Diagnostic Radiology
Comparison of a Vasoconstrictor and a Vasodilator in Pharmacoangiography of Bone and Soft-Tissue Tumors 1 Lei' Ekelund, M.D., Sven Laurin, M.D., and Anders Lunderqulst, M.D. The pharmacoangiographic effect of a vasoconstrictor (angiotensin) and a vasodilator (tolazoline) was compared in 18 patients with bone and soft-tissue tumors. Angiotensin was found to be the drug of choice in increasing diagnostic information on angiography. Ten to 15 J-Lg of angiotensin seems to be a convenient dose in the axillary, iliac, and femoral arteries. INDEX TERMS: Angiotensin. Bone neoplasms, diagnosis (Skeletal system, angiography, 4[8] .124) • Soft tissues, neoplasms. Tolazoline • Vasomotor system, effects of drugs on (Arteries of upper and lower extremities, pharmacological adjunct, 9[1].127; 9[2] .127)
Radiology 122:95-99, January 1977
HARMACOANGIOGRAPHY with both vasoconstrictors and vasodilators has been used for more than a decade to enhance demonstration of tumor vascularity. Recently it has also been found to be valuable in the diagnosis of bone and soft-tissue tumors (8, 10). We undertook a comparative investigation to determine whether a vasoconstrictor or a vasodilator is preferable for such angiographic studies.
Table I: Diagnostic Groups Comprising the Series of Bone and Soft-Tissue Tumors Studied
P
Diagnosis
MATERIAL AND METHODS
Eighteen patients (10 males and 8 females) 13-77 years of age were studied. Seven had primary malignant softtissue tumors, 4 had primary bone tumors, 2 had metastatic disease, and 5 had benign soft-tissue masses (TABLE I). Ten tumors were localized in the lower extremity, 4 in the upper extremity, and 4 in the pelvic region. Selective catheterization of the iliac, femoral, or axillary arteries was performed using a radiopaque catheter (l.d, 1.4 mm, o.d. 2.2 mm). Isopaque Cerebral (Nyegaard, Norway) was injected, with the rate and amount depending on the size of the artery. Fifteen to 20 minutes after routine angiography, 2-15 J.lg of angiotensin (Hypertensin N, Ciba, Switzerland) diluted in 10 ml of saline was injected by hand at a rate of about 5 ml per second. Fifteen to 45 seconds later, the examination was repeated using an equal amount of contrast medium but usually employing a somewhat slower injection rate than in the control study. Filming was also prolonged, usually consisting of one film per second for 12 seconds. Twenty to 30 minutes later, 25-50 mg of tolazoline in 10 ml of saline was injected slowly by hand. Contrast medium was injected approximately 30 seconds later, usually employing a faster rate of filming than that used for the control. In all instances, tolazoline, havinq a more long-lasting effect than angiotensin, was used for the last series. 1
No. of Cases
Fibrosarcoma Lipomyxosarcoma Liposarcoma Fibromyxosarcoma Mal ignant histiocytoma
2 (1 recurring) 2 1 1 1
Giant-cell tumor Chondrosarcoma Osteosarcoma
2
Metastatic cholangiocarcinoma Metastatic osteosarcoma
1 1
Lipoma Granulomatous inflammation Vascular malformation Muscle rupture
2 1 1 1
1 1
Following injection of angiotensin, most patients had an increased sensation of pain for a short time during angiography, and after tolazoline varying degrees of tachycardia occurred in all patients. Blood pressure was not monitored during drug injection or angiography, but no significant difference could be demonstrated at the end of the procedure. No serious complications were encountered. RESULTS
The results of pharmacoangiography with angiotensin and tolazoline are given in TABLE II. In five of the 7 primary malignant soft-tissue tumors, 4 of which were localized in the lower extremity-2 fibrosarcomas (one recurring), 1 liposarcoma, 1 lipomyxosarcoma, and 1 malignant histiocytoma-angiographic information was enhanced after 10-15 J.lg of angiotensin: more contrast medium accumulated within the tumor, the tumor was better demarcated, and in 2 cases arteriovenous shunting of contrast
From the Department of Diagnostic Radiology, University Hospital, Lund, Sweden. Accepted for publication in August 1976.
95
sjh
96
LEIF EKELUND AND OTHERS
January 1977
Fig. 1. Femoral angiograms of a 54-year-old woman with a poorly differentiated fibrosarcoma in the left thigh. A. Control series. B. After 15 fJ-g of angiotensin, accumulation of contrast medium within the tumor is increased. Arteriovenous shunting is also visible, though it was not demonstrated in the control series. The normal arteries are constricted. C. After 25 mg of tolazoline, diagnostic information is impaired compared to the control.
Table II:
No. of
Diagnostic Efficacy of Angiotensin and Tolazol ine Diagnostic Value of Angiotensin I mproved Unchanged Reduced
Diagnostic Value of Tolazol ine Improved Unchanged Reduced
Type of Lesion
Cases
Primary mal ignant soft-tissue tumor Primary bone tumor Metastasis Benign lesion
7
5
2
2
4
4 2 5
1 1
3 1 3
3 1
1 1
2
medium within the tumor was far better demonstrated. A larger number of tumor vessels containing a higher concentration of contrast medium were also visualized. Diagnostic information was decreased compared to the control in 4 of the 7 cases following 25-50 mg of tolazoline, due primarily to inferior demarcation of the tumor, which was "drowned" in all normal vessels. In 4 cases tumor stain was also less pronounced compared to the control and the concentration of contrast medium within the tumor vessels was decreased (Figs. 1-3). In one 21-year-old man with a giant-cell tumor of the right proximal tibia, accumulation of contrast medium within the-tumor was somewhat increased at angiography of the superficial femoral artery following injection of angiotensin. The tumor stain was less pronounced compared to the control after administration of tolazoline (Fig. 4). In 3 other primary bone tumors (1 giant-cell tumor, 1 chondrosarcoma, and 1 osteosarcoma), the diagnostic information obtained following pharmacoangiography was equivalent to that in the control.
5
In 2 patients with metastases to the pelvic wall and bony pelvis (1 cholangiocarcinoma and 1 osteosarcoma), diagnostic information was increased after pharmacoangiography with 5 and 15 J,Lg of angiotensin, respectively. A greater number of tumor vessels were filled with contrast medium in the cholangiocarcinoma and increased accumulation of contrast medium was seen in the osteosarcoma. In neither case was the diagnostic information increased following pharmacoangiography with 30 and 35 mg of tolazoline, respectively. Five benign soft-tissue lesions (2 lipomas, 1 vascular malformation, 1 granulomatous inflammatory mass, and 1 muscular rupture) were examined. One patient was a 13-year-old girl with a soft-tissue swelling lateral to the right knee joint but no history of trauma. At angiography of the right superficial femoral artery, a hypervascular mass was found. Following 10 Jlg of angiotensin, contrast accumulation within the lesion was increased and arteriovenous shunting was evident (Fig. 5). Following 30 mg of tolazoline, the stain within the mass was somewhat
Vol. 122
COMPARISON OF A VASOCONSTRICTOR AND A VASODILATOR
97
Diagnostic Radiology
Fig. 2. Femoral angiograms of a 72-year-old woman with a Iipomyxosarcoma above the left knee. A. Control series. B. After 15 J,Lg of angiotensin, more tumor vessels are seen and accumulation of contrast medium within the well-demarcated tumor is increased. C. After 37.5 mg of tolazoline, tumor vessels are almost "drowned" among normal vessels and the tumor is more difficult to demarcate.
Fig. 3. Femoral angiograms of a 54-year-old woman with a malignant histiocytoma of the right lower leg. Photographic subtraction. A. Control. B. After 10 J,Lg of angiotensin, accumulation of contrast medium within the tumor is increased and arteriovenous shunting is shown better. C. After 25 mg of tolazoline, accumulation of contrast medium within the tumor is slightly impaired compared to the control. No arteriovenous shunting can be been.
improved compared to the control but no arteriovenous shunting was evident. At exploration, only inflammatory tissue was found without evidence of malignancy. In an-
pther patient with soft-tissue swelling in the calf, which turned out to be caused by rupture of a muscle, visualization of an early draining vein was enhanced after 10 ~g
98
LEIF EKELUND AND OTHERS
January 1977
Fig. 4. Femoral angiograms of a 22-year-old man with a giant-cell tumor of the proximal tibia. Photographic subtraction. A. Control series. B. After 3 f.Lg of angiotensin, accumulation of contrast medium within the tumor is slightly increased. C. After 30 mg of tolazoline, accumulation of contrast medium is impaired compared to the control.
Fig. 5. Femoral angiograms of a 13-year-old girl with an inflammatory mass lateral to the right knee joint. A. Control. B. After 10 f.Lg of angiotensin, accumulation of contrast medium within the mass is increased and there is filling of early draining veins. C. After 30 mg of tolazoline, tumor stain is somewhat increased but there is no evidence of arteriovenous shunting.
of angiotensin but was not evident following tolazoline. No abnormal vessels were evident in this case. In general, blood flow was decreased to varying degrees in a dose-dependent fashion following administration of
angiotensin. No significant change in arterial diameter could be demonstrated. Following tolazoline, the circulation time was generally shortened and the normal venous drainage visualized better than after angiotensin.
Vol. 122
COMPARISON OF A VASOCONSTRICTOR AND A VASODILATOR
DISCUSSION
Since the walls of newly formed tumor vessels are usually made up of endothelial cells alone and lack contractile elements (3, 13, 14), they are not as capable of responding to a vasoactive stimulus. In order to direct the largest possible amount of contrast medium into these tumor vessels at angiography, it seems reasonable to use a vasoconstrictor to reduce the blood flow to surrounding normal vessels, and epinephrine has been used most often for this purpose (1,2). Elkin and Meng (9), however, found that in dogs, angiotensin acted farther peripherally in the vascular bed than epinephrine, at least in the kidney. To minimize the risk of constricting the feeding artery to the tumor, we therefore introduced angiotensin in clinical pharmacoangiography of various vascular fields with good results (7, 8). Even if it seems unreasonable that the same positive effect should be achieved using a vasodilator, promising results have been reported in bone and softtissue angiography using tolazoline (10). To test the efficacy of various vasoactive drugs in connection with angiography, a comparative study was undertaken in experimental renal and hepatic tumors in rats (6). Besides· angiotensin and tolazoline, norepinephrine (Norexadrin, Astra, Sweden), and vasopressin (Octapressin, Sandoz, Switzerland) were used. From this experimental study it was concluded that vasoconstrictors provided the most diagnostic information; and angiotensin was the drug of choice, which corresponded well with our clinical experience with this drug. In the present study, we extended this comparative pharmacoangiographic study into the clinic, using a number of bone and soft-tissue tumors. We chose to compare the effect of angiotensin with tolazoline, which has been reported to be of value in enhancing diagnosis in such tumors (10). Our results clearly indicate that angiotensin was superior in improving diagnosis. Following pharmacoangiography with tolazoline, tumor vessels were often "drowned" within the normal vasculature and significant abnormal arteriovenous shunting of contrast medium was usually masked. However, it should be emphasized that in order to keep the experimental conditions as strict as possible, the same amount of contrast medium was used for all angiographic series. Thus high-volume injections following tolazoline as recommended by Hawkins and Hudson (10) were not employed. Diagnosis was not solely dependent on the pharmacoangiographic findings in any patient in the present series. However, such cases have been reported at pharmacoangiography with angiotensin and tolazoline (8, 10). It should also be stressed that pharmacoangiography is by no means the key to all problems in the differential diagnosis of benign and malignant lesions. Inflammatory granulation tissue may also contain vessels lacking contractile elements in the wall; hence the same diagnostic effect may be achieved as in malignant tumors. This is clearly illustrated in Figure 5, where the "tumor" consisted only of inflammatory tissue. Similar differential diagnostic
99
Diagnostic Radiology
problems have been reported in pharmacoangiography of the kidney using epinephrine (4, 12). One interesting finding in the present study was the different optimal dose levels of angiotensin in various vascular fields. While 0.5 J.Lg of angiotensin was found to be optimal for pharmacoangiography of the kidney (5,7), higher doses were required in the extremities. The doseresponse relationship also seemed to vary between individuals, probably related to the electrolyte balance among other things. Thus it has been shown in rabbits that sodium restriction results in a striking reduction in the vascular response to angiotensin (15), while in normal man sodium restriction reduces the sensitivity to angiotensin tenfold (11). Based on our experience, 10-15 J.tg of angiotensin is a convenient and acceptable dose in the axillary, iliac, and femoral arteries, though a lower dosage may sometimes be adequate. Department of Diagnostic Radiology University Hospital S-221 85 Lund Sweden
REFERENCES 1. Abrams HL: The response of neoplastic renal vessels to epinephrine in man. Radiology 82:217-223, Feb 1964 2. Abrams HL, Obrez I: Epinephrine in the study of renal tumors. [In] Abrams HL, ed: Angiography. Boston, Little, Brown, 2d Ed, 1971, Vol 2, Chapt 54, pp 831-854 3. Billing L, Lindgren AGH: Die pathologisch-anatomische Unterlage der Geschwulstarteriographie. Eine Untersuchung der arteriellen Gefasse des Hypernephroms und des Magenkarzinoms. Acta Radiol 25:625-640, 1944 4. Caro G, Meisell R, Held B: Epinephrine-enhanced arteriography in renal and perirenal abscess. A differential diagnostic problem. Radiology 92: 1262-1264, May 1969 5. Ekelund L. GOthlin J: The effect of angiotensin on normal renal circulation determined by angiography and a dye dilution technique. Acta Radiol (to be published) 6. Ekelund L, GOthlinJ, Jonsson N, et al: Pharmacoangiography in experimental tumours. Evaluation of vasoactive drugs. Acta Radiol (Diag) 17:329-342, May 1976 7. Ekelund L, GOthlinJ, Lunderquist A: Diagnostic improvement with angiotensin in renal angiography. Radiology 105:33-37, Oct 1972 8. Ekelund L, Lunderquist A: Pharmacoangiography with angiotensin. Radiology 110:533-540, Mar 1974 9. Elkin M, Meng C-H: The effect of angiotensin on renal vascularity in dogs. Am J Roentgenol 98:927-934, Dec 1966 10. Hawkins IF Jr, Hudson T: Priscoline in bone and soft-tissue angiography. Radiology 110:541-546, Mar 1974 11. Hollenberg NK, Solomon HS, Adams DF, et al: Renal vascular responses to angiotensin and norepinephrine in normal man. Effect of sodium intake. Circ Res 31:750-757, Nov 1972 12. Kahn PC, Wise HM Jr: Simulation of renal tumor response to epinephrine by inflammatory disease. Radiology 89:1062-1064, Dec 1967 13. Lagergren C, Lindbom A, Soderberg G: The blood vessels of osteogenic sarcomas. Histologic, angiographic and microradiographic studies. Acta RadioI55:161-176, Mar 1961 14. Lagergren C, Lindbom A, Soderberg G: Vascularization of fibromatous and fibrosarcomatous tumors. Histopathologic, rnlcroangiog raphic and angiographic studies. Acta Radiol 53: 1-16, Jan 1960 15. Strewler GJ, Hinrichs KJ, Guiod LR, et al: Sodium intake and vascular smooth muscle responsiveness to norepinephrine and angiotensin in the rabbit. Circ Res 31:758-766, Nov 1972
Comparison of a Vasoconstrictor and a Vasodilator in Pharmacoangiography of Bone and Soft-Tissue Tumors 1 Lei' Ekelund, M.D., Sven Laurin, M.D., and Anders Lunderqulst, M.D. The pharmacoangiographic effect of a vasoconstrictor (angiotensin) and a vasodilator (tolazoline) was compared in 18 patients with bone and soft-tissue tumors. Angiotensin was found to be the drug of choice in increasing diagnostic information on angiography. Ten to 15 J-Lg of angiotensin seems to be a convenient dose in the axillary, iliac, and femoral arteries. INDEX TERMS: Angiotensin. Bone neoplasms, diagnosis (Skeletal system, angiography, 4[8] .124) • Soft tissues, neoplasms. Tolazoline • Vasomotor system, effects of drugs on (Arteries of upper and lower extremities, pharmacological adjunct, 9[1].127; 9[2] .127)
Radiology 122:95-99, January 1977
HARMACOANGIOGRAPHY with both vasoconstrictors and vasodilators has been used for more than a decade to enhance demonstration of tumor vascularity. Recently it has also been found to be valuable in the diagnosis of bone and soft-tissue tumors (8, 10). We undertook a comparative investigation to determine whether a vasoconstrictor or a vasodilator is preferable for such angiographic studies.
Table I: Diagnostic Groups Comprising the Series of Bone and Soft-Tissue Tumors Studied
P
Diagnosis
MATERIAL AND METHODS
Eighteen patients (10 males and 8 females) 13-77 years of age were studied. Seven had primary malignant softtissue tumors, 4 had primary bone tumors, 2 had metastatic disease, and 5 had benign soft-tissue masses (TABLE I). Ten tumors were localized in the lower extremity, 4 in the upper extremity, and 4 in the pelvic region. Selective catheterization of the iliac, femoral, or axillary arteries was performed using a radiopaque catheter (l.d, 1.4 mm, o.d. 2.2 mm). Isopaque Cerebral (Nyegaard, Norway) was injected, with the rate and amount depending on the size of the artery. Fifteen to 20 minutes after routine angiography, 2-15 J.lg of angiotensin (Hypertensin N, Ciba, Switzerland) diluted in 10 ml of saline was injected by hand at a rate of about 5 ml per second. Fifteen to 45 seconds later, the examination was repeated using an equal amount of contrast medium but usually employing a somewhat slower injection rate than in the control study. Filming was also prolonged, usually consisting of one film per second for 12 seconds. Twenty to 30 minutes later, 25-50 mg of tolazoline in 10 ml of saline was injected slowly by hand. Contrast medium was injected approximately 30 seconds later, usually employing a faster rate of filming than that used for the control. In all instances, tolazoline, havinq a more long-lasting effect than angiotensin, was used for the last series. 1
No. of Cases
Fibrosarcoma Lipomyxosarcoma Liposarcoma Fibromyxosarcoma Mal ignant histiocytoma
2 (1 recurring) 2 1 1 1
Giant-cell tumor Chondrosarcoma Osteosarcoma
2
Metastatic cholangiocarcinoma Metastatic osteosarcoma
1 1
Lipoma Granulomatous inflammation Vascular malformation Muscle rupture
2 1 1 1
1 1
Following injection of angiotensin, most patients had an increased sensation of pain for a short time during angiography, and after tolazoline varying degrees of tachycardia occurred in all patients. Blood pressure was not monitored during drug injection or angiography, but no significant difference could be demonstrated at the end of the procedure. No serious complications were encountered. RESULTS
The results of pharmacoangiography with angiotensin and tolazoline are given in TABLE II. In five of the 7 primary malignant soft-tissue tumors, 4 of which were localized in the lower extremity-2 fibrosarcomas (one recurring), 1 liposarcoma, 1 lipomyxosarcoma, and 1 malignant histiocytoma-angiographic information was enhanced after 10-15 J.lg of angiotensin: more contrast medium accumulated within the tumor, the tumor was better demarcated, and in 2 cases arteriovenous shunting of contrast
From the Department of Diagnostic Radiology, University Hospital, Lund, Sweden. Accepted for publication in August 1976.
95
sjh
96
LEIF EKELUND AND OTHERS
January 1977
Fig. 1. Femoral angiograms of a 54-year-old woman with a poorly differentiated fibrosarcoma in the left thigh. A. Control series. B. After 15 fJ-g of angiotensin, accumulation of contrast medium within the tumor is increased. Arteriovenous shunting is also visible, though it was not demonstrated in the control series. The normal arteries are constricted. C. After 25 mg of tolazoline, diagnostic information is impaired compared to the control.
Table II:
No. of
Diagnostic Efficacy of Angiotensin and Tolazol ine Diagnostic Value of Angiotensin I mproved Unchanged Reduced
Diagnostic Value of Tolazol ine Improved Unchanged Reduced
Type of Lesion
Cases
Primary mal ignant soft-tissue tumor Primary bone tumor Metastasis Benign lesion
7
5
2
2
4
4 2 5
1 1
3 1 3
3 1
1 1
2
medium within the tumor was far better demonstrated. A larger number of tumor vessels containing a higher concentration of contrast medium were also visualized. Diagnostic information was decreased compared to the control in 4 of the 7 cases following 25-50 mg of tolazoline, due primarily to inferior demarcation of the tumor, which was "drowned" in all normal vessels. In 4 cases tumor stain was also less pronounced compared to the control and the concentration of contrast medium within the tumor vessels was decreased (Figs. 1-3). In one 21-year-old man with a giant-cell tumor of the right proximal tibia, accumulation of contrast medium within the-tumor was somewhat increased at angiography of the superficial femoral artery following injection of angiotensin. The tumor stain was less pronounced compared to the control after administration of tolazoline (Fig. 4). In 3 other primary bone tumors (1 giant-cell tumor, 1 chondrosarcoma, and 1 osteosarcoma), the diagnostic information obtained following pharmacoangiography was equivalent to that in the control.
5
In 2 patients with metastases to the pelvic wall and bony pelvis (1 cholangiocarcinoma and 1 osteosarcoma), diagnostic information was increased after pharmacoangiography with 5 and 15 J,Lg of angiotensin, respectively. A greater number of tumor vessels were filled with contrast medium in the cholangiocarcinoma and increased accumulation of contrast medium was seen in the osteosarcoma. In neither case was the diagnostic information increased following pharmacoangiography with 30 and 35 mg of tolazoline, respectively. Five benign soft-tissue lesions (2 lipomas, 1 vascular malformation, 1 granulomatous inflammatory mass, and 1 muscular rupture) were examined. One patient was a 13-year-old girl with a soft-tissue swelling lateral to the right knee joint but no history of trauma. At angiography of the right superficial femoral artery, a hypervascular mass was found. Following 10 Jlg of angiotensin, contrast accumulation within the lesion was increased and arteriovenous shunting was evident (Fig. 5). Following 30 mg of tolazoline, the stain within the mass was somewhat
Vol. 122
COMPARISON OF A VASOCONSTRICTOR AND A VASODILATOR
97
Diagnostic Radiology
Fig. 2. Femoral angiograms of a 72-year-old woman with a Iipomyxosarcoma above the left knee. A. Control series. B. After 15 J,Lg of angiotensin, more tumor vessels are seen and accumulation of contrast medium within the well-demarcated tumor is increased. C. After 37.5 mg of tolazoline, tumor vessels are almost "drowned" among normal vessels and the tumor is more difficult to demarcate.
Fig. 3. Femoral angiograms of a 54-year-old woman with a malignant histiocytoma of the right lower leg. Photographic subtraction. A. Control. B. After 10 J,Lg of angiotensin, accumulation of contrast medium within the tumor is increased and arteriovenous shunting is shown better. C. After 25 mg of tolazoline, accumulation of contrast medium within the tumor is slightly impaired compared to the control. No arteriovenous shunting can be been.
improved compared to the control but no arteriovenous shunting was evident. At exploration, only inflammatory tissue was found without evidence of malignancy. In an-
pther patient with soft-tissue swelling in the calf, which turned out to be caused by rupture of a muscle, visualization of an early draining vein was enhanced after 10 ~g
98
LEIF EKELUND AND OTHERS
January 1977
Fig. 4. Femoral angiograms of a 22-year-old man with a giant-cell tumor of the proximal tibia. Photographic subtraction. A. Control series. B. After 3 f.Lg of angiotensin, accumulation of contrast medium within the tumor is slightly increased. C. After 30 mg of tolazoline, accumulation of contrast medium is impaired compared to the control.
Fig. 5. Femoral angiograms of a 13-year-old girl with an inflammatory mass lateral to the right knee joint. A. Control. B. After 10 f.Lg of angiotensin, accumulation of contrast medium within the mass is increased and there is filling of early draining veins. C. After 30 mg of tolazoline, tumor stain is somewhat increased but there is no evidence of arteriovenous shunting.
of angiotensin but was not evident following tolazoline. No abnormal vessels were evident in this case. In general, blood flow was decreased to varying degrees in a dose-dependent fashion following administration of
angiotensin. No significant change in arterial diameter could be demonstrated. Following tolazoline, the circulation time was generally shortened and the normal venous drainage visualized better than after angiotensin.
Vol. 122
COMPARISON OF A VASOCONSTRICTOR AND A VASODILATOR
DISCUSSION
Since the walls of newly formed tumor vessels are usually made up of endothelial cells alone and lack contractile elements (3, 13, 14), they are not as capable of responding to a vasoactive stimulus. In order to direct the largest possible amount of contrast medium into these tumor vessels at angiography, it seems reasonable to use a vasoconstrictor to reduce the blood flow to surrounding normal vessels, and epinephrine has been used most often for this purpose (1,2). Elkin and Meng (9), however, found that in dogs, angiotensin acted farther peripherally in the vascular bed than epinephrine, at least in the kidney. To minimize the risk of constricting the feeding artery to the tumor, we therefore introduced angiotensin in clinical pharmacoangiography of various vascular fields with good results (7, 8). Even if it seems unreasonable that the same positive effect should be achieved using a vasodilator, promising results have been reported in bone and softtissue angiography using tolazoline (10). To test the efficacy of various vasoactive drugs in connection with angiography, a comparative study was undertaken in experimental renal and hepatic tumors in rats (6). Besides· angiotensin and tolazoline, norepinephrine (Norexadrin, Astra, Sweden), and vasopressin (Octapressin, Sandoz, Switzerland) were used. From this experimental study it was concluded that vasoconstrictors provided the most diagnostic information; and angiotensin was the drug of choice, which corresponded well with our clinical experience with this drug. In the present study, we extended this comparative pharmacoangiographic study into the clinic, using a number of bone and soft-tissue tumors. We chose to compare the effect of angiotensin with tolazoline, which has been reported to be of value in enhancing diagnosis in such tumors (10). Our results clearly indicate that angiotensin was superior in improving diagnosis. Following pharmacoangiography with tolazoline, tumor vessels were often "drowned" within the normal vasculature and significant abnormal arteriovenous shunting of contrast medium was usually masked. However, it should be emphasized that in order to keep the experimental conditions as strict as possible, the same amount of contrast medium was used for all angiographic series. Thus high-volume injections following tolazoline as recommended by Hawkins and Hudson (10) were not employed. Diagnosis was not solely dependent on the pharmacoangiographic findings in any patient in the present series. However, such cases have been reported at pharmacoangiography with angiotensin and tolazoline (8, 10). It should also be stressed that pharmacoangiography is by no means the key to all problems in the differential diagnosis of benign and malignant lesions. Inflammatory granulation tissue may also contain vessels lacking contractile elements in the wall; hence the same diagnostic effect may be achieved as in malignant tumors. This is clearly illustrated in Figure 5, where the "tumor" consisted only of inflammatory tissue. Similar differential diagnostic
99
Diagnostic Radiology
problems have been reported in pharmacoangiography of the kidney using epinephrine (4, 12). One interesting finding in the present study was the different optimal dose levels of angiotensin in various vascular fields. While 0.5 J.Lg of angiotensin was found to be optimal for pharmacoangiography of the kidney (5,7), higher doses were required in the extremities. The doseresponse relationship also seemed to vary between individuals, probably related to the electrolyte balance among other things. Thus it has been shown in rabbits that sodium restriction results in a striking reduction in the vascular response to angiotensin (15), while in normal man sodium restriction reduces the sensitivity to angiotensin tenfold (11). Based on our experience, 10-15 J.tg of angiotensin is a convenient and acceptable dose in the axillary, iliac, and femoral arteries, though a lower dosage may sometimes be adequate. Department of Diagnostic Radiology University Hospital S-221 85 Lund Sweden
REFERENCES 1. Abrams HL: The response of neoplastic renal vessels to epinephrine in man. Radiology 82:217-223, Feb 1964 2. Abrams HL, Obrez I: Epinephrine in the study of renal tumors. [In] Abrams HL, ed: Angiography. Boston, Little, Brown, 2d Ed, 1971, Vol 2, Chapt 54, pp 831-854 3. Billing L, Lindgren AGH: Die pathologisch-anatomische Unterlage der Geschwulstarteriographie. Eine Untersuchung der arteriellen Gefasse des Hypernephroms und des Magenkarzinoms. Acta Radiol 25:625-640, 1944 4. Caro G, Meisell R, Held B: Epinephrine-enhanced arteriography in renal and perirenal abscess. A differential diagnostic problem. Radiology 92: 1262-1264, May 1969 5. Ekelund L. GOthlin J: The effect of angiotensin on normal renal circulation determined by angiography and a dye dilution technique. Acta Radiol (to be published) 6. Ekelund L, GOthlinJ, Jonsson N, et al: Pharmacoangiography in experimental tumours. Evaluation of vasoactive drugs. Acta Radiol (Diag) 17:329-342, May 1976 7. Ekelund L, GOthlinJ, Lunderquist A: Diagnostic improvement with angiotensin in renal angiography. Radiology 105:33-37, Oct 1972 8. Ekelund L, Lunderquist A: Pharmacoangiography with angiotensin. Radiology 110:533-540, Mar 1974 9. Elkin M, Meng C-H: The effect of angiotensin on renal vascularity in dogs. Am J Roentgenol 98:927-934, Dec 1966 10. Hawkins IF Jr, Hudson T: Priscoline in bone and soft-tissue angiography. Radiology 110:541-546, Mar 1974 11. Hollenberg NK, Solomon HS, Adams DF, et al: Renal vascular responses to angiotensin and norepinephrine in normal man. Effect of sodium intake. Circ Res 31:750-757, Nov 1972 12. Kahn PC, Wise HM Jr: Simulation of renal tumor response to epinephrine by inflammatory disease. Radiology 89:1062-1064, Dec 1967 13. Lagergren C, Lindbom A, Soderberg G: The blood vessels of osteogenic sarcomas. Histologic, angiographic and microradiographic studies. Acta RadioI55:161-176, Mar 1961 14. Lagergren C, Lindbom A, Soderberg G: Vascularization of fibromatous and fibrosarcomatous tumors. Histopathologic, rnlcroangiog raphic and angiographic studies. Acta Radiol 53: 1-16, Jan 1960 15. Strewler GJ, Hinrichs KJ, Guiod LR, et al: Sodium intake and vascular smooth muscle responsiveness to norepinephrine and angiotensin in the rabbit. Circ Res 31:758-766, Nov 1972
