L-arginine reduces endothelial inflammation and myocardial stunning during ischemia/reperfusion

1996 ◽  
Vol 10 (4) ◽  
pp. 559-560
Keyword(s):  
Myocardial Stunning ◽  
Ischemia Reperfusion ◽  
Endothelial Inflammation

l-Arginine reduces endothelial inflammation and myocardial stunning during ischemia/reperfusion

1995 ◽  
Vol 60 (5) ◽  
pp. 1275-1281 ◽  
Author(s):  
Daniel T. Engelman ◽  
Masazumi Watanabe ◽  
Nilanjana Maulik ◽  
Gerald A. Cordis ◽  
Richard M. Engelman ◽  
...  
Keyword(s):  
Myocardial Stunning ◽  
Ischemia Reperfusion ◽  
Endothelial Inflammation

Abstract P15: Periodic Acceleration (pGz) Preconditioning in Swine Increases Endothelial Derived NO and Phosphorylated eNOS via Akt Pathway

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Jose A Adams ◽  
Jaqueline Arias ◽  
Jorge Bassuk ◽  
Heng Wu ◽  
Arkady Uryash ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Myocardial Stunning ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Spontaneous Circulation ◽  
Akt Pathway ◽  
Phosphorylated Akt ◽  
Manual Chest Compression ◽  
Periodic Acceleration ◽  
Pulsatile Shear Stress

Periodic acceleration (pGz) is the motion of the supine body using a motorized platform (3Hz & ±0.4G). pGz produces pulsatile shear stress increasing release of endothelial derived NO (eNO) which, also decreases myocardial stunning and improves outcomes from ventricular fibrillation (VF) cardiac arrest. Preconditioning with pGz (PRE-pGz) prior to VF cardiac arrest ameliorates global post resuscitation cardiac dysfunction and reduces arrhythmias. To test whether pGz and PRE-pGz increase eNOS and phosphorylated eNOS (p-eNOS) via the PI3-kinase-Akt pathway, anesthetized, intubated male swine (40 –50lbs) were studied. Five animals had no intervention (BL) and 5 received 1 hr pGz preconditioning (pGz) followed by Western Blot of myocardial tissue. Additional animals (10 per group) received 1 hr pGz (PRE-pGz) or no treatment (CPR-CONT). In the latter groups VF was electrically induced and unsupported for 8 min followed by continuous manual chest compression and defibrillation for 10 min or until return of spontaneous circulation (ROSC). PRE-pGz animals showed less hemodynamically significant arrhythmias after ROSC than CPR-CONT (35 vs 7; p<0.05) and less myocardial stunning. eNOS and phosphorylated-eNOS (p-eNOS) significantly increased after pGz and after CPR but were significantly higher in pGz preconditioned animals along with increased phosphorylated Akt (p-Akt). The graph below shows % changes relative to BL (M±SD). *p < 0.01 PRE-pGz vs CPR-CONT. Conclusion: pGz applied prior to ischemia reperfusion injury increases eNOS and p-eNOS expression and increased p-Akt. Thus, pGz preconditioning protects myocardium during I-R in part by activating eNOS through p-Akt

Increases in myocardial cyclic GMP attenuate contractile delay in myocardial stunning

2002 ◽  
Vol 80 (8) ◽  
pp. 804-810 ◽  
Author(s):  
Mark W Huang ◽  
Peter M Scholz ◽  
Harvey R Weiss
Keyword(s):  
Cyclic Gmp ◽  
Myocardial Stunning ◽  
Ischemia Reperfusion ◽  
Rabbit Heart ◽  
Left Ventricular ◽  
Control Group ◽  
Wall Thickening ◽  
Maximal Rate ◽  
Myocardial Wall ◽  
New Zealand White Rabbits

We tested the hypothesis that the effects of myocardial stunning would be reduced by cyclic GMP in rabbit hearts. In three groups of anesthetized open-chest New Zealand white rabbits, myocardial stunning was produced by 15 min of occlusion of the left anterior descending coronary artery followed by 15 min of reperfusion repeated twice. Either control vehicle (saline plus 1% dimethyl sulfoxide) or 8-bromo-cyclic GMP (8-Br-cGMP (10–4 and 10–3 M)) was topically applied to the left ventricular surface. Hemodynamic (left ventricular and aortic pressures) and functional parameters (wall thickening, delay in onset of wall thickening, and rate of wall thickening) were determined. Coronary blood flow (microspheres) and O2 extraction (microspectrophotometry) were used to determine myocardial O2 consumption (VO2). Myocardial stunning was observed in the control group through an increased delay in onset of myocardial wall thickening (29 ± 7 versus 55 ± 16 ms) and decreased maximal rate of wall thickening (20 ± 8 versus 11 ± 3 mm·s–1). After treatment with 8-Br-cGMP 10–4 and 10–3 M, stunning did not increase the delay (37 ± 5 versus 39 ± 7 and 39 ± 7 versus 28 ± 8 ms). Myocardial stunning did not significantly alter V02. 8-Br-cGMP 10–3 M significantly decreased subepicardial V02 (6.2 ± 0.8 versus 3.7 ± 0.6 mL O2·min–1·100 g–1) and insignificantly decreased subendocardial V02 (8.6 ± 0.9 versus 6.3 ± 1.2 mL O2·min–1·100 g–1) when compared with the vehicle-treated rabbits. We conclude that increasing cyclic GMP reduced the effects of myocardial stunning in the rabbit heart by ameliorating the delay in onset of wall thickening and decreasing the local O2 costs in the stunned region. Key words: cyclic GMP, myocardial stunning, O2 consumption, ischemia, reperfusion, wall thickening, rabbit.

Differential effects of postconditioning on myocardial stunning and infarction: a study in conscious dogs and anesthetized rabbits

2006 ◽  
Vol 291 (3) ◽  
pp. H1345-H1350 ◽  
Author(s):  
Nicolas Couvreur ◽  
Laurence Lucats ◽  
Renaud Tissier ◽  
Alain Bize ◽  
Alain Berdeaux ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Infarct Size ◽  
Myocardial Stunning ◽  
Ischemia Reperfusion ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Left Ventricular ◽  
Segment Length ◽  
Wall Thickening ◽  
Area At Risk

Postconditioning, i.e., brief intermittent episodes of myocardial ischemia-reperfusion performed at the onset of reperfusion, reduces infarct size after prolonged ischemia. Our goal was to determine whether postconditioning is protective against myocardial stunning. Accordingly, conscious chronically instrumented dogs (sonomicrometry, coronary balloon occluder) were subjected to a control sequence (10 min coronary artery occlusion, CAO, followed by coronary artery reperfusion, CAR) and a week apart to postconditioning with four cycles of brief CAR and CAO performed at completion of the 10 min CAO. Three postconditioning protocols were investigated, i.e., 15 s CAR/15 s CAO ( n = 5), 30 s CAR/30 s CAO ( n = 7), and 1 min CAR/1 min CAO ( n = 6). Left ventricular wall thickening was abolished during CAO and similarly reduced during subsequent stunning in control and postconditioning sequences (e.g., at 1 h CAR, 33 ± 4 vs. 34 ± 4%, 30 ± 4 vs. 30 ± 4%, and 33 ± 4 vs. 32 ± 4% for 15 s postconditioning, 30 s postconditioning, and 1 min postconditioning vs. corresponding control, respectively). We confirmed this result in anesthetized rabbits by demonstrating that shortening of left ventricular segment length was similarly depressed after 10 min CAO in control and postconditioning sequences (4 cycles of 30 s CAR/30 s CAO). In additional rabbits, the same postconditioning protocol significantly reduced infarct size after 30 min CAO and 3 h CAR (39 ± 7%, n = 6 vs. 56 ± 4%, n = 7 of the area at risk in postconditioning vs. control, respectively). Thus, contrasting to its beneficial effects on myocardial infarction, postconditioning does not protect against myocardial stunning in dogs and rabbits. Conversely, additional episodes of ischemia-reperfusion with postconditioning do not worsen myocardial stunning.

Abstract 107: Mitochondrial Dysfunction Mediated Myocardial Stunning Following Resuscitation From Cardiac Arrest

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Willard W Sharp ◽  
Lin Piao ◽  
Yong Fang ◽  
David G Beiser ◽  
James K Liao ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Myocardial Stunning ◽  
Mitochondrial Dynamics ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Myocardial Necrosis ◽  
Spontaneous Circulation ◽  
Contractile Dysfunction ◽  
Myocardial Contractile ◽  
Induced Changes

Rationale: Severe myocardial contractile dysfunction following resuscitation from cardiac arrest (CA) is a major contributor to CA mortality. The pathophysiology and etiology of this dysfunction is not known and there are no pharmacological therapies known to improve outcomes. Previously, we demonstrated that Dynamin related protein 1 (Drp1) is activated and recruited to the mitochondria during CA and that the Drp1 inhibitor Mdivi-1 improves post CA survival. Objective: To determine the effects of CA length on myocardial and mitochondrial function. We also sought to determine the effects of Mdivi-1 on post CA outcomes. Methods and Results: Asystolic cardiac arrest (CA) was induced in mice by IV injection of 0.08 mg/g KCL. CPR begun at 4, 8, 12, and 16 minutes post-cardiac arrest had rates of return of spontaneous circulation (ROSC) of 100%(12/12), 93%(14/15), 71%(10/14), and 44% (4/9) and 2-hour survival of 100%(12/12), 67%(10/15), 50%(7/14), and 11%(1/9). Transthoracic echocardiography 15 min post-resuscitation demonstrated percent fractional shortening of 36±4% (Sham,n=6), 30±4% (4 minCA,n=11), 24±5% (8minCA,n=10), 15±2% (12minCA,n=12). In surviving animals, myocardial dysfunction persisted for 2 hours post-resuscitation, but slowly recovered to baseline by 72 hours. No evidence of myocardial necrosis, inflammation, or apoptosis was noted following resuscitation. Progressive increases in mitochondrial derived reactive oxygen species (ROS) during CA was observed by MitoSOX red myocardial tissue staining. Mitochondria isolated from 12 min CA hearts demonstrated decreased substrate coupled and uncoupled respiration. Mdivi-1, a mitochondrial inhibitor of division (fission), improved survival and neurological scores in mice following an 8 min cardiac arrest compared to controls. Conclusions: Severe, time dependent myocardial stunning (contractile dysfunction in the absence of irreversible injury) was observed following asystolic cardiac arrest. This myocardial stunning was associated with mitochondrial injury and improved by an inhibitor of Drp1. Strategies targeting ischemia/reperfusion-induced changes in mitochondrial dynamics hold promise for improving myocardial function and survival following cardiac arrest.

A highly potent peptide analgesic that protects against ischemia-reperfusion-induced myocardial stunning

2002 ◽  
Vol 283 (2) ◽  
pp. H783-H791 ◽  
Author(s):  
Dunli Wu ◽  
Yi Soong ◽  
Guo-Min Zhao ◽  
Hazel H. Szeto
Keyword(s):  
Myocardial Stunning ◽  
No Reduction ◽  
Specific Binding ◽  
Ischemia Reperfusion ◽  
Opioid Peptide ◽  
Binding Studies ◽  
Cardiac Membranes ◽  
Effect Binding ◽  
Perfused Hearts

We recently discovered an opioid peptide analgesic, 2′,6′-dimethyltyrosine (Dmt)-d-Arg-Phe-Lys-NH2([Dmt1]DALDA), that can protect against ischemia-induced myocardial stunning. In buffer-perfused hearts, 30-min global ischemia followed by reperfusion resulted in a significant increase in norepinephrine (NE) overflow immediately upon reperfusion and significant decline in contractile force (45%). Pretreatment with [Dmt1]DALDA before ischemia completely abolished myocardial stunning and significantly reduced NE overflow (68%). In contrast, pretreatment with morphine before ischemia only provided brief protection against myocardial stunning and no reduction in NE overflow. [Dmt1]DALDA inhibited [3H]NE uptake into cardiac synaptosomes in vitro (IC50 = 3.9 μM), whereas morphine had no effect. Surprisingly, protection against myocardial stunning was apparent even when hearts were perfused with [Dmt1]DALDA only upon reperfusion, whereas reperfusion with morphine had no effect. Binding studies with [3H][Dmt1]DALDA revealed no high-affinity specific binding in cardiac membranes, suggesting that the cardioprotective actions of [Dmt1]DALDA are not mediated via opioid receptors. These findings suggest that [Dmt1]DALDA is a potent analgesic that may be useful for myocardial stunning resulting from cardiac interventions or myocardial ischemia.

Loss of exercise-induced cardioprotection after cessation of exercise

2004 ◽  
Vol 96 (4) ◽  
pp. 1299-1305 ◽  
Author(s):  
Shannon L. Lennon ◽  
John Quindry ◽  
Karyn L. Hamilton ◽  
Joel French ◽  
Jessica Staib ◽  
...  
Keyword(s):  
Myocardial Stunning ◽  
Time Course ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Antioxidant Enzyme Activity ◽  
Male Rats ◽  
Sedentary Control ◽  
Cardiac Work ◽  
Exercise Induced ◽  
Working Heart

Endurance exercise provides cardioprotection against ischemia-reperfusion (I/R) injury. Exercise-induced cardioprotection is associated with increases in cytoprotective proteins, including heat shock protein 72 (HSP72) and increases in antioxidant enzyme activity. On the basis of the reported half-life of these putative cardioprotective proteins, we hypothesized that exercise-induced cardioprotection against I/R injury would be lost within days after cessation of exercise. To test this, male rats (4 mo) were randomly assigned to one of five experimental groups: 1) sedentary control, 2) exercise followed by 1 day of rest, 3) exercise followed by 3 days of rest, 4) exercise followed by 9 days of rest, and 5) exercise followed by 18 days of rest. Exercise-induced increases ( P < 0.05) in left ventricular catalase activity and HSP72 were evident at 1 and 3 days postexercise. However, at 9 days postexercise, myocardial HSP72 and catalase levels declined to sedentary control values. To evaluate cardioprotection during recovery from I/R, hearts were isolated, placed in working heart mode, and subjected to 20.5 min of global ischemia followed by 30 min of reperfusion. Compared with sedentary controls, exercised animals sustained less I/R injury as evidenced by maintenance of a higher ( P < 0.05) percentage of preischemia cardiac work during reperfusion at 1, 3, and 9 days postexercise. The exercise-induced cardioprotection vanished by 18 days after exercise cessation. On the basis of the time course of the loss of cardioprotection and the return of HSP72 and catalase to preexercise levels, we conclude that HSP72 and catalase are not essential for exercise-induced protection during myocardial stunning. Therefore, other cytoprotective molecules are responsible for providing protection during I/R.

scholarly journals Lack of the effect of superoxide dismutase and catalase on Na+,K+-ATPase activity in stunned rabbit hearts

2008 ◽  
pp. S61-S66
Author(s):  
P Kaplán ◽  
M Matejovičová ◽  
P Herijgers ◽  
W Flameng
Keyword(s):  
Superoxide Dismutase ◽  
Antioxidant Enzymes ◽  
Atpase Activity ◽  
Cardiac Dysfunction ◽  
Myocardial Stunning ◽  
Diastolic Pressure ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Significant Loss ◽  
Protective Effects

Reactive oxygen species (ROS) have been implicated in the mechanism of postischemic contractile dysfunction, known as myocardial stunning. In this study, we examined protective effects of antioxidant enzymes, superoxide dismutase (SOD) and catalase, against ischemia/reperfusion-induced cardiac dysfunction and inhibition of Na+,K+-ATPase activity. Isolated Langendorff-perfused rabbit hearts were subjected to 15 min of global normothermic ischemia followed by 10 min reperfusion. The hearts treated with SOD plus catalase did not show significant recovery of left ventricular (LV) end-diastolic pressure compared with untreated ischemic reperfused hearts. Treatment with antioxidants had no protective effects on developed LV pressure or its maximal positive and negative first derivatives (+/-LVdP/dt). Myocardial stunning was accompanied by significant loss in sarcolemmal Na+,K+-ATPase activity and thiol group content. Inhibition of enzyme activity and oxidation of SH groups were not prevented by antioxidant enzymes. These results suggest that administration of SOD and catalase in perfusate do not protect significantly against cardiac dysfunction in stunned rabbit myocardium.

scholarly journals Distinct Effects of Acute Pretreatment With Lipophilic and Hydrophilic Statins on Myocardial Stunning, Arrhythmias and Lethal Injury in the Rat Heart Subjected to Ischemia/Reperfusion

2011 ◽  
pp. 825-830 ◽  
Author(s):  
S. ČARNICKÁ ◽  
A. ADAMEOVÁ ◽  
M. NEMČEKOVÁ ◽  
J. MATEJÍKOVÁ ◽  
D. PANCZA ◽  
...  
Keyword(s):  
Infarct Size ◽  
Ventricular Arrhythmias ◽  
Myocardial Stunning ◽  
Water Solubility ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Heart Cells ◽  
Risk Area ◽  
Cardioprotective Effects ◽  
Developed Pressure

Although both lipophilic and more hydrophilic statins share the same pathway of the inhibition of HMG-CoA reductase, their pleiotropic cardioprotective effects associated with the ability to cross cellular membranes, including membranes of heart cells, may differ. To test this hypothesis, isolated rat hearts were Langendorff-perfused either with simvastatin (S, 10 μmol/l) or pravastatin (P, 30 μmol/l), 15 min prior to ischemia. Control untreated hearts (C) were perfused with perfusion medium only. Postischemic contractile dysfunction, reperfusion-induced ventricular arrhythmias and infarct size were investigated after exposure of the hearts to 30-min global ischemia and 2-h reperfusion. Both lipophilic S and hydrophilic P reduced the severity of ventricular arrhythmias (arrhythmia score) from 4.3±0.2 in C to 3.0±0 and 2.7±0.2 in S and P, respectively, (both P<0.05), decreased the duration of ventricular tachycardia and suppressed ventricular fibrillation. Likewise, the extent of lethal injury (infarct size) determined by tetrazolium staining and expressed in percentage of risk area, was significantly lower in both treated groups, moreover, the effect of P was more pronounced (27±2 % and 10±2 % in S and P groups, respectively, vs. 42±1 % in C; P<0.05). In contrast, only S, but not P, was able to improve postischemic recovery of left ventricular developed pressure (LVDP; 48±12 % of preischemic values vs. 25±4 % in C and 21±7 % in P groups; P<0.05). Our results suggest that differences in water solubility of statins indicating a different ability to cross cardiac membranes may underlie their distinct cardioprotective effects on myocardial stunning and lethal injury induced by ischemia/reperfusion.

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