scholarly journals Influence of Hypoxic and Hyperoxic Preconditioning on Endothelial Function in a Model of Myocardial Ischemia-Reperfusion Injury with Cardiopulmonary Bypass (Experimental Study)

2020 ◽  
Vol 21 (15) ◽  
pp. 5336
Author(s):  
Irina A. Mandel ◽  
Yuri K. Podoksenov ◽  
Irina V. Suhodolo ◽  
Darya A. An ◽  
Sergey L. Mikheev ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiopulmonary Bypass ◽  
Endothelial Function ◽  
Light Microscopy ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Endothelin 1 ◽  
Nitric Oxide Metabolites

The aim of the experiment was to evaluate the effect of preconditioning based on changes in inspiratory oxygen fraction on endothelial function in the model of ischemia-reperfusion injury of the myocardium in the condition of cardiopulmonary bypass. The prospective randomized study included 32 rabbits divided into four groups: hypoxic preconditioning, hyperoxic preconditioning, hypoxic-hyperoxic preconditioning, and control group. All animals were anesthetized and mechanically ventilated. We provided preconditioning, then started cardiopulmonary bypass, followed by induced acute myocardial infarction (ischemia 45 min, reperfusion 120 min). We investigated endothelin-1, nitric oxide metabolites, asymmetric dimethylarginine during cardiopulmonary bypass: before ischemia, after ischemia, and after reperfusion. We performed light microscopy of myocardium, kidney, lungs, and gut mucosa. The endothelin-1 level was much higher in the control group than in all preconditioning groups after ischemia. The endothelin-1 even further increased after reperfusion. The total concentration of nitric oxide metabolites was significantly higher after all types of preconditioning compared with the control group. The light microscopy of the myocardium and other organs revealed a diminished damage extent in the hypoxic-hyperoxic preconditioning group as compared to the control group. Hypoxic-hyperoxic preconditioning helps to maintain the balance of nitric oxide metabolites, reduces endothelin-1 hyperproduction, and enforces organ protection.

P0545DPP-4 INHIBITOR ATTENUATED RENAL VASOCONSTRICTION FOLLOWING ISCHEMIA-REPERFUSION INJURY IN CIRRHOTIC RATS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
CHIAO-LIN CHUANG ◽  
Hui-Chun Huang
Keyword(s):  
Nitric Oxide ◽  
Reperfusion Injury ◽  
Variceal Bleeding ◽  
Vascular Reactivity ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Renal Vasoconstriction ◽  
Endothelin 1 ◽  
Renal Vascular

Abstract Background and Aims Cirrhotic patients may develop gastroesophageal varices to cope with portal hypertension. Annual risk of variceal bleeding among small and large varices is 5% and 15%, respectively. Bleeding from varices is a medical emergency and is associated with a high morbidity and mortality. In those who survive the initial bleeding event, the risks of further bleeding and other serious complications remain high, such as hypotension and ischemia-reperfusion injury. Ischemia-reperfusion injury is a leading cause of acute kidney injury. In patients with advanced liver cirrhosis, variceal bleeding associated hypotension and ischemia-reperfusion injury may activated endogenous vasoconstrictors, leading to severe renal vasoconstriction and subsequent renal failure (so called hepatorenal syndrome). There was not effective treatment yet. Dipeptidyl peptidase-4 (DPP-4) inhibitors, a new class of oral hypoglycemic agents, have shown potential pleiotropic effects, such as anti-inflammatory and anti-oxidant properties. Previous studies reported that inhibition of DPP-4 could attenuate the development of ischemia-reperfusion injury in kidney. Cumulated evidences indicates that DPP-4 inhibitors could attenuate the endothelin-1 induced contraction and increase endothelial-dependent vasodilation related to activation of endothelial nitric oxide synthase and increased production of nitric oxide. In addition, DPP-4 inhibitors may suppress inflammation and fibrosis in the kidneys independently of glycemic control. The aim of this study is to delineate the effect of DPP-4 inhibitors in renal vascular reactivity of cirrhotic rats following ischemia-reperfusion injury. Method Male Sprague-Dawley rats weighing 240-270 g were used for experiments. Secondary biliary cirrhosis were created by common bile duct ligation (CBDL). Rats receiving sham surgery (SHAM) were used as the control group. Linagliptin (3 mg/kg/day) or distilled water (DW) was administered via oral gavage since the 1st day throughout the 28th day after surgery. On the 29th day, all rats were randomized to control group or ischemia-reperfusion injury. Bilateral renal pedicles of rats in the ischemia-reperfusion injury group were clamped for 45 minutes with microvascular clamps. Thereafter, the clamps were removed and reperfusion was allowed by visual control. After 60 minutes of reperfusion period, kidneys were perfused in situ via right renal artery for continuous monitoring of renal perfusion pressure using a non-recirculating system. Results There was no significant difference in mean arterial pressure, heart rate, and portal pressure between DW and DPP-4 inhibitor treated groups in both SHAM and CBDL rats. Ischemia-reperfusion injury enhanced renal vascular reactivity to endothelin-1 in both SHAM (p = 0.027) and CBDL (p = 0.016) rats, implying renal vasoconstriction. Compared with corresponding DW-treated rats, DPP-4 inhibitor treatment abrogated renal hyper-reactivity following ischemia-reperfusion injury in BDL rats (p = 0.038), but not in SHAM rats (p = 0.17). Conclusion We concluded that DPP-4 inhibitors may attenuate the development of renal vasoconstriction following ischemia-reperfusion injury in cirrhotic rats. The potentially mechanisms remained to be elucidated.

15-F2t-isoprostane exacerbates myocardial ischemia-reperfusion injury of isolated rat hearts

2005 ◽  
Vol 289 (4) ◽  
pp. H1366-H1372 ◽  
Author(s):  
Zhengyuan Xia ◽  
Kuo-Hsing Kuo ◽  
David V. Godin ◽  
Michael J. Walker ◽  
Michelle C. Y. Tao ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Saline Control ◽  
Control Group ◽  
Endothelin 1 ◽  
Rat Hearts ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Reactive oxygen species induce formation of 15-F2t-isoprostane (15-F2t-IsoP), a specific marker of in vivo lipid peroxidation, which is increased after myocardial ischemia and during the subsequent reperfusion. 15-F2t-IsoP possesses potent bioactivity under pathophysiological conditions. However, it remains unknown whether 15-F2t-IsoP, by itself, can influence myocardial ischemia-reperfusion injury (IRI). Adult rat hearts were perfused by the Langendorff technique with Krebs-Henseleit (KH) solution at a constant flow rate of 10 ml/min. 15-F2t-IsoP (100 nM), SQ-29548 (1 μM, SQ), a thromboxane receptor antagonist that can abolish the vasoconstrictor effect of 15-F2t-IsoP, 15-F2t-IsoP + SQ in KH, or KH alone (vehicle control) was applied for 10 min before induction of 40 min of global ischemia followed by 60 min of reperfusion. During ischemia, saline (control), 15-F2t-IsoP, 15-F2t-IsoP + SQ, or SQ in saline was perfused through the aorta at 60 μl/min. 15-F2t-IsoP, 15-F2t-IsoP + SQ, or SQ in KH was infused during the first 15 min of reperfusion. Coronary effluent endothelin-1 concentrations were significantly higher in the group treated with 15-F2t-IsoP than in the control group during ischemia and also in the later phase of reperfusion ( P < 0.05). Infusion of 15-F2t-IsoP increased release of cardiac-specific creatine kinase, reduced cardiac contractility during reperfusion, and increased myocardial infarct size relative to the control group. SQ abolished the deleterious effects of 15-F2t-IsoP. 15-F2t-IsoP exacerbates myocardial IRI and may, therefore, act as a mediator of IRI. 15-F2t-IsoP-induced endothelin-1 production during cardiac reperfusion may represent a mechanism underlying the deleterious actions of 15-F2t-IsoP.

scholarly journals Brief Periods of Nitric Oxide Inhalation Protect against Myocardial Ischemia–Reperfusion Injury

2008 ◽  
Vol 109 (4) ◽  
pp. 675-682 ◽  
Author(s):  
Yasuko Nagasaka ◽  
Bernadette O. Fernandez ◽  
Maria F. Garcia-Saura ◽  
Bodil Petersen ◽  
Fumito Ichinose ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Inhaled Nitric Oxide ◽  
Cardiac Ischemia ◽  
Nitric Oxide Inhalation ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Nitric Oxide Metabolites

Background Prolonged breathing of nitric oxide reduces myocardial ischemia-reperfusion injury, but the precise mechanisms responsible for the cardioprotective effects of inhaled nitric oxide are incompletely understood. Methods The authors investigated the fate of inhaled nitric oxide (80 parts per million) in mice and quantified the formation of nitric oxide metabolites in blood and tissues. The authors tested whether the accumulation of nitric oxide metabolites correlated with the ability of inhaled nitric oxide to protect against cardiac ischemia-reperfusion injury. Results Mice absorbed nitric oxide in a nearly linear fashion (0.19 +/- 0.02 micromol/g x h). Breathing nitric oxide rapidly increased a broad spectrum of nitric oxide metabolites. Levels of erythrocytic S-nitrosothiols, N-nitrosamines, and nitrosyl-hemes increased dramatically within 30 s of commencing nitric oxide inhalation. Marked increases of lung S-nitrosothiol and liver N-nitrosamine levels were measured, as well as elevated cardiac and brain nitric oxide metabolite levels. Breathing low oxygen concentrations potentiated the ability of inhaled nitric oxide to increase cardiac nitric oxide metabolite levels. Concentrations of each nitric oxide metabolite, except nitrate, rapidly reached a plateau and were similar after 5 and 60 min. In a murine cardiac ischemia-reperfusion injury model, breathing nitric oxide for either 5 or 60 min before reperfusion decreased myocardial infarction size as a fraction of myocardial area at risk by 31% or 32%, respectively. Conclusions Breathing nitric oxide leads to the rapid accumulation of a variety of nitric oxide metabolites in blood and tissues, contributing to the ability of brief periods of nitric oxide inhalation to provide cardioprotection against ischemia-reperfusion injury. The nitric oxide metabolite concentrations achieved in a target tissue may be more important than the absolute amounts of nitric oxide absorbed.

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