Cardiomyocyte Transplantation in a Porcine Myocardial Infarction Model

1998 ◽  
Vol 7 (3) ◽  
pp. 239-246 ◽  
Author(s):  
Eiichi Watanabe ◽  
Duane M. Smith ◽  
Joseph B. Delcarpio ◽  
Jian Sun ◽  
Frank W. Smart ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Detrimental Effect ◽  
Distal Portion ◽  
Embolization Coil ◽  
Therapeutic Molecules ◽  
Histologic Evaluation ◽  
Yorkshire Pigs ◽  
Neonatal Pig ◽  
Host Myocardium ◽  
Fetal Pig

Transplantation of cardiomyocytes into the heart is a potential treatment for replacing damaged cardiac muscle. To investigate the feasibility and efficiency of this technique, either a cardiac-derived cell line (HL-1 cells), or normal fetal or neonatal pig cardiomyocytes were grafted into a porcine model of myocardial infarction. The myocardial infarction was created by the placement of an embolization coil in the distal portion of the left anterior descending artery in Yorkshire pigs (n = 9). Four to 5 wk after creation of an infarct, the three preparations of cardiomyocytes were grafted, at 1 × 106 cells/20 μL into normal and into the middle of the infarcted myocardium. The hearts were harvested and processed for histologic examinations 4 to 5 wk after the cell grafts. Histologic evaluation of the graft sites demonstrated that HL-1 cells and fetal pig cardiomyocytes formed stable grafts within the normal myocardium without any detrimental effect including arrhythmia. In addition, a marked increase in angiogenesis was observed both within the grafts and adjacent host myocardium. Electron microscopy studies demonstrated that fetal pig cardiomyocytes and the host myocardial cells were coupled with adherens-type junctions and gap junctions. Histologic examination of graft sites from infarct tissue failed to show the presence of grafted HL-1 cells, fetal, or neonatal pig cardiomyocytes. Cardiomyocyte transplantation may provide the potential means for cell-mediated gene therapy for introduction of therapeutic molecules into the heart.

KV7.1 channel blockade inhibits neonatal renal autoregulation triggered by a step decrease in arterial pressure

2022 ◽  
Author(s):  
Dieniffer Peixoto-Neves ◽  
Praghalathan Kanthakumar ◽  
Jeremiah M Afolabi ◽  
Hitesh Soni ◽  
Randal K Buddington ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Functional Expression ◽  
Renal Autoregulation ◽  
Neonatal Pigs ◽  
Vascular Smcs ◽  
Neonatal Pig ◽  
Kidney Maturation ◽  
Renal Vascular ◽  
Renal Vascular Tone ◽  
Fetal Pig

KV7, the voltage-gated potassium channels encoded by KCNQ genes, mediate heterogeneous vascular responses in adult rodents. Postnatal changes in the functional expression of KV7 channels have been reported in rodent saphenous arteries, but their physiological function in the neonatal renal vascular bed is unclear. Here, we report that, unlike adult pigs, only KCNQ1 (KV7.1) out of the five members of KCNQ genes was detected in neonatal pig renal microvessels. KCNQ1 is present in fetal pig kidneys as early as day 50 of gestation, and the level of expression remains the same up to postnatal day 21. Activation of the renal vascular smooth muscle cell (SMC) KV7.1 stimulated whole-cell currents, inhibited by HMR1556 (HMR), a selective KV7.1 blocker. HMR did not change the steady-state diameter of isolated renal microvessels. Similarly, intrarenal artery infusion of HMR did not alter the mean arterial pressure (MAP), renal blood flow (RBF), and renal vascular resistance (RVR) in the pigs. An approximately 20 mmHg reduction in the MAP evoked effective autoregulation of the RBF, which HMR inhibited. We conclude that 1) The expression of KCNQ isoforms in porcine renal microvessels is dependent on kidney maturation, 2) KV7.1 is functionally expressed in neonatal pig renal vascular SMCs, 3) a decrease in arterial pressure up to 20 mmHg induces renal autoregulation in neonatal pigs, and 4) SMC KV7.1 does not control basal renal vascular tone but contributes to neonatal renal autoregulation triggered by a step decrease in arterial pressure.

scholarly journals Cardiac cell–integrated microneedle patch for treating myocardial infarction

2018 ◽  
Vol 4 (11) ◽  
pp. eaat9365 ◽  
Author(s):  
Junnan Tang ◽  
Jinqiang Wang ◽  
Ke Huang ◽  
Yanqi Ye ◽  
Teng Su ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stromal Cells ◽  
Heart Regeneration ◽  
Patch Application ◽  
Model Study ◽  
Heart Repair ◽  
Injured Myocardium ◽  
Cardiac Functions ◽  
Microneedle Patch ◽  
Host Myocardium

We engineered a microneedle patch integrated with cardiac stromal cells (MN-CSCs) for therapeutic heart regeneration after acute myocardial infarction (MI). To perform cell-based heart regeneration, cells are currently delivered to the heart via direct muscle injection, intravascular infusion, or transplantation of epicardial patches. The first two approaches suffer from poor cell retention, while epicardial patches integrate slowly with host myocardium. Here, we used polymeric MNs to create “channels” between host myocardium and therapeutic CSCs. These channels allow regenerative factors secreted by CSCs to be released into the injured myocardium to promote heart repair. In the rat MI model study, the application of the MN-CSC patch effectively augmented cardiac functions and enhanced angiomyogenesis. In the porcine MI model study, MN-CSC patch application was nontoxic and resulted in cardiac function protection. The MN system represents an innovative approach delivering therapeutic cells for heart regeneration.

scholarly journals CineCT imaging platform for in-vivo and ex-vivo measurement of myocardial biomechanics post myocardial infarction and following intramyocardial delivery of theranostic hydrogel

2021 ◽  
Vol 22 (Supplement_3) ◽  
Author(s):  
D Midgett ◽  
RA Ricardo Avendano ◽  
IM Inga Melvinsdottir ◽  
SU Selen Uman ◽  
SLT Stephanie Thorn ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ex Vivo ◽  
Myocardial Strain ◽  
Perfused Heart ◽  
Active Deformation ◽  
Intramyocardial Injection ◽  
Passive Deformation ◽  
Intramyocardial Delivery ◽  
Yorkshire Pigs

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute of Health (NIH) Purpose Myocardial infarction (MI) induces acute regional changes in myocardial strain and stiffness in the infarct and the remote areas of the left ventricle (LV), which lead to adverse changes in LV geometry and function. We hypothesize that cineCT imaging could evaluate these biomechanical changes along with the effects of intramyocardial delivery of theranostic hydrogels.  Introduction We present an experimental platform to assess changes in the deformation of the LV myocardium using contrast cineCT (CCT) imaging of the beating porcine heart (active deformation) before and after acute MI and intramyocardial delivery of an imageable theranostic hydrogel. We then assess the acute effects of hydrogel delivery early post-MI on biomechanics (passive deformation) using an ex vivo perfused heart preparation.  Methods Contrast cineCT imaging was performed using 64-slice CT on 5 Yorkshire pigs without MI (n = 3) or with MI (n = 2). MI pigs had serial imaging performed before and 1 hour after acute surgical coronary occlusion to induce anterolateral MI. One MI pig was also imaged 1 hour after intramyocardial injection of a novel imageable theranostic iodinated hydrogel within the MI region. Post euthanasia, excised hearts were flushed with chilled UW cardioplegic solution and mounted on a custom inflation apparatus for cineCT imaging during LV inflation by external pump. LV pressure was cycled between 10 and 60 mmHg at 35 bpm. Dilute iohexol was injected into aortic root and UW perfusate (15 ml, 1 ml/sec). CineCT image series were reconstructed, contrast enhanced, resampled to the LV long axis (Z), and exported as a series of 10 CT volumes covering 0-90% of the cardiac/inflation cycle. Volumes were registered incrementally using nonlinear image registration (BioImageSuite) and the calculated displacement at each time point was exported at a resolution of 1 mm. A custom Matlab program was used to fit the displacement field to local trilinear polynomials and then calculate the displacement gradients and 3D Lagrangian strains. To estimate the accuracy of this approach, cardiac volumes were also numerically deformed using a 10 pixel translation and 5% triaxial stretch. Results We successfully acquired serial in-vivo and ex-vivo 3D CineCT images for assessment of the active and passive LV myocardial deformation and tracked deformation through the full cardiac/inflation cycle (Figure 2). Numerical deformation tests showed average tracking errors of < 0.2 mm (1/4 pixel) in the X,Y,Z directions of the volume. These resulted in Lagrangian strain errors of < 0.47% for the in-plane strains EXX and EYY (radial and circumferential plane) and < 0.5% for EZZ (long axis).  Conclusions We have developed a novel CineCT imaging platform that allows for high resolution in-vivo and ex-vivo measurement of myocardial biomechanics post-MI and following intramyocardial delivery of imageable theranostic hydrogels, which may improve early active and passive biomechanics.

Myocardial Infarction by Percutaneous Embolization Coil Deployment in a Swine Model

10.3791/63172 ◽  
2021 ◽  
Author(s):  
Daina Martínez-Falguera ◽  
Edgar Fadeuilhe ◽  
Albert Teis ◽  
Julia Aranyo ◽  
Raquel Adeliño ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Swine Model ◽  
Percutaneous Embolization ◽  
Embolization Coil

scholarly journals Detrimental effect of perioperative myocardial infarction on late survival after coronary artery bypass

1984 ◽  
Vol 88 (6) ◽  
pp. 972-981 ◽  
Author(s):  
Hartzell V. Schaff ◽  
Bernard J. Gersh ◽  
Lloyd D. Fisher ◽  
Robert L. Frye ◽  
Michael B. Mock ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Coronary Artery Bypass ◽  
Detrimental Effect ◽  
Artery Bypass ◽  
Perioperative Myocardial Infarction ◽  
Late Survival

scholarly journals 248 The detrimental effect of pregnancy-associated bile acid homeostasis disorder on fetal pig death.

2018 ◽  
Vol 96 (suppl_3) ◽  
pp. 27-27
Author(s):  
Z Fang ◽  
H Zhong ◽  
P Yuan ◽  
S Lin ◽  
X Zhang ◽  
...  
Keyword(s):  
Bile Acid ◽  
Detrimental Effect ◽  
Fetal Pig

scholarly journals Cell Transplantation for the Treatment of Acute Myocardial Infarction Using Vascular Endothelial Growth Factor–Expressing Skeletal Myoblasts

Circulation ◽  
2001 ◽  
Vol 104 (suppl_1) ◽  
Author(s):  
Ken Suzuki ◽  
Bari Murtuza ◽  
Ryszard T. Smolenski ◽  
Ivan A. Sammut ◽  
Noriko Suzuki ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cardiac Function ◽  
Vascular Endothelial ◽  
Skeletal Myoblast ◽  
Skeletal Myoblasts ◽  
Endothelial Growth Factor ◽  
Host Myocardium

Background Vascular endothelial growth factor (VEGF) is a promising reagent for inducing myocardial angiogenesis. Skeletal myoblast transplantation has been shown to improve cardiac function in chronic heart failure models by regenerating muscle. We hypothesized that transplantation of VEGF-expressing myoblasts could effectively treat acute myocardial infarction by providing VEGF-induced cardioprotection through vasodilatation in the early phase, followed by angiogenesis effects in salvaging ischemic host myocardium combined with the functional benefits of newly formed, skeletal myoblast-derived muscle in the later phase. Methods and Results Primary rat skeletal myoblasts were transfected with the human VEGF 165 gene using hemagglutinating virus of Japan-liposome with >95% transfection efficiency. Four million of these myoblasts (VEGF group), control-transfected myoblasts (control group), or medium only (medium group) was injected into syngeneic rat hearts 1 hour after left coronary artery occlusion. Myocardial VEGF-expression increased for 2 weeks in the VEGF group, resulting in enhanced angiogenesis without the formation of tumors. Grafted myoblasts had differentiated into multinucleated myotubes within host myocardium. Infarct size (33.3±1.4%, 38.1±1.4%, and 43.7±1.6% for VEGF, control, and medium groups, respectively; P =0.0005) was significantly reduced with VEGF treatment, and cardiac function improved in the VEGF group (maximum dP/dt: 4072.0±93.6, 3772.5±101.1, and 3482.5±90.6 mm Hg/s in the 3 groups, respectively; P =0.0011; minimum dP/dt: −504.2±68.5, −2311.3±57.0, and −2124.0±57.9 mm Hg/s, respectively; P =0.0008). Conclusions This combined strategy of cell transplantation with gene therapy could be of importance for the treatment of acute myocardial infarction.

scholarly journals Identification of residual ischemia in the occluded coronary artery irrigation area using myocardial perfusion scintigraphy

2007 ◽  
Vol 64 (11) ◽  
pp. 783-786
Author(s):  
Branislav Baskot ◽  
Slobodan Obradovic ◽  
Branko Gligic ◽  
Saso Rafajlovski ◽  
Ljuba Markovic ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Myocardial Perfusion ◽  
Myocardial Perfusion Scintigraphy ◽  
Coronary Intervention ◽  
Distal Portion ◽  
Culprit Lesion ◽  
Perfusion Scintigraphy ◽  
Physiological Importance ◽  
The Right

Background. Inspite the indisputable significance of coronarography, the implications of a revealed stenosis - and how close it is to occlusion could vary in regard to its physiological importance. Myocardial perfusion scintigraphy (MPS) possibility to prove and objectivise the presence of ischemia and myocardial viability within an occlusion found coronarographically is especially significant since it makes possible to the clinician to choose an adequate therapy. Case report. We reported a 43- year-old male patient who had been hospitalized to another institution due to acute myocardial infarction (AMI) of posterolateral localisation. Following the acute AMI stage the ergometric test per Bruce protocole was performed, negative to ischemic heart disease, while multislice computed tomography showed no significant changes on the coronary arteries. The performed one-day-protocole MPS showed a massive area of residual ischemia within myocardial infarction (MI) type culprit lesion of the posterolateral zone starting from the subapical level to the basal cross-section. According to the MPS findings coronarography was indicated due to a revascularisation assessment. The performed coronarography revealed an occlusion of the circumflex coronary artery (CCA) right after the division of obtuse branch (OB) that presented discretely in the distal parts from the homo- and heterocolaterals. The distal portion of CCA presented discretely out off the right coronary artery (RCA). Echocardiography confirmed an ejection fraction of 50% with hypokinesia of inferior and posterior walls, as well as the septum, showing a mild reduction of the general contractility. Flows through confluences were well. A month after MI a percutane coronary intervention (PCI) was performed with the implantation of a drug-releasing stent (Taxus). Early after PCI (within two weeks) a control MPS was done to evaluate the effects of the therapy giving the normal findings of myocardial perfusion. Conclusion. Determination and identificantion of vivid but ischemic myocard of culprit lesion type in the occluded artery irrigation zone enable making choice of the best therapy for a patient.

scholarly journals Functionally Improved Mesenchymal Stem Cells to Better Treat Myocardial Infarction

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Zhi Chen ◽  
Long Chen ◽  
Chunyu Zeng ◽  
Wei Eric Wang
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Clinical Trials ◽  
Causes Of Death ◽  
The Other ◽  
Preclinical Studies ◽  
Significant Progress ◽  
Poor Survival ◽  
And Function ◽  
Host Myocardium

Myocardial infarction (MI) is one of the leading causes of death worldwide. Mesenchymal stem cell (MSC) transplantation is considered a promising approach and has made significant progress in preclinical studies and clinical trials for treating MI. However, hurdles including poor survival, retention, homing, and differentiation capacity largely limit the therapeutic effect of transplanted MSCs. Many strategies such as preconditioning, genetic modification, cotransplantation with bioactive factors, and tissue engineering were developed to improve the survival and function of MSCs. On the other hand, optimizing the hostile transplantation microenvironment of the host myocardium is also of importance. Here, we review the modifications of MSCs as well as the host myocardium to improve the efficacy of MSC-based therapy against MI.

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