- Email: [email protected]
Use of Saralasin as a Diagnostic Test in Hypertension: Report of a Consensus Committee
678
DISEASES OF BLOOD VESSELS, HYPERTENSION AND RENOV ASCULAR SURGERY
to prevent renovascular hypertension that may lead to loss of renal function. Lateral arterial or venous repair is the most effective way to treat renovascular lesions. Other treatments include segmental resection with end-to-end anastomosis, aortorenal bypass or interposition graft with saphenous vein. In cases of parenchymal arteriovenous fistula embolization with small coiled steel springs has been done, although extra-corporeal perfusion had been used in selected cases. In arterial embolic disease >90 per cent of the emboli originate either in the left atrium or left ventricle. Renal arteries are affected by embolization in 2.3 per cent of all arterial emboli. Severe flank pain and hematuria may be associated with renal infarction. IVPs may show nonvisualization or a defect in the nephrogram phase. The most accurate means of diagnosis is arteriography. If the diagnosis is made within 2 to 3 hours revascularization may be performed. Anticoagulation with heparin should be started once the diagnosis is made. If the diagnosis is made after 2 to 3 hours, probably revascularization should not be attempted unless collateral circulation is present or obstruction is incomplete. Embolectomy with the use of a Fogarty catheter is the most effective treatment. A high degree of suspicion toward renovascular lesions, patient history, physical examination, urinalysis, IVPs and renal angiography are important factors in treating all renovascular emergencies. F. T. A. 4 figures, 3 references Transluminal Angioplasty for Renovascular Hypertension Complicated by Pregnancy D. A. MCCARRON, F. s. KELLER, G. LUNDQUIST AND P. E. KIRK, Division of Nephrology and Hypertension, Department of Medicine, Department of Radiology, and Department of Obstetrics and Gynecology, the Oregon Health Sciences University, Portland, Oregon
Arch. Intern. Med., 142: 1737-1739 (Sept.) 1982 These authors present the case of a 24-year-old woman with severe hypertension (230/140 mm. Hg), headaches, shortness of breath, nose bleeds and ankle swelling unresponsive to diuretics and sedatives. Hypertensive retinopathy and an abdominal bruit were present. Blood pressure was reduced to 140/110 mm. Hg with nitroprusside and maintained at that level with 20 mg. propranolol 4 times daily. A hypertensive excretory urogram was suggestive of left renal vascular etiology. Angiography confirmed a 90 per cent stenosis of the left main renal artery, with branch disease suggesting fibromuscular hyperplasia. Renal vein renins lateralized to the left kidney. Multiple adjustments of the medication and poor compliance with the medical regimen resulted in a decision to attempt transluminal angioplasty. The main renal artery and both branch lesions were dilated successfully, resulting in immediate decrease in blood pressure to 90/55. The patient was noted to be pregnant 5 weeks later. Gestational age was estimated by ultrasound to be 21 weeks. A normal male newborn was delivered at term. Blood pressure has remained normal at 19 months post )artum. The pelvis was shielded during the arteriography and balloon angioplasty. The authors believe balloon angioplasty is a viable alternative to therapeutic abortion, surgical correction or pharmacologic management of pregnant women with renovascular hypertension. J. H. N. 2 figures, 19 references Use of Saralasin as a Diagnostic Test in Hypertension: Report of a Consensus Committee
E. D.
FROHLICH,
M.
H.
MAXWELL,
L.
BAER,
H.
GA VRAS,
J. w. HOLLIFIELD, L. R. KRAKOFF, M. D. FIFSCHITZ, A. LOGAN, E. PouTASSE AND D. H. P. STREETEN, Alton Ochsner Medical Foundation, New Orleans, Louisiana Arch. Intern. Med., 142: 1437-1440 (Aug.) 1982 Almost 60 million adults in the United States have arterial hypertension. Most will be judged to have primary (essential) hypertension and will, therefore, be consigned to a lifetime of physician visits and antihypertensive drug therapy to prolong life and reduce cardiovascular morbidity. The long-term cost, unpleasant or adverse side effects of life-long antihypertensive drug therapy and high rate of lack of adherence are adequate reasons to search for secondary potentially curable causes of high blood pressure, of which the most prevalent is renovascular hypertension. Recently, saralasin acetate has been approved by the Food and Drug Administration for use as a diagnostic agent for the detection of angiotensin II-dependent (renin-mediated) hypertension. Most experimental and clinical studies of saralasin have been published in specialty journals, so that many practicing physicians are unfamiliar with this drug or with its proper use. This committee of clinical investigators who have had extensive experience with saralasin was formed to outline the present potential uses of this agent in the diagnosis and treatment of various forms of hypertension. Although there was no unanimity on each point among the committee members this editorial summarizes the consensus of the members. Saralasin is an angiotensin II analogue that differs from the natural agent in that the terminal amino acids in the 1 and 8 positions are substituted. As a result it binds to angiotensin II tissue receptors but as a much weaker vasoconstrictor agonist than angiotensin II. It, therefore, may have dual action, depending on the circulating levels of the natural pressor substance, angiotensin II. At high levels of circulating angiotensin II saralasin completely inhibits binding of angiotensin II to the receptor sites of the vasculature, diminishing vasoconstriction and reducing arterial pressure. At low levels of circulating angiotensin II saralasin may act as an agonist, increasing the pressure. Therefore, its depressor action is mediated by reducing total peripheral resistance but this is unassociated with a compensatory increase in heart rate, cardiac output or myocardial contractility. The tests consist of an intravenous infusion of saralasin at a constant rate for 20 to 30 minutes or an infusion at increasing rates up to 45 minutes, while blood pressure is monitored constantly. To facilitate responsiveness mild sodium depletion is achieved by a single dose of oral furosemide 12 to 14 hours before the test. Antihypertensive medications, except diuretics, are withheld for at least 1 week before testing. The intravenous infusion of saralasin almost always is associated with an initial immediate transient elevation of arterial pressure, lasting 2 to 4 minutes. Test results are judged only by the subsequent pressure response, commencing 6 minutes after the start of the infusion. Control pressure is the average of the last 4 diastolic pressure readings, obtained just before saralasin infusion. Saralasin pressure is the average of the 4 consecutive diastolic pressures that differ most from control pressure. In the package insert a positive saralasin test is defined as a sustained decrease in diastolic pressure of at least 7 mm. Hg, indicating renin-mediated hypertension. Several members of the panel suggested that the specificity and sensitivity of the saralasin test could be improved by noting changes in plasma renin activity in addition to changes in diastolic pressure.
679 i\.s a rare, exaggerated. p:ressor or responses have been described after saralasin administration. However, in >6,000 tests no serious or side effects have been observed. In 1 patient catecholamine release from a chromocytoma was ,.n·vvvn.•cu.. For this and other reasons it would be wise to have an a-adrenergic receptor blocker ampules available in the case of a disturbing pressor response. Although saralasin is primarily a diagnostic agent it has proved useful for short-term (hours to days) emergency treatment of malignant hypertension, in severe congestive heart failure and in reducing pressure during and after renal arteriography. In summary, the intravenous saralasin test could be of use in screening for angiotensin II mediated hypertension. A certain percentage of false negative tests may occur. Because of the high prevalence of high renin and even some norn1al renin essential hypertension that is likely to respond to saralasin it is expected that false positive tests also will occur when screening for renovascular hypertension whose prevalence has been estimated at 3 to 10 per cent of the general hypertensive population. Therefore, the saralasin test must be used in conjunction with suggestive clinical findings and other tests. W. W. K. 1 table, 10 references
are the alternative procedurn is transureteroureterostomy. In cases of transection of the ureter, transection of the ureter and debridement an end-to-end anastomosis is preferred over simple suturing because of the higher incidence of fistula and stricture. In cases of ureteral injury secondary to penetrating missiles 01· other forms of external trauma the rate of complications is high, 18 per cent in the author's series, because of its relation to the high incidence of associated visceral and vascular injuries. The nephrectomy rate has been 7 per cent in the author's series. In the Parkland series the mortality rate of ureteral injury secondary to external violence was 11 per cent. The management of complications of ureteral injury is initiated by drainage of extravasated urine or abscess. In cases of urinary fistula a ureteral catheter or double J ureteral stent may be inserted. If this fails exploration and definitive ureteral repair are performed. F. T. A.. 7 figures, 3 tables, 3 references
TRANSPLANTATION Habitual Exce§sive Dietary Salt Intake and Blood Pre§su:re Levels in Renal Transplant Recipient§ J.
TRAUMA Erner1!.e,1tcv
,u,u,c,z~;.,,n~an
of the Injured Ureter
T. C.
BRIGHT, III, Division of Urology, Southwestern Nledical School and Pr'P.~nv,,,,·u-,n. ,.,v.,m,,u •. Dallas, Texas
Urol. Clin. N. Amer., 9: 285-291 (June) 1982 The ureter infrequently is external violence because of its small size and deep location in the retroperitoneal space. Frequently, there are no early signs and symptoms of ureteral In 59 cases of ureteral reviewed by the author 32 had hematuria (20 gross and 12 r-rc,.Qr,nm 19 were normal and 8 had no done. An excretory urogram (IVP) should be performed once a ureteral injury is suspected. In these 59 patients with ureteral injury the pyelographic were 11 10 with extravasation of contrast material, 1 ureteral dilatation, 1 nonvisualization of the ureter, l ureteral deviation and 1 bladder displacement. If suspicion of uretera.l perm:sts a normal IVP retrc)gr·adle will demonstrate most of the ureteral the site of injury cannot be found intravenous carmine may detect the site of extr:ivasation. tomography and ultrasound of the abdomen are to demonstrate loculated extravasated urine. The most common cause of ureternl injuries is abdominal hysterectomy, followed exploratory laparotomy, MarshallMarchetti procedure, colectomy and stone basket manipulation. When ureteral injury is discovered during the operative procedure it should be repaired immediately. In cases of upper third ureteral injury various pyeloplasty techniques may be done. The author prefers the dismembered flap technique. If the ureteropelvic juction is spared an end-to-end ureteral anastomosis may be performed. Other techniques are either cutaneous ureterostomy or placement of a stent into the ureter and bringing the catheter to the skin. In cases of middle third ureteral injury a simple end-to-end ureteral anastomosis is adequate treatment. In cases of lower third ureteral injury ureteroneocystostomy, vesico-psoas hitch or a bladder flap proarn.H
L. A. HERBERT, J. LEMANN, JR., J. A. BERES, and the Veterans Administration Research Service, Medical Wisconsin, Milwaukee, Wisconsin and the Department Medicine, Ohio State University, Columbus, Ohio H.
w.
KALBFLEISCH,
F.
PIERING AND
Amer. J. Med., 73: 205-210 (Aug.) 1982 Dietary salt intake and blood pressure were examined in 68 renal transplant patients and 80 healthy individuals. Renal function was normal in all subjects. Dietary salt intake was estimated from renal sodium excretion (24-hour urine sodium). Sodium intake was 43 per cent higher in the ents than in control subjects. Mild 29 transplant recipients and was controlled easily with diuretics alone. There was no correlation between dietary salt intake and blood pressure despite glucocorticoid administration and reduced renal mass. These observations are contrary to the widely held vievv that salt intake can contribute to the cmnl,wHno,nt or maintenance of hypertensiono The incidence of in the than 18 references
Abstracter's comment. The authors have put vvs,.v0"v" a argument ep1ctEim101og1c studies linkmg sodium and hypertEim:10,,1. was well constrncted. J. H. N.
DIVERSION Neoplasia and Ureterosigmoidostomy: A Colonoscopy Survey
M. STEWART, F. A. MACRAE AND C. B. WILLIAMS, Depart· ment of Applied Physiology and Surgical Sciences, Royal College of Surgeons of England and St. Mark's Hospital, London, England Brit. J. Surg., 69: 414-416 (July) 1982 The authors reviewed 34 consecutive patients who had un-
DISEASES OF BLOOD VESSELS, HYPERTENSION AND RENOV ASCULAR SURGERY
to prevent renovascular hypertension that may lead to loss of renal function. Lateral arterial or venous repair is the most effective way to treat renovascular lesions. Other treatments include segmental resection with end-to-end anastomosis, aortorenal bypass or interposition graft with saphenous vein. In cases of parenchymal arteriovenous fistula embolization with small coiled steel springs has been done, although extra-corporeal perfusion had been used in selected cases. In arterial embolic disease >90 per cent of the emboli originate either in the left atrium or left ventricle. Renal arteries are affected by embolization in 2.3 per cent of all arterial emboli. Severe flank pain and hematuria may be associated with renal infarction. IVPs may show nonvisualization or a defect in the nephrogram phase. The most accurate means of diagnosis is arteriography. If the diagnosis is made within 2 to 3 hours revascularization may be performed. Anticoagulation with heparin should be started once the diagnosis is made. If the diagnosis is made after 2 to 3 hours, probably revascularization should not be attempted unless collateral circulation is present or obstruction is incomplete. Embolectomy with the use of a Fogarty catheter is the most effective treatment. A high degree of suspicion toward renovascular lesions, patient history, physical examination, urinalysis, IVPs and renal angiography are important factors in treating all renovascular emergencies. F. T. A. 4 figures, 3 references Transluminal Angioplasty for Renovascular Hypertension Complicated by Pregnancy D. A. MCCARRON, F. s. KELLER, G. LUNDQUIST AND P. E. KIRK, Division of Nephrology and Hypertension, Department of Medicine, Department of Radiology, and Department of Obstetrics and Gynecology, the Oregon Health Sciences University, Portland, Oregon
Arch. Intern. Med., 142: 1737-1739 (Sept.) 1982 These authors present the case of a 24-year-old woman with severe hypertension (230/140 mm. Hg), headaches, shortness of breath, nose bleeds and ankle swelling unresponsive to diuretics and sedatives. Hypertensive retinopathy and an abdominal bruit were present. Blood pressure was reduced to 140/110 mm. Hg with nitroprusside and maintained at that level with 20 mg. propranolol 4 times daily. A hypertensive excretory urogram was suggestive of left renal vascular etiology. Angiography confirmed a 90 per cent stenosis of the left main renal artery, with branch disease suggesting fibromuscular hyperplasia. Renal vein renins lateralized to the left kidney. Multiple adjustments of the medication and poor compliance with the medical regimen resulted in a decision to attempt transluminal angioplasty. The main renal artery and both branch lesions were dilated successfully, resulting in immediate decrease in blood pressure to 90/55. The patient was noted to be pregnant 5 weeks later. Gestational age was estimated by ultrasound to be 21 weeks. A normal male newborn was delivered at term. Blood pressure has remained normal at 19 months post )artum. The pelvis was shielded during the arteriography and balloon angioplasty. The authors believe balloon angioplasty is a viable alternative to therapeutic abortion, surgical correction or pharmacologic management of pregnant women with renovascular hypertension. J. H. N. 2 figures, 19 references Use of Saralasin as a Diagnostic Test in Hypertension: Report of a Consensus Committee
E. D.
FROHLICH,
M.
H.
MAXWELL,
L.
BAER,
H.
GA VRAS,
J. w. HOLLIFIELD, L. R. KRAKOFF, M. D. FIFSCHITZ, A. LOGAN, E. PouTASSE AND D. H. P. STREETEN, Alton Ochsner Medical Foundation, New Orleans, Louisiana Arch. Intern. Med., 142: 1437-1440 (Aug.) 1982 Almost 60 million adults in the United States have arterial hypertension. Most will be judged to have primary (essential) hypertension and will, therefore, be consigned to a lifetime of physician visits and antihypertensive drug therapy to prolong life and reduce cardiovascular morbidity. The long-term cost, unpleasant or adverse side effects of life-long antihypertensive drug therapy and high rate of lack of adherence are adequate reasons to search for secondary potentially curable causes of high blood pressure, of which the most prevalent is renovascular hypertension. Recently, saralasin acetate has been approved by the Food and Drug Administration for use as a diagnostic agent for the detection of angiotensin II-dependent (renin-mediated) hypertension. Most experimental and clinical studies of saralasin have been published in specialty journals, so that many practicing physicians are unfamiliar with this drug or with its proper use. This committee of clinical investigators who have had extensive experience with saralasin was formed to outline the present potential uses of this agent in the diagnosis and treatment of various forms of hypertension. Although there was no unanimity on each point among the committee members this editorial summarizes the consensus of the members. Saralasin is an angiotensin II analogue that differs from the natural agent in that the terminal amino acids in the 1 and 8 positions are substituted. As a result it binds to angiotensin II tissue receptors but as a much weaker vasoconstrictor agonist than angiotensin II. It, therefore, may have dual action, depending on the circulating levels of the natural pressor substance, angiotensin II. At high levels of circulating angiotensin II saralasin completely inhibits binding of angiotensin II to the receptor sites of the vasculature, diminishing vasoconstriction and reducing arterial pressure. At low levels of circulating angiotensin II saralasin may act as an agonist, increasing the pressure. Therefore, its depressor action is mediated by reducing total peripheral resistance but this is unassociated with a compensatory increase in heart rate, cardiac output or myocardial contractility. The tests consist of an intravenous infusion of saralasin at a constant rate for 20 to 30 minutes or an infusion at increasing rates up to 45 minutes, while blood pressure is monitored constantly. To facilitate responsiveness mild sodium depletion is achieved by a single dose of oral furosemide 12 to 14 hours before the test. Antihypertensive medications, except diuretics, are withheld for at least 1 week before testing. The intravenous infusion of saralasin almost always is associated with an initial immediate transient elevation of arterial pressure, lasting 2 to 4 minutes. Test results are judged only by the subsequent pressure response, commencing 6 minutes after the start of the infusion. Control pressure is the average of the last 4 diastolic pressure readings, obtained just before saralasin infusion. Saralasin pressure is the average of the 4 consecutive diastolic pressures that differ most from control pressure. In the package insert a positive saralasin test is defined as a sustained decrease in diastolic pressure of at least 7 mm. Hg, indicating renin-mediated hypertension. Several members of the panel suggested that the specificity and sensitivity of the saralasin test could be improved by noting changes in plasma renin activity in addition to changes in diastolic pressure.
679 i\.s a rare, exaggerated. p:ressor or responses have been described after saralasin administration. However, in >6,000 tests no serious or side effects have been observed. In 1 patient catecholamine release from a chromocytoma was ,.n·vvvn.•cu.. For this and other reasons it would be wise to have an a-adrenergic receptor blocker ampules available in the case of a disturbing pressor response. Although saralasin is primarily a diagnostic agent it has proved useful for short-term (hours to days) emergency treatment of malignant hypertension, in severe congestive heart failure and in reducing pressure during and after renal arteriography. In summary, the intravenous saralasin test could be of use in screening for angiotensin II mediated hypertension. A certain percentage of false negative tests may occur. Because of the high prevalence of high renin and even some norn1al renin essential hypertension that is likely to respond to saralasin it is expected that false positive tests also will occur when screening for renovascular hypertension whose prevalence has been estimated at 3 to 10 per cent of the general hypertensive population. Therefore, the saralasin test must be used in conjunction with suggestive clinical findings and other tests. W. W. K. 1 table, 10 references
are the alternative procedurn is transureteroureterostomy. In cases of transection of the ureter, transection of the ureter and debridement an end-to-end anastomosis is preferred over simple suturing because of the higher incidence of fistula and stricture. In cases of ureteral injury secondary to penetrating missiles 01· other forms of external trauma the rate of complications is high, 18 per cent in the author's series, because of its relation to the high incidence of associated visceral and vascular injuries. The nephrectomy rate has been 7 per cent in the author's series. In the Parkland series the mortality rate of ureteral injury secondary to external violence was 11 per cent. The management of complications of ureteral injury is initiated by drainage of extravasated urine or abscess. In cases of urinary fistula a ureteral catheter or double J ureteral stent may be inserted. If this fails exploration and definitive ureteral repair are performed. F. T. A.. 7 figures, 3 tables, 3 references
TRANSPLANTATION Habitual Exce§sive Dietary Salt Intake and Blood Pre§su:re Levels in Renal Transplant Recipient§ J.
TRAUMA Erner1!.e,1tcv
,u,u,c,z~;.,,n~an
of the Injured Ureter
T. C.
BRIGHT, III, Division of Urology, Southwestern Nledical School and Pr'P.~nv,,,,·u-,n. ,.,v.,m,,u •. Dallas, Texas
Urol. Clin. N. Amer., 9: 285-291 (June) 1982 The ureter infrequently is external violence because of its small size and deep location in the retroperitoneal space. Frequently, there are no early signs and symptoms of ureteral In 59 cases of ureteral reviewed by the author 32 had hematuria (20 gross and 12 r-rc,.Qr,nm 19 were normal and 8 had no done. An excretory urogram (IVP) should be performed once a ureteral injury is suspected. In these 59 patients with ureteral injury the pyelographic were 11 10 with extravasation of contrast material, 1 ureteral dilatation, 1 nonvisualization of the ureter, l ureteral deviation and 1 bladder displacement. If suspicion of uretera.l perm:sts a normal IVP retrc)gr·adle will demonstrate most of the ureteral the site of injury cannot be found intravenous carmine may detect the site of extr:ivasation. tomography and ultrasound of the abdomen are to demonstrate loculated extravasated urine. The most common cause of ureternl injuries is abdominal hysterectomy, followed exploratory laparotomy, MarshallMarchetti procedure, colectomy and stone basket manipulation. When ureteral injury is discovered during the operative procedure it should be repaired immediately. In cases of upper third ureteral injury various pyeloplasty techniques may be done. The author prefers the dismembered flap technique. If the ureteropelvic juction is spared an end-to-end ureteral anastomosis may be performed. Other techniques are either cutaneous ureterostomy or placement of a stent into the ureter and bringing the catheter to the skin. In cases of middle third ureteral injury a simple end-to-end ureteral anastomosis is adequate treatment. In cases of lower third ureteral injury ureteroneocystostomy, vesico-psoas hitch or a bladder flap proarn.H
L. A. HERBERT, J. LEMANN, JR., J. A. BERES, and the Veterans Administration Research Service, Medical Wisconsin, Milwaukee, Wisconsin and the Department Medicine, Ohio State University, Columbus, Ohio H.
w.
KALBFLEISCH,
F.
PIERING AND
Amer. J. Med., 73: 205-210 (Aug.) 1982 Dietary salt intake and blood pressure were examined in 68 renal transplant patients and 80 healthy individuals. Renal function was normal in all subjects. Dietary salt intake was estimated from renal sodium excretion (24-hour urine sodium). Sodium intake was 43 per cent higher in the ents than in control subjects. Mild 29 transplant recipients and was controlled easily with diuretics alone. There was no correlation between dietary salt intake and blood pressure despite glucocorticoid administration and reduced renal mass. These observations are contrary to the widely held vievv that salt intake can contribute to the cmnl,wHno,nt or maintenance of hypertensiono The incidence of in the than 18 references
Abstracter's comment. The authors have put vvs,.v0"v" a argument ep1ctEim101og1c studies linkmg sodium and hypertEim:10,,1. was well constrncted. J. H. N.
DIVERSION Neoplasia and Ureterosigmoidostomy: A Colonoscopy Survey
M. STEWART, F. A. MACRAE AND C. B. WILLIAMS, Depart· ment of Applied Physiology and Surgical Sciences, Royal College of Surgeons of England and St. Mark's Hospital, London, England Brit. J. Surg., 69: 414-416 (July) 1982 The authors reviewed 34 consecutive patients who had un-