, Lindgren and Tornells reported a decrease in blood pressure and heart rate after the injection of sodium acetrizoate into the carotid artery. In carotid angiography with sodium acetrizoate, Gritz13 observed changes in blood pressure and heart rate in most of his patients. The changes usually consisted of a decrease in blood pressure of short duration, with an associated bradycardia and arrhythmia. Fischer, Eckstein, and
Perrett’j noted a decrease in blood pressure and bradycardia in patients who were underoing cerebral angiography with 60 per cent Renografin (methylglucamine salt of the diatrizoate compound) and 50 per cent sodium diatrizoate. In general, these responses were minor and brief. On the other hand, Smolik and NashI found no significant changes in blood pressure or heart rate in patients during carotid angiography carried out with 50 per cent sodium diatrizoate. In the present study,, a significant decrease in heart rate that lasted for approximately 20 seconds occurred after the intracarotid injection of 50 per cent sodium diatrizoate. There w;ere no significant or consistent changes in arterial pressure. An increase in the flow of blood to the brain after the administration of contrast media into its vascular bed is not a finding restricted to this organ. Increased flow to other organs after the administration of contrast agents has been reported by several investigators. Sakolq noted an in-
crease in femoral arterial flo\v in both dogs and man after the injection of contrast media, included among which were sodium acetrizoate, iodopyracet, and sodium diatrizoate. He believed that the increased flow resulted from a lowering of vascular resistance through vasodilatation. Lindgren and TBrnellr observed vasodilatation and an increase in blood flow in the skeletal muscle and intestine of cats after the injection of sodium acetrizoate and sodium diatrizoate into the vascular bed of these tissues. Although some workers have reported vasospasm,4n7**6 most investigators have found that the principal vascular reaction to an infusion of contrast medium is transient vasodilatation. In studies in cats, Schmidt6 observed vasodilatation in the pial arteries after the injection of contrast media into the carotid artery. He did not observe vasospasm at any time, even when high concentrations of the contrast media were used. In pathologic studies, Bloor, Wrenn, and Margolis” noted dilatation
Table I. E#ect of the intracarotid administration of 30 per cent sodium diatrizoate on mean Hood flow and intraaascular pressure in the internal carotid artery
-___-__--_-Cerebvospinal fluid pressure (wzwz. H20) 1.
45
a
2.
39
10
3.*
41
3
4.
38
8
5.
49
3
35.8
81.0
--
6.
32
8
38.0
78.0
276
7.
52
8
38.6
64.0
358
8.
72
8
38.0
69.0
19.5
9.
50
8
32.8
81.5
250
10.
36
8
36 8
75.0
3.58
*Values obtained I;: Flow, in cubic
during general anesthesia. centimeters wr minute.
32 3
59.0
---
37.0
78.5
----
24 0
P: Pressure.
200.0
--
--
260
in millimeters
of mercury.
Control / F P F P F P F P F P F P F P F P F P F P
111 106 207 88 137 149 205 85 13.5 108 154 88 220 128 113 96 198 92 117 88
--~~~145 149 205 82 144 88 154 88 294 140 161 104 186 88 135 85
132 106 423 64 150 152 2.55 90 148 108 176 96 308 160 161 108 2.50 112 165 88
204 111 467 88 175 141 238 90 172 112 190 96 290 128 178 96 281 92 22.5 100
204 111 449 102 17.5 141 238 87 197 104 176 84 248 120 1.58 98 229 92 135 90
104 311 90 163 141 230 87 172 104 154 88 234 120 133 96 213 96 128 90
Effect of sodium diatrizoate
of the parenchymal vessels of all caliber as an early change after cerebral angiography. Although the response of localized areas of the cerebral vasculature may vary, the findings of our study imply that the overall response of the cerebral blood vessels to the injection of contrast media is one of immediate vasodilatation. Since the p.v.r. decreased immediately after the injection and remained depressed throughout the observation period, no evidence for generalized vasospasm was found.
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Summary
1. The effect of the intracarotid injection of 50 per cent sodium diatrizoate on flow in the internal carotid artery, intravascular pressure in the carotid artery, and heart rate has been determined in 10 patients. 2. The average control value of mean flow in these subjects was 160 C.C. per minute. After the injection of 50 per cent sodium diatrizoate there was an immediate increase in flow in the internal carotid artery which reached an average peak at 20 seconds of 242 C.C. per minute for the group, and which lasted throughout the observation period of 60 seconds. 3. There were no consistent or significant changes in arterial pressure. 4. The heart rate decreased significantly immediately after injection, but returned to normal in 20 seconds. 5. There was a significant decrease in peripheral resistance in the vascular bed of the injected internal carotid artery which began within 5 seconds, and which persisted throughout the observation period of 60 seconds. 6. These data show that the over-all vascular response after an intracarotid injection of 50 per cent sodium diatrizoate is that of vasodilatation. We Maxine
are indebted Mangum
to Mr. Ezra Hayes for their technical
and Mrs. assistance.
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blood flow in carotid artery
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