Protective effects of 5-(N,N-dimethyl)amiloride on ischemia-reperfusion injury in hearts

1990 ◽  
Vol 258 (5) ◽  
pp. H1615-H1619 ◽  
Author(s):  
H. P. Meng ◽  
G. N. Pierce
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Significant Rise ◽  
Similar Degree ◽  
Protective Effects ◽  
Tension Development ◽  
Right Ventricular Wall ◽  
Dimethyl Amiloride

An Na(+)-H+ exchange inhibitor, 5-(N,N-dimethyl)amiloride (DMA), was used to probe the possible role of Na(+)-H+ exchange in ischemia-reperfusion injury in coronary perfused isolated rat right ventricular wall. In DMA-untreated hearts, 60 min of ischemia resulted in a significant rise in testing tension (RT: 174 +/- 8% of preischemic level). Thirty minutes of reperfusion further increased RT (273 +/- 12%) and induced a poor recovery in developed tension (DT: 28 +/- 4%). Both the rate of tension development and relaxation (+dT/dt and -dT/dt) recovered to a similar degree. When 1, 5, or 20 microM DMA was included in the perfusate (3 min before ischemia and in the first 3 min of reperfusion), the maximal postischemic RT of the heart was reduced to 204 +/- 21, 166 +/- 15, and 139 +/- 45% of the preischemic levels (P less than 0.05), respectively, and DT was 39 +/- 3, 63 +/- 10, and 79 +/- 8% of the preischemic levels (P less than 0.05), respectively. Similar qualitative recovery of +/- dT/dt was observed. Recovery was similar if DMA was present only during reperfusion. DMA treatment also significantly protected against creatine phosphokinase release during reperfusion. The results demonstrate that DMA can significantly protect the heart during the initial stages of reperfusion. The data suggest that Na(+)-H+ exchange may play an important role in the development of cardiac dysfunction and damage during the first minutes of reperfusion.

scholarly journals The protective role of carnosic acid in ischemic/reperfusion injury through regulation of autophagy under T2DM

2019 ◽  
Vol 244 (7) ◽  
pp. 602-611 ◽  
Author(s):  
Min Hu ◽  
Tianyu Li ◽  
Zixiang Bo ◽  
Feixiang Xiang
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Carnosic Acid ◽  
Protective Effects ◽  
Pre Treatment ◽  
Myocardial Ischemia Reperfusion

Ischemic heart disease (IHD) is the most common cardiovascular disease and is the main cause of death and disability worldwide. Myocardial ischemia/reperfusion (MI/R) injury has been linked to IHD-induced cardiomyocytes apoptosis and tissue damage. Recently, it has been reported that carnosic acid (CA) may function as a potent antioxidant in liver ischemia/reperfusion (I/R). However, whether it regulates I/R in the heart remains unclear. Here, we elucidated the emerging role of CA in MI/R under diabetic myocardial conditions. Diabetes mellitus (DM) was induced in mice by consumption of a high-fat diet for 16 weeks. To create the I/R in mice, the left anterior descending coronary artery was occluded for 30 min, and then occlusion was released to reperfuse the heart for 3 or 24 h. In diabetic myocardial ischemia/reperfusion (DMI/R) mice, pre-treatment with CA suppressed the overgeneration of reactive oxygen species (ROS) and production of cytokine. Importantly, the activation of autophagy was significantly increased by CA treatment, as assessed by p62 degradation and LC3-II/LC3-I conversion, as well as by phosphorylation of AMPKα, Akt, and mTOR. Interestingly, all of the protective effects of CA were impeded by the treatment with chloroquine, which is an autophagy inhibitor. These studies suggest that CA prevents DMI/R injury via regulation of autophagy. In conclusion, our findings indicate that CA has potential as a novel therapeutic to prevent DMI/R injury. Impact statement We have provided, for the first time, evidence that carnosic acid (CA) attenuates ischemia–reperfusion injury of diabetic myocardium, i.e. diabetic myocardial ischemia/reperfusion (DMI/R) injury, via enhancement of autophagy. A greater understanding of the target molecule in CA-enhanced autophagy is necessary for the development of potential chemotherapy for DMI/R injury.

Protective effects of adenosine on the diabetic myocardium against ischemia–reperfusion injury: Role of calpain

2012 ◽  
Vol 79 (4) ◽  
pp. 462-464 ◽  
Author(s):  
Yang Yang ◽  
Weixun Duan ◽  
Jingjun Zhou ◽  
Juanjuan Yan ◽  
Jincheng Liu ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Diabetic Myocardium

Effect of amiloride and selected analogues on postischemic recovery of cardiac contractile function

1993 ◽  
Vol 264 (6) ◽  
pp. H1831-H1835 ◽  
Author(s):  
H. P. Meng ◽  
T. G. Maddaford ◽  
G. N. Pierce
Keyword(s):  
Right Ventricular ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Ventricular Wall ◽  
Protective Effects ◽  
Cardiac Contractile Function ◽  
Drug Concentrations ◽  
Right Ventricular Wall

The purpose of the present study was to compare the protective effects of amiloride and three of its derivatives (which are selective inhibitors of Na(+)-H+ exchange) during postischemic reperfusion. Previously, amiloride has been shown to have a protective effect on ischemia-reperfusion injury. However, because of its nonselective actions, the mechanism of its effect is unclear. 5-(N,N-dimethyl)-amiloride (DMA) is also protective and appears to act via inhibition of the Na(+)-H+ exchanger. However, corroborative effects using other selective Na(+)-H+ exchange blockers are needed. Amiloride, DMA, ethylisopropyl amiloride (EIPA), and 5-(N,N-hexamethylene)-amiloride (HMA) were included for 10 min in the reperfusion period after 60 min of global ischemia in the rat right ventricular wall. Peak developed tension and the rates of tension generation and relaxation were significantly improved during reperfusion in the presence of 100 microM amiloride, 10 microM DMA, 2.5 microM HMA, or 1 microM EIPA compared with those of drug-untreated muscles. Contracture formation was significantly depressed in the presence of these drug concentrations as was release of creatine kinase from the ventricular wall into the coronary effluent. The efficacy of these drugs for protecting the right ventricular wall from postischemic contractile dysfunction correlates well with their potency as blockers of Na(+)-H+ exchange. The results provide further evidence in support of a role for Na(+)-H+ exchange. The results provide further evidence in support of a role for Na(+)-H+ exchange in determining ischemia-reperfusion injury in the heart.

scholarly journals A Possible Cardio-Protective Role of Early Remote Ischemia Preconditioning Against Ischemia Reperfusion Injury I’m Isolated Hearts of Adult Albino Rats: Possible Involvement of Hypoxia Inducible Factor

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
M S Abdelhamid ◽  
R S Mansour ◽  
A T Ebrahim ◽  
B M Elkafoury
Keyword(s):  
Lactate Dehydrogenase ◽  
Reperfusion Injury ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Hypoxia Inducible Factor ◽  
Remote Ischemic Preconditioning ◽  
Albino Rats ◽  
Protective Effects

Abstract Background Inspite of the claimed cardio-protective effects of ischemic preconditioning (IPC), it is invasive and so using remote ischemic preconditioning (RIPC) may offer an alternative. Meanwhile, RIPC cardioprotective role is controversial, with an equivocal underlying mechanism. The hypoxia inducible factor 1 alpha (HIF-1-alpha) which is increased following ischemic insults is claimed as a humoral mediator for RIPC. Objective To investigate the effect of remote ischemic pre-conditioning on myocardial ischemia/reperfusion injury in rats, and to elucidate the possible role of hypoxia inducible factor in this protection. Materials and Methods The present study was performed on 28 adult female albino rats in the same estrus cycle evaluated by vaginal smear, and they were allocated into 3 groups: Group I: control rats subjected to ischemic/reperfusion injury (I/R) only, group II: early RIPC rats (RIPC 2 hours prior to I/R), group III: acriflavine-treated early RIPC rats. Acriflavine is a drug that binds directly to HIF-1 alpha and HIF-2 alpha subunits, thus inhibiting its dimerization and transcriptional activity, and it was injected IP 10 days prior to RIPC. On sacrifice day, ECG was recorded and isolated heart studies were performed. Later, cardiac chambers weight, serum HIF-1-alpha, myocardial perfusate lactate dehydrogenase, and cardiac oxidative markers: Malonaldehyde and glutathione perioxidase were measured. Results Compared to the control group, the early RIPC group showed significant increase in the heart rate (HR), QTc interval in the ECG recording, glutathione peroxidase and the HIF 1α levels together with reduction in the percent of decrease in PT and PT/LV, in the percent of prolongation in time to peak tension (TPT), perfusate lactate dehydrogenase and MDA levels, while no significant changes were recorded in the heart chronotropic activity, in the percent of half relaxation time (HRT) prolongation, or in the percent of decrease of MFR. Following acriflavine treatment, the effects of RIPC were abolished highlighting the role of HIF-1-alpha in mediating RIPC protective effects. Conclusion The non-invasive and non-pharmological remote ischemic preconditioning technique can ameliorate the cardiac ischemic reperfusion injury with an obvious role of HIF-1α in mediating these protective effects.

Sign in / Sign up

Export Citation Format

Share Document