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Enhanced intravenous urography in renal trauma with low dose dopamine
ENHANCED INTRAVENOUS UROGRAPHY IN RENAL TRAUMA WITH LOW-DOSE DOPAMINE PRASHANT H. MEHTA, M.D. YOSH TAGUCHI, M.D. IRWIN W. KUZMAROV, M.D.
From the Department of Urology, Royal Victoria Hospital, and McGill University, Montreal, Canada
ABSTRACT-Intravenous pyelography is the standard first-line investigation for suspected renal trauma. A faint, and/or delayed visualization, or nonvisualization of the damaged renal unit is not uncommon. Low-dose dopamine (3 pg/ kg/min) increases renal blood flow without deleterious side effects. An experimental rat model was developed to evaluate the effects of low-dose dopamine on intravenous pyelograms in animals with unilateral renal trauma. A consistent and significant improvement in the visualization of the injured kidney was noted in the dopamine-treated animals compared with controls that received equivalent volumes of normal saline.
The intravenous urogram is the initial study carried out in most cases of renal trauma. Significant injury to the kidney, or its vasculature, can lead to a poor, delayed, or nonvisualization of the injured kidney on the intravenous urogram. This often necessitates more elaborate studies to define the injury. The ability to enhance the radiologic image on the initial intravenous urogram could lead to a more prompt definition of the traumatized renal unit, and could avoid further costly studies. An experimental model was first developed which reproduced the clinical finding of poor contrast excretion from the injured kidney. The model was then used to study the effects of lowdose dopamine on the urographic images, and the results were compared with control animals that received no dopamine, but were given an equivalent volume of saline.
toneal pentobarbital (20 mg/kg body weight). Through a midline incision, the left kidney was exposed and an unprotected hemostat applied to crush-transect the lower third of the kidney. The organ was then returned and the wound was closed. Twenty-four hours later, the animals were reanesthetized, and a groin dissection was made to expose the femoral vein. The vein was isolated and cannulated using a PE 10 tubing glued to a PE 50 tubing. A bolus injection of diatrizoate sodium (60% Hypaque) was administered at a dosage of 2 mL/kg body weight. X-ray films were obtained on a Picker singlephase unit using a nongrid technique at 52 kV and 1.22 milli-amps per second exposure at a focal distance of 40 inches. The films were read as showing good, faint, or nonvisualization.
Material and Methods
The experimental animals received intravenous dopamine at a dosage of 3 pglkglmin for fifteen minutes. Control animals received equivalent volumes of saline. Immediately thereafter, diatrizoate sodium was injected
Animal model Fisher rats weighing 200-400 g were used. The animals were anesthetized using intraperi-
88
Dopamine studies
UROLOGY
/ JANUARY 1993
I
VOLUME
41, NUMBER
1
n 12 rats
14
rats
64
60 % 46
/
20
experiment
catltrol -10
minutes~
-
control 30
experhmi
minutes-
2. intravenous urogram ten and thirty minutes after injection of contrast medium in control animal pretreated with saline.
FIGURE
Histogram of compiled results. Animals FIGURE 1. treated with dopamine demonstrated markedly improved urogram visualization at ten and thirty minutes.
through the same cannula at a dosage of2 ml2 per kg body weight. X-ray films were obtained ten and thirty minutes later. Results Twelve animals that received no dopamine showed nonvisualization (83 % ) or faint visualization (17 % ) of the contrast medium in the onlle&ncr ---‘“-““b
cvctem ‘J “-----
nf -_
the ____
inirnd “‘,_‘__
kirlnev l.__AA_ J
at ..-
ten c.,*_
minutes, and nonvisualization (58%) or faint visualization (42 % ) at thirty minutes. Fourteen animals that received dopamine demonstrated good visualization (64%) or faint visualization (36%) of the contrast medium in the collecting system at ten minutes, and good visualization (79%) or faint visualization (21%) at thirty minutes (Figs. l-3). Comment The animal model was developed after considerable trials and errors. We tried manually squeezing the exposed kidney, crushing the kidney under a pre-set vise grip plier, and crushclamping the renal pedicle for varying periods of time. The most consistent findings of faint or _lYsl__:-:.___I .._.__1 __~.I._ ~~~ nonvisiialization or CII~qurea renal units were obtained by crush-clamping the lower third of
UROLOGY
/ JANUARY 1993
i
VOLUME
41, NUMBER 1
FIGURE3. Intravenous urogram ten and thirty minutes after injection of contrast medium in experimental animal pretreated with dopamine. the kidney with an unprotected hemostat. Urographic studies were carried out at one, twelve, and twenty-four hours after injury with no significant differences in the x-ray findings. The most consistent results were obtained at twentyfour hours, and thus this timing was selected for the study. Dopamine was selected as the drug to test afL_- 1-L _.?~_~. 1 .I rer aeoarmg wnerner we shouid first try the caicium ion antagonists or other drugs that relax
89
smooth muscles. Low-dose dopamine was chosen because it has selective and localized renal effects. Dopamine (3,4 dihydroxyphenylethinemine) is an endogenous catecholamine and is the immediate precursor of norepinephrine.’ In low dosage (0.5 to 3 pg/kg/ min), dopamine has a selective dose-dependent effect on the kidney. It dilates the renal vasculature, leading to increased blood flow, natriuresis, and diuresis. Specific dopaminergic postsynaptic receptors have been demonstrated in the renal vasculature of ratse4 When the receptors are activated, the enzyme adenyl cyclase increases the formation of cyclic AMP. This causes a dilatation of the renal, mesenteric, cerebral, ahd coronary vessels5 There is an improvement of the subcortico-outer medullary renal blood flo~.~,’ Low-dose dopamine increases cardiac output without increasing the heart rate. l-6 In dogs, the vasodilatational effects of dopamine persist after renal denervation.* These pharmacologic effects of low-dose dopamine have been utilized in critically ill patients such as those suffering from drug overdose and in patients in shock with acute renal shut down. Dopamine at a dosage of 3 pg/kg/ min doubles renal blood flow, while increasing cardiac output 15 percent.e Other studies reported increased glomerular filtration rate of 11 to 75 percent1*4~eand diuresis6JoJ1 From these experiments and clinical observations, it seems reasonable to suggest that spasms of the renal vasculature often accompany renal injury. What is less certain is whether a phar-
90
macologic attempt to combat the vasoconstriction is helpful or harmful in limiting injury to the kidney and in aiding recovery. This is the question that is being addressed in experiments presently underway. 687 Pine Avenue West Montreal, Canada H3A 1Al (DR. TAGUCHI) References 1. McDonald RH, Goldberg LI, &Nay JL, and ‘Ihttle EP: Effects of dopamine in man: augmentation of sodium excretion, glomerular filtration rate, and renal plasma flow, J Clin Invest 43: 1116 (1964). 2. Chapman BJ, Horn NM, Munday KA, and Robertson MJ: The actions of dopamine on regional blood flows in the rat, J Physiol 298: 437 (1980). 3. Woodman OL, and Lang WJ: Dopamine-induced vasodilatation in the isolated perfused rat kidney, Arch Int Pharmacodyn 243: 228 (1980). 4. Pendleton RG, and Sherman SS: Studies concerning dopamine diuresis in the rat, Arch Int Pharmacodyn 222: 94 (1976). 5. Goldberg LI: Dopamine: receptors and clinical applications, Clin Physiol Biochem 3: 120 (1985). 6. Goldberg LI: Cardiovascular and renal actions of dopamine: potential clinical applications, Pharmacol Rev 24: 1 (1972). 7. Neiberger RE, and Passmore JC: Effects of dopamine on canine intrarenal blood flow distribution during hemorrhage, Kidney Int 15: 219 (1979). 8. Sophasan S, Sanposu W, Kraisawekwisai S, and Chatsudthipong V: The effects of dopamine on kidney function of rats, Arch Int Pharmacodyn 252: 219 (1981). 9. Dasta JF, and Giray Kirby M: Pharmacology and therapeutic use of low-dose dopamine, Pharmacotherapy 6: 304 (1986). 10. McNay JL, McDonald RH, and Goldberg LI: Direct renal vasodilatation produced by dopamine in the dog, Circ Res 16: 510 (1965). 11. Parker S, et al: Dopamine administration in oliguria and oliguric renal failure, Crit Care Med 9: 630 (1981).
UROLOGY
I JANUARY 1993
I VOLUME 41, NUMBER 1
From the Department of Urology, Royal Victoria Hospital, and McGill University, Montreal, Canada
ABSTRACT-Intravenous pyelography is the standard first-line investigation for suspected renal trauma. A faint, and/or delayed visualization, or nonvisualization of the damaged renal unit is not uncommon. Low-dose dopamine (3 pg/ kg/min) increases renal blood flow without deleterious side effects. An experimental rat model was developed to evaluate the effects of low-dose dopamine on intravenous pyelograms in animals with unilateral renal trauma. A consistent and significant improvement in the visualization of the injured kidney was noted in the dopamine-treated animals compared with controls that received equivalent volumes of normal saline.
The intravenous urogram is the initial study carried out in most cases of renal trauma. Significant injury to the kidney, or its vasculature, can lead to a poor, delayed, or nonvisualization of the injured kidney on the intravenous urogram. This often necessitates more elaborate studies to define the injury. The ability to enhance the radiologic image on the initial intravenous urogram could lead to a more prompt definition of the traumatized renal unit, and could avoid further costly studies. An experimental model was first developed which reproduced the clinical finding of poor contrast excretion from the injured kidney. The model was then used to study the effects of lowdose dopamine on the urographic images, and the results were compared with control animals that received no dopamine, but were given an equivalent volume of saline.
toneal pentobarbital (20 mg/kg body weight). Through a midline incision, the left kidney was exposed and an unprotected hemostat applied to crush-transect the lower third of the kidney. The organ was then returned and the wound was closed. Twenty-four hours later, the animals were reanesthetized, and a groin dissection was made to expose the femoral vein. The vein was isolated and cannulated using a PE 10 tubing glued to a PE 50 tubing. A bolus injection of diatrizoate sodium (60% Hypaque) was administered at a dosage of 2 mL/kg body weight. X-ray films were obtained on a Picker singlephase unit using a nongrid technique at 52 kV and 1.22 milli-amps per second exposure at a focal distance of 40 inches. The films were read as showing good, faint, or nonvisualization.
Material and Methods
The experimental animals received intravenous dopamine at a dosage of 3 pglkglmin for fifteen minutes. Control animals received equivalent volumes of saline. Immediately thereafter, diatrizoate sodium was injected
Animal model Fisher rats weighing 200-400 g were used. The animals were anesthetized using intraperi-
88
Dopamine studies
UROLOGY
/ JANUARY 1993
I
VOLUME
41, NUMBER
1
n 12 rats
14
rats
64
60 % 46
/
20
experiment
catltrol -10
minutes~
-
control 30
experhmi
minutes-
2. intravenous urogram ten and thirty minutes after injection of contrast medium in control animal pretreated with saline.
FIGURE
Histogram of compiled results. Animals FIGURE 1. treated with dopamine demonstrated markedly improved urogram visualization at ten and thirty minutes.
through the same cannula at a dosage of2 ml2 per kg body weight. X-ray films were obtained ten and thirty minutes later. Results Twelve animals that received no dopamine showed nonvisualization (83 % ) or faint visualization (17 % ) of the contrast medium in the onlle&ncr ---‘“-““b
cvctem ‘J “-----
nf -_
the ____
inirnd “‘,_‘__
kirlnev l.__AA_ J
at ..-
ten c.,*_
minutes, and nonvisualization (58%) or faint visualization (42 % ) at thirty minutes. Fourteen animals that received dopamine demonstrated good visualization (64%) or faint visualization (36%) of the contrast medium in the collecting system at ten minutes, and good visualization (79%) or faint visualization (21%) at thirty minutes (Figs. l-3). Comment The animal model was developed after considerable trials and errors. We tried manually squeezing the exposed kidney, crushing the kidney under a pre-set vise grip plier, and crushclamping the renal pedicle for varying periods of time. The most consistent findings of faint or _lYsl__:-:.___I .._.__1 __~.I._ ~~~ nonvisiialization or CII~qurea renal units were obtained by crush-clamping the lower third of
UROLOGY
/ JANUARY 1993
i
VOLUME
41, NUMBER 1
FIGURE3. Intravenous urogram ten and thirty minutes after injection of contrast medium in experimental animal pretreated with dopamine. the kidney with an unprotected hemostat. Urographic studies were carried out at one, twelve, and twenty-four hours after injury with no significant differences in the x-ray findings. The most consistent results were obtained at twentyfour hours, and thus this timing was selected for the study. Dopamine was selected as the drug to test afL_- 1-L _.?~_~. 1 .I rer aeoarmg wnerner we shouid first try the caicium ion antagonists or other drugs that relax
89
smooth muscles. Low-dose dopamine was chosen because it has selective and localized renal effects. Dopamine (3,4 dihydroxyphenylethinemine) is an endogenous catecholamine and is the immediate precursor of norepinephrine.’ In low dosage (0.5 to 3 pg/kg/ min), dopamine has a selective dose-dependent effect on the kidney. It dilates the renal vasculature, leading to increased blood flow, natriuresis, and diuresis. Specific dopaminergic postsynaptic receptors have been demonstrated in the renal vasculature of ratse4 When the receptors are activated, the enzyme adenyl cyclase increases the formation of cyclic AMP. This causes a dilatation of the renal, mesenteric, cerebral, ahd coronary vessels5 There is an improvement of the subcortico-outer medullary renal blood flo~.~,’ Low-dose dopamine increases cardiac output without increasing the heart rate. l-6 In dogs, the vasodilatational effects of dopamine persist after renal denervation.* These pharmacologic effects of low-dose dopamine have been utilized in critically ill patients such as those suffering from drug overdose and in patients in shock with acute renal shut down. Dopamine at a dosage of 3 pg/kg/ min doubles renal blood flow, while increasing cardiac output 15 percent.e Other studies reported increased glomerular filtration rate of 11 to 75 percent1*4~eand diuresis6JoJ1 From these experiments and clinical observations, it seems reasonable to suggest that spasms of the renal vasculature often accompany renal injury. What is less certain is whether a phar-
90
macologic attempt to combat the vasoconstriction is helpful or harmful in limiting injury to the kidney and in aiding recovery. This is the question that is being addressed in experiments presently underway. 687 Pine Avenue West Montreal, Canada H3A 1Al (DR. TAGUCHI) References 1. McDonald RH, Goldberg LI, &Nay JL, and ‘Ihttle EP: Effects of dopamine in man: augmentation of sodium excretion, glomerular filtration rate, and renal plasma flow, J Clin Invest 43: 1116 (1964). 2. Chapman BJ, Horn NM, Munday KA, and Robertson MJ: The actions of dopamine on regional blood flows in the rat, J Physiol 298: 437 (1980). 3. Woodman OL, and Lang WJ: Dopamine-induced vasodilatation in the isolated perfused rat kidney, Arch Int Pharmacodyn 243: 228 (1980). 4. Pendleton RG, and Sherman SS: Studies concerning dopamine diuresis in the rat, Arch Int Pharmacodyn 222: 94 (1976). 5. Goldberg LI: Dopamine: receptors and clinical applications, Clin Physiol Biochem 3: 120 (1985). 6. Goldberg LI: Cardiovascular and renal actions of dopamine: potential clinical applications, Pharmacol Rev 24: 1 (1972). 7. Neiberger RE, and Passmore JC: Effects of dopamine on canine intrarenal blood flow distribution during hemorrhage, Kidney Int 15: 219 (1979). 8. Sophasan S, Sanposu W, Kraisawekwisai S, and Chatsudthipong V: The effects of dopamine on kidney function of rats, Arch Int Pharmacodyn 252: 219 (1981). 9. Dasta JF, and Giray Kirby M: Pharmacology and therapeutic use of low-dose dopamine, Pharmacotherapy 6: 304 (1986). 10. McNay JL, McDonald RH, and Goldberg LI: Direct renal vasodilatation produced by dopamine in the dog, Circ Res 16: 510 (1965). 11. Parker S, et al: Dopamine administration in oliguria and oliguric renal failure, Crit Care Med 9: 630 (1981).
UROLOGY
I JANUARY 1993
I VOLUME 41, NUMBER 1