scholarly journals Adenosine A3receptor activation protects the myocardium from reperfusion/reoxygenation injury

2002 ◽  
Vol 283 (4) ◽  
pp. H1307-H1313 ◽  
Author(s):  
Helen L. Maddock ◽  
Mihaela M. Mocanu ◽  
Derek M. Yellon
Keyword(s):  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Annexin V ◽  
Receptor Activation ◽  
Isolated Rat Heart ◽  
Beneficial Effects ◽  
Isolated Hearts ◽  
Rat Hearts ◽  
Apoptosis And Necrosis ◽  
Isolated Rat

Ischemia-reperfusion induces both necrotic and apoptotic cell death. The ability of adenosine to attenuate reperfusion-induced injury (RI) and the role played by adenosine receptors are unclear. We therefore studied the role of the A3receptor (A3R) in ameliorating RI using the specific A3R agonist 1-[2-chloro-6-[[(3-iodophenyl)methyl]amino]-9 H-purin-9-yl]-1-deoxi- N-methyl-b-d-ribofuranuronamide (2-Cl-IB-MECA). Isolated rat hearts and cardiomyocytes were subjected to ischemia or simulated ischemia, followed by reperfusion/reoxygenation. The end points were percent infarction/risk zone and annexin-V (apoptosis) and/or propidium iodide positivity (necrosis), respectively. In isolated hearts, 2-Cl-IB-MECA significantly limited infarct size (44.2 ± 2.7% in control vs. 21.9 ± 2.4% at 1 nM and 35.8 ± 3.3% at 0.1 nM, P < 0.05). In isolated myocytes, apoptosis and necrosis were significantly reduced compared with controls (5.7 ± 2.6% vs. 17.1 ± 1.3% and 13.7 ± 2.0% vs. 23.1 ± 1.5%, respectively, P < 0.0001). In both models, the beneficial effects were abrogated using the A3R antagonist MRS-1191. The involvement of A2areceptor activation was also examined. This is the first study to demonstrate that A3R activation at reperfusion limits myocardial injury in the isolated rat heart and improves survival in isolated myocytes, possibly by antiapoptotic and antinecrotic mechanisms.

Adenosine A3 agonist cardioprotection in isolated rat and rabbit hearts is blocked by the A1 antagonist DPCPX

2001 ◽  
Vol 281 (2) ◽  
pp. H847-H853 ◽  
Author(s):  
Eric L. Kilpatrick ◽  
Prakash Narayan ◽  
Robert M. Mentzer ◽  
Robert D. Lasley
Keyword(s):  
Infarct Size ◽  
Receptor Activation ◽  
Left Ventricular ◽  
Ischemic Myocardium ◽  
Beneficial Effects ◽  
Rat Hearts ◽  
Rabbit Myocardium ◽  
Independent Effects ◽  
Developed Pressure ◽  
Isolated Rat

Adenosine A3 agonists have been shown to protect ischemic rat and rabbit myocardium. However, these agonists have been reported to exert A3 independent effects, and no cardiac A3 receptor has yet been identified. We thus tested whether A3 agonist protection is due to A1receptor activation. Isolated rat and rabbit hearts were subjected to 25 and 45 min of global ischemia, respectively. Rat hearts pretreated with adenosine (100 μM), the A3 agonist 2-chloro- N 6-(3-iodobenzyl)-adenosine-5′- N-methyluronamide (Cl-IB-MECA, 50 nM), and vehicle recovered 73 ± 2%, 75 ± 4%, and 46 ± 4%, respectively, of preischemic left ventricular developed pressure (LVDP) after 30 min of reperfusion. The A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 nM) blocked the beneficial effects of Cl-IB-MECA (51 ± 5%) and adenosine (47 ± 6%). In rabbit hearts, the beneficial effects of the A3 agonist N 6-(3-iodobenzyl)-adenosine-5′- N-methyluronamide (50 nM) and the A1 agonist 2-chloro- N 6-cyclopentyladenosine (100 nM) on postischemic LVDP (75 ± 4 and 74 ± 5%, respectively) were blocked by DPCPX (34 ± 4 and 36 ± 3%, respectively). The reduction in infarct size with both agonists was also completely blocked by DPCPX. These results suggest that these A3 agonists protect ischemic myocardium via A1 receptor activation.

Promotion of copper excretion from the isolated rat heart attenuates postischemic cardiac oxidative injury

1999 ◽  
Vol 277 (3) ◽  
pp. H956-H962 ◽  
Author(s):  
Saul R. Powell ◽  
Ellen M. Gurzenda ◽  
Mark A. Wingertzahn ◽  
Raul A. Wapnir
Keyword(s):  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Oxidative Injury ◽  
Isolated Rat Heart ◽  
Protein Carbonyls ◽  
Rate Pressure Product ◽  
Beneficial Effects ◽  
Rat Hearts ◽  
Postischemic Period ◽  
Isolated Rat

This study examined the role of Cu as a mediator of cardiac postischemic oxidative injury. Isolated rat hearts were subjected to 20 min of normothermic global ischemia, followed by 30 min of reperfusion; after 20 min of preischemic loading with Krebs-Henseleit buffer ± 20 or 30 μM zinc-bis-histidinate (Zn-His2), 0.5 mM deferoxamine (DEF) or 42 μM neocuproine (NEO). Postischemic developed systolic pressure and rate-pressure product were highest and postischemic end-diastolic pressure was lowest in hearts treated with 20 or 30 μM Zn-His2 and 0.5 mM DEF. Cu efflux was significantly increased by 225 and 290% (end of preischemic loading), and 325 and 375% (immediate postischemic period) of control basal rates in hearts treated with 30 μM Zn-His2 and 0.5 mM DEF, respectively. NEO did not effect any of these parameters. By the end of ischemia, protein carbonyls were lowest in Zn-His2-treated hearts and highest in DEF-treated hearts when compared with control hearts. The results of this study suggest that removal of redox-active Cu before ischemia has beneficial effects, indicating a mediatory role in postischemic cardiac oxidative injury.

Acute treatment with polyphenol quercetin improves postischemic recovery of isolated perfused rat hearts after global ischemia

2010 ◽  
Vol 88 (4) ◽  
pp. 465-471 ◽  
Author(s):  
Monika Barteková ◽  
Slávka Čarnická ◽  
Dezider Pancza ◽  
Mária Ondrejčáková ◽  
Albert Breier ◽  
...  
Keyword(s):  
Cardiovascular System ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Global Ischemia ◽  
Functional Parameters ◽  
Beneficial Effects ◽  
Isolated Hearts ◽  
Positive Effects ◽  
Rat Hearts ◽  
Postischemic Recovery

Quercetin is a plant-derived bioflavonoid with potentially beneficial effects on the cardiovascular system. Studies focused on the efficiency of flavonoids against ischemia–reperfusion (I/R) injury have demonstrated that quercetin exerts robust protective effects in renal, cerebral, and hepatic I/R models. However, there is only limited evidence about the effect of quercetin on myocardial I/R injury. Therefore, the aim of the current study was to examine the effect of quercetin on isolated rat heart during ischemia and reperfusion. Rat hearts perfused according to Langendorff at 37 °C were examined during 25 min global ischemia followed by 120 min reperfusion. Quercetin (15 µmol/L) was administered either 15 min before ischemia (group Q1), or during the entire reperfusion period (group Q2). Changes in functional parameters of the hearts were measured during the initial 40 min of reperfusion. At the end of the experiment, the hearts were stained with tetrazolium to estimate the size of infarction (IS). Our study showed that quercetin improved postischemic recovery of functional parameters of isolated hearts in both treated groups. This improvement was manifested by significantly higher values of left ventricular developed pressure (LVDP) and the maximal rates of pressure development and fall (+(dP/dt)max and –(dP/dt)max) and by significantly lower increase of end-diastolic pressure. Coronary flow was not significantly changed during reperfusion in the group treated before ischemia, but was significantly increased in the group treated during reperfusion. Quercetin also significantly reduced IS in both groups, more markedly in postischemically treated group. We conclude that acute quercetin treatment exerts significant positive effects on isolated hearts during I/R injury. These results are consistent with the beneficial effects of quercetin and other flavonoids on the cardiovascular system.

Cardiac effects of acetylcholine in rat hearts: role of endothelium-derived relaxing factor and prostaglandins

1993 ◽  
Vol 264 (5) ◽  
pp. H1388-H1393
Author(s):  
B. C. Yang ◽  
W. W. Nichols ◽  
J. L. Mehta
Keyword(s):  
Receptor Activation ◽  
Isolated Rat Heart ◽  
Cardiac Contraction ◽  
Coronary Perfusion ◽  
Cardiac Effects ◽  
Relaxing Factor ◽  
Rat Hearts ◽  
Adrenergic Antagonist ◽  
Endothelium Derived Relaxing Factor ◽  
Isolated Rat

We examined the effects of acetylcholine (ACh) on coronary perfusion pressure (CPP) and force of cardiac contraction (FCC) in isolated rat hearts. Perfusion of hearts with ACh increased both CPP and the FCC, whereas cardiac contraction rate fell. These effects of ACh were abolished by atropine but were not affected by the beta 1-adrenergic antagonist metoprolol. The nonselective beta-adrenergic antagonist propranolol decreased ACh-mediated increase in FCC but did not affect the rise in CPP. Pretreatment of hearts with cyclooxygenase inhibitor indomethacin or thromboxane (Tx) A2-endoperoxide receptor antagonist SQ 29,548 decreased ACh-mediated increase in CPP and FCC, suggesting release of TxA2 in the microvasculature, which may partially account for the increase in CPP and FCC with ACh infusion. In contrast to the effect of indomethacin and SQ 29,548, pretreatment of hearts with endothelium-derived relaxing factor (EDRF) synthetase inhibitor NG-monomethyl-L-arginine (L-NMMA) or guanylate cyclase inhibitor methylene blue potentiated ACh-mediated increase in CPP and attenuated the increase in FCC, suggesting that ACh-mediated increase in CPP is modified by basal EDRF release. Thus the cardiac effects of ACh are related to muscarinic receptor activation, and the release of prostaglandins and EDRF modulates the effects of ACh in isolated rat heart.

Effect of estrogen replacement treatment on ischemic preconditioning in isolated rat hearts

2004 ◽  
Vol 82 (5) ◽  
pp. 339-344 ◽  
Author(s):  
Wei-Jie Peng ◽  
Jing Yu ◽  
Sheng Deng ◽  
Jun-Ling Jiang ◽  
Han-Wu Deng ◽  
...  
Keyword(s):  
Ischemic Preconditioning ◽  
Ischemia Reperfusion ◽  
Ovariectomized Rats ◽  
Mechanical Function ◽  
Estrogen Replacement ◽  
Isolated Hearts ◽  
Replacement Treatment ◽  
Rat Hearts ◽  
Isolated Rat

In the present study, we tested the effects of long-term estrogen replacement treatment on myocardial ischemia-reperfusion injury and on the cardioprotection of ischemic preconditioning in isolated hearts from ovariectomized rats. Ovariectomized rats were treated with 17β-estradiol (30 µg/kg/d, s.c.) for 12 weeks. Isolated rat hearts were perfused in the Langendorff mode. Heart rate, coronary flow, left ventricular pressure and its first derivative (±LVdp/dtmax) were recorded. Fifteen-min global ischemia and 30-min reperfusion caused a significant decrease of cardiac mechanical function, which were not affected by ovariectomy or estrogen replacement treatment. The isolated hearts in all groups could be preconditioned, and the cardioprotection afforded by preconditioning in the sham-operated rats was greater compared with ovariectomized rats with or without estrogen treatment. These results suggest that long-term estrogen replacement treatment exerts no effect on the inhibition of mechanical function after ischemia-reperfusion, and this study also suggests that estrogen does not affect ischemic preconditioning in isolated hearts of ovariectomized rats.Key words: ERT (estrogen replacement treatment), ischemia-reperfusion, ischemic preconditioning, heart, rat.

Effect of Hydrogen Sulfide on Reactions of Isolated Rat Heart under Volume Load and Ischemia-Reperfusion

2013 ◽  
Vol 4 (3) ◽  
pp. 201-212
Author(s):  
Tetyana V Shimanskaya ◽  
Yulia V. Goshovska ◽  
Olena M. Semenykhina ◽  
Vadim F. Sagach
Keyword(s):  
Hydrogen Sulfide ◽  
Rat Heart ◽  
Ischemia Reperfusion ◽  
Isolated Rat Heart ◽  
Volume Load ◽  
Isolated Rat

scholarly journals Attenuation of extracellular ATP response in cardiomyocytes isolated from hearts subjected to ischemia-reperfusion

2005 ◽  
Vol 289 (2) ◽  
pp. H614-H623 ◽  
Author(s):  
Harjot K. Saini ◽  
Vijayan Elimban ◽  
Naranjan S. Dhalla
Keyword(s):  
Cardiac Function ◽  
Positive Inotropic Effect ◽  
Ischemia Reperfusion ◽  
Cardiac Contractility ◽  
Extracellular Atp ◽  
Binding Characteristics ◽  
Rat Hearts ◽  
The Status ◽  
Intracellular Ca ◽  
Isolated Rat

Extracellular ATP is known to augment cardiac contractility by increasing intracellular Ca2+ concentration ([Ca2+]i) in cardiomyocytes; however, the status of ATP-mediated Ca2+ mobilization in hearts undergoing ischemia-reperfusion (I/R) has not been examined previously. In this study, therefore, isolated rat hearts were subjected to 10–30 min of global ischemia and 30 min of reperfusion, and the effect of extracellular ATP on [Ca2+]i was measured in purified cardiomyocytes by fura-2 microfluorometry. Reperfusion for 30 min of 20-min ischemic hearts, unlike 10-min ischemic hearts, revealed a partial depression in cardiac function and ATP-induced increase in [Ca2+]i; no changes in basal [Ca2+]i were evident in 10- or 20-min I/R preparations. On the other hand, reperfusion of 30-min ischemic hearts for 5, 15, or 30 min showed a marked depression in both cardiac function and ATP-induced increase in [Ca2+]i and a dramatic increase in basal [Ca2+]i. The positive inotropic effect of extracellular ATP was attenuated, and the maximal binding characteristics of 35S-labeled adenosine 5′-[γ-thio]triphosphate with crude membranes from hearts undergoing I/R was decreased. ATP-induced increase in [Ca2+]i in cardiomyocytes was depressed by verapamil and Cibacron Blue in both control and I/R hearts; however, this response in I/R hearts, unlike control hearts, was not affected by ryanodine. I/R-induced alterations in cardiac function and ATP-induced increase in [Ca2+]i were attenuated by treatment with an antioxidant mixture and by ischemic preconditioning. The observed changes due to I/R were simulated in hearts perfused with H2O2. The results suggest an impairment of extracellular ATP-induced Ca2+ mobilization in I/R hearts, and this defect appears to be mediated through oxidative stress.

Effect of cicletanine on ischemia/reperfusion-induced ion shifts in isolated rat hearts

1990 ◽  
Vol 22 ◽  
pp. S64
Author(s):  
Arpad Tosaki ◽  
Matyas Koltai ◽  
Thierry Tarrade ◽  
Pierre Braquet
Keyword(s):  
Ischemia Reperfusion ◽  
Rat Hearts ◽  
Ion Shifts ◽  
Isolated Rat
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