Acute Myocardial Infarction In Swine Research Articles

Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties

Direct intramyocardial injection of mesenchymal stem cells (MSCs) improves left ventricular ejection fraction (LVEF) and may increase ventricular arrhythmia in hearts with myocardial infarction (MI). We hypothesized that intravenous MSCs given early after acute MI would engraft in injured myocardium, improve LV function, and result in pro-arrhythmic electrical remodeling. We created an apical infarction in swine by balloon occlusion/reperfusion, administered diI-labeled allogeneic bone marrow derived MSCs intravenously 30 min post-reperfusion and measured LVEF and wall thickness at baseline, 1 month, and 3 months. Epicardial effective refractory periods (ERPs) were determined before sacrifice. At 3 months, treated pigs [ n = 7] had significantly higher LVEF than controls [ n = 8] (49 ± 2% vs. 44 ± 3%, P = 0.015)and significantly less wall thickening of non-infarcted myocardium. ERPs were significantly shorter than controls at all pacing cycle lengths ( P ≤ 0.002), suggesting a pro-arrhythmic potential. DiI was found in the lungs, in infarct, and peri-infarct myocardium. Conclusion: IV infusion of MSCs soon after acute MI in swine improves LVEF and limits wall thickening in the remote non-infarcted myocardium, consistent with a beneficial effect on post-MI ventricular remodeling. Since there is no need for immune suppression or clinical expertise, IV infusion of MSCs may expand the potential clinical application of stem cell therapy.

Effects of G-CSF on cardiac remodeling after acute myocardial infarction in swine

We examined whether granulocyte colony-stimulating factor (G-CSF) prevents cardiac dysfunction and remodeling after myocardial infarction (MI) in large animals. MI was produced by ligation of left anterior descending coronary artery in swine. G-CSF (10 μg/kg/day, once a day) was injected subcutaneously from 24 h after ligation for 7 days. Echocardiographic examination revealed that the G-CSF treatment induced improvement of cardiac function and attenuation of cardiac remodeling at 4 weeks after MI. In the ischemic region, the number of apoptotic endothelial cells was smaller and the number of vessels was larger in the G-CSF treatment group than in control group. Moreover, vascular endothelial growth factor was more abundantly expressed and Akt was more strongly activated in the ischemic region of the G-CSF treatment group than of control group. These findings suggest that G-CSF prevents cardiac dysfunction and remodeling after MI in large animals.

From Vivendi to Veolia environnement

In 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).We 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.AMI 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.A 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%.Although 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.

Assisted ventilation during 'bystander' CPR in a swine acute myocardial infarction model does not improve outcome.

Mouth-to-mouth rescue breathing is a barrier to the performance of bystander cardiopulmonary resuscitation (CPR). We evaluated the need for assisted ventilation during simulated single-rescuer bystander CPR in a swine myocardial infarction model of prehospital cardiac arrest. Steel cylinders were placed in the mid left anterior descending coronary arteries of 43 swine. Two minutes after ventricular fibrillation, animals were randomly assigned to 10 minutes of hand-bag-valve ventilation with 17% oxygen and 4% carbon dioxide plus chest compressions (CC+V), chest compressions only (CC), or no CPR (control group). Standard advanced life support was then provided. Animals successfully resuscitated received 1 hour of intensive care support and were observed for 24 hours. Five of 14 CC animals, 3 of 15 CC+V animals, and 1 of 14 controls survived for 24 hours (CC versus controls, P=.07). Myocardial oxygen delivery and consumption were greater among surviving animals than nonsurvivors but did not differ between CC and CC+V animals. In this acute myocardial infarction model of prehospital single-rescuer bystander CPR, assisted ventilation did not improve outcome.

Effects of intracoronary diltiazem on certain hemostatic parameters during acute myocardial infarction in swine

Controversy currently exists regarding the use of diltiazem in the treatment of acute myocardial infarction (AMI), due to conflicting results from clinical trials and animal studies. The purpose of this project was to evaluate the changes in the hemostatic profile during AMI following low dose intracoronary diltiazem infusion. Fourteen Yorkshire swine underwent thoracotomy and 50 min LAD occlusion, followed by 3 h of reperfusion. The first group (n=8) received 2.5 mg of diltiazem intracoronary at a rate of 5.6 μgkgmin−1 at the onset of reperfusion. The second group (n=6) received 0.9% saline intracoronary at the onset of reperfusion and served as the control. The dynamics of plasma antithrombin-III (AT-III), Protein C, total Protein S, fibronectin, endothelin-1 (ET-1), and the stable metabolites of thromboxane (TxB2) and prostacyclin (6-keto- PGF1a) were determined at baseline, then twice during occlusion and finally three times during reperfusion. Diltiazem infusion resulted in diminished ET-1 (34.5%), fibronectin (23.2%), and TxB2 (35.6%); and elevated Protein C (29.3%) when compared with controls. We conclude that intracoronary diltiazem favorably influences hemostasis during AMI in swine. The cardioprotective effects of diltiazem during AMI may be related to the improved hemostatic profile and the reduced incidence of thrombotic complications in such patients.

Intracoronary magnesium and diltiazem affect to a similar extent certain hemostatic factors during acute myocardial infarction in swine.

The use of calcium antagonists and magnesium (Mg) in the treatment of acute myocardial infarction is controversial. We compared changes in hemostasis during acute myocardial infarction after either low-dose intracoronary Mg or diltiazem infusion in 20 Yorkshire swine undergoing thoracotomy and coronary artery occlusion for 50 min, followed by 3 h of reperfusion. The first group received MgSO4 (250 mg), delivered at the onset of reperfusion, the second group received diltiazem (2.5 mg) at the beginning of reperfusion. Six controls received saline. Plasma antithrombin III, protein C, total protein S, fibronectin, endothelin 1, and metabolites of thromboxane and prostacyclin were measured at baseline, twice during occlusion, and three times during reperfusion. Compared to controls, Mg and diltiazem infusion diminished endothelin 1 (32.9 vs. 34.5%) and fibronectin. (21.7 vs. 23.2%), but increased protein C (31.9 vs. 29.3%). Intracoronary Mg, like diltiazem, improved hemostasis in swine.