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Evaluation of Coronary Flow Reserve After Myocardial Ischemia Reperfusion in Rats
Published on: June 28, 2019
Low dose nitrite improves reoxygenation following renal ischemia in rats
Kathleen Cantow1, Bert Flemming1, Mechthild Ladwig-Wiegard1,2
1Institut für vegetative Physiologie, Center for Cardiovascular Research, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Abstract:
In hypoxic and acidic tissue environments, nitrite is metabolised to nitric oxide, thus, bringing about novel therapeutic options in myocardial infarction, peripheral artery disease, stroke, and hypertension. Following renal ischemia, reperfusion of the kidney remains incomplete and tissue oxygenation is reduced for several minutes to hours. Thus, in renal ischemia-reperfusion injury, providing nitrite may have outstanding therapeutic value. Here we demonstrate nitrite's distinct potential to rapidly restore tissue oxygenation in the renal cortex and medulla after 45 minutes of complete unilateral kidney ischemia in the rat. Notably, tissue oxygenation was completely restored, while tissue perfusion did not fully reach pre-ischemia levels within 60 minutes of reperfusion. Nitrite was infused intravenously in a dose, which can be translated to the human. Specifically, methaemoglobin did not exceed 3%, which is biologically negligible. Hypotension was not observed. Providing nitrite well before ischemia and maintaining nitrite infusion throughout the reperfusion period prevented the increase in serum creatinine by ischemia reperfusion injury. In conclusion, low-dose nitrite restores renal tissue oxygenation in renal ischemia reperfusion injury and enhances regional kidney post-ischemic perfusion. As nitrite provides nitric oxide predominantly in hypoxic tissues, it may prove a specific measure to reduce renal ischemia reperfusion injury.
Insights
Administering nitrite rapidly restores oxygenation in kidney tissue after ischemia-reperfusion injury. This therapeutic approach shows promise for reducing kidney damage and improving perfusion without adverse effects.
Area of Science:
- Biomedical Science
- Renal Physiology
- Pharmacology
Background:
- Hypoxic and acidic tissues metabolize nitrite to nitric oxide, offering therapeutic potential for various conditions.
- Renal ischemia-reperfusion injury leads to incomplete reperfusion and prolonged tissue hypoxia.
- Nitrite administration presents a promising therapeutic strategy for renal ischemia-reperfusion injury.
Purpose of the Study:
- To investigate the efficacy of nitrite in restoring tissue oxygenation and perfusion in the kidney following ischemia.
- To evaluate the safety and impact of nitrite administration on renal function markers.
Main Methods:
- A rat model of unilateral kidney ischemia (45 minutes) followed by reperfusion was utilized.
- Intravenous nitrite was administered at a human-translatable dose, before and during reperfusion.
- Tissue oxygenation, perfusion, serum creatinine levels, and methaemoglobin were monitored.
Main Results:
- Nitrite rapidly and completely restored oxygenation in the renal cortex and medulla.
- Tissue perfusion did not fully recover to pre-ischemic levels within 60 minutes of reperfusion.
- Nitrite administration prevented the increase in serum creatinine and did not cause hypotension or significant methaemoglobinemia.
Conclusions:
- Low-dose nitrite effectively restores renal tissue oxygenation in ischemia-reperfusion injury.
- Nitrite enhances regional kidney perfusion post-ischemia and mitigates injury.
- Nitrite's targeted nitric oxide release in hypoxic tissues suggests specific therapeutic benefits for renal ischemia-reperfusion injury.
