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.

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.

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.

Effects of Ketamine and Its Isomers on Ischemic Preconditioning in the Isolated Rat Heart

2001 ◽  
Vol 94 (4) ◽  
pp. 623-629 ◽  
Author(s):  
Andrei Molojavyi ◽  
Benedikt Preckel ◽  
Thomas Comfère ◽  
Jost Müllenheim ◽  
Volker Thämer ◽  
...  
Keyword(s):  
Ischemic Preconditioning ◽  
Katp Channels ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Protective Effects ◽  
Treatment Groups ◽  
Rat Hearts ◽  
Developed Pressure ◽  
And Control ◽  
Isolated Rat

Background Ischemic preconditioning protects the heart against subsequent ischemia. Opening of the adenosine triphosphate-sensitive potassium (KATP) channel is a key mechanism of preconditioning. Ketamine blocks KATP channels of isolated cardiomyocytes. The authors investigated the effects of ketamine and its stereoisomers on preconditioning. Methods Isolated rat hearts (n = 80) underwent 30 min of no-flow ischemia and 60 min of reperfusion. Two groups with eight hearts each underwent the protocol without intervention (control-1 and control-2), and, in eight hearts, preconditioning was elicited by two 5-min periods of ischemia before the 30 min ischemia. In the six treatment groups (each n = 8), ketamine, R(-)- or S(+)-ketamine were administered at concentrations of 2 or 20 microg/ml before preconditioning. Eight hearts received 20 microg/ml R(-)-ketamine before ischemia. Left ventricular (LV) developed pressure and creatine kinase (CK) release during reperfusion were determined as variables of ventricular function and cellular injury. Results Baseline LV developed pressure was similar in all groups: 104 +/- 28 mmHg (mean +/- SD). Controls showed a poor recovery of LV developed pressure (17 +/- 8% of baseline) and a high CK release (70 +/- 17 IU/g). Ischemic preconditioning improved recovery of LV developed pressure (46 +/- 14%) and reduced CK release (47 +/- 17 IU/g, both P < 0.05 vs. control-1). Ketamine (2 microg/ml) and 2 or 20 microg/ml S(+)-ketamine had no influence on recovery of LV developed pressure compared with preconditioning (47 +/- 18, 43 +/- 8, 49 +/- 36%) and CK release (39 +/- 8, 30 +/- 14, 41 +/- 25 IU/g). After administration of 20 microg/ml ketamine and 2 or 20 microg/ml R(-)-ketamine, the protective effects of preconditioning were abolished (LV developed pressure-recovery, 16 +/- 14, 22 +/- 21, 18 +/- 11%; CK release, 67 +/- 11, 80 +/- 21, 82 +/- 41 IU/g; each P < 0.05 vs. preconditioning). Preischemic treatment with R(-)-ketamine had no effect on CK release (74 +/- 8 vs. 69 +/- 9 IU/g in control-2, P = 0.6) and functional recovery (LV developed pressure 12 +/- 4 vs. 9 +/- 2 mmHg in control-2, P = 0.5). Conclusion Ketamine can block the cardioprotective effects of ischemic preconditioning. This effect is caused by the R(-)-isomer.

Effective protection by NHE-1 inhibition in ischemic and reperfused heart under preconditioning blockade

2003 ◽  
Vol 284 (3) ◽  
pp. H798-H803 ◽  
Author(s):  
James V. Haist ◽  
Claire N. Hirst ◽  
Morris Karmazyn
Keyword(s):  
Ischemic Preconditioning ◽  
Channel Blocker ◽  
Left Ventricular ◽  
Cardiac Cells ◽  
Protective Effects ◽  
Effective Protection ◽  
Intact Cells ◽  
Rat Hearts ◽  
Developed Pressure ◽  
Isolated Rat

We compared the protective effects of ischemic preconditioning (IPC) and the Na+/H+ exchanger-1 (NHE-1) inhibitor cariporide in isolated rat hearts subjected to global ischemia (45 or 90 min) and 30-min reperfusion and determined the protective effects of cariporide under IPC blockade with the mitochondrial ATP-sensitive K+ channel blocker 5-hydroxydecanoate (5-HD). With 45-min ischemia, both IPC and cariporide equally increased maximum recovery of left ventricular developed pressure twofold ( P < 0.05), although recovery was significantly greater with cariporide for the first 15 min of reperfusion. 5-HD almost completely blocked the protective effects of IPC on recovery but had no influence on the salutary effects of cariporide. With 90-min ischemic control, recovery was only 3% of preischemia and was unaffected by IPC, although cariporide increased recovery to ∼30% ( P < 0.05). This was associated with a 37% preservation of viable cardiac cells, whereas no structurally intact cells were found in either IPC or control hearts. Our study shows that NHE-1 inhibition is a more effective cardioprotective strategy than IPC in this model, possibly because of enhanced myocyte salvage, and because protection by NHE-1 inhibition is completely unaffected by IPC blockade with 5-HD.

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.

Adenosine antagonism decreases metabolic but not functional recovery from ischemia

1991 ◽  
Vol 260 (1) ◽  
pp. H193-H200 ◽  
Author(s):  
D. A. Angello ◽  
J. P. Headrick ◽  
N. M. Coddington ◽  
R. M. Berne
Keyword(s):  
Functional Recovery ◽  
Left Ventricular ◽  
Low Flow ◽  
Ischemia And Reperfusion ◽  
Constant Flow ◽  
Hemodynamic Parameters ◽  
Isolated Hearts ◽  
Rat Hearts ◽  
Adenosine Antagonism ◽  
Developed Pressure

The effect of adenosine receptor antagonism on function and metabolism was examined in isolated hearts during low flow ischemia and reperfusion. Isovolumic rat hearts perfused at constant flow were subjected to 30 min of ischemia followed by 30 min of reperfusion. Infusion of vehicle or 10 microM 8-phenyltheophylline (8-PT) was initiated 10 min before ischemia and maintained throughout reperfusion. 8-PT infusion had no significant effects on hemodynamic parameters or metabolism preischemia. During ischemia, left ventricular developed pressure declined to approximately 15% of preischemic values in control and 8-PT hearts, and ATP and PCr decreased to approximately 73 and 60% of preischemic values. Inorganic phosphate (Pi) increased to 353 = 41 and 424 +/- 53% of preischemic values in control and 8-PT hearts, respectively. After reperfusion, function recovered to greater than 95% of preischemic levels in control and 8-PT hearts. Unlike control hearts, recovery of metabolites was significantly different during reperfusion in 8-PT hearts (P less than 0.05); ATP, phosphocreatine, and Pi recovered to 82 +/- 8, 71 +/- 8, and 281 +/- 27% of preischemic values, respectively. Venous purine washout was significantly greater (P less than 0.05) during reperfusion in 8-PT hearts (327 +/- 113 nmol) than in control hearts (127 +/- 28 nmol). Blockade of adenosine receptors appears to adversely affect metabolic but not functional recovery in the ischemic-reperfused myocardium.

Differential role of sarcolemmal and mitochondrial KATP channels in adenosine-enhanced ischemic preconditioning

2000 ◽  
Vol 279 (6) ◽  
pp. H2694-H2703 ◽  
Author(s):  
Yoshiya Toyoda ◽  
Ingeborg Friehs ◽  
Robert A. Parker ◽  
Sidney Levitsky ◽  
James D. McCully
Keyword(s):  
Infarct Size ◽  
Functional Recovery ◽  
Ischemic Preconditioning ◽  
Channel Blocker ◽  
Katp Channels ◽  
Size Reduction ◽  
Ischemia And Reperfusion ◽  
Infarct Size Reduction ◽  
Mitochondrial Katp Channels

Adenosine-enhanced ischemic preconditioning (APC) extends the protection afforded by ischemic preconditioning (IPC) by both significantly decreasing infarct size and significantly enhancing postischemic functional recovery. The purpose of this study was to determine whether APC is modulated by ATP-sensitive potassium (KATP) channels and to determine whether this modulation occurs before ischemia or during reperfusion. The role of KATP channels before ischemia (I), during reperfusion (R), or during ischemia and reperfusion (IR) was investigated using the nonspecific KATP blocker glibenclamide (Glb), the mitochondrial (mito) KATP channel blocker 5-hydroxydecanoate (5-HD), and the sarcolemmal (sarc) KATPchannel blocker HMR-1883 (HMR). Infarct size was significantly increased ( P < 0.05) in APC hearts with Glb-I, Glb-R, and 5-HD-I treatment and partially with 5-HD-R. Glb-I and Glb-R treatment significantly decreased APC functional recovery ( P < 0.05 vs. APC), whereas 5-HD-I and 5-HD-R had no effect on APC functional recovery. HMR-IR significantly decreased postischemic functional recovery ( P < 0.05 vs. APC) but had no effect on infarct size. These data indicate that APC infarct size reduction is modulated by mitoKATP channels primarily during ischemia and suggest that functional recovery is modulated by sarcKATP channels during ischemia and reperfusion.

scholarly journals A Sphingosine Kinase Form 2 Knockout Sensitizes Mouse Myocardium to Ischemia/Reoxygenation Injury and Diminishes Responsiveness to Ischemic Preconditioning

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Donald A. Vessey ◽  
Luyi Li ◽  
Zhu-Qiu Jin ◽  
Michael Kelley ◽  
Norman Honbo ◽  
...  
Keyword(s):  
Protective Effect ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Sphingosine Kinase ◽  
Left Ventricular ◽  
Cardiac Damage ◽  
Sphingosine 1 Phosphate ◽  
Reoxygenation Injury ◽  
Developed Pressure

Sphingosine kinase (SphK) exhibits two isoforms, SphK1 and SphK2. Both forms catalyze the synthesis of sphingosine 1-phosphate (S1P), a sphingolipid involved in ischemic preconditioning (IPC). Since the ratio of SphK1 : SphK2 changes dramatically with aging, it is important to assess the role of SphK2 in IR injury and IPC. Langendorff mouse hearts were subjected to IR (30 min equilibration, 50 min global ischemia, and 40 min reperfusion). IPC consisted of 2 min of ischemia and 2 min of reperfusion for two cycles. At baseline, there were no differences in left ventricular developed pressure (LVDP), ± dP/dtmax, and heart rate between SphK2 null (KO) and wild-type (WT) hearts. In KO hearts, SphK2 activity was undetectable, and SphK1 activity was unchanged compared to WT. Total SphK activity was reduced by 53%. SphK2 KO hearts subjected to IR exhibited significantly more cardiac damage (% infarct size) compared with WT (% infarct size); postischemic recovery of LVDP was lower in KO hearts. IPC exerted cardioprotection in WT hearts. The protective effect of IPC against IR was diminished in KO hearts which had much higher infarction sizes (%) compared to the IPC/IR group in control hearts (%). Western analysis revealed that KO hearts had substantial levels of phosphorylated p38 which could predispose the heart to IR injury. Thus, deletion of the SphK2 gene sensitizes the myocardium to IR injury and diminishes the protective effect of IPC.

Adenosine-enhanced ischemic preconditioning: adenosine receptor involvement during ischemia and reperfusion

2001 ◽  
Vol 280 (2) ◽  
pp. H591-H602 ◽  
Author(s):  
James D. McCully ◽  
Yoshiya Toyoda ◽  
Masahisa Uematsu ◽  
Robert D. Stewart ◽  
Sidney Levitsky
Keyword(s):  
Infarct Size ◽  
Functional Recovery ◽  
Ischemic Preconditioning ◽  
Adenosine Receptor ◽  
Adenosine Receptors ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Ischemia And Reperfusion ◽  
Infarct Size Reduction

Adenosine-enhanced ischemic preconditioning (APC) extends the cardioprotection of ischemic preconditioning (IPC) by both significantly decreasing myocardial infarct size and significantly enhancing postischemic functional recovery. In this study, the role of adenosine receptors during ischemia-reperfusion was determined. Rabbit hearts ( n = 92) were used for Langendorff perfusion. Control hearts were perfused for 180 min, global ischemia hearts received 30-min ischemia and 120-min reperfusion, and IPC hearts received 5-min ischemia and 5-min reperfusion before ischemia. APC hearts received a bolus injection of adenosine coincident with IPC. Adenosine receptor (A1, A2, and A3) antagonists were used with APC before ischemia and/or during reperfusion. GR-69019X (A1/A3) and MRS-1191/MRS-1220 (A3) significantly increased infarct size in APC hearts when administered before ischemia and significantly decreased functional recovery when administered during both ischemia and reperfusion ( P < 0.05 vs. APC). DPCPX (A1) administered either before ischemia and/or during reperfusion had no effect on APC cardioprotection. APC-enhanced infarct size reduction is modulated by adenosine receptors primarily during ischemia, whereas APC-enhanced postischemic functional recovery is modulated by adenosine receptors during both ischemia and reperfusion.

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.

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