Rationale and Objectives
The aim of this study was to investigate the short-term effects of furosemide on renal perfusion by using arterial spin labeling (ASL) magnetic resonance imaging.
Materials and Methods
Eleven healthy human subjects were enrolled in the study. The measurement of renal blood flow (RBF) was performed by applying an ASL technique with flow-sensitive alternating inversion recovery spin preparation and a single-shot fast spin-echo imaging strategy on a 3.0-T magnetic resonance scanner. For all subjects, the ASL magnetic resonance images were obtained before agent injection as a baseline scan. Then 20 mg of furosemide was injected intravenously. Postfurosemide ASL images were acquired following administration to evaluate the renal hemodynamic response.
Results
Postinjection scans showed that cortical RBF decreased from 366.59 ± 41.19 mL/100 g/min at baseline to 314.33 ± 48.83 mL/100 g/min at 10 minutes after the administration of furosemide (paired t test, P = .04 vs baseline), and medullary RBF decreased from 118.59 ± 24.69 mL/100 g/min at baseline to 97.38 ± 18.40 mL/100 g/min at 10 minutes after the administration of furosemide (paired t test, P = .01 vs baseline). There was a negative correlation between the furosemide-induced diuretic effect and the reduction of RBF (Spearman’s r = −0.61).
Conclusions
The dominant hemodynamic effect of furosemide on the kidney is associated with a decrease in both cortical and medullary blood perfusion. Furthermore, the quantitative ASL technique may provide an alternative way to noninvasively monitor the change in renal function due to furosemide administration.
Furosemide, a powerful diuretic acting on the thick ascending limb of the loop of Henle to promote the renal excretion of both water and solutes from the body, is commonly used in patients with congestive heart failure or oliguric acute renal failure . Like other loop diuretics, furosemide exerts its action by inhibiting NKCC2, the luminal Na + -K + -2Cl − cotransporter in the thick ascending limb of the loop of Henle . It has also been reported that loop diuretics inhibit NKCC1 . As the other isoform of the Na + -K + -2Cl − cotransporter, NKCC1 is widely expressed in the vasculature. The inhibition of NKCC1 by loop diuretics may produce direct vascular effects such as vasodilation in most vasculatures.
The well-established mechanisms of Na + -K + -2Cl − cotransporters suggest that the vascular effects of loop diuretics in the kidney should include vasodilatation . However, data from previous studies of the renal hemodynamic effect of furosemide are conflicting and difficult to reconcile. The expected increase of renal blood flow (RBF) induced by loop diuretic administration has been monitored in several studies in humans and dogs . In contrast, in some rat or mice experiments, prominent reductions in RBF were observed . Moreover, the previously established data were performed mostly in anesthetized animals or by invasive facilities, which possibly upset the true actions of loop diuretics on renal autoregulation. Given these irreconcilable contradictions and the clinical importance of this class of drugs, it would be useful to achieve a better understanding of the mechanisms that may underlie the response of the renal vasculature to loop diuretics.
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Materials and methods
Human Subjects and MR Protocols
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Quantitative Analysis of MR Perfusion Data
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ΔM(TI)=Msel(TI)−Mnonsel(TI)=2M0TIfλeTI/T1, Δ
M
(
TI
)
=
M
sel
(
TI
)
−
M
nonsel
(
TI
)
=
2
M
0
TI
f
λ
e
TI
/
T
1
,
where Δ M is the difference in magnetization between section-selective ( M sel ) and nonselective ( M nonsel ) measurements, M 0 represents the tissue equilibrium magnetization per unit mass of the tissue, T 1 is the longitudinal relaxation time of tissue, f is the perfusion rate (usually expressed in milliliters per 100 grams per minute), and λ is the blood-tissue water partition coefficient, which is thought to be nearly constant at 0.80. Perfusion maps can be calculated pixel by pixel by analyzing Δ M at a given TI, M 0 , and T 1 using the following equation:
f=λ⋅ΔM(TI)⋅f2⋅TI⋅M0eTI/T1. f
=
λ
⋅
Δ
M
(
TI
)
⋅
f
2
⋅
TI
⋅
M
0
e
TI
/
T
1
.
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Statistical Analysis
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Results
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Table 1
Changes in RBF from before to after Furosemide Infusion
Cortex Medulla RBF (mL/100 g/min) ( n = 11 × 2) ( n = 11 × 2) Prefurosemide 366.59 ± 41.19 118.59 ± 24.69 Postfurosemide 314.33 ± 48.83 ∗ 97.38 ± 18.40 †
RBF, renal blood flow.
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Discussion
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Conclusions
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