Quantification of Murine Myocardial Infarct Size using 2D and 4D High Frequency Ultrasound

2022 ◽  
Author(s):  
Melissa M. Dann ◽  
Sydney Q. Clark ◽  
Natasha A. Trzaskalski ◽  
Conner C. Earl ◽  
Luke E. Schepers ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Infarct Size ◽  
Surface Area ◽  
Infarct Volume ◽  
Strain Analysis ◽  
The United States ◽  
Surface Strain ◽  
Coronary Artery Ligation ◽  
Myocardial Infarct Size

Background: Ischemic heart disease is the leading cause of death in the United States, Canada, and worldwide. Severe disease is characterized by coronary artery occlusion, loss of blood flow to the myocardium, and necrosis of tissue, with subsequent remodeling of the heart wall, including fibrotic scarring. The current study aims to demonstrate the efficacy of quantitating infarct size via 2D echocardiographic akinetic length and 4D echocardiographic infarct volume and surface area as in vivo analysis techniques. We further describe and evaluate a new surface area strain analysis technique for estimating myocardial infarction (MI) size after ischemic injury. Methods: Experimental MI was induced in mice via left coronary artery ligation. Ejection fraction and infarct size were measured through 2D and 4D echocardiography. Infarct size established via histology was compared to ultrasound-based metrics via linear regression analysis. Results: 2D echocardiographic akinetic length (r = 0.76, p = 0.03), 4D echocardiographic infarct volume (r = 0.85, p = 0.008) and surface area (r = 0.90, p = 0.002) correlate well with histology. While both 2D and 4D echocardiography were reliable measurement techniques to assess infarct, 4D analysis is superior in assessing asymmetry of the left ventricle and the infarct. Strain analysis performed on 4D data also provides additional infarct sizing techniques, which correlate with histology (surface strain: r = 0.94, p < 0.001, transmural thickness: r = 0.76, p = 0.001). Conclusions: 2D echocardiographic akinetic length, 4D echocardiography ultrasound and strain provide effective in vivo methods for measuring fibrotic scarring after MI.

Abstract 411: Endogenous miRNA Induced By Ischemic Preconditioning Reduces Myocardial Infarct Size following Ischemia/Reperfusion In Mice

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Chang Yin ◽  
Fadi N Salloum ◽  
Rakesh C Kukreja
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Coronary Artery Ligation ◽  
Myocardial Infarct Size ◽  
Artery Ligation ◽  
Buffer Control

BACKGROUND: Due to its short length (~24 nt) and non-coding nature, microRNA (miRNA) used to be regarded as “evolutionary transcriptional debris”. Recent evidence suggests that miRNA is a novel regulator for transcription and translation. It is known that brief episodes of ischemia during ischemic preconditioning (IPC) trigger complex genetic pro-survival program that results in modulation of several key proteins involved in protection against I/R injury. We hypothesized that miRNA synthesized during IPC is the potential mediator of such protection. METHODS / RESULTS : Hearts were isolated from 3 groups (n = 6/group) of adult ICR mice and subjected to the following treatments in Langendorff mode: 120 min of perfusion with Krebs-Henseleit buffer (control); 30 min global ischemia followed by 1 hr reperfusion (I/R); 2 cycles of 30 sec ischemia and 90 sec reperfusion followed by 30 min ischemia and 1 hr reperfusion (IPC). Infarct size (IS) was measured by triphenyl tetrazolium staining. IPC in the Langendorff model reduced IS from 29.7 ± 2.1% in the I/R hearts to 9.1 ± 1.8 % in the IPC group. This protection was associated with a significant induction of miRNA-1 (162 ± 13%), miRNA-21 (118 ± 6%), and miRNA-24 (46 ± 12%). To test its protective role, miRNA was extracted from 6 hearts following the IPC protocol; and then injected in vivo into the left ventricle wall in another group of 6 mice. Forty-eight hrs later, these mice were subjected to I/R injury in vivo by left coronary artery ligation for 30 min followed by reperfusion for 24 hr. In addition, a subset of mice was treated with miRNA inhibitors (methylated antisense miRNA) in conjunction with miRNA from IPC hearts. The results show that miRNA extracted from the IPC hearts reproduced a protective phenotype with significantly lower infarction (18.8 ± 2.5 %) in vivo as compared to saline-treated control (37.5 ± 2.2%). This protective effect was totally abolished by specific inhibitors of miRNA-1 and miRNA-21 (IS: 43.7 ± 2.1%). CONCLUSION : miRNA extracted from preconditioned hearts shows a protective role against I/R injury. The detection of miRNA in preconditioned hearts offers a novel strategy in cardioprotection. Further studies are needed to identify the gene targets by which miRNA generate protective phenotype.

Loss of Sema4D Signaling in Platelets Impairs the Formation and Stability of Arterial Thrombi In Vivo and Reduces Myocardial Infarct Size.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3631-3631 ◽  
Author(s):  
Li Zhu ◽  
Timothy J. Stalker ◽  
Tao Wang ◽  
Hong Jiang ◽  
Atushi Kumanogoh ◽  
...  
Keyword(s):  
Infarct Size ◽  
Platelet Function ◽  
Ischemia Reperfusion Injury ◽  
Thrombus Formation ◽  
Infarct Volume ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Cremaster Muscle

Abstract Contact-dependent signaling between platelets helps to promote thrombus growth and stability. One mechanism for contact-dependent signaling involves the binding of cell surface ligands to corresponding receptors on the surface of adjacent cells. In our efforts to identify novel participants in this process, we have recently reported that platelets express on their surface the semaphorin family member, sema4D, and its two known receptors, CD72 and plexin-B1 (Zhu, et al, PNAS, 2007). We have also shown that although their initial tail bleeding time is normal, platelets from sema4D(−/−) mice have a defect in collagen-induced signaling and platelet aggregation in vitro. In the present studies, we used matched sema4D(−/−) and wild type (WT) mice to examine the consequences of impaired sema4D signaling in models of platelet function in vivo. In the first model, irradiated Rose Bengal dye was used to produce an arteriolar injury in an exteriorized cremaster muscle. Platelets were identified with a fluorescent CD41 antibody and detected in real time using digital microscopy. The results showed that thrombus formation occurred in all of the mice that were tested, but while stable occlusion was observed in approximately half of the control mice, none of the sema4D(−/−) mice developed stable occlusions during the period of observation (p&lt;0.02). Similarly, when a laser was used to produce a focal injury in cremaster muscle arterioles, both the initial rate of platelet accumulation and the peak extent of accumulation were approximately 50% lower in the sema4D(−/−) mice than in the matched controls. To test the contribution of sema4D to platelet responses in a larger artery, the right common carotid was injured by transient exposure to FeCl3 and changes in flow were measured using a Doppler probe. The results showed that the time to occlusion was 35% greater in the sema4D(−/−) mice than in controls (p&lt;0.02). Furthermore, stable occlusion occurred in only 9 of 16 (56%) sema4D(−/−) mice Vs. 7 of 9 (78%) WT mice. Finally, myocardial infarct size was measured in an ischemia/reperfusion injury model 48 hrs after transient ligation of the left anterior descending coronary artery. Although infarction occurred in all cases, infarct volume was 56% smaller in the sema4D(−/−) mice than the matched controls (p&lt;0.01). In summary, these results show that there is a substantial impairment of platelet function in vivo in mice that lack sema4D. This impairment was observed in both arterioles and arteries using several different methods to evoke platelet activation. When combined with our earlier observations, the results show that signaling by sema4D and its receptors provides a novel mechanism to promote thrombus growth and stability.

Role of the β1-Adrenergic Pathway in Anesthetic and Ischemic Preconditioning against Myocardial Infarction in the Rabbit Heart In Vivo 

2006 ◽  
Vol 105 (3) ◽  
pp. 503-510 ◽  
Author(s):  
Markus Lange ◽  
Thorsten M. Smul ◽  
Christoph A. Blomeyer ◽  
Andreas Redel ◽  
Karl-Norbert Klotz ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Coronary Artery ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Myocardial Infarct ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Myocardial Infarct Size ◽  
Area At Risk

Background Anesthetic and ischemic preconditioning share similar signal transduction pathways. The authors tested the hypothesis that the beta1-adrenergic signal transduction pathway mediates anesthetic and ischemic preconditioning in vivo. Methods Pentobarbital-anesthetized (30 mg/kg) rabbits (n = 96) were instrumented for measurement of systemic hemodynamics and subjected to 30 min of coronary artery occlusion and 3 h of reperfusion. Sixty minutes before occlusion, vehicle (control), 1.0 minimum alveolar concentration desflurane, or sevoflurane, and esmolol (30.0 mg x kg(-1) x h(-1)) were administered for 30 min, respectively. Administration of a single 5-min cycle of ischemic preconditioning was instituted 35 min before coronary artery occlusion. In separate groups, the selective blocker esmolol or the protein kinase A inhibitor H-89 (250 microg/kg) was given alone and in combination with desflurane, sevoflurane, and ischemic preconditioning. Results Baseline hemodynamics and area at risk were not significantly different between groups. Myocardial infarct size (triphenyltetrazolium staining) as a percentage of area at risk was 61 +/- 4% in control. Desflurane, sevoflurane, and ischemic preconditioning reduced infarct size to 34 +/- 2, 36 +/- 5, and 23 +/- 3%, respectively. Esmolol did not alter myocardial infarct size (65 +/- 5%) but abolished the protective effects of desflurane and sevoflurane (57 +/- 4 and 52 +/- 4%, respectively) and attenuated ischemic preconditioning (40 +/- 4%). H-89 did not alter infarct size (60 +/- 4%) but abolished preconditioning by desflurane (57 +/- 5%) and sevoflurane (61 +/- 1%). Ischemic preconditioning (24 +/- 7%) was not affected by H-89. Conclusions The results demonstrate that anesthetic preconditioning is mediated by the beta1-adrenergic pathway, whereas this pathway is not essential for ischemic preconditioning. These results indicate important differences in the mechanisms of anesthetic and ischemic preconditioning.

scholarly journals Sufentanil–medetomidine anaesthesia compared with fentanyl/fluanisone–midazolam is associated with fewer ventricular arrhythmias and death during experimental myocardial infarction in rats and limits infarct size following reperfusion

2017 ◽  
Vol 52 (3) ◽  
pp. 271-279 ◽  
Author(s):  
Ellis N ter Horst ◽  
Paul A J Krijnen ◽  
Paul Flecknell ◽  
Klaas W Meyer ◽  
Klaas Kramer ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Rate ◽  
Coronary Artery ◽  
Infarct Size ◽  
Ventricular Arrhythmias ◽  
Anaesthetic Agent ◽  
Therapeutic Interventions ◽  
Coronary Artery Ligation ◽  
Artery Ligation

To improve infarct healing following myocardial infarction in humans, therapeutic interventions can be applied during the inflammatory response. Animal models are widely used to study this process. However, induction of MI in rodents is associated with high mortality due to ventricular fibrillation (VF) during coronary artery ligation. The anaesthetic agent used during the procedure appears to influence the frequency of this complication. In this retrospective study, the effect on ventricular arrhythmia incidence during ligation and infarct size following in vivo reperfusion of two anaesthetic regimens, sufentanil–medetomidine (SM) and fentanyl/fluanisone–midazolam (FFM) was evaluated in rats. Anaesthetics were administered subcutaneously using fentanyl/fluanisone (0.5 mL/kg) with midazolam (5 mg/kg) (FFM group, n = 48) or sufentanil (0.05 mg/kg) with medetomidine (0.15 mg/kg) (SM group, n = 47). The coronary artery was ligated for 40 min to induce MI. Heart rate and ventricular arrhythmias were recorded during ligation, and infarct size was measured via histochemistry after three days of reperfusion. In the SM group, heart rate and VF incidence were lower throughout the experiment compared with the FFM group (6% versus 30%) ( P < 0.01). Fatal VF did not occur in the SM group whereas this occurred in 25% of the animals in the FFM group. Additionally, after three days of reperfusion, the infarcted area following SM anaesthesia was less than half as large as that following FFM anaesthesia (8.5 ± 6.4% versus 20.7 ± 5.6%) ( P < 0.01). Therefore, to minimize the possibility of complications related to VF and acute death arising during ligation, SM anaesthesia is recommended for experimental MI in rats.

scholarly journals Effect of thrombolysis on myocardial injury: recombinant tissue plasminogen activator vs. alfimeprase

2006 ◽  
Vol 290 (3) ◽  
pp. H959-H967 ◽  
Author(s):  
Ting-Ting Hong ◽  
Jinbao Huang ◽  
Benedict R. Lucchesi
Keyword(s):  
Coronary Artery ◽  
Infarct Size ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Myocardial Infarct ◽  
Recombinant Tissue Plasminogen Activator ◽  
Saline Control ◽  
Coronary Artery Ligation ◽  
Myocardial Infarct Size ◽  
Tissue Plasminogen

Plasmin-dependent thrombolytic agents are potentially prothrombotic and proinflammatory. Alfimeprase, a zinc-containing metalloproteinase, degrades fibrin directly and achieves thrombolysis independent of plasmin formation. This study examines the hypothesis that thrombolysis in the absence of plasmin generation results in improved myocardial salvage on reperfusion. The thrombolytic effects of recombinant tissue plasminogen activator [rt-PA; 0.022 mg/kg, 1/10 of which was administered as a loading dose; the rest (9/10) was infused over 60 min by intracoronary (ic) administration] or alfimeprase (0.5 mg/kg over 1 min ic) were evaluated in a canine model of arterial thrombosis involving electrolytic injury of the left circumflex (LCX) coronary artery. Both agents induced thrombolysis, with onset of reperfusion being more rapid after alfimeprase compared with rt-PA (1.5 ± 0.6 vs. 10.1 ± 2.1 min). In the absence of adjunctive therapy, time to reocclusion after alfimeprase was 3.2 ± 0.5 min compared with 77.5 ± 31.9 min with rt-PA. The glycoprotein IIb/IIIa platelet receptor antagonist CRL-42796 prolonged reperfusion time after thrombolysis with alfimeprase or rt-PA. The effect of each lytic agent on myocardial infarct size was examined in a separate group of dogs subjected to 60 min of LCX coronary artery ligation and 4 h of reperfusion. Myocardial infarct size, expressed as percentage of the risk region, was larger (32.16 ± 3.95%) after rt-PA compared with alfimeprase (19.85 ± 3.61%) or that of the saline control group (18.46 ± 3.34%). rt-PA in contrast to alfimeprase, a direct-acting fibrinolytic agent, is associated with an increase in myocyte reperfusion injury.

Abstract 12: EMMPRIN-Targeted Magnetic Nanoparticles for in vivo Visualization and Regression of Acute Myocardial Infarction in a Model of Acute Coronary Artery Occlusion

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Irene Cuadrado ◽  
Maria Jose Garcia Miguel ◽  
Irene Herruzo ◽  
Mari Carmen Turpin ◽  
Ana Martin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Extracellular Matrix ◽  
Coronary Artery ◽  
Left Ventricle ◽  
Infarct Size ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Gadolinium Enhancement

Extracellular matrix metalloproteinase inducer EMMPRIN, is highly expressed in patients with acute myocardial infarction (AMI), and induces activation of several matrix metalloproteinases (MMPs), including MMP-9 and MMP-13. To prevent Extracellular matrix degradation and cardiac cell death we targeted EMMPRIN with paramagnetic/fluorescent micellar nanoparticles with an EMMPRIN binding peptide AP9 conjugated (NAP9), or an AP9 scramble peptide as a negative control (NAPSC). NAP9 binds to endogenous EMMPRIN as detected by confocal microscopy of cardiac myocytes and macrophages incubated with NAP and NAPSC in vitro, and in vivo in mouse hearts subjected to left anterior descending coronary artery occlusion (IV injection 50mγ/Kg NAP9 or NAP9SC). Administration of NAP9 at the same time or 1 hour after AMI reduced infarct size over a 20% respect to untreated and NAPSC injected mice, recovered left ventricle ejection fraction (LVEF) similar to healthy controls, and reduced EMMPRIN downstream MMP9 expression. In magnetic resonance scans of mouse hearts 2 days after AMI and injected with NAP9, we detected a significant gadolinium enhancement in the left ventricle respect to non-injected mice and to mice injected with NAPSC. Late gadolinium enhancement assays exhibited NAP9-mediated left ventricle signal enhancement as early as 30 minutes after nanoprobe injection, in which a close correlation between the MRI signal enhancement and left ventricle infarct size was detected. Taken together, these results point EMMPRIN targeted nanoprobes as a new tool for the treatment of AMI.

scholarly journals Right coronary artery ligation in mice: a novel method to investigate right ventricular dysfunction and biventricular interaction

2019 ◽  
Vol 316 (3) ◽  
pp. H684-H692 ◽  
Author(s):  
Pierre Sicard ◽  
Timothée Jouitteau ◽  
Thales Andrade-Martins ◽  
Abdallah Massad ◽  
Glaucy Rodrigues de Araujo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Infarct Size ◽  
Right Ventricular ◽  
Right Coronary Artery ◽  
Ventricular Dysfunction ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Inferior Myocardial Infarction ◽  
Acute Inferior Myocardial Infarction

Right ventricular (RV) dysfunction can lead to complications after acute inferior myocardial infarction (MI). However, it is unclear how RV failure after MI contributes to left-sided dysfunction. The aim of the present study was to investigate the consequences of right coronary artery (RCA) ligation in mice. RCA ligation was performed in C57BL/6JRj mice ( n = 38). The cardiac phenotypes were characterized using high-resolution echocardiography performed up to 4 wk post-RCA ligation. Infarct size was measured using 2,3,5-triphenyltetrazolium chloride staining 24 h post-RCA ligation, and the extent of the fibrotic area was determined 4 wk after MI. RV dysfunction was confirmed 24 h post-RCA ligation by a decrease in the tricuspid annular plane systolic excursion ( P < 0.001) and RV longitudinal strain analysis ( P < 0.001). Infarct size measured ex vivo represented 45.1 ± 9.1% of the RV free wall. RCA permanent ligation increased the RV-to-left ventricular (LV) area ratio ( P < 0.01). Septum hypertrophy ( P < 0.01) was associated with diastolic septal flattening. During the 4-wk post-RCA ligation, LV ejection fraction was preserved, yet it was associated with impaired LV diastolic parameters ( E/ E′, global strain rate during early diastole). Histological staining after 4 wk confirmed the remodeling process with a thin and fibrotic RV. This study validates that RCA ligation in mice is feasible and induces RV heart failure associated with the development of LV diastolic dysfunction. Our model offers a new opportunity to study mechanisms and treatments of RV/LV dysfunction after MI. NEW & NOTEWORTHY Right ventricular (RV) dysfunction frequently causes complications after acute inferior myocardial infarction. How RV failure contributes to left-sided dysfunction is elusive because of the lack of models to study molecular mechanisms. Here, we created a new model of myocardial infarction by permanently tying the right coronary artery in mice. This model offers a new opportunity to unravel mechanisms underlying RV/left ventricular dysfunction and evaluate drug therapy.

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