Corrigendum to: PCSK9 expression in the ischaemic heart and its relationship to infarct size, cardiac function, and development of autophagy

Inhaled nitric oxide (NO) has been reported to decrease the infarct size in cardiac ischemia-reperfusion (I/R) injury. However, reactive nitrogen species (RNS) produced by NO cause myocardial dysfunction and injury. Because H2 is reported to eliminate peroxynitrite, it was expected to reduce the adverse effects of NO. In mice, left anterior descending coronary artery ligation for 60 min followed by reperfusion was performed with inhaled NO [80 parts per million (ppm)], H2 (2%), or NO + H2, starting 5 min before reperfusion for 35 min. After 24 h, left ventricular function, infarct size, and area at risk (AAR) were assessed. Oxidative stress associated with reactive oxygen species (ROS) was evaluated by staining for 8-hydroxy-2′-deoxyguanosine and 4-hydroxy-2-nonenal, that associated with RNS by staining for nitrotyrosine, and neutrophil infiltration by staining for granulocyte receptor-1. The infarct size/AAR decreased with breathing NO or H2 alone. NO inhalation plus H2 reduced the infarct size/AAR, with significant interaction between the two, reducing ROS and neutrophil infiltration, and improved the cardiac function to normal levels. Although nitrotyrosine staining was prominent after NO inhalation alone, it was eliminated after breathing a mixture of H2 with NO. Preconditioning with NO significantly reduced the infarct size/AAR, but not preconditioning with H2. In conclusion, breathing NO + H2 during I/R reduced the infarct size and maintained cardiac function, and reduced the generation of myocardial nitrotyrosine associated with NO inhalation. Administration of NO + H2 gases for inhalation may be useful for planned coronary interventions or for the treatment of I/R injury.

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Cardioprotection with esmolol-based cardioplegia for non-infarcted and infarcted rat hearts

European Journal of Cardio-Thoracic Surgery ◽

10.1093/ejcts/ezab117 ◽

2021 ◽

Author(s):

Alexander B Veitinger ◽

Audrey Komguem ◽

Lena Assling-Simon ◽

Martina Heep ◽

Julia Schipke ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Function ◽

Infarct Size ◽

Myocardial Infarct ◽

Lactate Production ◽

Left Ventricular ◽

Myocardial Infarct Size ◽

Cardioplegic Arrest ◽

Blood Cardioplegia ◽

Rat Hearts

Abstract OBJECTIVES Esmolol-based cardioplegic arrest offers better cardioprotection than crystalloid cardioplegia but has been compared experimentally with blood cardioplegia only once. We investigated the influence of esmolol crystalloid cardioplegia (ECCP), esmolol blood cardioplegia (EBCP) and Calafiore blood cardioplegia (Cala) on cardiac function, metabolism and infarct size in non-infarcted and infarcted isolated rat hearts. METHODS Two studies were performed: (i) the hearts were subjected to a 90-min cardioplegic arrest with ECCP, EBCP or Cala and (ii) a regional myocardial infarction was created 30 min before a 90-min cardioplegic arrest. Left ventricular peak developed pressure (LVpdP), velocity of contractility (dLVP/dtmax), velocity of relaxation over time (dLVP/dtmin), heart rate and coronary flow were recorded. In addition, the metabolic parameters were analysed. The infarct size was determined by planimetry, and the myocardial damage was determined by electron microscopy. RESULTS In non-infarcted hearts, cardiac function was better preserved with ECCP than with EBCP or Cala relative to baseline values (LVpdP: 100 ± 28% vs 86 ± 11% vs 57 ± 7%; P = 0.002). Infarcted hearts showed similar haemodynamic recovery for ECCP, EBCP and Cala (LVpdP: 85 ± 46% vs 89 ± 55% vs 56 ± 26%; P = 0.30). The lactate production with EBCP was lower than with ECCP (0.6 ± 0.7 vs 1.4 ± 0.5 μmol/min; P = 0.017). The myocardial infarct size and (ECCP vs EBCP vs Cala: 16 ± 7% vs 15 ± 9% vs 24 ± 13%; P = 0.21) the ultrastructural preservation was similar in all groups. CONCLUSIONS In non-infarcted rat hearts, esmolol-based cardioplegia, particularly ECCP, offers better myocardial protection than Calafiore. After an acute myocardial infarction, cardioprotection with esmolol-based cardioplegia is similar to that with Calafiore.

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c-Jun DNAzymes Inhibit Myocardial Inflammation, ROS Generation, Infarct Size, and Improve Cardiac Function After Ischemia-Reperfusion Injury

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.109.189753 ◽

2009 ◽

Vol 29 (11) ◽

pp. 1836-1842 ◽

Cited By ~ 31

Author(s):

Xiao Luo ◽

Hong Cai ◽

Jun Ni ◽

Ravinay Bhindi ◽

Harry C. Lowe ◽

...

Keyword(s):

Cardiac Function ◽

Infarct Size ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Ros Generation ◽

Myocardial Inflammation

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Suppression of Long Non-Coding RNA LINC00652 Restores Sevoflurane-Induced Cardioprotection Against Myocardial Ischemia-Reperfusion Injury by Targeting GLP-1R Through the cAMP/PKA Pathway in Mice

Cellular Physiology and Biochemistry ◽

10.1159/000493450 ◽

2018 ◽

Vol 49 (4) ◽

pp. 1476-1491 ◽

Cited By ~ 9

Author(s):

Shu-Bo Zhang ◽

Tie-Jun Liu ◽

Guo-Hua Pu ◽

Bao-Yong Li ◽

Xiao-Zeng Gao ◽

...

Keyword(s):

Myocardial Ischemia ◽

Cardiac Function ◽

Infarct Size ◽

Ischemia Reperfusion ◽

Myocardial Cells ◽

Non Coding Rna ◽

Tnf Α ◽

Myocardial Ischemia Reperfusion ◽

Pka Pathway ◽

Long Non Coding Rna

Background/Aims: Long non-coding RNA (lncRNA) and glucagon-like peptide 1 receptor (GLP-1R) are crucial for heart development and for adult heart structural maintenance and function. Herein, we performed a study to explore the effect of lncRNA LINC00652 (LINC00652) on myocardial ischemia-reperfusion (I/R) injury by targeting GLP-1R through the cyclic adenosine monophosphate-protein kinase A (cAMP/PKA) pathway. Methods: Bioinformatics software was used to screen the long-chain non-coding RNAs associated with myocardial ischemia-reperfusion and to predict target genes. The mRNA and protein levels of LINC00652, GLP-1R and CREB were detected by RT-qPCR and western blotting. In order to identify the interaction between LINC00652 and myocardial I/R injury, the cardiac function, the hemodynamic changes, the pathological changes of the myocardial tissues, the myocardial infarct size, and the apoptosis of myocardial cells of mice were measured. Meanwhile, the levels of serum IL-1β and TNF-α were detected. Results: LINC00652 was overexpressed in the myocardial cells of mice with myocardial I/R injury. GLP-1R is the target gene of LINC00652. We also determined higher levels of LINC00652 and GLP-1R in the I/R modeled mice. Additionally, si-LINC00652 decreased cardiac pathology, infarct size, apoptosis rates of myocardial cells, and levels of IL-1β and TNF-α, and increased GLP-1R expression cardiac function, normal hemodynamic index, and the expression and phosphorylation of GLP-1R and CREB proteins. Conclusion: Taken together, our key findings of the present highlight LINC00652 inhibits the activation of the cAMP/PKA pathway by targeting GLP-1R to reduce the protective effect of sevoflurane on myocardial I/R injury in mice.

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Abstract 16708: Cathelicidin Related Antimicrobial Peptide Treated Bone Marrow Derived Mononuclear Cells Improves Cardiac Function in a Mouse Model of Acute Myocardial Infarction: Potential Therapeutic Targets in Ischemic Heart Disease

Circulation ◽

10.1161/circ.130.suppl_2.16708 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Yuri M Klyachkin ◽

Prabhakara R Nagareddy ◽

Ahmed Asfour ◽

Shaojing Ye ◽

Erhe Gao ◽

...

Keyword(s):

Heart Disease ◽

Cardiac Function ◽

Ischemic Heart Disease ◽

Infarct Size ◽

Left Ventricular ◽

Ischemic Heart ◽

In Vivo Studies ◽

Boyden Chamber ◽

Acute Ischemic Heart Disease

Introduction: Limited stem cell retention following intracoronary administration for ischemic heart disease has reduced the clinical efficacy of this novel therapy. Cathelicidins have been shown to prime BMMNC migration towards low gradients of SDF-1 suggesting a potential role in BMMNC retention. We sought to assess the safety and efficacy of BMMNC pre-treatment with CRAMP for treatment of acute ischemic heart disease. METHODS: BMMNCs isolated from GFP mice were incubated with recombinant CRAMP (2.5 μg/ml) or placebo for 1 hour followed by chemotaxis studies towards low levels of SDF-1 (2 ng/ml) using a Boyden chamber in vitro. During the in vivo studies, mice were randomized into 3 groups: AMI followed by injection of phosphate buffered saline (PBS), BMMNCs alone, or BMMNCs incubated with CRAMP. Scar size, survival and retention of injected BMNNCs were examined by immunohistochemistry at 5 weeks. Left ventricular function was measured by echocardiography at baseline, 48 hours, and 5 weeks after MI. Changes in infarct size between 5 days and 5 weeks after AMI was assessed by cardiac MRI utilizing delayed gadolinium enhancement. RESULTS: Treatment of BMNNCs with CRAMP enhanced their migration towards low, yet physiological, levels of SDF-1 (Fig 1A). In vivo, a greater proportion of cell survival and retention was observed in the BMNNC+CRAMP group than in the BMNNC-alone group (Fig 1B) and this was associated with higher percentage of BrdU positive cells (Fig 1C). Moreover, BMNNC+CRAMP administration led to significantly better survival, improvement of cardiac function (Fig 1D-H) and reduction in infarct size compared with other control groups (Fig 1I). CONCLUSIONS: Cathelicidins enhance BMMNC retention after intramyocardial administration for acute ischemic heart disease resulting in enhanced recovery. Therapies employing this strategy may represent an effective method for improving cardiac recovery and survival rate after AMI in human studies.

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Abstract 19478: Endothelial and Cardiomyocyte -derived C-type Natriuretic Peptide Coordinate Heart Structure and Function

Circulation ◽

10.1161/circ.132.suppl_3.19478 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Amie J Moyes ◽

Sandy M Chu ◽

Reshma S Baliga ◽

Adrian J Hobbs

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Cardiac Function ◽

Infarct Size ◽

Natriuretic Peptide ◽

Vascular Tone ◽

Ex Vivo ◽

Pressure Overload ◽

Structure And Function ◽

And Function

Background: Endothelium-derived C-type natriuretic peptide (CNP) plays a key vascular homeostatic role governing vascular tone, blood pressure, leukocyte flux, platelet reactivity and the integrity of the vessel wall. However, relatively little is known about physiological role(s) for endogenous CNP in regulating cardiac structure and function. Herein, we have utilised novel mouse strains with endothelium or cardiomyocyte -specific deletion of CNP to determine if the peptide modulates heart function under basal conditions and during cardiac stress. Methods: Blood pressure and ECG were assessed by radiotelemetry. A Langendorff heart model was used to study coronary vascular reactivity and ischemia-reperfusion (I/R) injury ex vivo. Echocardiography was performed to determine cardiac function at baseline and following pressure overload (trans-aortic constriction; 6 weeks) -induced left ventricular hypertrophy/heart failure. Results: Hearts from endothelium-specific CNP knockout (ecCNP KO) mice exhibited smaller reductions in coronary perfusion pressure (CPP) compared to wildtype (WT) littermates in response to the vasodilators bradykinin (ΔCPP: WT=31.7±2.7%, KO=21.1±2.9%, n=8, p<0.05) and acetylcholine (ΔCPP: WT=36.4±4.4%, KO=18.5±3.8%, n=6, p<0.05). Shear-stress induced coronary dilatation (i.e. reactive hyperaemia) was also blunted in ecCNP KO hearts (AUC: WT=2804±280 [a.u.], KO=1493±280 [a.u.], n=8, p<0.05). Under basal conditions the heart rate (BPM: WT=605±5, KO 579±4, n=5, p<0.001) and contractility (QA interval; WT=13.7±0.1ms, KO=14.8±0.1ms, n=5, p<0.001) were significantly reduced in cardiomyocyte-specific CNP (cmCNP) KO mice compared to WT. Myocardial infarct size was larger in cmCNP KO following I/R injury ex vivo (Infarct size: WT=14.1±6.3%, KO=21.8±1.8 %, n=6, p<0.05). Furthermore, cmCNP KO mice exhibited greater cardiac dysfunction following pressure-overload (e.g. fractional shortening: WT=34.4±0.9%, KO=30.5±1.4%, n=8, p<0.05). Conclusion: These data suggest that CNP of endothelial and cardiomyocyte origin preserves cardiac function and morphology via the regulation of coronary vascular tone, heart rate, and myocardial contractility/hypertrophy.

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Abstract 284: Loss of Micu3 Confers Cardioprotection Against Cardiac Injury

Circulation Research ◽

10.1161/res.127.suppl_1.284 ◽

2020 ◽

Vol 127 (Suppl_1) ◽

Author(s):

Bao Puente ◽

Junhui Sun ◽

Maria Fergusson ◽

Julia Liu ◽

Anna Kosmach ◽

...

Keyword(s):

Cardiac Function ◽

Infarct Size ◽

Reperfusion Injury ◽

Calcium Uptake ◽

Cardiac Injury ◽

Mitochondrial Calcium ◽

Wild Type ◽

Ischemic Reperfusion ◽

Mitochondrial Calcium Uptake

Background: Mitochondrial calcium flux and signaling is integral to cardiac function and contraction. However, during pathologic conditions such as ischemic/reperfusion injury, mitochondrial calcium overload can induce the opening of the mitochondrial permeability transitioning pore (PTP), resulting in the collapse of mitochondrial membrane potential, ATP depletion, and generation of reactive oxygen species, all together leading to cell death. Hence, modulation of mitochondrial calcium and inhibition of the PTP is a promising target for cardioprotection and prevention of cardiomyocyte death. The mitochondrial calcium uniporter (MCU) complex mediates rapid mitochondrial calcium uptake. MICU3 is a regulator of the MCU complex and has been shown to be a highly potent stimulator of MCU-dependent calcium uptake in neuronal cells. We found that MICU3 is expressed in hearts and we therefore investigated the role of MICU3 in the heart. We examined the role of MICU3 in the development of hypertrophy and in a separate study we examined the response to ischemic-reperfusion (I/R) injury. Given its role in regulating mitochondrial calcium uptake, we hypothesized that loss of MICU3 confers protection against cardiac injury. Methods: Mice with global deletion of Micu3 (Micu3 -/- ) were created utilizing CRISPR-Cas9 technology. Adult knockout and littermate wild type mice were treated with Isoproterenol (15mg/kg/day) for two weeks to induce hypertrophy. Echocardiograms were performed at baseline and after treatment to assess changes in left ventricular size and function. I/R injury was studied using Langendorff ex vivo perfused heart system, exposing knockout and wild type hearts to 20 minutes of ischemia and 90 minutes of reperfusion. Hemodynamic data and infarct size were collected and compared. Student t-test and 2-way ANOVA were used for statistical analysis. Result: Micu3 -/- mice had normal cardiac function at baseline. There was no sex difference in cardiac function. Micu3 -/- mice continued to show normal function after 2 weeks of treatment with Isoproterenol, whereas wild type mice exhibited depressed function (median FS 35% vs. 24% p = 0.0001, EF 64% vs. 50% p = 0.0001). Wild type mice developed LV dilation from baseline (median 4.15mm vs. 4.57mm, p = 0.0014), whereas LV dimension remained stable in Micu3 -/- mice (median 4.12mm vs. 4.18mm, p= 0.9892). Micu3 - /- mice were also protected from I/R injury. Compared to wild types, Micu3 -/- hearts demonstrated less contractile dysfunction at end reperfusion (median rate pressure product 62% vs. 41%, p = 0.002), and significantly smaller infarct size (median 33% vs. 53%, p = 0.0001). Conclusion: Loss of MICU3 confers cardioprotection against ischemic reperfusion injury and Isoproterenol induced cardiac dysfunction.

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SGLT2 inhibitors reduce infarct size in reperfused ischemic heart and improve cardiac function during ischemic episodes in preclinical models

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ◽

10.1016/j.bbadis.2020.165770 ◽

2020 ◽

Vol 1866 (7) ◽

pp. 165770 ◽

Cited By ~ 6

Author(s):

Ioanna Andreadou ◽

Robert M. Bell ◽

Hans Erik Bøtker ◽

Coert J. Zuurbier

Keyword(s):

Cardiac Function ◽

Infarct Size ◽

Sglt2 Inhibitors ◽

Ischemic Heart ◽

Preclinical Models ◽

Reduce Infarct Size

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Cardiac surgery in acute myocardial infarction: crystalloid versus blood cardioplegia – an experimental study

Journal of Cardiothoracic Surgery ◽

10.1186/s13019-020-1058-9 ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Andreas Boening ◽

Maximilian Hinke ◽

Martina Heep ◽

Kerstin Boengler ◽

Bernd Niemann ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Cardiac Surgery ◽

Cardiac Function ◽

Infarct Size ◽

Left Ventricular ◽

Coronary Artery Ligation ◽

Cardioplegic Arrest ◽

Blood Cardioplegia ◽

Cardioplegia Solution

Abstract Background Because hearts in acute myocardial infarction are often prone to ischemia-reperfusion damage during cardiac surgery, we investigated the influence of intracellular crystalloid cardioplegia solution (CCP) and extracellular blood cardioplegia solution (BCP) on cardiac function, metabolism, and infarct size in a rat heart model of myocardial infarction. Methods Following euthanasia, the hearts of 50 rats were quickly excised, cannulated, and inserted into a blood-perfused isolated heart apparatus. A regional myocardial infarction was created in the infarction group (18 hearts) for 120 min; the control group (32 hearts) was not subjected to infarction. In each group, either Buckberg BCP or Bretschneider CCP was administered for an aortic clamping time of 90 min. Functional parameters were recorded during reperfusion: coronary blood flow, left ventricular developed pressure (LVDP) and contractility (dp/dt max). Infarct size was determined by planimetry. The results were compared between the groups using analysis of variance or parametric tests, as appropriate. Results Cardiac function after acute myocardial infarction, 90 min of cardioplegic arrest, and 90 min of reperfusion was better preserved with Buckberg BCP than with Bretschneider CCP relative to baseline (BL) values (LVDP 54 ± 11% vs. 9 ± 2.9% [p = 0.0062]; dp/dt max. 73 ± 11% vs. 23 ± 2.7% [p = 0.0001]), whereas coronary flow was similarly impaired (BCP 55 ± 15%, CCP 63 ± 17% [p = 0.99]). The infarct in BCP-treated hearts was smaller (25% of myocardium) and limited to the area of coronary artery ligation, whereas in CCP hearts the infarct was larger (48% of myocardium; p = 0.029) and myocardial necrosis was distributed unevenly to the left ventricular wall. Conclusions In a rat model of acute myocardial infarction followed by cardioplegic arrest, application of BCP leads to better myocardial recovery than CCP.

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