Myocardial Infarction In Pigs Research Articles

Development of a closed-artery catheter-based myocardial infarction in pigs using sponge and lidocaine hydrochloride infusion to prevent irreversible ventricular fibrillation.

The objectives of this study were to develop a robust, homogeneous, viable and inexpensive model of closed‐artery catheter‐based model of myocardial infarction (MI) in pigs without major cardiac dysfunction. Suitable animal models that mimic human cardiovascular conditions are of paramount importance to understand the effects of novel therapeutic strategies to improve tissue perfusion and prevent cardiac deterioration post‐MI. Pigs (N = 21, BW = 17 ± 1 kg) receiving continuous iv lidocaine hydrochloride were subjected to percutaneous intracoronary implant of foam sponge into the proximal left circumflex coronary artery. Intraprocedure mortality was 23.8%. ST segment elevation and increased serum Troponin T and CK‐MB were documented in all animals. Thirty days after occlusion, echocardiography (95% IC [9.3–12.4%]) and anatomopathological (95% CI [9.3–12.6%]) analyses confirmed a significant and reproducible MI. Taken together, we provide evidence for a suitable closed‐artery catheter‐based method to produce MI in pigs accompanied by tissue hypoperfusion and absence of overt heart failure.

0268: TREM-1 modulation improves cardiac function during myocardial infarction in pigs

The widespread use of reperfusion therapy have led to an important improvement in short-term mortality after acute myocardial infarction (MI), but long-term mortality remains high. The Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) belongs to the immunoreceptors superfamily and acts as an amplifier of the inflammatory response triggered by TLRs engagement during both infectious and aseptic inflammatory diseases. We hypothesized that administration of LR12, a synthetic peptide able to inhibit TREM-1 activation, could be beneficial at the acute phase of MI, in a clinically relevant model of experimental MI in pigs. MI was induced in fifteen anesthetized and mechanically ventilated pigs weighing 45–55 kg, by inflation of an angioplasty balloon in the proximal left anterior descending (LAD) coronary artery cannulated under X-ray guidance, during 60 minutes. Fifteen minutes before deflation, animals were randomized to receive either LR12 (n=7) or LR12-scramble (n=8). Complete hemodynamic and functional parameters were monitored through arterial line, swan-ganz and intraventricular conductance catheters. Resuscitation was conducted by experienced intensivists according to standard protocols used in clinical practice. The monitoring was prolonged until H18, then survivors were euthanized. The decrease in mean arterial pressure (MAP) was significantly limited during the monitoring period from H12 to the end (-22.1% vs -3.9%, p<.01). Cardiac index and cardiac power index, one of the strongest hemodynamic correlate of mortality in cardiogenic shock, were preserved under LR12 regimen (72% vs 45% from baseline value, p<.05) as well as SvO2 value (74% vs 62%, p<.05). Ejection fraction and parameters of systolic function improved under LR12 treatment. TREM-1 inhibition by LR12 at the acute phase of myocardial infarction in invasively monitored pigs limits reperfusion injury and alteration of ventricular contractility.

Local Hydrogel Release of Recombinant TIMP-3 Attenuates Adverse Left Ventricular Remodeling After Experimental Myocardial Infarction

An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) contributes to the left ventricle (LV) remodeling that occurs after myocardial infarction (MI). However, translation of these observations into a clinically relevant, therapeutic strategy remains to be established. The present study investigated targeted TIMP augmentation through regional injection of a degradable hyaluronic acid hydrogel containing recombinant TIMP-3 (rTIMP-3) in a large animal model. MI was induced in pigs by coronary ligation. Animals were then randomized to receive targeted hydrogel/rTIMP-3, hydrogel alone, or saline injection and followed for 14 days. Instrumented pigs with no MI induction served as referent controls. Multimodal imaging (fluoroscopy/echocardiography/magnetic resonance imaging) revealed that LV ejection fraction was improved, LV dilation was reduced, and MI expansion was attenuated in the animals treated with rTIMP-3 compared to all other controls. A marked reduction in proinflammatory cytokines and increased smooth muscle actin content indicative of myofibroblast proliferation occurred in the MI region with hydrogel/rTIMP-3 injections. These results provide the first proof of concept that regional sustained delivery of an MMP inhibitor can effectively interrupt adverse post-MI remodeling.

Ultrasound-mediated Microbubble Destruction Promotes Bone Marrow Mesenchymal Stem Cell Transplantation for Myocardial Infarction Therapy

The study was designed to investigate whether ultrasound-mediated microbubble destruction can enhance the transplantation of bone marrow mesenchymal stem cells (BMSCs) for myocardial infarction therapy, twenty myocardial infarction pigs were assigned into the ultrasound microbubble destruction group (n=12, Sonovue were infused into coronary artery with ultrasonic radiation, then BMSCs were injected into infarction region) and the cell control group (n=8, only subjected to BMSCs treatment). The increase of left ventricular ejection fraction was larger in the ultrasound microbubble destruction group (P<0.01), and more Prussian blue-positive cells and higher density of heart muscle capillary in the peripheral infarct regions were found (P<0.01). Prussian blue-positive cells were differentiated into new vascular endothelial cells in two cases, among which the gaps were widened in the microbubble destruction group. Our study first time testifies in pig models that ultrasound-mediated microbubble destruction promotes BMSC transplantation for myocardial infarction therapy.

Extracorporeal cardiac shock wave therapy ameliorates myocardial fibrosis by decreasing the amount of fibrocytes after acute myocardial infarction in pigs

Extracorporeal shock wave (SW) therapy ameliorates cardiac remodeling after acute myocardial infarction (AMI). However, it remains to be examined whether and how SW therapy ameliorates myocardial fibrosis after AMI. Fibrocytes are associated with myocardial fibrosis. Thus, we examined whether SW therapy ameliorates myocardial fibrosis and whether fibrocytes are associated after AMI in pigs. AMI was created by coronary embolism. Twenty-five pigs were divided into three groups: AMI+SW group (AMI with SW therapy, n=15), AMI group (without SW therapy, n=5), and sham+SW group (SW therapy without AMI, n=5). The collagen area fraction was examined by Masson's trichrome staining. The presence of fibrocytes was identified by immunofluorescence and confocal microscopy. The location of CXCL12 was examined by immunohistochemistry. Compared with the AMI group, the AMI+SW group showed significantly ameliorated myocardial fibrosis in terms of collagen area fraction (27.21±8.13 vs. 10.13±4.96, P<0.05) and reduced fibrocytes (CD34/α-smooth muscle actin: 35.40±11.72 vs. 12.27±7.71, P<0.05; CXCR4/α-smooth muscle actin: 40.80±8.96 vs. 16.54±6.38, P<0.05). There were positive correlations between the collagen area fraction and the number of fibrocytes (r=0.936; P<0.05) and between the number of CXCR4 fibrocytes and the SDF-1/CXCL12 cells (r=0.802; P<0.05) in the three groups. The results show that SW therapy ameliorates myocardial fibrosis after AMI in pigs, which is associated with the decreased amount of fibrocytes.

Remodeling of small intramyocardial coronary arteries distal to total occlusions after myocardial infarction in pigs

The present study was designed to investigate whether microvascular remodeling could occur in hibernating myocardium and infarction regions distal to a total occluded coronary artery after acute myocardial infarction. Copper stents were implanted in the left descending coronary arteries of 64 pigs to induce anterior wall myocardial infarction. The pigs were assigned randomly to group A (n=8; killed at 1 week), group B (n=8; killed at 2 weeks), group C (n=16; killed at 4 weeks), group D (n=16; killed at 3 months), and group E (n=16; killed at 6 months). The control group included six pigs that were subjected to the same procedures but without implantation of copper stents. The wall area (WA) and lumen area (LA) of small intramyocardial coronary arteries (SIMCA) distal to occlusions were measured and the ratios of WA/LA and LA/total vessel area (%L) were calculated. The composition of the arterial wall was determined by Masson's trichrome stain, transmission electron microscope. A significant increase in WA/LA and decrease %L in SIMCA were observed in group B (P<0.05), group C (P<0.01), group D (P<0.01), and group E (P<0.01) compared with the control. There was increased area of collagen fiber in the thickened arterial wall in group C (P<0.05), group D (P<0.01), and group E (P<0.01) compared with the control group, group A, and group B. A significantly increased ratio of the synthetic phenotype vascular smooth muscle cells were found in group B (P<0.05), group C (P<0.01), group D (P<0.01), and group E (P<0.01) compared with the control group. Several weeks after occlusion of epicardial coronary, the SIMCAs distal to occlusion developed remodeling, with an increase in wall thickness and a decrease in lumen size. These structural changes may restrict blood flow to ischemic or hibernating myocardium after revascularization.

Acute effects of catheter-based renal sympathetic denervation on hemodynamics after acute myocardial infarction in pigs

Acute effects of catheter-based renal sympathetic denervation on hemodynamics after acute myocardial infarction in pigs

A Fast pH‐Switchable and Self‐Healing Supramolecular Hydrogel Carrier for Guided, Local Catheter Injection in the Infarcted Myocardium

Minimally invasive intervention strategies after myocardial infarction use state-of-the-art catheter systems that are able to combine mapping of the infarcted area with precise, local injection of drugs. To this end, catheter delivery of drugs that are not immediately pumped out of the heart is still challenging, and requires a carrier matrix that in the solution state can be injected through a long catheter, and instantaneously gelates at the site of injection. To address this unmet need, a pH-switchable supramolecular hydrogel is developed. The supramolecular hydrogel is switched into a liquid at pH > 8.5, with a viscosity low enough to enable passage through a 1-m long catheter while rapidly forming a hydrogel in contact with tissue. The hydrogel has self-healing properties taking care of adjustment to the injection site. Growth factors are delivered from the hydrogel thereby clearly showing a reduction of infarct scar in a pig myocardial infarction model.

Safety and Efficacy of an Injectable Extracellular Matrix Hydrogel for Treating Myocardial Infarction

New therapies are needed to prevent heart failure after myocardial infarction (MI). As experimental treatment strategies for MI approach translation, safety and efficacy must be established in relevant animal models that mimic the clinical situation. We have developed an injectable hydrogel derived from porcine myocardial extracellular matrix as a scaffold for cardiac repair after MI. We establish the safety and efficacy of this injectable biomaterial in large- and small-animal studies that simulate the clinical setting. Infarcted pigs were treated with percutaneous transendocardial injections of the myocardial matrix hydrogel 2 weeks after MI and evaluated after 3 months. Echocardiography indicated improvement in cardiac function, ventricular volumes, and global wall motion scores. Furthermore, a significantly larger zone of cardiac muscle was found at the endocardium in matrix-injected pigs compared to controls. In rats, we establish the safety of this biomaterial and explore the host response via direct injection into the left ventricular lumen and in an inflammation study, both of which support the biocompatibility of this material. Hemocompatibility studies with human blood indicate that exposure to the material at relevant concentrations does not affect clotting times or platelet activation. This work therefore provides a strong platform to move forward in clinical studies with this cardiac-specific biomaterial that can be delivered by catheter.

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Evaluation of Multimeric Tyrosine-O-Sulfate as a Cytoprotectant in an in vivo Model of Acute Myocardial Infarction in Pigs

Objectives: Intracoronary administration of glycosaminoglycan analogs, including the complement inhibitor dextran sulfate, attenuates myocardial ischemia/reperfusion injury (I/R injury). However, dextran sulfate has a distinct anticoagulatory effect, possibly limiting its use in specific situations in vivo. We therefore developed multimeric tyrosine sulfate (sTyr-PAA), a novel, minimally anticoagulatory, fully synthetic non-carbohydrate-containing polyacrylamide conjugate, for in vivo testing in an acute closed-chest porcine model of acute myocardial infarction. Methods: Following balloon occlusion of the left anterior descending artery just after the first diagonal branch (60-minute ischemia), sTyr-PAA (approx. 10 mg/kg bodyweight, fraction with strongest complement-inhibitory and minimal anticoagulatory properties, n = 11) or phosphate-buffered saline (controls, n = 9) was administered intracoronarily into ischemic myocardium prior to 120 min of reperfusion. Results: sTyr-PAA significantly reduced infarct size (from 61.0 ± 12.0% of the ischemic area at risk to 39.4 ± 17.0%), plasma creatine kinase, local complement deposition and tissue factor upregulation, without affecting systemic coagulation. Protection was associated with significantly reduced myocardial neutrophil extravasation and translated into a significant improvement of ejection fraction and left ventricular enddiastolic pressure. Conclusions: sTyr-PAA protected significantly against myocardial I/R injury without substantially affecting systemic coagulation. Local intravascular sTyr-PAA administration may prove advantageous in situations where bleeding complications are likely or are to be avoided at all costs.

Effect of extracorporeal cardiac shock wave therapy on MMP 1& TIMP1 after acute myocardial infarction in pigs

ObjectiveThis experiment aimed to observe the effect of CSWT on matrix metalloproteinase and relative inhibitive factors, and explore the potential biology mechanism that inhibit ventricular remodeling after acute myocardial infarction...

Microvolt T-wave alternans and beat-to-beat variability of repolarization during early postischemic remodeling in a pig heart

Repolarization variability is considered to predict sudden cardiac death. T-wave alternans (TWA) has been the subject of exhaustive research, whereas beat-to-beat variability of repolarization (BVR) is a new parameter that possibly predicts proarrhythmia. How these parameters interact has not been tested. The purpose of this study was to compare TWA and BVR as predictors of proarrhythmic substrate early after myocardial infarction (MI). In nine pigs, MI was induced by 1-hour occlusion of the left anterior descending coronary artery. Cardiac magnetic resonance imaging was performed at day 21. Six sham pigs served as control. Spectral TWA was tested during right atrial pacing before induction of MI and after 21 days. BVR was calculated from 60 consecutive QT intervals. Magnetic resonance imaging showed transmural MI. TWA was negative in all pigs at clinical threshold rate and equally present in MI versus sham pigs at higher rates (170 bpm: 55% vs 50% positive TWA). In MI pigs, BVR of QT intervals increased significantly during acute ischemia (2.44 ± 0.43 ms vs 3.55 ± 0.41 ms, P <.01) and even more on day 21 (5.80 ± 1.12 ms), but it differed significantly from sham (2.14 ± 0.54 ms, P <.01). A clinical ventricular tachycardia induction protocol was positive in 2 of 8 MI pigs and in none of 6 shams. In early remodeling after MI, BVR at intrinsic heart rate was a consistent phenomenon, whereas TWA during atrial pacing or baseline QT-interval changes were not. TWA and BVR could reflect different post-MI remodeling processes. BVR may be a new technique for predicting a potentially proarrhythmic substrate in the early postinfarction period.

ST-segment dynamics during reperfusion period and the size of myocardial injury in experimental myocardial infarction

Background Exacerbation of ST elevation associated with reperfusion has been reported in patients with myocardial infarction. However, the cause of the “reperfusion peak” and relation of its magnitude to the size of myocardial damage has not been explored. The aim of our study was to assess the correlation between the ST-dynamics during reperfusion, the myocardium at risk (MaR), and the infarct size (IS). Methods Infarction was induced in 15 pigs by a 40-minute-long balloon inflation in the left anterior descending coronary artery. Tetrofosmin Tc 99m was given intravenously after 20 minutes of occlusion, and ex vivo single photon emission computed tomography was performed to assess MaR. Maximal ST elevation in a single lead and maximal sum of ST deviations in 12 leads were measured before, during, and after occlusion from continuous 12-lead electrocardiographic monitoring. A gadolinium-based contrast agent was given intravenously 30 minutes before explantation of the heart. Final IS was estimated using ex vivo cardiac magnetic resonance imaging. Results All pigs developed an anteroseptal infarct with MaR = 42% ± 9% and IS = 26% ± 7% of left ventricle. In all pigs, reperfusion was accompanied by transitory exacerbation of ST elevation that measured 1300 ± 500 μV as maximum in a single lead compared with 570 ± 220 μV at the end of occlusion ( P < .001). The transitory exacerbation of ST elevation exceeded the maximal ST elevation during occlusion (920 ± 420 μV, P < .05). The ST elevation resolved by the end of the reperfusion period (90 ± 30 μV, P < .001). Exacerbation of ST elevation after reperfusion correlated with the final IS ( r = 0.64, P = .025 for maximal ST elevation in a single lead and r = 0.80, P = .002 for sum of ST deviations) but not with MaR ( r = 0.43, P = .17 for maximal ST elevation in a single lead and r = 0.49, P = .11 for sum of ST deviations). The maximal ST elevation in a single lead and the sum of ST deviations during occlusion did not correlate with either MaR or final IS. Conclusion In the experiment, exacerbation of ST elevation is common during restoration of blood flow in the occluded coronary artery. The magnitude of the exacerbation of ST elevation after reperfusion in experimentally induced myocardial infarction in pigs is associated with infarct size but not with MaR.

E0369 Extracorporeal cardiac shock wave therapy promotes angiogenesis after acute myocardial infarction in pigs evaluated by realtime myocardial contrast echocardiography

ObjectiveTo evaluate the effect of neovascularization of extracorporeal cardiac shock wave therapy in a porcine model in vivo.MethodsAcute myocardial infarction was created by balloon occlusion of left anterior descending coronary...

Intramyocardial Peptide Nanofiber Injection Improves Postinfarction Ventricular Remodeling and Efficacy of Bone Marrow Cell Therapy in Pigs

Growing evidence suggests that intramyocardial biomaterial injection improves cardiac functions after myocardial infarction (MI) in rodents. Cell therapy is another promising approach to treat MI, although poor retention of transplanted cells is a major challenge. In this study, we hypothesized that intramyocardial injection of self-assembling peptide nanofibers (NFs) thickens the infarcted myocardium and increases transplanted autologous bone marrow mononuclear cell (MNC) retention to attenuate cardiac remodeling and dysfunction in a pig MI model. A total of 40 mature minipigs were divided into 5 groups: sham, MI+normal saline, MI+NFs, MI+MNCs, and MI+MNCs/NFs. MI was induced by coronary occlusion followed by intramyocardial injection of 2 mL normal saline or 1% NFs with or without 1×10(8) isolated autologous MNCs. NF injection significantly improved diastolic function and reduced ventricular remodeling 28 days after treatment. Injection of MNCs alone ameliorated systolic function only, whereas injection of MNCs with NFs significantly improved both systolic and diastolic functions as indicated by +dP/dt and -dP/dt (1214.5±91.9 and -1109.7±91.2 mm Hg/s in MI+NS, 1693.7±84.7 and -1809.6±264.3 mm Hg/s in MI+MNCs/NFs, respectively), increased transplanted cell retention (29.3±4.5 cells/mm(2) in MI+MNCs and 229.4±41.4 cells/mm(2) in MI+MNCs/NFs) and promoted capillary density in the peri-infarct area. We demonstrated that NF injection alone prevents ventricular remodeling, whereas cell implantation with NFs improves cell retention and cardiac functions after MI in pigs. This unprecedented combined treatment in a large animal model has therapeutic effects, which can be translated to clinical applications in the foreseeable future.

Pulmonary Blood Volume Variation Decreases after Myocardial Infarction in Pigs: A Quantitative and Noninvasive MR Imaging Measure of Heart Failure

To prospectively evaluate the usefulness of magnetic resonance (MR) imaging for estimating pulmonary blood volume (PBV) and the variation in PBV throughout the cardiac cycle in experimental heart failure. The animal care committee approved this prospective study. Seven pigs were studied before and after myocardial infarction. PBV measurement was validated in a phantom and calculated as the product of cardiac output determined with velocity-encoded MR imaging and the pulmonary transit time for an intravenous bolus of contrast material to pass through the pulmonary circulation. The difference in arterial and venous pulmonary flow during the cardiac cycle was integrated for calculation of the PBV variation (expressed as percentage of stroke volume). Differences were evaluated with the Wilcoxon test. Calculated and direct phantom measurements of PBV differed by a mean of 4% +/- 3 (standard deviation) (R(2) = 0.97, P < .001). Infarction induced a decrease in left ventricular stroke volume (44 mL +/- 6 vs 27 mL +/- 7; P = .02), ejection fraction (55% +/- 5 vs 41% +/- 4; P = .02), and PBV variation (61% +/- 12 vs 43% +/- 15; P = .04) but not PBV (225 mL +/- 23 vs 211 mL +/- 42; P = .50). The mean pulmonary artery pressure increased after infarction (19 mm Hg +/- 6 vs 27 mm Hg +/- 4; P = .04). Following infarction, the PBV variation but not PBV decreased. PBV variation was the noninvasive measure exhibiting the greatest percentage of change following infarction. MR imaging can be used to assess the variation of the PBV during the cardiac cycle as a marker of heart failure.

Letter by Madias Regarding Article, “Peripheral Nociception Associated With Surgical Incision Elicits Remote Nonischemic Cardioprotection via Neurogenic Activation of Protein Kinase C Signaling”

HomeCirculationVol. 121, No. 16Letter by Madias Regarding Article, “Peripheral Nociception Associated With Surgical Incision Elicits Remote Nonischemic Cardioprotection via Neurogenic Activation of Protein Kinase C Signaling” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Madias Regarding Article, “Peripheral Nociception Associated With Surgical Incision Elicits Remote Nonischemic Cardioprotection via Neurogenic Activation of Protein Kinase C Signaling” John E. Madias, MD John E. MadiasJohn E. Madias Mount Sinai School of Medicine, New York University, New York, NY Search for more papers by this author Originally published27 Apr 2010https://doi.org/10.1161/CIR.0b013e3181ddf949Circulation. 2010;121:e388To the Editor:The elegant study of Jones et al1 on peripheral nociception-based remote nonischemic preconditioning, published in the September 15, 2009, issue of Circulation, constitutes an advancement in the field of noninvasive cardioprotection for ischemic/reperfusion injury. Not only were the authors able to establish that peripheral skin nociception, resulting from abdominal surgical incision in their murine model and via the axis of neurogenic signaling–bradykinin stimulation of bradykinin 2 receptors–KATP channels, leads to marked reduction in eventual infarct size, but by implementing topical capsaicin in parallel experiments, they also showed that its selective stimulation of skin C sensory fibers leads to equally marked cardioprotection, as could be ascertained from a comparison of Figures 2 and 7 in their article. The authors emphasize that this novel cardioprotective phenomenon is associated with an 80% decrease in infarct size, the largest such beneficial effect described in a murine model. They stress that capsaicin is already approved by the Food and Drug Administration, is used to treat pain, and is devoid of serious adverse effects. Thus, if shown to be effective in humans, this simple therapy has the potential to reduce myocardial injury in the setting of ischemia/reperfusion, thereby reducing the extent and consequences of acute myocardial infarction. However, in reviewing the parallel experiments that these authors have carried out, one cannot overlook that the intervention (either abdominal incision or topical capsaicin application) was implemented before the inception of the 45 minutes of myocardial ischemia and the subsequent reperfusion. Thus, this study design allows the “therapeutic” interventions to qualify as nociception-based remote nonischemic preconditioning, whereas the clinical reality permits only “ischemic and nonischemic postconditioning” implementation for patients who have experienced an acute myocardial infarction. Perhaps the authors could supplement their observations by performing a study in which topical application of capsaicin is implemented after the inception of the 45-minute period of ischemia and during reperfusion; such additional experiments will provide clinical insight into what effects “capsaicin nonischemic postconditioning” could be expected to have in patients with an acute myocardial infarction already in progress before and after reperfusion therapy, by either primary percutaneous coronary intervention or thrombolysis. Whether postconditioning is beneficial in the setting of acute myocardial infarction is still controversial on the basis of animal studies in which very brief periods of coronary ischemic postconditioning in the early phase of reperfusion did not alter the extent of acute myocardial infarction in the rabbit,2 whereas remote postconditioning did reduce the infarct size in the pig.3 The authors could help by contributing in this pivotal area.DisclosuresNone. References 1 Jones WK, Fan GC, Liao S, Zhang JM, Wang Y, Weintraub NL, Kranias EG, Schultz JE, Lorenz J, Ren X. Peripheral nociception associated with surgical incision elicits remote nonischemic cardioprotection via neurogenic activation of protein kinase C signaling. Circulation. 2009; 120 (suppl): S1–S9.LinkGoogle Scholar2 Hale SL, Mehra A, Leeka J, Kloner RA. Postconditioning fails to improve no reflow or alter infarct size in an open-chest rabbit model of myocardial ischemia-reperfusion. Am J Physiol Heart Circ Physiol. 2008; 294: H421–H425.CrossrefMedlineGoogle Scholar3 Andreka G, Vertesaljai M, Szantho G, Font G, Piroth Z, Fontos G, Juhasz ED, Szekely L, Szelid Z, Turner MS, Ashrafian H, Frenneaux MP, Andreka P. Remote ischaemic postconditioning protects the heart during acute myocardial infarction in pigs. Heart. 2007; 93: 749–752.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails April 27, 2010Vol 121, Issue 16 Advertisement Article InformationMetrics https://doi.org/10.1161/CIR.0b013e3181ddf949PMID: 20421525 Originally publishedApril 27, 2010 PDF download Advertisement SubjectsAcute Coronary SyndromesMyocardial Infarction

CD151 Gene Delivery after Myocardial Infarction Promotes Functional Neovascularization and Activates FAK Signaling

Our previous studies showed that tetraspanin CD151 promotes neovascularization in rat hindlimb and myocardial ischemia models. This study is to assess whether CD151 induces arteriogenesis and promotes functional neovascularization in a pig myocardial infarction model, and to determine the signaling pathways involved. CD151 cDNA and antiCD151 sequence were constructed into a recombinant adeno-associated virus (rAAV) vector. All 26 pigs used either were subjected to coronary artery ligation or did not undergo surgery. Eight wks after viral administration, the expression of CD151 protein was measured by Western blot. The densities of capillaries and arterioles were determined using immunohistochemistry. Regional myocardial perfusion and other myocardial functions were evaluated by (13)N-labeled NH(3) positron emission computed tomography ((13)N-NH(3) PET) and echocardiography. Western blot was performed for assessing the signaling mechanisms. Overexpression of CD151 markedly increased the densities of capillaries and arterioles, significantly enhanced the regional myocardial perfusion, reduced myocardial ischemia, and improved the myocardial contraction, wall motion, and wall thickness. Conversely, antiCD151 gene delivery reversed the above changes. In addition, CD151 activated focal adhesion kinase (FAK), extracellular signal-regulated kinase (ERK), c-Jun N-teminal kinase (JNK), phosphatidylinositol-3 kinase (PI3K), protein kinase B (Akt), and endothelial nitric-oxide synthase (eNOS), and increased nitric oxide (NO) level. These findings demonstrate a robust role of CD151 in inducing and/or upregulating neovascularization. CD151-dependent neovascularization correlates with the activations of FAK, mitogen activated protein kinases (MAPKs), and PI3K signaling, suggesting that CD151 may promote neovascularization via MAPKs and PI3K pathways.

Serial Assessment of Left Ventricular Remodeling and Function by Echo-Tissue Doppler Imaging After Myocardial Infarction in Streptozotocin-Induced Diabetic Swine

The aim of this study was to determine the value of Doppler tissue imaging (DTI) in detecting serial changes in left ventricular (LV) geometry and function after myocardial infarction (MI) in diabetic swine. Thirteen minipigs with streptozotocin-induced diabetes for 1 month and 13 controls were subjected to occlusion of the left anterior descending coronary artery. Echocardiography and DTI were performed before, 30 minutes, 90 minutes, and 4 weeks after left anterior descending coronary artery occlusion. At baseline, LV end-diastolic volume and mass were greater in pigs with diabetes. After MI, LV ejection fractions and systolic mitral annular velocities were decreased and LV chambers dilated in both groups, which were exacerbated in animals with diabetes. At 30 minutes, 90 minutes, and 4 weeks after MI, strain rates were significantly lower in both infarct and noninfarct areas in the diabetic group than in controls. DTI proved to be a useful tool in the serial assessment of subclinical LV dysfunction after MI in pigs with diabetes.