oru.sePublikationer
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
The novel nitric oxide donor PDNO attenuates ovine ischemia-reperfusion induced renal failure
Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Cardiothoracic and Vascular Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Physiology & Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Department of Physiology & Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Department of Physiology & Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Department of Physiology & Pharmacology, Karolinska Institutet, Stockholm, Sweden; Department of Surgical Sciences, Section of Anesthesia and Intensive Care, Uppsala University, Uppsala, Sweden.
2017 (English)In: Intensive Care Medicine Experimental, ISSN 1646-2335, E-ISSN 2197-425X, Vol. 5, no 1, 29Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Renal ischemia-reperfusion injury is a common cause of acute kidney injury in intensive care and surgery. Recently, novel organic mononitrites of 1,2-propanediol (PDNO) were synthesized and shown to rapidly and controllably deploy nitric oxide in the circulation when administered intravenously. We hypothesized that intravenous infusion of PDNO during renal ischemia reperfusion would improve post-ischemic renal function and microcirculation.

METHODS: Sixteen sheep were anesthetized, mechanically ventilated, and surgically instrumented. The left renal artery was clamped for 90 min, and the effects of ischemia were studied for a total of 8 h. Fifteen minutes prior to the release of the clamp, intravenous infusions of PDNO (n = 8) or vehicle (1,2 propanediol + inorganic nitrite, n = 8) were initiated (180 nmol/kg/min for 30 min, thereafter 60 nmol/kg/min for the remainder of the experiment).

RESULTS: Renal artery blood flow, cortical and medullary perfusion, and diuresis and creatinine clearance decreased in the left kidney post ischemia. However, in the sheep treated with PDNO, diuresis and creatinine clearance in the left kidney were significantly higher post ischemia compared to vehicle-treated animals (1.7 ± 0.5 vs 0.7 ± 0.3 ml/kg/h, p = 0.04 and 7.5 ± 2.1 vs 1.7 ± 0.6 ml/min, p = 0.02, respectively). Left renal medullary perfusion and oxygen uptake were higher in the PDNO group (73 ± 9 vs 37 ± 5% of baseline, p = 0.004 and 2.6 ± 0.4 vs 1.6 ± 0.3 ml/min, p = 0.02, respectively). PDNO significantly increased renal oxygen consumption and reduced the oxygen utilization for sodium reabsorption (p = 0.03 for both). Mean arterial blood pressure was significantly reduced by PDNO (83 ± 3 vs 94 ± 3 mmHg, p = 0.02) but was still within normal limits. Total renal blood flow was not affected, and there were no signs of increased blood methemoglobin concentrations or tachyphylaxis.

CONCLUSIONS: The novel nitric oxide donor PDNO improved renal function after ischemia. PDNO also prevented the persistent reduction in medullary perfusion during reperfusion and improved renal oxygen utilization without severe side effects.

Place, publisher, year, edition, pages
London, UK: BioMed Central, 2017. Vol. 5, no 1, 29
Keyword [en]
AKI, acute kidney injury, kidney, microcirculation, nitrites, renal oxygen consumption, sheep
National Category
Anesthesiology and Intensive Care
Identifiers
URN: urn:nbn:se:oru:diva-60830DOI: 10.1186/s40635-017-0143-4PubMedID: 28600797OAI: oai:DiVA.org:oru-60830DiVA: diva2:1147974
Available from: 2017-10-09 Created: 2017-10-09 Last updated: 2017-12-07Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Nilsson, Kristofer F.

Search in DiVA

By author/editor
Nilsson, Kristofer F.
By organisation
School of Medical SciencesÖrebro University Hospital
In the same journal
Intensive Care Medicine Experimental
Anesthesiology and Intensive Care

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 33 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf