The role of nitric oxide and NO-donor agents in myocardial protection from surgical ischemic-reperfusion injury

The present study was designed to investigate the role of combined administration of Ramipril and Candesartan againstin vitromyocardial ischemic reperfusion injury in rat. Male Wistar albino rats were divided into five groups (n=6) and treated with saline (10 mL/kg), Ramipril (2 mg/kg), Candesartan (1 mg/kg), and the combination of both drugs, respectively 24 h before induction of global ischemia (5 min of stabilization, 9 min of global ischemia, and 12 min of reflow). Combination of Ramipril and Candesartan when compared to the monotherapy significantly increased the levels of superoxide dismutase, reduced glutathione, catalase, and nitric oxide and decreased the levels of thiobarbituric acid reactive substances. In addition, the superior protective role of combination of Ramipril and Candesartan on ischemia induced myocardial damage was further confirmed by well preserved myocardial tissue architecture in light microscopy and transmission electron microscopy analysis studies. The combination was proved to be effective in salvaging the myocardial tissue against ischemic reperfusion injury when compared to the monotherapy of individual drugs and further investigations on protective mechanism of drugs by increasing the nitric oxide level at molecular levels are needed.

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Myocardium protection against ischemic-reperfusion injury by nitric oxide supplied to the extracorporeal circulation line during cardiopulmonary bypass (experimental study)

Patologiya krovoobrashcheniya i kardiokhirurgiya ◽

10.21688/1681-3472-2017-4-79-86 ◽

2017 ◽

Vol 21 (4) ◽

pp. 79 ◽

Cited By ~ 2

Author(s):

N. O. Kamenshchikov ◽

I. A. Mandel ◽

Yu. K. Podoksenov ◽

S. L. Mikheev ◽

S. S. Sementsov ◽

...

Keyword(s):

Nitric Oxide ◽

Reperfusion Injury ◽

Extracorporeal Circulation ◽

Myocardial Protection ◽

Area Ratio ◽

Main Group ◽

Control Group ◽

Risk Area ◽

Ischemic Reperfusion Injury ◽

Ischemic Reperfusion

Aim. The study was designed to assess the efficiency of exogenous nitric oxide supply to the extracorporeal circulation line for myocardial protection against ischemic-reperfusion injury in acute myocardial infarction simulation during cardiopulmonary bypass (CPB) in the experiment. Methods. Acute ischemia was simulated in rabbits (n = 20) with subsequent myocardial reperfusion. All animals were anesthetized and mechanically ventilated through a nasotracheal tube. The experiment included occlusion of the left coronary artery by its clamping with a ligature for 45 min with subsequent reperfusion for 120 min during CPB. All animals were divided into 2 equal groups: 10 rabbits received nitric oxide supply to the extracorporeal circulation line in a dose of 40 ppm throughout the entire CPB period (the main group); 10 rabbits made up the control group. The ratio of the infarction area to the risk area was determined, and the quantity and nature of ventricular arrhythmias were accessed. Results. It was established that nitric oxide supply through the extracorporeal circulation line during CPB had a pronounced infarct-limiting effect, the infarct area to the risk area ratio decreased by 15% as compared to the control group, р = 0.0002. There was also a significant antiarrhythmic effect. A lesser quantity of polytopic and polymorphic ventricular extrasystoles were observed in the main group during periods of ischemia and reperfusion (p = 0.003 and p = 0.012). A statistically significant decrease in the venoarterial gradient of the partial pressure of carbon dioxide in the main group was associated with an increase in the urine flow rate amounting to 1.4 [1.3; 1.5] ml/kg/h in the main group and 1.15 [1; 1.3] ml/kg/h in the control group, p = 0.013. Conclusion. The data obtained during the experiment demonstrate the presence of cardioprotective properties of nitric oxide delivered to the extracorporeal circulation line when simulating myocardial ischemic-reperfusion injury. These properties manifest themselves as a 15% decrease of the infarction zone-risk area ratio, a fewer number of arrhythmias and improvement of tissue perfusion during CPB. Intraoperative myocardial protection by nitric oxide in patients operated with CPB should be the object of further clinical research.Received 19 June 2017. Revised 9 October 2017. Accepted 15 October 2017.Funding: The study did not have sponsorship.Conflict of interest: Authors declare no conflict of interest.Author contributions: All the authors comply with 4 ICMJE authorship criteria and contributed equally at every stage of the study.Acknowledgement: The authors express their gratitude to Ekaterina S. Tokareva and Aleksandra A. Nenakhova for support in preparation of the article.

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Role of NAD(P)H Oxidase- and Mitochondria-Derived Reactive Oxygen Species in Cardioprotection of Ischemic Reperfusion Injury by Angiotensin II

Hypertension ◽

10.1161/01.hyp.0000163462.98381.7f ◽

2005 ◽

Vol 45 (5) ◽

pp. 860-866 ◽

Cited By ~ 185

Author(s):

Shoji Kimura ◽

Guo-Xing Zhang ◽

Akira Nishiyama ◽

Takatomi Shokoji ◽

Li Yao ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Angiotensin Ii ◽

Reperfusion Injury ◽

Reactive Oxygen ◽

Oxygen Species ◽

Ischemic Reperfusion Injury ◽

Ischemic Reperfusion

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Role of IL-1 in renal ischemic reperfusion injury.

Journal of the American Society of Nephrology ◽

10.1681/asn.v94614 ◽

1998 ◽

Vol 9 (4) ◽

pp. 614-619 ◽

Cited By ~ 2

Author(s):

M Haq ◽

J Norman ◽

S R Saba ◽

G Ramirez ◽

H Rabb

Keyword(s):

Renal Function ◽

Reperfusion Injury ◽

Interleukin 1 ◽

Organ Injury ◽

Central Component ◽

Ischemic Reperfusion Injury ◽

Ischemic Reperfusion ◽

And Control ◽

Renal Ischemic Reperfusion Injury

Interleukin-1 (IL-1) is a central component of many acute inflammatory processes. Blocking IL-1 receptor (IL-1R) with IL-1R antagonist (IL-1Ra) has attenuated ischemic reperfusion injury in brain, heart, and liver models. However, the role of IL-1 in renal ischemic reperfusion injury (IRI) is not known. Therefore, the role of IL-1 in renal IRI was evaluated using the complementary approaches of IL-1R blockade in wild-type mice in addition to the study of renal IRI in IL-1R knockout (KO) mice. Ischemia was induced by bilateral renal pedicle clamping for 30 min. IL-1Ra was administered at 10 mg/kg every 4 h, high doses that have been protective in previous organ injury models in mice. IL-1R KO animals, previously characterized as insensitive to IL-1, had the absence of IL-1R1 confirmed by DNA blots. IL-1Ra, IL-1R KO, and control groups had similar elevations of blood urea nitrogen (114 +/- 13, 133 +/- 11, and 120 +/- 11 mg/dl) and serum creatinine (1.7 +/- 0.3, 2.1 +/- 0.2, and 1.6 +/- 0.3 mg/dl) 24 h after ischemia. Furthermore, acute tubular necrosis scores were also similar in IL-1Ra-treated mice (3.0 +/- 0.3), IL-1R KO mice (2.7 +/- 0.3), and control mice (3.1 +/- 0.2). However, both IL-1Ra and IL-1R KO groups, compared with control animals, developed significantly less infiltration of polymorphonuclear leukocytes per 10 high-power fields in postischemic renal tissue (1111 +/- 228 and 967 +/- 198 versus 1820 +/- 190, P < 0.05). In contrast to the comparable renal functions at 24 h, recovery of renal function was significantly accelerated in the IL-1R KO group compared with control at both 48 (P < 0.05) and 72 (P < 0.05) h. Recovery in the IL-1Ra group was similar to that in the control animals. These data demonstrate that IL-1 is unlikely to be beneficial in the recovery of renal function after ischemia and may play a deleterious role.

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