scholarly journals The continuing evolution of the Langendorff and ejecting murine heart: new advances in cardiac phenotyping

2012 ◽  
Vol 303 (2) ◽  
pp. H156-H167 ◽  
Author(s):  
Ronglih Liao ◽  
Bruno K. Podesser ◽  
Chee Chew Lim
Keyword(s):  
Vascular Reactivity ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Isolated Heart ◽  
Ischemia Reperfusion ◽  
In Vitro Assays ◽  
Mouse Heart ◽  
Heart Preparation ◽  
The Impact

The isolated retrograde-perfused Langendorff heart and the isolated ejecting heart have, over many decades, resulted in fundamental discoveries that form the underpinnings of our current understanding of the biology and physiology of the heart. These two experimental methodologies have proven invaluable in studying pharmacological effects on myocardial function, metabolism, and vascular reactivity and in the investigation of clinically relevant disease states such as ischemia-reperfusion injury, diabetes, obesity, and heart failure. With the advent of the genomics era, the isolated mouse heart preparation has gained prominence as an ex vivo research tool for investigators studying the impact of gene modification in the intact heart. This review summarizes the historical development of the isolated heart and provides a practical guide for the establishment of the Langendorff and ejecting heart preparations with a particular emphasis on the murine heart. In addition, current applications and novel methods of recording cardiovascular parameters in the isolated heart preparation will be discussed. With continued advances in methodological recordings, the isolated mouse heart preparation will remain physiologically relevant for the foreseeable future, serving as an integral bridge between in vitro assays and in vivo approaches.

scholarly journals Targeted disruption of PDE3B, but not PDE3A, protects murine heart from ischemia/reperfusion injury

2015 ◽  
Vol 112 (17) ◽  
pp. E2253-E2262 ◽  
Author(s):  
Youn Wook Chung ◽  
Claudia Lagranha ◽  
Yong Chen ◽  
Junhui Sun ◽  
Guang Tong ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Mouse Heart ◽  
Targeted Disruption

Although inhibition of cyclic nucleotide phosphodiesterase type 3 (PDE3) has been reported to protect rodent heart against ischemia/reperfusion (I/R) injury, neither the specific PDE3 isoform involved nor the underlying mechanisms have been identified. Targeted disruption of PDE3 subfamily B (PDE3B), but not of PDE3 subfamily A (PDE3A), protected mouse heart from I/R injury in vivo and in vitro, with reduced infarct size and improved cardiac function. The cardioprotective effect in PDE3B−/− heart was reversed by blocking cAMP-dependent PKA and by paxilline, an inhibitor of mitochondrial calcium-activated K channels, the opening of which is potentiated by cAMP/PKA signaling. Compared with WT mitochondria, PDE3B−/− mitochondria were enriched in antiapoptotic Bcl-2, produced less reactive oxygen species, and more frequently contacted transverse tubules where PDE3B was localized with caveolin-3. Moreover, a PDE3B−/− mitochondrial fraction containing connexin-43 and caveolin-3 was more resistant to Ca2+-induced opening of the mitochondrial permeability transition pore. Proteomics analyses indicated that PDE3B−/− heart mitochondria fractions were enriched in buoyant ischemia-induced caveolin-3–enriched fractions (ICEFs) containing cardioprotective proteins. Accumulation of proteins into ICEFs was PKA dependent and was achieved by ischemic preconditioning or treatment of WT heart with the PDE3 inhibitor cilostamide. Taken together, these findings indicate that PDE3B deletion confers cardioprotective effects because of cAMP/PKA-induced preconditioning, which is associated with the accumulation of proteins with cardioprotective function in ICEFs. To our knowledge, our study is the first to define a role for PDE3B in cardioprotection against I/R injury and suggests PDE3B as a target for cardiovascular therapies.

Effects of Endotoxin on Neutrophil-Mediated Ischemia/Reperfusion Injury in the Rat Heart In Vivo

2001 ◽  
Vol 226 (4) ◽  
pp. 320-327 ◽  
Author(s):  
Brian P. Lipton ◽  
Joseph B. Delcarpio ◽  
Kathleen H. McDonough
Keyword(s):  
At Risk ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Isolated Heart ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Necrotic Area ◽  
Area At Risk

We have previously shown that a nonlethal dose of lipopolysaccharide (LPS) decreases L-selectin expression of neutrophils (PMNs), thereby preventing PMN-mediated reperfusion injury in the isolated heart. In the present study we determined whether or not that dose of LPS would protect hearts during in vivo ischemia and reperfusion by preventing PMN-induced reperfusion injury. Rats receiving saline vehicle showed marked myocardial injury (necrotic area/area at risk = 82% ± 2%) and significant depression in left ventricular function as assessed in the isolated isovolumic heart preparation at constant flow rates of 5, 10, 15, and 20 ml/min. The administration of LPS (100 μg/kg body wt) 7 hr prior to ischemia resulted in a reduction in myocardial damage (necrotic area/area at risk = 42% ± 3%) and preservation of function. Myocardial function was similar to that of sham ischemic saline- and LPS-treated rats. Moreover, PMN infiltration as determined by histology was quantitatively more severe in hearts of saline-treated rats than in hearts of LPS-treated rats. Isolated hearts from vehicle- and LPS-treated animals undergoing sham ischemia in vivo recovered to the same extent after in vitro ischemia/reperfusion, suggesting that LPS did not induce protection by altering intrinsic properties of the heart. Our results indicate that LPS-induced protection of the heart from in vivo PMN-mediated ischemia/reperfusion injury may be due to decreased L-selectin expression of PMNs in LPS-treated animals.

scholarly journals In Vitro/Ex Vivo Models for the Study of Ischemia Reperfusion Injury during Kidney Perfusion

2020 ◽  
Vol 21 (21) ◽  
pp. 8156
Author(s):  
Sebastien Giraud ◽  
Raphaël Thuillier ◽  
Jérome Cau ◽  
Thierry Hauet
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Kidney Graft ◽  
Kidney Preservation ◽  
Hypothermic Machine Perfusion ◽  
Kidney Perfusion ◽  
Marginal Donors

Oxidative stress is a key element of ischemia–reperfusion injury, occurring during kidney preservation and transplantation. Current options for kidney graft preservation prior to transplantation are static cold storage (CS) and hypothermic machine perfusion (HMP), the latter demonstrating clear improvement of preservation quality, particularly for marginal donors, such as extended criteria donors (ECDs) and donation after circulatory death (DCDs). Nevertheless, complications still exist, fostering the need to improve kidney preservation. This review highlights the most promising avenues of in kidney perfusion improvement on two critical aspects: ex vivo and in vitro evaluation.

Vascular reactivity in old spontaneously hypertensive stroke-prone rats- effects of in vitro ischemia/reperfusion injury

2021 ◽  
Vol 04 (03) ◽  
Author(s):  
Sevil Korkmaz-Icöz ◽  
Mona Isabella Benker ◽  
Shiliang Li ◽  
Sivakkanan Loganathan ◽  
Patricia Kraft ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Vascular Reactivity ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Spontaneously Hypertensive ◽  
In Vitro Ischemia

Acute rosiglitazone treatment is cardioprotective against ischemia-reperfusion injury by modulating AMPK, Akt, and JNK signaling in nondiabetic mice

2011 ◽  
Vol 301 (3) ◽  
pp. H895-H902 ◽  
Author(s):  
Alex Morrison ◽  
Xiaoyan Yan ◽  
Chao Tong ◽  
Ji Li
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Mouse Heart ◽  
Jnk Signaling ◽  
Ppar Γ ◽  
Increased Risk ◽  
Amp Activated Protein Kinase

Rosiglitazone (RGZ), a peroxisome proliferator-activated receptor (PPAR)-γ agonist, has been demonstrated to possess cardioprotective properties during ischemia-reperfusion. However, this notion remains controversial as recent evidence has suggested an increased risk in cardiac events associated with long-term use of RGZ in patients with type 2 diabetes. In this study, we tested the hypothesis that acute RGZ treatment is beneficial during I/R by modulating cardioprotective signaling pathways in a nondiabetic mouse model. RGZ (1 μg/g) was injected intravenously via the tail vein 5 min before reperfusion. Myocardial infarction was significantly reduced in mice treated with RGZ compared with vehicle controls (8.7% ± 1.1% vs. 20.2% ± 2.5%, P < 0.05). Moreover, isolated hearts were subjected to 20 min of global, no-flow ischemia in an ex vivo heart perfusion system. Postischemic recovery was significantly improved with RGZ treatment administered at the onset of reperfusion compared with vehicle ( P < 0.001). Immunoblot analysis data revealed that the levels of both phospho-AMP-activated protein kinase (Thr172) and phospho-Akt (Ser473) were significantly upregulated when RGZ was administered 5 min before reperfusion compared with vehicle. On the other hand, inflammatory signaling [phospho-JNK (Thr183/Tyr185)] was significantly downregulated as a result of RGZ treatment compared with vehicle ( P < 0.05). Intriguingly, pretreatment with the selective PPAR-γ inhibitor GW-9662 (1 μg/g iv) 10 min before reperfusion significantly attenuated these beneficial effects of RGZ on the ischemic heart. Taken together, acute treatment with RGZ can reduce ischemic injury in a nondiabetic mouse heart via modulation of AMP-activated protein kinase, Akt, and JNK signaling pathways, which is dependent on PPAR-γ activation.

Ultrafine particulate matter exposure augments ischemia-reperfusion injury in mice

2006 ◽  
Vol 291 (2) ◽  
pp. H894-H903 ◽  
Author(s):  
Emily Cozzi ◽  
Surovi Hazarika ◽  
Howard W. Stallings ◽  
Wayne E. Cascio ◽  
Robert B. Devlin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Particulate Matter ◽  
Cardiovascular Events ◽  
Vascular Reactivity ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Relative Size ◽  
Blood Leukocytes

Epidemiological studies have linked ambient particulate matter (PM) levels to an increased incidence of adverse cardiovascular events. Yet little is definitively known about the mechanisms accounting for the cardiovascular events associated with PM exposure. The goal of this study was to determine the effects of ultrafine (<0.1 μm) PM exposure on ischemia-reperfusion (I/R) injury. ICR mice were exposed to 100 μg of PM or vehicle by intratracheal instillation. Twenty-four hours later, mice were anesthetized with pentobarbital sodium (60 mg/kg), the left anterior descending coronary artery was ligated for 20 min, flow was restored for 2 h, and the resulting myocardial infarct (MI) size was evaluated. PM exposure doubled the relative size of the MI compared with the vehicle control. No difference was observed in the percentage of the left ventricle at risk for ischemia. PM exposure increased the level of oxidative stress in the myocardium after I/R. The density of neutrophils in the reperfused myocardium was increased by PM exposure, but differences in the number of blood leukocytes, expression of adhesion molecules on circulating neutrophils, and activation state of circulating neutrophils 24 h after PM exposure could not be correlated to the increased I/R injury observed. Additionally, aortas isolated from PM-exposed animals and studied in vitro exhibited a reduced endothelium-dependent relaxation response to acetylcholine. These results indicate that exposure to ultrafine PM increases oxidative stress in the myocardium, alters vascular reactivity, and augments injury after I/R in a murine model.

scholarly journals Cardiomyocyte-specific overexpression of an active form of Rac predisposes the heart to increased myocardial stunning and ischemia-reperfusion injury

2013 ◽  
Vol 304 (2) ◽  
pp. H294-H302 ◽  
Author(s):  
M. A. Hassan Talukder ◽  
Mohammad T. Elnakish ◽  
Fuchun Yang ◽  
Yoshinori Nishijima ◽  
Mazin A. Alhaj ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Ischemia Reperfusion Injury ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Active Form ◽  
Mutant Form ◽  
Cardiac Contractile Function ◽  
The Impact

The GTP-binding protein Rac regulates diverse cellular functions including activation of NADPH oxidase, a major source of superoxide production (O2·−). Rac1-mediated NADPH oxidase activation is increased after myocardial infarction (MI) and heart failure both in animals and humans; however, the impact of increased myocardial Rac on impending ischemia-reperfusion (I/R) is unknown. A novel transgenic mouse model with cardiac-specific overexpression of constitutively active mutant form of Zea maize Rac D (ZmRacD) gene has been reported with increased myocardial Rac-GTPase activity and O2·− generation. The goal of the present study was to determine signaling pathways related to increased myocardial ZmRacD and to what extent hearts with increased ZmRacD proteins are susceptible to I/R injury. The effect of myocardial I/R was examined in young adult wild-type (WT) and ZmRacD transgenic (TG) mice. In vitro reversible myocardial I/R for postischemic cardiac function and in vivo regional myocardial I/R for MI were performed. Following 20-min global ischemia and 45-min reperfusion, postischemic cardiac contractile function and heart rate were significantly reduced in TG hearts compared with WT hearts. Importantly, acute regional myocardial I/R (30-min ischemia and 24-h reperfusion) caused significantly larger MI in TG mice compared with WT mice. Western blot analysis of cardiac homogenates revealed that increased myocardial ZmRacD gene expression is associated with concomitant increased levels of NADPH oxidase subunit gp91phox, O2·−, and P21-activated kinase. Thus these findings provide direct evidence that increased levels of active myocardial Rac renders the heart susceptible to increased postischemic contractile dysfunction and MI following acute I/R.

Vascular reactivity in old spontaneously hypertensive stroke-prone rats- effects of in vitro ischemia/reperfusion injury

2021 ◽  
Vol 04 (03) ◽  
Author(s):  
Sevil Korkmaz-Icöz ◽  
Mona Isabella Benker ◽  
Shiliang Li ◽  
Sivakkanan Loganathan ◽  
Patricia Kraft ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Vascular Reactivity ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Spontaneously Hypertensive ◽  
In Vitro Ischemia
Sign in / Sign up

Export Citation Format

Share Document