Howard Florey Institute, University of Melbourne, Parkville, Victoria, Australia.
Crit Care Med. 2011 Apr;39(4):770-6. doi: 10.1097/CCM.0b013e318206c1fb.
In experimental hyperdynamic sepsis, renal function deteriorates despite renal vasodilatation and increased renal blood flow. Because nitric oxide is increased in sepsis and participates in renal blood flow control, we investigated the effects of intrarenal Nω-nitro-L-arginine methyl ester, a nonspecific nitric oxide synthase inhibitor, in mild and severe sepsis.
Prospective crossover and randomized control interventional studies.
University-affiliated research institute.
Thirty-two merino ewes.
Examination of responses to intrarenal infusion of Nω-nitro-L-arginine methyl ester for 8 hrs in unilaterally nephrectomized normal sheep and in sheep administered Escherichia coli.
: In normal sheep, Nω-nitro-L-arginine methyl ester decreased renal blood flow (301 ± 30 to 228 ± 26 mL/min) and creatinine clearance (40.0 ± 5.8 to 31.1 ± 2.8 mL/min), whereas plasma creatinine increased, but fractional excretion of sodium was unchanged. In sheep with nonhypotensive hyperdynamic sepsis, plasma creatinine increased and there were decreases in creatinine clearance (34.5 ± 4.6 to 20.1 ± 3.7 mL/min) and fractional excretion of sodium despite increased renal blood flow. Infusion of Nω-nitro-L-arginine methyl ester normalized renal blood flow and increased urine output, but creatinine clearance did not improve and plasma creatinine and fractional excretion of sodium increased. In sheep with severe hypotensive sepsis, creatinine clearance decreased further (31.1 ± 5.4 to 16.0 ± 1.7 mL/min) despite increased renal blood flow. Infusion of Nω-nitro-L-arginine methyl ester restored mean arterial pressure and reduced renal blood flow but did not improve plasma creatinine or creatinine clearance.
In hyperdynamic sepsis, with or without hypotension, creatinine clearance decreased despite increasing renal blood flow. Intrarenal Nω-nitro-L-arginine methyl ester infusion reduced renal blood flow but did not improve creatinine clearance. These data indicate that septic acute kidney injury is not the result of decreased renal blood flow nor is it improved by nonspecific nitric oxide synthase inhibition.
在实验性高动力性败血症中，尽管存在肾血管扩张和肾血流量增加，肾功能仍会恶化。由于败血症中一氧化氮增加并参与肾血流控制，我们研究了肾内 Nω-硝基-L-精氨酸甲酯（一种非特异性一氧化氮合酶抑制剂）在轻度和重度败血症中的作用。
前瞻性交叉和随机对照干预研究。
大学附属研究所。
32 只美利奴羊。
在单侧肾切除的正常绵羊和给予大肠杆菌的绵羊中，检查肾内输注 Nω-硝基-L-精氨酸甲酯 8 小时的反应。
在正常绵羊中，Nω-硝基-L-精氨酸甲酯降低了肾血流量（301 ± 30 至 228 ± 26 mL/min）和肌酐清除率（40.0 ± 5.8 至 31.1 ± 2.8 mL/min），而血浆肌酐升高，但钠的分数排泄不变。在非低血压性高动力性败血症的绵羊中，血浆肌酐升高，肌酐清除率降低（34.5 ± 4.6 至 20.1 ± 3.7 mL/min），尽管肾血流量增加，但钠的分数排泄减少。输注 Nω-硝基-L-精氨酸甲酯使肾血流量正常化并增加尿量，但肌酐清除率未改善，血浆肌酐和钠的分数排泄增加。在严重低血压性败血症的绵羊中，尽管肾血流量增加，肌酐清除率进一步降低（31.1 ± 5.4 至 16.0 ± 1.7 mL/min）。输注 Nω-硝基-L-精氨酸甲酯恢复平均动脉压并减少肾血流量，但未改善血浆肌酐或肌酐清除率。
在高动力性败血症中，无论是否伴有低血压，尽管肾血流量增加，肌酐清除率仍会降低。肾内 Nω-硝基-L-精氨酸甲酯输注降低了肾血流量，但并未改善肌酐清除率。这些数据表明，败血症性急性肾损伤不是肾血流量减少的结果，也不能通过非特异性一氧化氮合酶抑制来改善。
