Acute Myocardial Infarction In Swine Research Articles

Abstract 4137267: A novel reproducible low-cost model of acute myocardial infarction in swine

Background: Traditional open- and closed-chest methods for inducing acute myocardial infarction (AMI) in pigs typically require extensive and expensive instrumentation, including ventilators and inhalation anesthesia. This study aims to evaluate a reproducible and low-cost model for AMI in pigs using lower hemisternotomy. Methods: Twenty Yorkshire swine (15-20 kg, 45-50 days of age) underwent permanent ligation of the roots of the first and second diagonal branches of the left anterior descending coronary artery. The procedure was performed under intramuscular anesthesia (1ml 0.5mg/kg Zoletil™ and 2ml 10mg/kg xylazine hydrochloride) with spontaneous respiration. Cardiac function was assessed via echocardiography and cardiac PET/MRI scans at 1 and 4 weeks post-MI. Heart tissue was collected for pathological analysis to evaluate the establishment of the AMI model. Results: All animals exhibited ECG changes, including premature ventricular complexes and ST-segment elevation immediately after ligation. No ventricular tachycardia and fibrillation was observed during the operation. No animals (0%) died during infarct creation. The "Skin-to-Skin" procedure time was 18±3.3 minutes. this procedure produced an infarction that occupies ~10% of the left ventricular mass accompanied with the decrease of LV heart function and LV anterior wall thickness 4 weeks post-MI. Conclusions: This novel low-cost technique provides reproducible acute coronary artery occlusion at a selected location with subsequent AMI. It avoids ventilation, inhalation anesthesia, major surgery and does not require expensive instrumentation for intracoronary intervention.

Human-umbilical cord matrix mesenchymal cells improved left ventricular contractility independently of infarct size in swine myocardial infarction with reperfusion.

Human umbilical cord matrix-mesenchymal stromal cells (hUCM-MSC) have demonstrated beneficial effects in experimental acute myocardial infarction (AMI). Reperfusion injury hampers myocardial recovery in a clinical setting and its management is an unmet need. We investigated the efficacy of intracoronary (IC) delivery of xenogeneic hUCM-MSC as reperfusion-adjuvant therapy in a translational model of AMI in swine. In a placebo-controlled trial, pot-belied pigs were randomly assigned to a sham-control group (vehicle-injection; n = 8), AMI + vehicle (n = 12) or AMI + IC-injection (n = 11) of 5 × 105 hUCM-MSC/Kg, within 30 min of reperfusion. AMI was created percutaneously by balloon occlusion of the mid-LAD. Left-ventricular function was blindly evaluated at 8-weeks by invasive pressure-volume loop analysis (primary endpoint). Mechanistic readouts included histology, strength-length relationship in skinned cardiomyocytes and gene expression analysis by RNA-sequencing. As compared to vehicle, hUCM-MSC enhanced systolic function as shown by higher ejection fraction (65 ± 6% vs. 43 ± 4%; p = 0.0048), cardiac index (4.1 ± 0.4 vs. 3.1 ± 0.2 L/min/m2; p = 0.0378), preload recruitable stroke work (75 ± 13 vs. 36 ± 4 mmHg; p = 0.0256) and end-systolic elastance (2.8 ± 0.7 vs. 2.1 ± 0.4 mmHg*m2/ml; p = 0.0663). Infarct size was non-significantly lower in cell-treated animals (13.7 ± 2.2% vs. 15.9 ± 2.7%; Δ = -2.2%; p = 0.23), as was interstitial fibrosis and cardiomyocyte hypertrophy in the remote myocardium. Sarcomere active tension improved, and genes related to extracellular matrix remodelling (including MMP9, TIMP1 and PAI1), collagen fibril organization and glycosaminoglycan biosynthesis were downregulated in animals treated with hUCM-MSC. Intracoronary transfer of xenogeneic hUCM-MSC shortly after reperfusion improved left-ventricular systolic function, which could not be explained by the observed extent of infarct size reduction alone. Combined contributions of favourable modification of myocardial interstitial fibrosis, matrix remodelling and enhanced cardiomyocyte contractility in the remote myocardium may provide mechanistic insight for the biological effect.

99mTc-3SPboroxime: A neutral 99mTc(III) radiotracer with high heart uptake and long myocardial retention

Background99mTc-3SPboroxime is a 99mTc(III) complex with high initial heart uptake comparable to that of 99mTc-Teboroxime, but with significantly longer myocardial retention in Sprague–Dawley rats. This study was performed to demonstrate its feasibility on myocardial perfusion imaging and myocardial blood flow quantification in swine models. MethodsDynamic single-photon emission computed tomography (SPECT) studies with 99mTc-3SPboroxime were performed in normal (with/without dipyridamole, n = 9) and acute myocardial infarction (AMI) swine (n = 3) in comparison with 99mTc-Teboroxime and 99mTc-Sestamibi. List-mode acquisitions were immediately started after injection and continued for 15 minutes. Regions of interest were drawn on heart (infarct and remote areas of AMI swine) and liver to generate time activity curves. Heart/liver and infarct/remote radioactivity ratios were calculated. One-tissue compartment model was implemented to obtain K1 and K2 values. ResultsThe initial heart uptake of 99mTc-3SPboroxime was close to that of 99mTc-Teboroxime, but higher than that of 99mTc-Sestamibi. 99mTc-3SPboroxime had a myocardial retention longer than that of 99mTc-Teboroxime. The heart/liver ratio of 99mTc-3SPboroxime was higher than that of 99mTc-Teboroxime at later stage (13-15 minutes post-injection). The K1 value of 99mTc-3SPboroxime was much higher than that of 99mTc-Sestamibi, and the K2 value was significantly lower than that of 99mTc-Teboroxime both at rest and dipyridamole stress (rest K1: 0.63 ± 0.11 vs 0.40 ± 0.04 mL·min−1·g−1, P = 0.027; stress K1: 0.89 ± 0.05 vs 0.54 ± 0.08 mL·min−1·g−1, P = 0.031; rest K2: 0.22 ± 0.04 vs 0.33 ± 0.11 mL·min−1·g−1, P = 0.003; stress K2: 0.31 ± 0.03 vs 0.60 ± 0.30 mL·min−1·g−1, P = 0.047). High quality SPECT images could be obtained in any of the 5 minutes windows over the first 15 minutes after injection of 99mTc-3SPboroxime in normal and AMI swine models. Apical and anterior perfusion defects were clearly visualized in AMI swine. Conclusion99mTc-3SPboroxime is a promising radiotracer for future clinical translation considering its heart uptake, heart/liver ratio and SPECT image quality, as well as the advantage over 99mTc-Sestamibi in the definition of stress flow.

Microencapsulated Insulin-Like Growth Factor-1 therapy improves cardiac function and reduces fibrosis in a porcine acute myocardial infarction model

Insulin-like growth factor-1 (IGF-1) has demonstrated beneficial effects after myocardial infarction (MI). Microencapsulation of IGF-1 could potentially improve results. We aimed to test the effect of an intracoronary (IC) infusion of microencapsulated IGF-1 in a swine acute MI model. For that purpose IC injection of a 10 ml solution of 5 × 106 IGF-1 loaded microspheres (MSPs) (n = 8, IGF-1 MSPs), 5 × 106 unloaded MSPs (n = 9; MSPs) or saline (n = 7; CON) was performed 48 hours post-MI. Left ventricular ejection fraction (LVEF), indexed ventricular volumes and infarct size (IS) were determined by cardiac magnetic resonance at pre-injection and 10 weeks. Animals were euthanized at 10 weeks, and myocardial fibrosis and vascular density were analysed. End-study LVEF was significantly greater in IGF-1 MSPs compared to MSPs and CON, while ventricular volumes exhibited no significant differences between groups. IS decreased over time in all groups. Collagen volume fraction on the infarct area was significantly reduced in IGF-1 MSPs compared to CON and MSPs. Vascular density analysis of infarct and border zones showed no significant differences between groups. In conclusion, the IC injection of 5 × 106 IGF-1 loaded MSPs in a porcine acute MI model successfully improves cardiac function and limits myocardial fibrosis, which could be clinically relevant.

Is Cyclosporine Immunosuppression Required to Effect Improved Myocardial Function Following Global Intracoronary Cardiosphere‐Derived Cells After Acute Myocardial Infarction in Swine?

ObjectiveWe previously demonstrated that allogeneic cardiosphere‐derived cells (CDCs) improve myocardial function after infarction via paracrine effects when animals are pretreated with oral cyclosporine (CsA) prior to injury. The present study directly compared the efficacy of CDCs with and without CsA administered at the time of reperfusion after acute myocardial infarction (AMI) in a 3‐armed, blinded pre‐clinical study.MethodsStudies were completed in closed‐chest, propofol‐anesthetized swine (n=29). After assessing baseline hemodynamics, the LAD artery was occluded with a balloon catheter for 90 minutes and contrast‐enhanced cardiac CT performed to assess the area‐at‐risk (AAR). Thirty minutes after reperfusion, animals were randomized to receive a global intracoronary infusion of saline, CDCs (20×106 cells), or CDCs with CsA (2.5 mg/kg, iv; 200 mg, po qd). LV function and TTC infarct size (IS) were assessed 1 month later.ResultsBaseline hemodynamics and LV function were similar between groups. There was no difference between the CT AAR (% of LV mass; Saline: 22.2±1.0%, CDC: 23.7±0.7%, CDC+CsA: 24.7±1.4%, p=0.26). Infarct size was not different between groups (% of LV mass; Saline: 6.7±0.7%, CDC: 6.7±0.3%, CDC+CsA: 6.9±0.6%, p=0.95), or when normalized to risk area (% of AAR; Saline: 46.2±4.0%, CDC: 46.4±2.1%, CDC+CsA: 49.2±3.1%, p=0.79). There was no difference in CT ejection fraction (Saline: 49±2% vs. CDC: 46±2% vs. CDC+CsA: 47±2%, p=0.72). Wall thickening by echocardiography in the LAD‐perfused (Saline: 26±8% vs. CDC: 18±4% vs. CDC+CsA: 18±5%, p=0.56) and the remote, non‐infarcted (Saline: 100±7% vs. CDC: 111±10% vs. CDC+CsA: 119±11%, p=0.40) areas of the LV were also similar between groups.ConclusionGlobal infusion of allogeneic CDCs in the absence of CsA immunosuppression does not reduce chronic myocardial infarct size nor improve global or regional measures of LV function. Surprisingly, CDC therapy with IV CsA administered at the time of reperfusion does not appear to elicit previously demonstrated reparative effects. These data indicate that oral CsA pretreatment may be required to effect improved LV function with global intracoronary CDC therapy.Support or Funding InformationSupported by the National Heart Lung and Blood Institute (HL‐061610), the American Heart Association (17SDG33660200), the National Center for Advancing Translational Sciences (UL1TR001412), the Department of Veterans Affairs (1IO1BX002659), the New York State Department of Health (NYSTEM CO24351), and the Albert and Elizabeth Rekate Fund in Cardiovascular Medicine.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Route of Delivery Modulates the Efficacy of Mesenchymal Stem Cell Therapy for Myocardial Infarction: A Meta-Analysis of Preclinical Studies and Clinical Trials.

Accumulating data support a therapeutic role for mesenchymal stem cell (MSC) therapy; however, there is no consensus on the optimal route of delivery. We tested the hypothesis that the route of MSC delivery influences the reduction in infarct size and improvement in left ventricular ejection fraction (LVEF). We performed a meta-analysis investigating the effect of MSC therapy in acute myocardial infarction (AMI) and chronic ischemic cardiomyopathy preclinical studies (58 studies; n=1165 mouse, rat, swine) which revealed a reduction in infarct size and improvement of LVEF in all animal models. Route of delivery was analyzed in AMI swine studies and clinical trials (6 clinical trials; n=334 patients). In AMI swine studies, transendocardial stem cell injection reduced infarct size (n=49, 9.4% reduction; 95% confidence interval, -15.9 to -3.0), whereas direct intramyocardial injection, intravenous infusion, and intracoronary infusion indicated no improvement. Similarly, transendocardial stem cell injection improved LVEF (n=65, 9.1% increase; 95% confidence interval, 3.7 to 14.5), as did direct intramyocardial injection and intravenous infusion, whereas intracoronary infusion demonstrated no improvement. In humans, changes of LVEF paralleled these results, with transendocardial stem cell injection improving LVEF (n=46, 7.0% increase; 95% confidence interval, 2.7 to 11.3), as did intravenous infusion, but again intracoronary infusion demonstrating no improvement. MSC therapy improves cardiac function in animal models of both AMI and chronic ischemic cardiomyopathy. The route of delivery seems to play a role in modulating the efficacy of MSC therapy in AMI swine studies and clinical trials, suggesting the superiority of transendocardial stem cell injection because of its reduction in infarct size and improvement of LVEF, which has important implications for the design of future studies.

Magnetic resonance hypointensive signal primarily originates from extracellular iron particles in the long-term tracking of mesenchymal stem cells transplanted in the infarcted myocardium

PurposeThe long-lasting hypointensities in cardiac magnetic resonance (CMR) were believed to originate from superparamagnetic iron oxide (SPIO)-engulfed macrophages during long-term stem cell tracking. However, the iron clearance capacity of the ischemic heart was limited. Therefore, we speculated that the extracellular SPIO particles may also be involved in the generation of false-positive signals.Methods and resultsMale swine mesenchymal stem cells (MSCs) were incubated with SPIO for 24 hours, and SPIO labeling had no significant effects on either cell viability or differentiation. In vitro studies showed that magnetic resonance failed to distinguish SPIO from living SPIO-MSCs or dead SPIO-MSCs. Two hours after the establishment of the female swine acute myocardial infarction model, 2×107 male SPIO-labeled MSCs (n=5) or unlabeled MSCs (n=5) were transextracardially injected into the infarcted myocardium at ten distinct sites. In vivo CMR with T2 star weighted imaging-flash-2D sequence revealed a signal void corresponding to the initial SPIO-MSC injection sites. At 6 months after transplantation, CMR identified 32 (64%) of the 50 injection sites, where massive Prussian blue-positive iron deposits were detected by pathological examination. However, iron particles were predominantly distributed in the extracellular space, and a minority was distributed within CD68-positive macrophages and other CD68-negative cells. No sex-determining region Y DNA of donor MSCs was detected.ConclusionCMR hypointensive signal is primarily caused by extracellular iron particles in the long-term tracking of transplanted MSCs after myocardial infarction. Consideration should be given to both the false-positive signal and the potential cardiac toxicity of long-standing iron deposits in the heart.

The Ventricular Fibrillation Waveform Approach to Direct Postshock Chest Compressions in a Swine Model of VF Arrest

BackgroundIn retrospective swine and human investigations of ventricular fibrillation (VF) cardiac arrest, the amplitude-spectral area (AMSA), determined from the VF waveform, can predict defibrillation and a return of spontaneous circulation (ROSC). ObjectivesWe hypothesized that an algorithm using AMSA in real time to direct postshock chest compression (CC) duration would shorten the time to ROSC and improve neurological outcome in a swine model of VF cardiac arrest with acute myocardial infarction (AMI) or nonischemic myocardium. MethodsAMI was induced by occlusion of the left anterior descending artery. VF was untreated for 10 min. Animals were randomized to either traditional resuscitation with 2 min of CC after each shock or to an AMSA-guided algorithm where postshock CCs were shortened to 1 min if the preshock AMSA exceeded 20 mV-Hz. ResultsA total of 48 animals were studied, 12 in each group (AMI vs. normal, and traditional vs. AMSA-guided). There was a nonsignificant shorter time to ROSC with an AMSA-guided approach in AMI swine (17.2 ± 3.4 vs. 18.5 ± 4.7 min, p = NS), and in normal swine (13.5 ± 1.1 vs. 14.4 ± 1.2, p = NS). Neurological outcome was similar between traditional and AMSA-guided animals. AMSA predicted ROSC (p < 0.001), and a threshold of 20 mV-Hz gave a sensitivity of 89%, with specificity of 29%. ConclusionAlthough AMSA predicts ROSC in a swine model of VF arrest in both AMI and normal swine, a waveform-guided approach that uses AMSA to direct postshock CC duration does not significantly shorten the time to ROSC or alter neurological outcome.

ENOS Overexpressing Bone Marrow Cells are Safe and Effective in a Porcine Model of Myocardial Regeneration Following Acute Myocardial Infarction

Cell therapy has been shown to be effective in improving LV function postmyocardial infarction (MI). We hypothesized that eNOS-transfected bone marrow cells (BMCs) are safe in a swine model of myocardial infarction (MI). We also hypothesized that endothelial nitric oxide synthase (eNOS) transfection would enhance cell function, as assessed by myocardial functional recovery post-MI. Fifteen female Yorkshire pigs underwent bone marrow aspiration and creation of MI. Bone marrow cells were cultured for 7days, and each pig received either autologous BMCs transiently transfected with eNOS plasmid (eNOS-BMC, n=5), nontransfected BMCs (nt-BMC, n=4), or phosphate-buffered saline (PBS) control (n=6). Cardiac MRI was performed at baseline (1week post-MI) and 6weeks post-MI. There was no difference in safety outcomes between groups. Absolute left ventricular ejection fraction (LVEF) at 6weeks showed a trend toward improvement in both cell therapy groups compared with baseline but worsened in the PBS control group. The absolute improvement in LVEF was significantly greater in both cell therapy groups compared with PBS control. Infarct mass was significantly lower in the eNOS-BMC group between baseline and 6weeks, but the absolute change in infarct mass was not different between groups. Finally, there was a trend toward reduced LV mass in the eNOS-BMC group. Bone marrow cell delivery, with and without eNOS overexpression, is safe and leads to improvement in LVEF when administered in the coronary circulation 7days following acute MI in swine. Transfection of healthy BMCs with eNOS resulted in some improvement in left ventricular remodeling. Further study is warranted in a preclinical model that approximates the impact of cardiovascular risk factors on BMC function.

A New Drug Delivery System for Intravenous Coronary Thrombolysis With Thrombus Targeting and Stealth Activity Recoverable by Ultrasound

The purpose of this study was to develop a new intelligent drug delivery system for intracoronary thrombolysis with a strong thrombolytic effect without increasing bleeding risk. Rapid recanalization of an occluded coronary artery is essential for better outcomes in acute myocardial infarction. Catheter-based recanalization is widely accepted, but it takes time to transport patients. Although the current fibrinolytic therapy can be started quickly, it cannot achieve a high reperfusion rate. Recently, we generated nanoparticles comprising tissue-type plasminogen activator (tPA), basic gelatin, and zinc ions, which suppress tPA activity by 50% with 100% recovery by ultrasound (US) in vitro. The thrombus-targeting property of nanoparticles was examined by an in vitro binding assay with von Wilbrand factor and with a mouse arterial thrombosis model in vivo. The thrombolytic efficacy of nanoparticles was evaluated with a swine acute myocardial infarction model. Nanoparticles bound to von Wilbrand factor in vitro and preferentially accumulated at the site of thrombus in a mouse model. In a swine acute myocardial infarction model, plasma tPA activity after intravenous injection of nanoparticles was approximately 25% of tPA alone and was recovered completely by transthoracic US (1.0 MHz, 1.0 W/cm(2)). During US application, plasma tPA activity near the affected coronary artery was recovered and was higher than that near the femoral artery. Although treatment with tPA alone (55,000 IU/kg) recanalized the occluded coronary artery in only 1 of 10 swine, nanoparticles containing the same dose of tPA with US achieved recanalization in 9 of 10 swine within 30 min. We developed an intelligent drug delivery system with promising potential for better intravenous coronary thrombolysis.

Analysis of molecular changes after autologous cell therapy in swine myocardial infarction tissue can reveal novel targets for future therapy

Although several studies have demonstrated a functional recovery of infarcted myocardial tissue after cell therapy, little is known about the molecular mechanisms behind it. The aim of this study was to characterize the effect of cell therapy at the molecular level to screen for novel target candidates for future therapy of infarcted myocardial tissue. We used a swine acute myocardial infarction model evoked by transient occlusion of the circumflex coronary artery. Autologous bone marrow-derived mononuclear cells (BMMCs) or saline were injected intramyocardially or into the circumflex coronary artery. Samples for protein and RNA analysis were collected from the infarction area and healthy myocardium after a 3 week recovery period and analysed by two-dimensional gel electrophoresis (2DE) and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Proteomic screening detected 13 protein spots which were altered after infarction but had been restored by BMMC treatment. The identification of seven proteins by mass spectrometry revealed that five proteins with decreased expression after infarction corresponded to mitochondrial proteins involved in energy metabolism. Their restored levels after BMMC treatment indicate their involvement in the recovery of heart function. In contrast, the elevated levels of α-crystallin B chain and cathepsin D after infarction suggest an involvement in the pathological mechanisms causing a decreased heart function. This study reveals that cell therapy with BMMCs after myocardial infarction causes restoration of several altered protein levels after 3 weeks and identifies potential marker proteins involved in the pathology of infarction.

Transplantation With Autologous Mesenchymal Stem Cells After Acute Myocardial Infarction Evaluated by Magnetic Resonance Imaging

The purpose of this study was to track and investigate the effects of autologous bone marrow-derived mesenchymal stem cells (MSCs) transplantation after acute myocardial infarction in swine assessed by magnetic resonance imaging (MRI). Twenty-four Chinese mini-pigs (27±3 kg) were divided into 4 groups, including control groups (groups 1 and 3) and MSCs transplantation groups (group 2, super paramagnetic iron oxide labeled and group 4, 4',6-diamidino-2-phenylindole labeled). Super paramagnetic iron oxide-labeled and 4',6-diamidino-2-phenylindole-labeled MSCs (3.0×10⁶ cells/mL) with a volume of 10 mL were injected into the left anterior descending artery by a catheter at 1 week after acute myocardial infarction, respectively. Cell distribution, cardiac functions, and scar tissue were quantitatively assessed by MRI. The reduction of the T2* value in the myocardium, spleen, and liver in group 2 was significantly greater than that in group 1. MRI showed that function and scar size at baseline and 3 days after cell infusion were not significantly different between groups 1 and 2. Six weeks later left ventricular ejection fraction (P<0.0001), end-systolic volume (P<0.05), the number of dyskinetic segments (P<0.0001), left ventricular weight index (P<0.0001), and the infarcted size (P<0.0001) in group 4 were all improved comparing with those in group 3. The majority of MSCs entrapped by the extracardial organs were mainly in the spleen. Catheter-based delivery of autologous bone marrow-derived MSCs into infarcted myocardium is feasible and effective.

Effect of transplantation with mesenchymal stem cells on acute myocardial infarction in swine

ObjectiveTo investigate the effects of treatment with autologous MSCs by transplantation on AMI in swine.MethodMSCs were injected by OTW balloon in the experimental group (n=10), while normal saline was injected...

Utility of the Ventricular Fibrillation Waveform to Predict a Return of Spontaneous Circulation and Distinguish Acute From Post Myocardial Infarction or Normal Swine in Ventricular Fibrillation Cardiac Arrest

In cardiac arrest, the ventricular fibrillation (VF) waveform, particularly amplitude spectral area (AMSA) and slope, predicts the return of spontaneous circulation (ROSC), but it is unknown whether the predictive utility differs in an acute myocardial infarction (MI), prior MI, or normal myocardium and if the waveform can distinguish the underlying myocardial state. We hypothesized that in a swine model of VF cardiac arrest, AMSA and slope predict ROSC after a shock independent of substrate and distinguish an acute from nonacute MI state. MI was induced by occlusion of the left anterior descending artery. Post MI swine recovered for a 2-week period before induction of VF. VF was untreated for 8 minutes in 10 acute MI, 10 post MI, and 10 control swine. AMSA and slope predicted ROSC after a shock independent of myocardial state. For AMSA >31 mV-Hz, the odds ratio was 62 (P≤0.001) compared with AMSA <19 mV-Hz. For slope >3.1 mV/s, odds ratio was 52 (P≤0.001) compared with slope <1.8 mV/s. With chest compressions, AMSA and slope were significantly lower for acute MI swine compared with control swine, whereas in post MI swine the waveform characteristics were similar to control swine. In particular, for an AMSA >33.5 mV-Hz, the sensitivity to identify an acute from nonacute (control or post MI) state was 83%. In a swine model of VF cardiac arrest, AMSA and slope predict ROSC independent of myocardial substrate. Furthermore, with chest compressions, the VF waveform evolves differently and may offer a means to distinguish an acute MI.

Predictors of resuscitation in a swine model of ischemic and nonischemic ventricular fibrillation cardiac arrest: Superiority of amplitude spectral area and slope to predict a return of spontaneous circulation when resuscitation efforts are prolonged*

We have demonstrated that a return of spontaneous circulation in the first 3 mins of resuscitation in swine is predicted by ventricular fibrillation waveform (amplitude spectral area or slope) when untreated ventricular fibrillation duration or presence of acute myocardial infarction is unknown. We hypothesized that in prolonged resuscitation efforts that return of spontaneous circulation immediately after a second or later shock with postshock chest compression is independently predicted by end-tidal CO2, coronary perfusion pressure, and ventricular fibrillation waveform measured before that shock in a swine model of ischemic and nonischemic ventricular fibrillation arrest. Animal intervention study with comparison to a control group. University animal laboratory. Twenty swine. Myocardial infarction was induced by steel plug occlusion of the left anterior descending coronary artery. Ventricular fibrillation was untreated for 8 mins in normal swine (n=10) and acute myocardial infarction swine (n=10). End-tidal CO2, coronary perfusion pressure, and ventricular fibrillation waveform characteristics of amplitude spectral area and slope were analyzed before second or later shocks. For an amplitude spectral area>35 mV-Hz, the odds ratio for achieving return of spontaneous circulation after that shock was 72 (95% confidence interval, 3.8-1300; p=.004) compared with an amplitude spectral area<28 mV-Hz and with an area under the receiver operator characteristic curve of 0.86. For slope>3.6 mV/s, the odds ratio for achieving return of spontaneous circulation was 36 (95% confidence interval, 2.7-480; p=.007) compared with slope<2.72 mV/s with an area under the curve of 0.86. End-tidal CO2 and coronary perfusion pressure were not predictive of return of spontaneous circulation after a shock, although coronary perfusion pressure was significantly related to both amplitude spectral area (p<.001) and slope (p<.001). : In prolonged untreated ventricular fibrillation arrest, the waveform characteristics of amplitude spectral area and slope predict the attainment of return of spontaneous circulation with a second or later shock. This has implications for the ideal means to customize the timing of shocks and chest compressions when return of spontaneous circulation is not promptly obtained.

Predictors of resuscitation outcome in a swine model of VF cardiac arrest: A comparison of VF duration, presence of acute myocardial infarction and VF waveform

Introduction Factors that affect resuscitation to a perfusing rhythm (ROSC) following ventricular fibrillation (VF) include untreated VF duration, acute myocardial infarction (AMI), and possibly factors reflected in the VF waveform. We hypothesized that resuscitation of VF to ROSC within 3 min is predicted by the VF waveform, independent of untreated VF duration or presence of acute MI. Methods AMI was induced by the occlusion of the left anterior descending coronary artery. VF was induced in normal ( N = 30) and AMI swine ( N = 30). Animals were resuscitated after untreated VF of brief (2 min) or prolonged (8 min) duration. VF waveform was analyzed before the first shock to compute the amplitude-spectral area (AMSA) and slope. Results Unadjusted predictors of ROSC within 3 min included untreated VF duration (8 min vs 2 min; OR 0.11, 95%CI 0.02–0.54), AMI (AMI vs normal; OR 0.11, 95%CI 0.02–0.54), AMSA (highest to lowest tertile; OR 15.5, 95%CI 1.7–140), and slope (highest to lowest tertile; OR 12.7, 95%CI 1.4–114). On multivariate regression, untreated VF duration ( P = 0.011) and AMI ( P = 0.003) predicted ROSC within 3 min. Among secondary outcome variables, favorable neurological status at 24 h was only predicted by VF duration (OR 0.22, 95% CI 0.05–0.92). Conclusions In this swine model of VF, untreated VF duration and AMI were independent predictors of ROSC following VF cardiac arrest. AMSA and slope predicted ROSC when VF duration or the presence of AMI were unknown. Importantly, the initial treatment of choice for short duration VF is defibrillation regardless of VF waveform.

Effects of salvianolate on cardiomyocytic apoptosis and heart function in a swine model of acute myocardial infarction

To observe the effects of salvianolate on cardiomyocytes apoptosis and heart function in a swine model of acute myocardial infarction (AMI). A total of 21 young swine were randomly divided into untreated group, low-dose salvianolate (LS) group and high-dose salvianolate (HS) group (7 in each group). AMI was induced by ligaturing left anterior descending coronary artery. After the operation, 400 or 200 mg salvianolate dissolved in 250 mL 5% glucose saline was administered by intravenous drip to swine in the HS group and the LS group respectively for 7 days. The swine in the untreated group were administered with 250 mL 5% glucose saline. The left ventricular ejection fraction (LVEF) and myocardial perfusion were measured by gated myocardial perfusion imaging at the end of the 4th week after operation. And myocardial apoptosis was detected by TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. Apoptosis index was calculated under an optical microscope. Myocardial apoptotic index in the edge of myocardial infarction was decreased in the HS group and the LS group, which in the HS group was lower than that in the untreated group (P<0.05). Radioactive defect regions were found by gated myocardial perfusion imaging in all the three groups, but those in the HS group and the LS group were less than those in the untreated group (P<0.05). And the levels of myocardial perfusion and LVEF in the HS group were significantly higher than those in the untreated group (P<0.05). Salvianolate administered by intravenous drip can inhibit the cardiomyocytes apoptosis and improve the function of heart after AMI in swine.

Coronary occlusion by balloon to instruct swine acute myocardial infarction and following ventricualr remodeling model

Objective To investigate the effects of established swine acute myocardial infarction and following ventricular remodeling model by occluding Coronary with balloon. Methods Ten healthy Domestic swine are enrolled. Each swine's left anterior descending coronary artery was occluded for three hours by dilated balloon, and then reperfusion was performed. During the whole course of operation, the electro-cardiogram was monitored. B-ultrasound and single -photon emission computed tomography examination (SPECT) were performed to detect left ventricular end diastolic dimension, left ventricular tip wall thickness, left ventricular end diastolic volume and left ventricula ejection fraction before operation and one week, three month, six month after acute myocardial infarction. Results Five swine died during the period of opera-tion for lack of experience, the remains survived. Electrocardiogram revealed significant ST-elevation and Q-wave formation. B-untrasound and SPECT witnessed deteriorating left ventricular end diastolic dimension expansion, left ventricular tip wall thickness thinning, left ventricular end diastolic volume expansion and left ventricular ejection fraction depression. Conclusions Coronary artery occlusion by balloon can successfully establish acute myocardial infarction and following left ventricular remodeling models. Key words: Angioplasty, transluminal, pereutaneous coronary ; Disease models, animal ; Myocardial infarction ; Swine

Hands-Only (Compression-Only) Cardiopulmonary Resuscitation: A Call to Action for Bystander Response to Adults Who Experience Out-of-Hospital Sudden Cardiac Arrest

Hands-Only (Compression-Only) Cardiopulmonary Resuscitation: A Call to Action for Bystander Response to Adults Who Experience Out-of-Hospital Sudden Cardiac Arrest

Acute Myocardial Infarction in Swine Rapidly and Selectively Releases Highly Proliferative Endothelial Colony Forming Cells (ECFCs) into Circulation

We have recently identified endothelial colony forming cells (ECFCs) in human blood and blood vessels, and ECFC are elevated in patients with coronary artery disease. Because pigs are a favored model for studying myocardial ischemia, we questioned whether ECFCs also exist in swine and whether myocardial ischemia would alter the number of ECFC in circulation. ECFCs were present in circulating blood and aortic endothelium of healthy pigs. In pigs with an acute myocardial infarction (AMI) (n = 9), the number of circulating ECFC was markedly increased compared to sham control pigs (15 +/- 6 vs. 1 +/- 1 colonies/100 cc blood, p < 0.05). Moreover, the percentage of circulating high proliferative potential ECFCs (HPP-ECFCs) was significantly increased following AMI induction compared to sham control (38.4 +/- 5.8% vs. 0.4 +/- 0.4%, p < 0.05) and to baseline (38.4 +/- 5.8% vs. 2.4 +/- 2.4%, p < 0.05) blood samples. This is the first study to report that ECFCs are present in blood and aorta in healthy pigs and that the number and distribution of circulating ECFCs is altered following AMI. Because circulating ECFC are also altered in human subjects with severe coronary artery disease, the pig model of AMI may be an excellent preclinical model to test the role of ECFC in the pathophysiology of AMI.