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

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.

Download Full-text

Cardiac venous endothelial dysfunction after myocardial ischemia and reperfusion in dogs

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1992.263.3.h850 ◽

1992 ◽

Vol 263 (3) ◽

pp. H850-H856 ◽

Cited By ~ 2

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)

Download Full-text

Correlation between apoptosis and left ventricular remodeling in subacute phase of myocardial ischemia and reperfusion

EJNMMI Research ◽

10.1186/s13550-015-0152-9 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 11

Author(s):

Hiroshi Wakabayashi ◽

Junichi Taki ◽

Anri Inaki ◽

Kazuhiro Shiba ◽

Ichiro Matsunari ◽

...

Keyword(s):

Myocardial Ischemia ◽

Ventricular Remodeling ◽

Left Ventricular Remodeling ◽

Left Ventricular ◽

Ischemia And Reperfusion ◽

Myocardial Ischemia And Reperfusion ◽

Subacute Phase

Download Full-text

Effect of postconditioning on dynamic expression of tenascin-C and left ventricular remodeling after myocardial ischemia and reperfusion

EJNMMI Research ◽

10.1186/s13550-015-0100-8 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 7

Author(s):

Junichi Taki ◽

Anri Inaki ◽

Hiroshi Wakabayashi ◽

Ichiro Matsunari ◽

Kyoko Imanaka-Yoshida ◽

...

Keyword(s):

Myocardial Ischemia ◽

Ventricular Remodeling ◽

Left Ventricular Remodeling ◽

Left Ventricular ◽

Ischemia And Reperfusion ◽

Myocardial Ischemia And Reperfusion ◽

Tenascin C ◽

Dynamic Expression

Download Full-text

Endogenous endothelin-1 impairs endothelium-dependent relaxation after myocardial ischemia and reperfusion

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1994.267.5.h1833 ◽

1994 ◽

Vol 267 (5) ◽

pp. H1833-H1841 ◽

Cited By ~ 1

Author(s):

J. M. Hagar

Keyword(s):

Myocardial Ischemia ◽

Control Release ◽

Microvascular Dysfunction ◽

Coronary Perfusion Pressure ◽

Left Ventricular ◽

Coronary Perfusion ◽

Ischemia And Reperfusion ◽

Myocardial Ischemia And Reperfusion ◽

Developed Pressure ◽

Eta Receptor Antagonist

Endothelin (ET)-1 is produced in response to myocardial ischemia and reperfusion. It is a potent constrictor of coronary resistance vessels and may therefore contribute to myocardial injury and postischemic microvascular dysfunction. Isolated buffer-perfused rabbit hearts, under conditions of constant flow and isovolumic contraction, underwent 60 min of global ischemia and 60 min of reperfusion after pretreatment with selective ETA receptor antagonist BQ-123 (10(-7) M) in perfusate, exogenous ET-1 (10(-11) M), or control. Release of ET increased significantly at 20 and 60 min of reperfusion. BQ-123 did not enhance the recovery of left ventricular developed pressure or coronary perfusion pressure, whereas exogenous ET tended to worsen them. Cumulative creatine kinase release over 20 min of reperfusion did not differ significantly between groups. Maximum endothelium-dependent dilation to acetylcholine (ACh) was initially 62 +/- 6, 71 +/- 6, and 63 +/- 8% (SE) of U-46619-induced preconstriction in control, BQ-123-, and ET-treated hearts. At 20 min of reperfusion it was 37 +/- 5, 73 +/- 9, and 22 +/- 5%, and at 60 min of reperfusion it was 35 +/- 7, 79 +/- 6, and 22 +/- 3% (P < 0.001 for BQ-123 vs. control at 20 min and P < 0.0001 at 60 min). Endothelium-independent dilation to nitroglycerin was unaltered by ischemia and reperfusion. Neither BQ-123 alone nor a 1-h infusion of ET (10(-10) M) altered the response to ACh in nonischemic hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

Download Full-text

P4 High dose β-blockade lessens myocardial edema and preserves left ventricular function in acute myocardial ischemia and reperfusion

Cardiovascular Surgery ◽

10.1016/s0967-2109(97)88884-9 ◽

1997 ◽

Vol 5 ◽

pp. S8-S9

Author(s):

H GEISSLER ◽

K DAVIS ◽

S ALLEN ◽

R WARTERS ◽

E DEVIVIE ◽

...

Keyword(s):

Myocardial Ischemia ◽

Left Ventricular Function ◽

Ventricular Function ◽

Myocardial Edema ◽

Left Ventricular ◽

Acute Myocardial Ischemia ◽

High Dose ◽

Ischemia And Reperfusion ◽

Myocardial Ischemia And Reperfusion

Download Full-text

Abstract 20587: Myocyte-Specific Over-Expression of Hdac4 Promotes Myocardial Ischemia and Reperfusion Injury

Circulation ◽

10.1161/circ.130.suppl_2.20587 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Ling Zhang ◽

Jian Feng Du ◽

Yu Zhao ◽

Ting C Zhao

Keyword(s):

Myocardial Ischemia ◽

Infarct Size ◽

Reperfusion Injury ◽

Left Ventricular ◽

Heart Weight ◽

Ischemia And Reperfusion ◽

Wild Type ◽

Ischemia And Reperfusion Injury ◽

Myocardial Ischemia And Reperfusion ◽

Over Expression

Background: Histone deacetylases (HDACs) have been recently demonstrated to play a critical role in modulating myocardial protection and cardiomyocyte survival. However, the specific HDAC in mediating myocardial ischemia/reperfusion injury is currently unknown. Objective: The goal of this study is sought to define whether cardiac specific over-expression of HDAC4 would exacerbate myocardial ischemia and reperfusion injury. Methods: We created myocyte-specific HDAC4 transgenic mice, in which cDNA encoding HDAC4 was cloned into an expression vector encoding alpha-myosine heavy chain (the α-MHC promoter). Langendorff isovolumetrically perfused hearts from wild type (WT) control (n=5) and α-MHC-HDAC4 mice (n=5) were subjected to 30 minutes of ischemia followed by 30 minutes of reperfusion. Infarct size was measured by triphenyl tetrazolium chloride staining. HDAC4 protein and activity in myocardium were determined. Results: The HDAC4 protein levels in the hearts of α-MHC-HDAC4 mice were significantly higher than those of control wild type. HDAC activity was elevated in MHC-HDAC4 mice as compared with wild type mice. In adult mice, there was no significant difference in the heart weight-body weight ratio between α-MHC-HDAC and wild-type mice. As compared to wild type mice, myocyte-specific over-expression of HDAC4 resulted in an elevation of left ventricular end-diastolic pressure (LVEDP) and reduction in the recovery of rate and pressure products (RPP) at the end of reperfusion. Furthermore, over-expression of HDAC4 increased myocardial infarct size as compared to wild type mice. Conclusions: These findings indicate that specific over-expression of HDAC4 exacerbates myocardial ischemia and reperfusion injury.

Download Full-text

Myocardial ischemia and reperfusion injury is dependent on both IgM and mannose-binding lectin

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00049.2009 ◽

2009 ◽

Vol 297 (5) ◽

pp. H1853-H1859 ◽

Cited By ~ 71

Author(s):

Marc N. Busche ◽

Vasile Pavlov ◽

Kazue Takahashi ◽

Gregory L. Stahl

Keyword(s):

Myocardial Ischemia ◽

Complement Activation ◽

Tissue Injury ◽

Left Ventricular ◽

Mannose Binding Lectin ◽

Left Ventricular Ejection ◽

Ischemia And Reperfusion ◽

Myocardial Ischemia And Reperfusion ◽

Mannose Binding ◽

Binding Lectin

Complement activation has been shown to play an important role in the inflammation and tissue injury following myocardial ischemia and reperfusion (MI/R). Several recent studies from our laboratory demonstrated the importance of mannose-binding lectin (MBL) as the initiation pathway for complement activation and the resulting pathological effects following MI/R. However, other studies from the past suggest an important role of the classical pathway and perhaps natural antibodies. In the present study, we used newly generated genetically modified mice that lack secreted IgM (sIgM), MBL-A, and MBL-C (sIgM/MBL null) in a plasma reconstitution mouse model of MI/R. Following 30 min of ischemia and 4 h of reperfusion, left ventricular ejection fractions were significantly higher in sIgM/MBL null mice reconstituted with MBL null or sIgM/MBL null plasma compared with reconstitution with wild-type (WT) plasma or WT mice reconstituted with WT plasma following MI/R. Serum troponin I concentration, myocardial polymorphonuclear leukocyte infiltration, and C3 deposition were dependent on the combined presence of sIgM and MBL. These results demonstrate that MI/R-induced complement activation, inflammation, and subsequent tissue injury require both IgM and MBL. Thus MBL-dependent activation of the lectin pathway may not be completely antibody independent in I/R models.

Download Full-text