Cardiac venous endothelial dysfunction after myocardial ischemia and reperfusion in dogs

1992 ◽  
Vol 263 (3) ◽  
pp. H850-H856 ◽  
Author(s):  
D. J. Lefer ◽  
K. Nakanishi ◽  
J. Vinten-Johansen ◽  
X. L. Ma ◽  
A. M. Lefer
Keyword(s):  
Coronary Artery ◽  
Endothelial Dysfunction ◽  
Myocardial Ischemia ◽  
Ischemia Reperfusion ◽  
Coronary Artery Occlusion ◽  
Significant Degree ◽  
Ischemia And Reperfusion ◽  
Area At Risk ◽  
Myocardial Ischemia And Reperfusion ◽  
Coronary Veins

Endothelial dysfunction is a prominent occurrence in coronary arteries after myocardial ischemia and reperfusion. However, this has not been studied in coronary veins. Endothelium-dependent vasorelaxation was studied in cardiac venous rings obtained from dogs subjected to 60 min of coronary artery occlusion followed by 270 min of reperfusion, as well as from dogs subjected to sham ischemia-reperfusion. Myocardial ischemia resulted in a 96 +/- 2% decrease in coronary flow to the ischemic area 60 min after occlusion of the left anterior descending (LAD) coronary artery, which led to a significant degree of cardiac necrosis (i.e., 32.9 +/- 3.9% of area at risk). Cardiac venous rings isolated from sham ischemia-reperfusion dogs relaxed 68 +/- 3% to 200 microM ADP, 65 +/- 3% to 2 microM A23187, and 76 +/- 4% to 200 microM sodium nitrite (NaNO2). Corresponding values for cardiac venous rings isolated from ischemic-reperfused dogs were 32 +/- 3% for 200 microM ADP (P less than 0.01 vs. sham), 31 +/- 3% for 2 microM A23187 (P less than 0.01 vs. sham), and 74 +/- 3% for 200 microM NaNO2 (NS from sham). In rings from control dogs, vasorelaxation to ADP and A23187 was markedly inhibited by 4 mM NG-methyl-L-arginine (L-NMMA) and 10 methylene blue and restored after NG-nitro-L-arginine by 3 mM L-arginine. These results demonstrate that a significant degree of endothelial dysfunction occurred in cardiac venous rings after ischemia and reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Sabiporide Reduces Ischemia-Induced Arrhythmias and Myocardial Infarction and Attenuates ERK Phosphorylation and iNOS Induction in Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Henri Doods ◽  
Dongmei Wu
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Troponin I ◽  
Ischemia Reperfusion ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Myocardial Infarct Size ◽  
Myocardial Ischemia And Reperfusion

The aim of the present study was to investigate the effects of sabiporide, a potent and selective NHE1 inhibitor, on myocardial ischemia-induced arrhythmias and myocardial infarction and the possible pathways related to the cardioprotection afforded by sabiporide treatment. Anesthetized rats were subjected to myocardial ischemia via left main coronary artery occlusion for 30 minutes, followed by 2 hours of reperfusion. Administration of sabiporide (0.01–3.0 mg/kg) prior to coronary artery occlusion dose-dependently reduced ischemia-induced arrhythmias and infarct size with an ED50 value of 0.14 mg/kg. Administration of sabiporide (1.0 mg/kg) prior to reperfusion also reduced infarct size by 38.6%. The reduction in infarct size was accompanied by a decrease in circulating levels of creatine phosphokinase and troponin I. In addition, sabiporide (1.0 mg/kg) given prior to coronary artery occlusion or immediately before reperfusion significantly reduced phosphorylation of the extracellular signal-regulated kinase (ERK1/2) and the expression of the inducible nitric oxide synthase (iNOS) following myocardial ischemia-reperfusion. This study demonstrates that sabiporide is a potent and effective cardioprotective agent during myocardial ischemia and reperfusion, by reducing serious ventricular arrhythmias and myocardial infarct size. The cardioprotection afforded by sabiporide is attributed in part to inhibition of ERK1/2 phosphorylation and suppression of iNOS expression.

scholarly journals Remote Ischemic Perconditioning Ameliorates Myocardial Ischemia and Reperfusion-Induced Coronary Endothelial Dysfunction and Aortic Stiffness in Rats

2021 ◽  
pp. 107424842110313
Author(s):  
Petra Lujza Szabó ◽  
Christopher Dostal ◽  
Patrick Michael Pilz ◽  
Ouafa Hamza ◽  
Eylem Acar ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Endothelial Dysfunction ◽  
Myocardial Ischemia ◽  
Aortic Stiffness ◽  
Vascular Reactivity ◽  
Ventricular Remodeling ◽  
Left Ventricular ◽  
Ischemia And Reperfusion ◽  
Myocardial Ischemia And Reperfusion ◽  
Remote Ischemic Perconditioning

Background: Vascular stiffness and endothelial dysfunction are accelerated by acute myocardial infarction (AMI) and subsequently increase the risk for recurrent coronary events. Aim: To explore whether remote ischemic perconditioning (RIPerc) protects against coronary and aorta endothelial dysfunction as well as aortic stiffness following AMI. Methods: Male OFA-1 rats were subjected to 30 min of occlusion of the left anterior descending artery (LAD) followed by reperfusion either 3 or 28 days with or without RIPerc. Three groups: (1) sham operated (Sham, without LAD occlusion); (2) myocardial ischemia and reperfusion (MIR) and (3) MIR + RIPerc group with 3 cycles of 5 minutes of IR on hindlimb performed during myocardial ischemia were used. Assessment of vascular reactivity in isolated septal coronary arteries (non-occluded) and aortic rings as well as aortic stiffness was assessed by wire myography either 3 or 28 days after AMI, respectively. Markers of pro-inflammatory cytokines, adhesion molecules were assessed by RT-qPCR and ELISA. Results: MIR promotes impaired endothelial-dependent relaxation in septal coronary artery segments, increased aortic stiffness and adverse left ventricular remodeling. These changes were markedly attenuated in rats treated with RIPerc and associated with a significant decline in P-selectin, IL-6 and TNF-α expression either in infarcted or non-infarcted myocardial tissue samples. Conclusions: Our study for the first time demonstrated that RIPerc alleviates MIR-induced coronary artery endothelial dysfunction in non-occluded artery segments and attenuates aortic stiffness in rats. The vascular protective effects of RIPerc are associated with ameliorated inflammation and might therefore be caused by reduced inflammatory signaling.

Myocardial ischemia and reperfusion: a murine model

1995 ◽  
Vol 269 (6) ◽  
pp. H2147-H2154 ◽  
Author(s):  
L. H. Michael ◽  
M. L. Entman ◽  
C. J. Hartley ◽  
K. A. Youker ◽  
J. Zhu ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Myocardial Ischemia ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Blue Dye ◽  
Large Animal ◽  
Ischemia And Reperfusion ◽  
Ischemia And Reperfusion Injury ◽  
Myocardial Ischemia And Reperfusion ◽  
Permanent Occlusion

Myocardial ischemia followed by reperfusion promotes a complex series of inflammatory reactions as noted in a variety of large animal studies. With development of genetically altered mice, there is intense interest in developing murine models to study mechanisms operative in cardiovascular disease. We developed a mouse model to study coronary artery occlusion and reperfusion effects and the method required to perform these studies both acutely and chronically. In mice, we applied a left anterior descending coronary artery occlusion either permanently or for 30 or 60 min followed by reperfusion allowing flow through the previously occluded coronary artery bed. Reperfusion was documented visually as well as by using Doppler ultrasound and histopathological techniques. The area at risk (AAR) and infarct size (IS) were assessed by EVans blue dye and triphenyltetrazolium chloride staining with computerized planimetry using an image analysis software program. The infarct as percentage of AAR and IS as percentage of the left ventricle in 13 mice with permanent occlusion was 68.6 +/- 4.4 and 28.0 +/- 2.8%, respectively. Reperfusion after occlusions of 60 and 30 min resulted in a significant decrease in IS as a percentage of the AAR compared with permanent occlusion. Histological examination of the ischemic and reperfused myocardium shows infiltration of leukocytes into the ischemic region as well as contraction bands classically associated with reperfusion. This new model allows assessment of AAR, IS, cardiac function, and pathophysiology in the mouse. With the current technology to develop genetically altered mice for overexpression or targeted mutations of various genes, this model is used to understand the complex pathophysiology of ischemia and reperfusion injury.

Overexpression of Bcl-2 attenuates apoptosis and protects against myocardial I/R injury in transgenic mice

2001 ◽  
Vol 280 (5) ◽  
pp. H2313-H2320 ◽  
Author(s):  
Zhongyi Chen ◽  
Chu Chang Chua ◽  
Ye-Shih Ho ◽  
Ronald C. Hamdy ◽  
Balvin H. L. Chua
Keyword(s):  
Coronary Artery ◽  
Lactate Dehydrogenase ◽  
Transgenic Mice ◽  
Ischemia Reperfusion ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Fragmentation Pattern ◽  
Area At Risk ◽  
Antiapoptotic Protein

To test whether the antiapoptotic protein Bcl-2 prevents apoptosis and injury of cardiomyocytes after ischemia-reperfusion (I/R), we generated a line of transgenic mice that carried a human Bcl-2 transgene under the control of a mouse α-myosin heavy chain promoter. High levels of human Bcl-2 transcripts and 26-kDa Bcl-2 protein were expressed in the hearts of transgenic mice. Functional recovery of the transgenic hearts significantly improved when they were perfused as Langendorff preparations. This protection was accompanied by a threefold decrease in lactate dehydrogenase (LDH) released from the transgenic hearts. The transgenic mice were subjected to 50 min of ligation of the left descending anterior coronary artery followed by reperfusion. The infarct sizes, expressed as a percentage of the area at risk, were significantly smaller in the transgenic mice than in the nontransgenic mice (36.6 ± 5 vs 69.9 ± 7.3%, respectively). In hearts subjected to 30 min of coronary artery occlusion followed by 3 h of reperfusion, Bcl-2 transgenic hearts had significantly fewer terminal deoxynucleodidyl-transferase nick-end labeling-positive or in situ oligo ligation-positive myocytes and a less prominent DNA fragmentation pattern. Our results demonstrate that overexpression of Bcl-2 renders the heart more resistant to apoptosis and I/R injury.

Beneficial effects of SPM-5185, a cysteine-containing NO donor in myocardial ischemia-reperfusion

1992 ◽  
Vol 263 (3) ◽  
pp. H771-H777 ◽  
Author(s):  
M. R. Siegfried ◽  
C. Carey ◽  
X. L. Ma ◽  
A. M. Lefer
Keyword(s):  
At Risk ◽  
Endothelial Dysfunction ◽  
Myocardial Ischemia ◽  
Ethyl Ester ◽  
Ischemia Reperfusion ◽  
Myocardial Oxygen Demand ◽  
Area At Risk ◽  
No Donor ◽  
Beneficial Effects ◽  
Myocardial Ischemia Reperfusion

Intravenous administration of SPM-5185 [N-nitratopivaloyl-S-(N–-acetylalanyl)-cysteine ethyl ester], a cysteine-containing nitric oxide (NO) donor, or SPM-5267 [pivaloyl-S-(N–-acetylalanyl)-cysteine ethyl ester], an analogue of SPM-5185 that lacks the NO moiety, was studied in a feline myocardial ischemia-reperfusion model. Administration of SPM-5185 (1 mg/kg), followed by a 2-mg.kg-1.h-1 infusion starting 10 min before reperfusion, resulted in significant protection 4.5 h postreperfusion. In the myocardial ischemia (MI)+SPM-5267 group, 38 +/- 4% of the area at risk was necrotic, whereas the necrotic area/area at risk was only 7 +/- 2% in the MI+SPM-5185 group (P less than 0.01). Moreover, SPM-5185 treatment markedly attenuated the endothelial dysfunction observed in the left anterior descending coronary artery after reperfusion by 50%. These beneficial effects occurred despite the absence of a significant change in myocardial oxygen demand, as measured by the pressure-rate index. In vitro experiments demonstrated that SMP-5185, but not SPM-5267, decreased adherence of neutrophils to the coronary vascular endothelium and decreased production of superoxide radicals. Therefore, a likely mechanism of the observed cardioprotection by SPM-5185 involves attenuation of polymorphonuclear leukocyte-induced endothelial dysfunction.

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.

scholarly journals Leukocyte trafficking and myocardial reperfusion injury in ICAM-1/P-selectin-knockout mice

2001 ◽  
Vol 280 (1) ◽  
pp. H60-H67 ◽  
Author(s):  
Stephanie A. Briaud ◽  
Zhi-Ming Ding ◽  
Lloyd H. Michael ◽  
Mark L. Entman ◽  
Sherita Daniel ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Ischemia Reperfusion ◽  
Intercellular Adhesion Molecule ◽  
Myeloperoxidase Activity ◽  
Wild Type ◽  
Area At Risk ◽  
Myocardial Ischemia And Reperfusion ◽  
Significant Difference ◽  
Deficient Mice

P-selectin and intercellular adhesion molecule-1 (ICAM-1) mediate early interaction and adhesion of neutrophils to coronary endothelial cells and myocytes after myocardial ischemia and reperfusion. In the present study, we examined the physiological consequences of genetic deletions of ICAM-1 and P-selectin in mice. In wild-type mice, after 1 h of ischemia followed by reperfusion, neutrophil influx into the area of ischemia was increased by 3 h with a peak at 24 h and a decline by 72 h. ICAM-1/P-selectin-deficient mice showed a significant reduction in neutrophils by immunohistochemistry or by myeloperoxidase activity at 24 h but no significant difference at 3 h. Infarct size (area of necrosis/area at risk) assessed 24 h after reperfusion was not different between wild-type and deficient mice after 30 min and 1 h of occlusion. Mice with a deficiency in both ICAM-1 and P-selectin have impaired neutrophil trafficking without a difference in infarct size due to myocardial ischemia-reperfusion.

Abstract 19185: Upregulation of DJ-1 Protein after Prolonged Ischemia in a Murine Model for Myocardial Ischemia and Reperfusion

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Tamas Seres ◽  
Jelena Klawitter ◽  
Uwe Christians ◽  
Tobias Eckle
Keyword(s):  
Map Kinases ◽  
Ischemia Reperfusion ◽  
Pten Expression ◽  
Glutathione Metabolism ◽  
Protective Mechanism ◽  
Ischemia And Reperfusion ◽  
Area At Risk ◽  
Tissue Samples ◽  
Myocardial Ischemia And Reperfusion ◽  
Potential Marker

Introduction: Upregulation of cardiac DJ-1 protein might be a cardio-protective mechanism under conditions of ischemia or ischemia and reperfusion by regulating mitogen activated protein (MAP) kinases or inducing enzymes for detoxification and glutathione metabolism. We recently observed that significantly elevated DJ-1 protein expression was associated with decreased expression of phosphatase and tensin homolog (PTEN) and increased phosphorylation of the cell protective kinase AKT (protein kinase B) in human heart tissue samples from patients with chronic ischemic cardiomyopathy. Hypothesis: The expression of DJ-1 protein and its interaction with PTEN and AKT during ischemia or ischemia and reperfusion in a murine heart model might play a cardio-protective role. Methods: The level of DJ-1 was analyzed from the area at risk after 30 or 60-minute ischemia or 30-minute ischemia with 30 or 60 minutes of reperfusion using C57BL/6J mice (n=3). The changes in DJ-1 expression were correlated with the expression of PTEN and AKT and phosphorylation of ERK1/2 (extracellular signal regulated kinase) and P38. The protein levels and their phosphorylation were evaluated by Western blot analysis. Results: Expression of DJ-1 increased significantly after 60 minutes of ischemia while PTEN decreased after 30 minutes of ischemia followed by 30 or 60 minutes of reperfusion both were associated with increased phosphorylation of AKT. The phosphorylation of ERK1/2 was increased at all time points of ischemia or ischemia and reperfusion while phosphorylation of P38 was increased only during ischemia and reperfusion. Conclusions: The increased expression of DJ-1 protein is a potential marker for prolonged ischemia. Although, PTEN expression were not decreased with increased DJ-1 levels, a direct inhibiting effect of DJ-1 on PTEN might increase the phosphorylation of the cell protective AKT during 60-minute ischemia. A DJ-1 independent decrease of PTEN expression might contribute to the increased AKT phosphorylation during ischemia reperfusion. Phosphorylation of ERK1/2 was a sensitive marker of early or late ischemia and ischemia and reperfusion. The role of the DJ-1-AKT interaction in preventing P38 phosphorylation during ischemia needs further investigation.

Abstract 1483: The Absence of PI3K γ is Beneficial in a Mouse Model of Myocardial Ischemia/Reperfusion

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Bernhard J Haubner ◽  
Julia Schwaighofer ◽  
Florian Huber ◽  
Greg Neely ◽  
Keiji Kuba ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Troponin T ◽  
Interstitial Fibrosis ◽  
Ischemia Reperfusion ◽  
Serum Levels ◽  
Ischemia And Reperfusion ◽  
Myocardial Ischemia And Reperfusion ◽  
Myocardial Ischemia Reperfusion

Introduction - Phosphoinositide 3-Kinase gamma (PI3Kγ) is a well-known key enzyme in inflammation pathways. Emerging data demonstrate that PI3Kγ plays a distinct role in cardiomyocytes, but its influence in the setting of myocardial ischemia and reperfusion is still an enigma. To clarify these effects we examined the morphology and contractility of PI3Kγ−/−hearts after ischemia and reperfusion. Methods - PI3Kγ knock out (KO) mice and C57 Bl6 wild type (WT) mice were subjected to 30 minutes of ischemia followed by 3 hours, 1 week and 3 weeks of reperfusion. We therefore reversibly ligated the left anterior descending artery (LAD) in an in vivo model and harvested the myocardium after the defined time of reperfusion. Histological sections were stained with H&E and Masson Trichrome in order to measure the area of infartion and the amount of interstitial fibrosis. Furthermore, Troponin T serum levels were determined and transthoracic echocardiography was performed for measuring the differences in myocardial contractiliy. Results - Comparing PI3Kγ KO mice with WT mice, we found a significant decrement of Troponin T serum levels in the transgenic group 3 hours after reperfusion (0.77±0.28 vs. 1.28±0.48 ng/ml, p<0.001). In addition, a distinct reduction of myocardial infarction was observed in the KO group compared to the WT mice (3 hours: 1.18±0.31 vs. 1.78±0.45 mm 2 , p=0.001; 1 week: 0.88±0.32 vs. 1.29±0.34 mm 2 , p=0.001; 3 weeks: 0.62±0.18 vs. 1.87±0.59 mm 2 , p<0.001). Furthermore, we showed a matching smaller quantity of myocardial fibrosis in the transgenic cohort (1 week: score 1.23±0.6 vs. 2.13±0.74, p=0.005; 3 weeks: score 1.08±0.79 vs. 2±0.71, p=0.014). Fractional shortening (FS) analysis determined by echocardiography revealed significantly enhanced myocardial contractility in PI3Kγ lacking mice after ischemia and reperfusion (1 week: 37.85±7.71 vs. 23.75±8.78 %FS, p=0.007; 3 weeks: 30.67±4.87 vs. 23.7±7.47 %FS, p=0.043). Conclusions - Our data provide the first evidence for the crucial role of PI3Kγ signalling in myocardial ischemia/reperfusion injury: PI3Kγ deficient mice show a significantly better outcome concerning infarction area, Troponin T elevation, scar size, fibrosis, and contractility at all stages of reperfusion (3 hours to 3 weeks).

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