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.

Effect of preconditioning on ryanodine-sensitive Ca2+ release from sarcoplasmic reticulum of rat heart

1996 ◽  
Vol 271 (3) ◽  
pp. H876-H881 ◽  
Author(s):  
M. Tani ◽  
Y. Asakura ◽  
H. Hasegawa ◽  
K. Shinmura ◽  
Y. Ebihara ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Function ◽  
Rat Heart ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Ventricular Tachyarrhythmias ◽  
Beneficial Effects ◽  
Rat Hearts ◽  
Developed Pressure ◽  
Isolated Rat

The effect of varying the number of preconditioning (PC) episodes on the recovery of cardiac function and on the function of the sarcoplasmic reticulum (SR) was investigated to determine the correlation between the effect of PC and SR function. Isolated rat hearts were subjected to zero to three 5-min episodes of global ischemia with intermittent perfusion (PC0-PC3) followed by 25 min of ischemia (I) and 30 min of reperfusion. The left ventricular (LV) pressure and SR 45Ca2+ uptake in the absence or presence of ryanodine were then measured. The increase in LV end-diastolic pressure and the incidence and duration of ventricular tachyarrhythmias during reperfusion decreased. The recovery of LV developed pressure, LV dP/dtmax and dP/dtmin, increased as the number of episodes of PC increased. The rates of SR 45Ca2+ uptake after PC and after reperfusion were lower in PC3 than in PC0. Conversely, the rate of 45Ca2+ uptake after I did not differ between PC0 and PC3. The ryanodine-sensitive Ca2+ release increased after I, and additional increases were observed during reperfusion in PC0, whereas the release after I and reperfusion decreased progressively in PC3. These observations show that the beneficial effects of PC are associated with a decrease in ryanodine-sensitive SR Ca2+ release.

Acute inhibition of monoamine oxidase and ischemic preconditioning in isolated rat hearts: interference with postischemic functional recovery but no effect on infarct size reduction

2015 ◽  
Vol 93 (9) ◽  
pp. 819-825 ◽  
Author(s):  
Maria D. Dănilă ◽  
Andreea I. Privistirescu ◽  
Silvia N. Mirica ◽  
Adrian Sturza ◽  
Valentin Ordodi ◽  
...  
Keyword(s):  
Infarct Size ◽  
Functional Recovery ◽  
Ischemic Preconditioning ◽  
Left Ventricular ◽  
Mao Inhibitors ◽  
Rat Hearts ◽  
System Generation ◽  
Infarct Size Reduction ◽  
Developed Pressure ◽  
Isolated Rat

Monoamine oxidases (MAOs) have recently emerged as important mitochondrial sources of oxidative stress in the cardiovascular system. Generation of reactive oxygen species during the brief episodes of ischemic preconditioning (IPC) is responsible for the cardioprotection at reperfusion. The aim of this study was to assess the effects of two MAO inhibitors (clorgyline and pargyline) on the IPC-related protection in isolated rat hearts. Animals subjected to 30 min global ischemia and 120 min reperfusion were assigned to the following groups: (i) Control, no additional intervention; (ii) IPC, 3 cycles of 5 min ischemia and 5 min reperfusion before the index ischemia; (iii) IPC-clorgyline, IPC protocol bracketed for 5 min with clorgyline (50 μmol/L); (iv) IPC-pargyline, IPC protocol bracketed for 5 min with pargyline (0.5 mmol/L). The postischemic functional recovery was assessed by the left ventricular developed pressure (LVDP) and the indices of contractility (+dLVP/dt max) and relaxation (–dLVP/dt max). Infarct size (IS) was quantified by TTC staining. In both genders, IPC significantly improved functional recovery that was further enhanced in the presence of either clorgyline or pargyline. IS reduction was comparable among all the preconditioned groups, regardless of the presence of MAO inhibitors. In isolated rat hearts, acute inhibition of MAOs potentiates the IPC-induced postischemic functional recovery without interfering with the anti-necrotic protection.

Abstract 1712: The P2Y 12 Antagonist Cangrelor and the GP IIb/IIIa Blocker Abciximab Reduce Platelet-Mediated Myocardial Injury After Ischemia and Reperfusion

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Jose A Barrabes ◽  
Javier Inserte ◽  
Maribel Mirabet ◽  
Adoracion Quiroga ◽  
Victor Hernando ◽  
...  
Keyword(s):  
Myocardial Injury ◽  
Myocardial Damage ◽  
Left Ventricular ◽  
Myocardial Salvage ◽  
Ischemia And Reperfusion ◽  
Activated Platelets ◽  
Rat Hearts ◽  
Developed Pressure ◽  
Enddiastolic Pressure ◽  
Isolated Rat

Objective: Platelets activated during experimental acute myocardial infarction (AMI) contribute to myocardial injury. We aimed to investigate whether platelets from patients with AMI increase myocardial damage after transient ischemia in isolated rat hearts and the modification of this effect by the P2Y 12 receptor antagonist cangrelor and the GPIIb/IIIa receptor blocker abciximab. Methods: Platelets were obtained from 9 AMI patients (7 thrombolyzed, all on aspirin) within 24 h after symptom onset. Incubation with 100 μM cangrelor or 50 μg/ml abciximab resulted, respectively, in 78 ± 4 and 90 ± 2% inhibition of aggregation (optical aggregometry). Isolated rat hearts (four simultaneous experiments per patient) were subjected to 40 min of global ischemia and 60 min of reperfusion. Hearts received no additional intervention (Control) or were infused during the 5 min prior to ischemia with platelets (22.5x10 6 /min), either untreated or treated with cangrelor or abciximab. Results: P-selectin expression (flow cytometry) in isolated platelets before infusion was 31 ± 3% (P = NS between groups). Platelets augmented myocardial injury, as demonstrated by worse left ventricular developed pressure (LVDevP), higher left ventricular enddiastolic pressure (LVEDP) and coronary resistance, and greater LDH release and infarct size (TTC staining), and both cangrelor and abciximab greatly attenuated these effects (Table ). Conclusions: Activated platelets from patients with AMI increase myocardial injury after ischemia and reperfusion, and cangrelor and abciximab attenuate this effect. The results support the notion that very early antiplatelet treatment may increase myocardial salvage by direct effects on the microcirculation in these patients.

Effect of Salidroside on Cardiac Functional Recovery

2013 ◽  
Vol 798-799 ◽  
pp. 1030-1032
Author(s):  
Yan Zhang ◽  
Zhong Hua Zheng ◽  
Yue Peng Wang ◽  
Guo Liang Peng ◽  
Liu Hang Wang
Keyword(s):  
Flow Rate ◽  
Functional Recovery ◽  
Rat Heart ◽  
Coronary Flow ◽  
Left Ventricular ◽  
Cardioprotective Effect ◽  
Decrease Rate ◽  
Rat Hearts ◽  
Developed Pressure ◽  
Isolated Rat

To investigate the cardioprotective effect of salidroside to rat heart subjected to 8-hour hypothermic storage and 2-hour normothermic reperfusion. Isolated rat hearts were perfused with Langendorff model; after 30 minutes of baseline, the hearts were arrested and stored by St. Thomas solution (STS) without (STS group) or with different concentration salidroside at 4 °C for 8 hours, then reperfused for 2 hours. Compared with STS group, both middle and high dosage in STS greatly improved the recovery of left ventricular developed pressure (LVDP), maximum LVDP increase and decrease rate (±dp/dt), coronary flow rate (CF). Our study demonstrated that the salidroside was beneficial to improving cardiac functional recovery.

Role of Adenosine Receptors in Volatile Anesthetic Preconditioning against Neutrophil-induced Contractile Dysfunction in Isolated Rat Hearts

2005 ◽  
Vol 103 (2) ◽  
pp. 287-295 ◽  
Author(s):  
Guochang Hu ◽  
M Ramez Salem ◽  
George J. Crystal
Keyword(s):  
Adenosine Receptors ◽  
Platelet Activating Factor ◽  
Volatile Anesthetics ◽  
Left Ventricular ◽  
Superoxide Production ◽  
Contractile Dysfunction ◽  
Myeloperoxidase Activity ◽  
Rat Hearts ◽  
Developed Pressure ◽  
Isolated Rat

Background The authors tested the hypothesis that adenosine receptors in polymorphonuclear neutrophils and the heart mediate the preconditioning effects of volatile anesthetics against neutrophil-induced contractile dysfunction. Methods Studies were conducted in buffer-perfused and paced isolated rat hearts. Left ventricular developed pressure served as index of contractility. Neutrophils and platelet-activating factor were added to perfusate for 10 min followed by 30 min of recovery. The effect of selective pretreatment of the neutrophils and the hearts with 1.0 minimum alveolar concentration isoflurane or sevoflurane on the neutrophil-induced contractile dysfunction was assessed. Studies were performed in the absence and presence of the nonselective adenosine receptor antagonist 8-phenyltheophylline (10 microM). Neutrophil retention was determined from difference between those administered and collected in coronary effluent and from myeloperoxidase concentration in myocardial samples. Superoxide production of neutrophils was measured by spectrophotometry. Results Under control conditions (no anesthetic pretreatment), activated neutrophils caused marked and persistent reductions in left ventricular developed pressure, associated with increases in neutrophil retention and myeloperoxidase activity. Pretreatment of the neutrophils or the heart with either isoflurane or sevoflurane abolished these effects. Pretreatment of the neutrophils also reduced the platelet-activating factor-induced increase in superoxide production by 29 and 33%, respectively. 8-Phenyltheophylline blunted the effects of anesthetic pretreatment of the neutrophils, whereas it did not alter the effects of anesthetic pretreatment of the heart. Conclusion An activation of adenosine receptors in neutrophils, but not in the heart, plays a role in the preconditioning effects of volatile anesthetics against neutrophil-induced contractile dysfunction.

scholarly journals Hemidesmus indicusandHibiscus rosa-sinensisAffect Ischemia Reperfusion Injury in Isolated Rat Hearts

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Vinoth Kumar Megraj Khandelwal ◽  
R. Balaraman ◽  
Dezider Pancza ◽  
Táňa Ravingerová
Keyword(s):  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Moderate Increase ◽  
Dependent Manner ◽  
Hemidesmus Indicus ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Developed Pressure

Hemidesmus indicus(L.) R. Br. (HI) andHibiscus rosa-sinensisL. (HRS) are widely used traditional medicine. We investigated cardioprotective effects of these plants applied for 15 min at concentrations of 90, 180, and 360 μg/mL in Langendorff-perfused rat hearts prior to 25-min global ischemia/120-min reperfusion (I/R). Functional recovery (left ventricular developed pressure—LVDP, and rate of development of pressure), reperfusion arrhythmias, and infarct size (TTC staining) served as the endpoints. A transient increase in LVDP (32%–75%) occurred at all concentrations of HI, while coronary flow (CF) was significantly increased after HI 180 and 360. Only a moderate increase in LVDP (21% and 55%) and a tendency to increase CF was observed at HRS 180 and 360. HI and HRS at 180 and 360 significantly improved postischemic recovery of LVDP. Both the drugs dose-dependently reduced the numbers of ectopic beats and duration of ventricular tachycardia. The size of infarction was significantly decreased by HI 360, while HRS significantly reduced the infarct size at all concentrations in a dose-dependent manner. Thus, it can be concluded that HI might cause vasodilation, positive inotropic effect, and cardioprotection, while HRS might cause these effects at higher concentrations. However, further study is needed to elucidate the exact mechanism of their actions.

Isoflurane and Halothane Increase Adenosine Triphosphate Preservation, but Do Not Provide Additive Recovery of Function after Ischemia, in Preconditioned Rat Hearts

1997 ◽  
Vol 86 (1) ◽  
pp. 109-117 ◽  
Author(s):  
Ashraf Boutros ◽  
Jun Wang ◽  
Christine Capuano
Keyword(s):  
Adenosine Triphosphate ◽  
Coronary Flow ◽  
Recovery Of Function ◽  
Left Ventricular ◽  
Untreated Group ◽  
Control Group ◽  
Time Control ◽  
Rat Hearts ◽  
Developed Pressure ◽  
Isolated Rat

Background Brief ischemic periods render the myocardium resistant to infarction from subsequent ischemic insults by a process called ischemic preconditioning. Volatile anesthetics have also been shown to be cardioprotective if administered before ischemia. The effect of preconditioning alone and combined with halothane or isoflurane on hemodynamic recovery and preservation of adenosine triphosphate content in isolated rat hearts was evaluated. Methods Seven groups of isolated rat hearts (n = 6 each) were perfused in a retrograde manner at constant temperature and pressure. A latex balloon was placed in the left ventricle to obtain isovolumetric contraction. Heart rhythm, coronary flow, left ventricular pressure and its derivative dP/dt (positive and negative), and developed pressure were monitored. The hearts were paced at 300 beats per minute. Each heart was randomly allocated to (1) a time-control group that received no ischemia, (2) an untreated group that received 25 min of normothermic ischemia only. (3 and 4) an isoflurane group and a halothane group that received 40 min of anesthetic (2.2% and 1.5%, respectively) before ischemia; (5) a preconditioning group that received two 5-min periods of ischemia separated by 10 min of reperfusion before ischemia; or (6 and 7) a isoflurane+preconditioning group and a halothane+preconditioning group that received anesthetic for 10 min at concentrations of 2.2% or 1.5%, respectively, before two 5-min periods of ischemia separated by 10 min of reperfusion. All treated groups received 25 min of normothermic ischemia followed by 30 min of reperfusion. Results The time-control group remained hemodynamically stable for the entire experiment, and the adenosine triphosphate content was 18.3 +/- 1.7 (SEM) microM/g at the end of 115 min. The untreated group had depressed recovery after 25 min of normothermic ischemia, and the developed pressure was significantly depressed and recovered only 30 +/- 9% (P < 0.001) of its preischemic value. There was also a significant increase in the incidence of ventricular fibrillation (P < 0.001). Adenosine triphosphate content was significantly lower in this group than in all other groups. Five minutes of ischemia in the preconditioning group had little effect on hemodynamics and decreased developed pressure only 6.4%. Halothane depressed developed pressure by 16 +/- 5% (P < 0.001), and isoflurane increased coronary flow by 145 +/- 9% (P < 0.001) but had no significant hemodynamic effect. The treated groups had significantly better recovery of postischemic function than did the untreated group. In the preconditioning group, developed pressure recovered to 85% of control and dP/dt+ to 87% of control. The addition of halothane or isoflurane to preconditioning did not provide additional functional recovery but did increase the level of adenosine triphosphate preservation (13.1 +/- 1.1 and 12.4 +/- 1.1 microM/g, respectively). Conclusions The results indicate that preconditioning, halothane, and isoflurane provide significant protection against ischemia. The combination of preconditioning and halothane or isoflurane did not improve hemodynamic recovery but did increase preservation of adenosine triphosphate.

Effects of the AT1 Receptor Blocker Candesartan on Myocardial Ischemia/Reperfusion in Isolated Rat Hearts

2014 ◽  
Vol 17 (5) ◽  
pp. 263 ◽  
Author(s):  
C. Murat Songur ◽  
Merve Ozenen Songur ◽  
Sinan Sabit Kocabeyoglu ◽  
Bilgen Basgut
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Relaxation Rates ◽  
Cardioplegic Solution ◽  
Rat Hearts ◽  
Developed Pressure ◽  
Contraction And Relaxation ◽  
Isolated Rat

<p><b>Background:</b> We sought to investigate the effects of the angiotension II receptor blocker candesartan on ischemia-reperfusion injury using a cardioplegia arrested isolated rat heart model.</p><p><b>Methods:</b> Ischemia-reperfusion injury was induced in isolated rat hearts with 40 minutes of global ischemia followed by a 30-minute reperfusion protocol. Throughout the experiment, constant pressure perfusion was achieved using a Langendorff apparatus. Cardioplegic solution alone, and in combination with candesartan, was administered before ischemia and 20 minutes after ischemia. Post-ischemic recovery of contractile function, left ventricular developed pressure, left ventricular end-diastolic pressure and contraction and relaxation rates were evaluated.</p><p><b>Results:</b> In the control group, left ventricular developed pressure, rate pressure product, contraction and relaxation rates and coronary flow significantly decreased but coronary resistance increased following reperfusion. With the administration of candesartan alone, parameters did not differ compared to controls. Contractile parameters improved in the group that received candesartan in combination with the cardioplegia compared to the group that received cardioplegia alone; however, the difference between these two groups was insignificant.</p><p><b>Conclusion:</b> In this study, the addition of candesartan to a cardioplegic arrest protocol routinely performed during cardiac surgery did not provide a significant advantage in protection against ischemia-reperfusion injury compared with the administration of cardioplegic solution alone.</p>

Cardioprotective effects of novel tetrahydroisoquinoline analogs of nitrobenzylmercaptopurine riboside in an isolated perfused rat heart model of acute myocardial infarction

2007 ◽  
Vol 292 (6) ◽  
pp. H2921-H2926 ◽  
Author(s):  
Z. Zhu ◽  
P. A. Hofmann ◽  
J. K. Buolamwini
Keyword(s):  
Infarct Size ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Nucleoside Transport ◽  
Total Risk ◽  
Risk Area ◽  
Perfused Heart ◽  
Rat Hearts ◽  
Cardioprotective Effects ◽  
Developed Pressure

We have investigated the cardioprotective effects of novel tetrahydroisoquinoline nitrobenzylmercaptopurine riboside (NBMPR) analog nucleoside transport (NT) inhibitors, compounds 2 and 4, in isolated perfused rat hearts. Langendorff-perfused heart preparations were subjected to 10 min of treatment with compound 2, compound 4, or vehicle (control) followed by 30 min of global ischemia and 120 min of reperfusion. For determination of infarct size, reperfusion time was 180 min. At 1 μM, compounds 2 and 4 provided excellent cardioprotection, with left ventricular developed pressure (LVDP) recovery and end-diastolic pressure (EDP) increase of 82.9 ± 4.0% ( P < 0.001) and 14.1 ± 2.0 mmHg ( P < 0.03) for compound 2-treated hearts and 79.2 ± 5.9% ( P < 0.002) and 7.5 ± 2.7 mmHg ( P < 0.01) for compound 4-treated hearts compared with 41.6 ± 5.2% and 42.5 ± 6.5 mmHg for control hearts. LVDP recovery and EDP increase were 64.1 ± 4.2% and 29.1 ± 2.5 mmHg for hearts treated with 1 μM NBMPR. Compound 4 was the best cardioprotective agent, affording significant cardioprotection, even at 0.1 μM, with LVDP recovery and EDP increase of 76.0 ± 4.9% ( P < 0.003) and 14.1 ± 1.0 mmHg ( P < 0.03). At 1 μM, compound 4 and NBMPR reduced infarct size, with infarct area-to-total risk area ratios of 29.13 ± 3.17 ( P < 0.001) for compound 4 and 37.5 ± 3.42 ( P < 0.01) for NBMPR vs. 51.08 ± 5.06% for control hearts. Infarct size was more effectively reduced by compound 4 than by NBMPR ( P < 0.02). These new tetrahydroisoquinoline NBMPR analogs are not only potent cardioprotective agents but are, also, more effective than NBMPR in this model.

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.

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