Abstract 11: Beneficial Effects of Hcn Inhibitor on Post-Resuscitation Myocardial Dysfunction in a Porcine Model of Cardiac Arrest

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Min Yang ◽  
Tianfeng Hua ◽  
Limin Chen ◽  
Yangyang Zou
Keyword(s):  
Heart Rate ◽  
Cardiac Arrest ◽  
Placebo Group ◽  
Porcine Model ◽  
Troponin I ◽  
Myocardial Dysfunction ◽  
Velocity Ratio ◽  
Left Ventricular ◽  
Control Group ◽  
Histopathological Analysis

Introduction: Previous studies have demonstrated that β-adrenergic blocking agents improved neurologic function and the rate of survival. However, its negative inotrope effects that increased the severity of PRMD (post-resuscitation myocardial dysfunction). We studied whether ivabradine (IVA) improves PRMD in a cardiac arrest model. Hypothesis: we hypothesized that the rational use of IVA would improve severity of PRMD and prognosis in a porcine model of CA. Methods: Ventricular fibrillation was induced and untreated for 8 minutes in anesthetized domestic swine while defibrillation was attempted after 6 minutes of cardiopulmonary resuscitation. Hemodynamic parameters were monitored continuously after ROSC. Mitral E/A ratio and E/e′ velocity ratio were assessed by echocardiography at Baseline, PR 1, 2, 4, 8 and 24hours after ROSC. The levels of cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured by ELISA method at Baseline, PR 1, 4 and 24hours. The animals were euthanized 24h after ROSC, and the cardiac tissue was removed for histopathological analysis. Results: Heart rate in the IVA group reduced significantly compared with the control group (all P < 0.05) at PR 1, 2, 4, 8hours. Animals subjected to IVA groups presented significantly better post-resuscitation relaxation function (E/A, E/e′) than those in the Placebo groups (all P < 0.05) (Figure1). IVA group had a lower cTnI and NT-proBNP levels than Placebo group at PR 1, 4 and 24hours (all P < 0.05) (Figure1). Biopsy score in the IVA group was significantly lower at PR 24hours when compared with the Placebo group (all P < 0.05) (Figure2). Conclusions: Heart rate reduction with IVA, improved left ventricular diastolic function and reduced myocardial injury.

Cardiopulmonary resuscitation in a rat model of chronic myocardial ischemia

2006 ◽  
Vol 101 (4) ◽  
pp. 1091-1096 ◽  
Author(s):  
Xiangshao Fang ◽  
Wanchun Tang ◽  
Shijie Sun ◽  
Lei Huang ◽  
Yun-Te Chang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Coronary Artery ◽  
Cardiopulmonary Resuscitation ◽  
Myocardial Ischemia ◽  
Rat Model ◽  
Myocardial Dysfunction ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Control Group ◽  
Chronic Myocardial Ischemia

Our group has developed a rat model of cardiac arrest and cardiopulmonary resuscitation (CPR). However, the current rat model uses healthy adult animals. In an effort to more closely reproduce the event of cardiac arrest and CPR in humans with chronic coronary disease, a rat model of coronary artery constriction was investigated during cardiac arrest and CPR. Left coronary artery constriction was induced surgically in anesthetized, mechanically ventilated Sprague-Dawley rats. Echocardiography was used to measure global cardiac performance before surgery and 4 wk postsurgery. Coronary constriction provoked significant decreases in ejection fraction, increases in left ventricular end-diastolic volume, and increases left ventricular end-systolic volume at 4 wk postintervention, just before induction of ventricular fibrillation (VF). After 6 min of untreated VF, CPR was initiated on three groups: 1) coronary artery constriction group, 2) sham-operated group, and 3) control group (without preceding surgery). Defibrillation was attempted after 6 min of CPR. All the animals were resuscitated. Postresuscitation myocardial function as measured by rate of left ventricular pressure increase at 40 mmHg and the rate of left ventricular pressure decline was more significantly impaired and left ventricular end-diastolic pressure was greater in the coronary artery constriction group compared with the sham-operated group and the control group. There were no differences in the total shock energy required for successful resuscitation and duration of survival among the groups. In summary, this rat model of chronic myocardial ischemia was associated with ventricular remodeling and left ventricular myocardial dysfunction 4 wk postintervention and subsequently with severe postresuscitation myocardial dysfunction. This model would suggest further clinically relevant investigation on cardiac arrest and CPR.

Lactic Acidosis and the Cardiovascular System in the Dog

1983 ◽  
Vol 64 (6) ◽  
pp. 573-580 ◽  
Author(s):  
Allen I. Arieff ◽  
Edward W. Gertz ◽  
Robert Park ◽  
Will Leach ◽  
Virginia C. Lazarowitz
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Cardiac Output ◽  
Lactic Acid ◽  
Lactic Acidosis ◽  
Cardiac Function ◽  
Myocardial Dysfunction ◽  
Left Ventricular ◽  
Control Group ◽  
Type B

1. Lactic acidosis is a clinical syndrome characterized by metabolic acidaemia (pH < 7.25) and hyperlactaemia (lactate >5 mmol/l). Many patients with type B lactic acidosis have no evidence of tissue hypoxia or myocardial dysfunction when first evaluated. Although it is considered that cardiac dysfunction is secondary to the systemic effects of lactic acidosis, the reverse may sometimes be true. To evaluate this possibility, studies were carried out in 43 dogs consisting of a control group and three groups which had hyperlactataemia and metabolic acidaemia related to either: (1) phenformin infusion; (2) hepatectomy; (3) lactic acid infusion. Serial studies of cardiac function, as well as measurements of GFR (glomerular filtration rate) and hepatic portal vein (HPV) blood flow, were carried out. 2. in dogs infused with phenformin for 99 min, the arterial pH, lactate, bicarbonate, heart rate and mean blood pressure (BP) were normal. However, there was significant deterioration (P < 0.01) in several indices of cardiac function, including the peak positive dP/dt, cardiac output, LVEDP (left ventricular end-diastolic pressure) and percentage extraction of oxygen and lactate by the heart. After 3 h of phenformin, the blood lactate exceeded 5 mmol/l and there were further significant decrements (P < 0.01) in cardiac output, LVEDP and dP/dt, as well as BP and heart rate. in dogs subjected to hepatectomy, the decrement in cardiac output was similar to that with phenformin infusion. However, in animals infused with lactic acid, despite a similar blood pH and lactate, cardiac output was unaffected. Although percentage myocardial oxygen extraction declined in phenformin-infused animals, there was a concomitant increase in coronary sinus blood flow such that myocardial oxygen utilization was probably unaltered. 3. Thus, in certain types of experimental type B lactic acidosis, myocardial dysfunction may be a primary event, with other associated systemic manifestations being secondary.

scholarly journals Sodium–glucose co-transporter 2 inhibition with empagliflozin improves cardiac function in rats after cardiac arrest

2021 ◽  
Author(s):  
Yunke Tan ◽  
Kai Yu ◽  
Lian Liang ◽  
Yuanshan Liu ◽  
Fengqing Song ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Arrest ◽  
Cardiac Function ◽  
Structural Integrity ◽  
Troponin I ◽  
Myocardial Dysfunction ◽  
Left Ventricular ◽  
Mitochondrial Activity ◽  
Myocardial Oxidative Stress ◽  
Sglt2 Inhibition

Abstract Background: Sodium–glucose co-transporter 2 (SGLT2) inhibition reduces hyperglycaemia and has beneficial effects in heart failure. However, the effect of SGLT2 inhibition with empagliflozin on acute myocardial dysfunction after cardiac arrest (CA) remains unknown.Methods: Non-diabetic male Sprague–Dawley rats underwent ventricular fibrillation to induce CA, or sham surgery. Rats received 10 mg/kg of empagliflozin or vehicle at 10 minutes after return of spontaneous circulation by intraperitoneal injection. Cardiac function was assessed by echocardiography, histological analysis, molecular markers of myocardial injury, oxidative stress, mitochondrial ultrastructural integrity and metabolism. Results: Empagliflozin did not influence heart rate and blood pressure, but left ventricular function and survival time were significantly higher in the empagliflozin treated group compared to the group treated with vehicle. Empagliflozin also reduced myocardial contraction band necrosis, myocardial fibrosis, serum cardiac troponin I levels and myocardial oxidative stress after CA. Moreover, empagliflozin maintained the structural integrity of myocardial mitochondria and increased mitochondrial activity after CA. In addition, empagliflozin increased circulating and myocardial ketone levels as well as myocardial expression of the 𝛽-hydroxy butyrate dehydrogenase 1. Together these metabolic changes were associated with an increase in cardiac ATP production.Conclusions: Empagliflozin favorably affects cardiac function in non-diabetic rats with acute myocardial dysfunction after CA, associated with reducing glucose levels and increasing ketone body oxidized metabolism. Our data suggest that empagliflozin might be of benefit in patients with acute myocardial dysfunction after CA.

Abstract 253: Complete Reversal of Xylazine-induced Bradycardia With Intralipid in Female Mice

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Negar Motayagheni ◽  
Mansoureh Eghbali
Keyword(s):  
Heart Rate ◽  
Cardiac Arrest ◽  
Isolated Heart ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Control Group ◽  
Heart Rates ◽  
Female Mice

Sudden cardiac arrest accounts for 300 000 to 400 000 deaths annually in united states both in men and women. Cardiac arrest could be due to abnormally slow heart rate known as bradycardia. Bradycardia is a catastrophic event which is associated with significant mortality and morbidity. We have previously shown that Intralipid, an emulsion of soy bean oil, egg yolk phospholipids and glycerol, protects the heart against ischemia/reperfusion injury as well as Bupivacaine induced cardiotoxicity. Here we examined whether intralipid can protects the heart against bradycardia. Wild type female mice C57/Bl6 (2-4 month old) were anesthetized by isoflurane after heparinization. The heart was removed immediately and placed in cold Krebs-Henseleit buffer. The aorta was cannulated and the isolated heart (Langendorff) was perfused with Krebs-Henseleit at 37°C for 15 min for stabilization. Xylazine (100-300 mg) was directly applied to the heart surface for 1-2 min until bradycardia was achieved. The heart was then perfused with either Krebs-Henseleit (KH) solution (control group), or 1% ILP (intralipid group). Hemodynamic parameters and heart rates were recorded with a catheter directly inserted into left ventricle (n=5-8 per group). The heart rates at the baseline before inducing bradycardia was 224±7 beats/min and the left ventricular pressures was 64±4 mmHg. Administration of Xylazine decreased the heart rate significantly to 81±9 beats/min and left ventricular pressure to 5±2 mmHg (p<0.001). Perfusion of the heart with intralipid rapidly restored the heart rate to 209±30 and left ventricular pressure to 59±4 which were not significantly different than their values before inducing bradycardia at the baseline. In the hearts that received Krebs-Henseleit after bradycardia, the heart rate (81±10 beats/min) and left ventricular pressure (20±8 mmHg) were significantly lower than intralipid group. In conclusion Intralipid has the ability to rapidly reverse bradycardia in female mice.

Abstract 359: Systemic Administration of Allogeneic Mesenchymal Stem Cells Attenuates Post-Resuscitation Left Ventricular Dysfunction in a Porcine Model of Cardiac Arrest

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Dorcas Nsumbu ◽  
Kristen Kosmerl ◽  
Drew Ashbery ◽  
Shannon Allen ◽  
John M Canty ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Porcine Model ◽  
Troponin I ◽  
Left Ventricular ◽  
Lv Function ◽  
Wall Thickening ◽  
Similar Degree ◽  
Myocardial Inflammation ◽  
Allogeneic Bone ◽  
Anti Inflammatory

Introduction: Advances in CPR have increased the likelihood of achieving ROSC after cardiac arrest (CA), but >50% of initially resuscitated patients die before hospital discharge. Evidence that a systemic inflammatory response exacerbates post-ROSC injury supports investigation of anti-inflammatory therapies in this setting. Accordingly, we tested the efficacy of allogeneic mesenchymal stem cell (MSC) administration early after ROSC in a porcine model of CA. Methods: Swine (n=33) were subjected to 10 min CA followed by mechanical CPR with defibrillation and intravenous epinephrine (EPI; 0.015 mg/kg). Animals that achieved ROSC (n=19) were blindly randomized to intraventricular saline (n=9) or allogeneic bone marrow-derived MSCs (55±2 x 10 6 ; n=10) 30 min post-ROSC. Intravenous EPI was given during the post-ROSC period as needed to maintain MAP ≥60 mmHg. Left ventricular (LV) function and plasma cardiac troponin I (cTnI) were assessed for 4 hr post-ROSC, at which time heart tissue was collected to assess myocardial inflammation (RT-PCR). Results: Compared with saline-treated controls, MSC-treated animals exhibited improved post-ROSC LV wall thickening ( A ) and lower cTnI levels, indicative of reduced myocardial injury. By design, both groups had a similar post-ROSC MAP and cardiac output, but the saline group required significantly more EPI ( B ). Although a similar degree of monocyte infiltration (CCR2) and macrophage expansion (CD68) was observed in both groups, MSCs increased expression of the anti-inflammatory marker Arginase1 ( C ) and tended to attenuate the post-ROSC rise in circulating IL-6 ( D ). Conclusion: Early post-ROSC delivery of allogeneic MSCs attenuates LV dysfunction and reduces the need for pharmacologic hemodynamic support after CA in swine. These results indicate that systemic MSC administration may be an effective immunomodulatory strategy to reduce post-resuscitation injury, particularly if protective effects extend to the brain.

scholarly journals Sodium–Glucose Co-Transporter 2 Inhibition With Empagliflozin Improves Cardiac Function After Cardiac Arrest in Rats by Enhancing Mitochondrial Energy Metabolism

2021 ◽  
Vol 12 ◽  
Author(s):  
Yunke Tan ◽  
Kai Yu ◽  
Lian Liang ◽  
Yuanshan Liu ◽  
Fengqing Song ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Arrest ◽  
Energy Metabolism ◽  
Cardiac Function ◽  
Troponin I ◽  
Myocardial Dysfunction ◽  
Left Ventricular ◽  
Mitochondrial Activity ◽  
Mitochondrial Energy Metabolism ◽  
Myocardial Oxidative Stress

Empagliflozin is a newly developed antidiabetic drug to reduce hyperglycaemia by highly selective inhibition of sodium–glucose co-transporter 2. Hyperglycaemia is commonly seen in patients after cardiac arrest (CA) and is associated with worse outcomes. In this study, we examined the effects of empagliflozin on cardiac function in rats with myocardial dysfunction after CA. Non-diabetic male Sprague–Dawley rats underwent ventricular fibrillation to induce CA, or sham surgery. Rats received 10 mg/kg of empagliflozin or vehicle at 10 min after return of spontaneous circulation by intraperitoneal injection. Cardiac function was assessed by echocardiography, histological analysis, molecular markers of myocardial injury, oxidative stress, mitochondrial ultrastructural integrity and metabolism. We found that empagliflozin did not influence heart rate and blood pressure, but left ventricular function and survival time were significantly higher in the empagliflozin treated group compared to the group treated with vehicle. Empagliflozin also reduced myocardial fibrosis, serum cardiac troponin I levels and myocardial oxidative stress after CA. Moreover, empagliflozin maintained the structural integrity of myocardial mitochondria and increased mitochondrial activity after CA. In addition, empagliflozin increased circulating and myocardial ketone levels as well as heart β-hydroxy butyrate dehydrogenase 1 protein expression. Together, these metabolic changes were associated with an increase in cardiac energy metabolism. Therefore, empagliflozin favorably affected cardiac function in non-diabetic rats with acute myocardial dysfunction after CA, associated with reducing glucose levels and increasing ketone body oxidized metabolism. Our data suggest that empagliflozin might benefit patients with myocardial dysfunction after CA.

Abstract 2629: High Dose Erythropoietin Improves the Postresuscitation Myocardial Dysfunction and Survival in an Appropriate Therapeutic Time Window

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Chien-Hua Huang ◽  
Chiung-Yuan Hsu ◽  
Huei-Wen Chen ◽  
Wei-Tien Chang ◽  
Wen-Jone Chen
Keyword(s):  
Cardiac Arrest ◽  
Time Window ◽  
Myocardial Dysfunction ◽  
Treated Group ◽  
Left Ventricular ◽  
Control Group ◽  
Male Adult ◽  
Term Survival ◽  
Therapeutic Time Window ◽  
Induced Cardiac Arrest

Introduction: The myocardial dysfunction carries high mortality rate in the postresuscitation period. Interventions for improving myocardial dysfunction may improve the outcomes of resuscitated victims. The erythropoietin (EPO) provides protective effects for the myocardium with ischemia-reperfusion injuries. However, its effects on the treatment of cardiopulmonary arrest and post-resuscitation myocardial dysfunction remain unknown. Hypothesis: EPO can improve the postresuscitation myocardial dysfunction in an appropriate therapeutic time window. Methods: Asphyxia-induced cardiac arrest was performed in male adult Wistar rats. Cardiopulmonary resuscitation including chest compressions, mechanical ventilation and epinephrine (0.01 mg/kg) was begun after 6.5 or 9.5 minutes of asphyxia. Animals were randomized to undergo treatment with intravenous EPO (5000 U/kg) or equivalent volume of 0.9% saline placebo. These agents were administrated 3 minutes after the return of spontaneous circulation. Results: The better left ventricular dP/dt 40 (2958±827 vs. 1321±1200 mmHg/s, P<0.05) and maximal -dP/dt (2562±546 vs. 745±877 mmHg/s, P<0.05) at 120 minutes after cardiac arrest, and better left ventricular fraction shortening (32.0 ± 2.0 vs. 24 ± 6.7 %, P<0.05) by echocardiography at 90 minutes after cardiac arrest were noted in the EPO-treated group compared to the control group in the condition of 6.5 minutes of asphyxia. The EPO treated group had better neurological recovery at 24 hours after resuscitation. Survival rate at 72 hours after 6.5 minutes of asphyxia was better in the EPO-treated group (50% vs. 20 %, P=0.02). No animal survived 72 hours after 9.5 minutes of asphyxia either in EPO-treated or control group. More activation of cardiac Akt and ERK 42/44 signaling pathways were noted in the EPO-treated group than the control group. Conclusions: EPO has the potential to improve postresuscitation myocardial dysfunction and short term survival in rats after asphyxia-induced cardiac arrest in an appropriate therapeutic time window.

Glutamine Is Cardioprotective in Patients with Ischemic Heart Disease following Cardiopulmonary Bypass

2011 ◽  
Vol 14 (6) ◽  
pp. 384 ◽  
Author(s):  
Vladimir V. Lomivorotov ◽  
Sergey M. Efremov ◽  
Vladimir A. Shmirev ◽  
Dmitry N. Ponomarev ◽  
Vladimir N. Lomivorotov ◽  
...  
Keyword(s):  
Heart Disease ◽  
Placebo Group ◽  
Cardiopulmonary Bypass ◽  
Ischemic Heart Disease ◽  
Troponin I ◽  
Left Ventricular ◽  
Ischemic Heart ◽  
Left Ventricular Ejection ◽  
Study Group ◽  
Cardioprotective Effects

<p><b>Background:</b> The aim of the present study was to investigate the cardioprotective effects of the perioperative use of N(2)-L-alanyl-L-glutamine (GLN) in patients with ischemic heart disease (IHD) who undergo their operations under cardiopulmonary bypass (CPB).</p><p><b>Methods:</b> This double-blind, placebo-controlled, randomized study included 50 patients who underwent cardiac surgery with CPB. Exclusion criteria were a left ventricular ejection fraction <50%, diabetes mellitus, <3 months since the onset of myocardial infarction, and emergency surgery. Patients in the study group (n = 25) received 0.4 g/kg GLN (Dipeptiven, 20% solution) per day. Patients in the control group (n = 25) were administered a placebo (0.9% NaCl). The primary end point was the dynamics of troponin I at the following stages: (1) prior to anesthesia, (2) 30 minutes after CPB, (3) 6 hours after CPB, (4) 24 hours after surgery, and (5) 48 hours after surgery. Secondary end points included measurements of hemodynamics with a Swan-Ganz catheter.</p><p><b>Results:</b> On the first postoperative day after the surgery, the median troponin I level was significantly lower in the study group than in the placebo group: 1.280 ng/mL (interquartile range [IQR], 0.840-2.230 ng/mL) versus 2.410 ng/mL (IQR, 1.060-6.600 ng/mL) (<i>P</i> = .035). At 4 hours after cardiopulmonary bypass (CPB), the median cardiac index was higher in the patients in the study group: 2.58 L/min per m<sup>2</sup> (IQR, 2.34-2.91 L/min per m<sup>2</sup>) versus 2.03 L/min per m<sup>2</sup> (IQR, 1.76-2.32 L/min per m<sup>2</sup>) (<i>P</i> = .002). The median stroke index also was higher in the patients who received GLN: 32.8 mL/m<sup>2</sup> (IQR, 27.8-36.0 mL/m<sup>2</sup>) versus 26.1 mL/m<sup>2</sup> (IQR, 22.6-31.8 mL/m<sup>2</sup>) (<i>P</i> = .023). The median systemic vascular resistance index was significantly lower in the study group than in the placebo group: 1942 dyn�s/cm<sup>5</sup> per m<sup>2</sup> (IQR, 1828-2209 dyn�s/cm<sup>5</sup> per m<sup>2</sup>) versus 2456 dyn�s/cm<sup>5</sup> per m<sup>2</sup> (IQR, 2400-3265 dyn�s/cm<sup>5</sup> per m<sup>2</sup>) (<i>P</i> = .001).</p><p><b>Conclusion:</b> Perioperative administration of GLN during the first 24 hours has cardioprotective effects in IHD patients following CPB. This technique enhances the troponin concentration at 24 hours after surgery and is associated with improved myocardial function.</p>

Abstract 138: Remote Ischemic Postconditioning Alleviates Postresuscitation Inflammatory Response and Pulmonary Edema in a Porcine Model of Cardiac Arrest

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jiefeng Xu ◽  
Sen Ye ◽  
Zilong Li ◽  
Moli Wang ◽  
Zhengquan Wang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Inflammatory Response ◽  
Pulmonary Edema ◽  
Porcine Model ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Limb Ischemia ◽  
Multiple Organ ◽  
Control Group ◽  
Lung Water

Introduction: Systemic ischemia-reperfusion injury produced by CA and resuscitation can result in severe post-cardiac arrest syndrome; which includes systemic inflammatory response and multiple organ dysfunction syndrome such as acute pulmonary edema. We previously demonstrated that remote ischemic post-conditioning (RIpostC) improved post-resuscitation myocardial and cerebral function in a rat model of CA. In this study, we investigated the effects of RIpostC on inflammatory response and pulmonary edema after CPR in a porcine model. Hypothesis: RIpostC would alleviate post-resuscitation inflammatory response and pulmonary edema in a porcine model of CA. Methods: Fourteen male domestic pigs weighing 37 ± 2 kg were utilized. Ventricular fibrillation was electrically induced and untreated for 10 mins. The animals were then randomized to receive RIpostC or control. Coincident with the start of CPR, RIpostC was induced by four cycles of 5 mins of limb ischemia and then 5 mins of reperfusion. Defibrillation was attempted after 5 mins of CPR. The resuscitated animals were monitored for 4 hrs and observed for an additional 68 hrs. Results: Six of the seven animals in each group were successfully resuscitated. After resuscitation, significantly lower levels of tumor necrosis factor-α and interleukin-6 were measured in the animals that received RIpostC when compared with the control group. Post-resuscitation extra-vascular lung water index was lower in the RIpostC group than in the control group; in which the differences were significant at 2,3 and 4 hrs (Table). Conclusion: In a porcine model of CA, RIpostC significantly alleviates post-resuscitation inflammatory response and pulmonary edema.

Abstract 12836: Low-Intensity Pulsed Ultrasound Ameliorates Left Ventricular Dysfunction in a Porcine Model of Chronic Myocardial Ischemia -Potential Involvement of Mechanotransduction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Tomohiko Shindo ◽  
Kenta Ito ◽  
Kenichiro Hanawa ◽  
Kentaro Aizawa ◽  
Takashi Shiroto ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Porcine Model ◽  
Left Ventricular ◽  
Control Group ◽  
Β1 Integrin ◽  
Vascular Endothelial ◽  
Pulsed Ultrasound ◽  
Caveolin 1 ◽  
Low Intensity Pulsed Ultrasound ◽  
Chronic Myocardial Ischemia

Purpose: Despite recent progress in the management of ischemic heart disease (IHD), the number of patients with severe IHD is increasing. In this study, we aimed to develop low-intensity pulsed ultrasound (LIPUS) therapy for the treatment of IHD and to elucidate the underlying molecular mechanisms for the LIPUS-induced angiogenesis. Methods and Results: We first confirmed that the LIPUS up-regulated mRNA expression of vascular endothelial growth factor (VEGF) with a peak at 32-cycle in cultured human vascular endothelial cells (HUVECs). Then, we examined the in vivo effects of LIPUS in a porcine model of chronic myocardial ischemia with reduced left ventricular ejection fraction (LVEF) (n=28). The heart was treated with either sham or LIPUS (32-cycle, 20 min) at 3 different short axis levels (n=14 each). Four weeks after the therapy, LVEF was significantly improved in the LIPUS group (46±4 to 57±5%, P<0.05), whereas it remained unchanged in the control group. Capillary density and regional myocardial blood flow in the ischemic region were also increased in the LIPUS group but not in the control group. The protein expressions of VEGF, eNOS and bFGF in the ischemic area were enhanced in the LIPUS group compared with the control group. To further examine the signaling pathways responsible for the LIPUS-induced angiogenesis, HUVECs were transfected with siRNA or scrambled siRNA of either β1 integrin or caveolin-1. Knockdown of either β1 integrin or caveolin-1 with siRNA suppressed the LIPUS-induced up-regulation of VEGF. siRNA-mediated suppression of either focal adhesion kinase (FAK) or Fyn also inhibited the LIPUS-induced up-regulation of VEGF. Knockdown of these molecules with siRNA was confirmed with real-time PCR. Conclusions: These results suggest that the LIPUS therapy is promising as a new, non-invasive therapy for IHD and that β1 integrin and caveolin-1 may be involved in underlying molecular mechanisms for the beneficial effects of the LIPUS.

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