Mechanical Left Ventricular Unloading to Reduce Infarct Size During Acute Myocardial Infarction: Insight from Preclinical and Clinical Studies

Kapur, Navin K.; Reyelt, Lara; Swain, Lija; Esposito, Michele; Qiao, Xiaoying; Annamalai, Shiva; Meyns, Bart; Smalling, Richard W.

doi:10.1007/s12265-019-09876-3

Cited by 19 publications

(10 citation statements)

References 35 publications

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“…Trans-valvular mechanical support devices like the Impella device family uncouple the myocardial workload from the systemic cardiac output (which is then primarily provided by the pump), leading to adequate end-organ perfusion while resting the heart [3,25]. Previous studies [26][27][28] have demonstrated the e cacy of this intravascular resuscitation, and the present study in an animal model con rms the results and provides additional insights on the temporal evolution of the effect.…”

Section: Discussionsupporting

confidence: 77%

Inhaled Nitric Oxide Preserves Ventricular Function During Resuscitation Using a Percutaneous Mechanical Circulatory Support Device in a Porcine Cardiac Arrest Model – An Echocardiographic Myocardial Work Analysis

Nix

Zayat

Ebeling

et al. 2020

Preprint

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BackgroundResuscitation using a percutaneous mechanical circulatory support device (iCPR) improves survival after cardiac arrest (CA). We hypothesized that the addition of inhaled nitric oxide (iNO) during iCPR might prove synergistic, leading to improved myocardial performance due to lowering of right ventricular (RV) afterload, left ventricular (LV) preload, and myocardial energetics. This study aimed to characterize the changes in LV and RV function and global myocardial work indices (GWI) following iCPR, both with and without iNO, using 2-D transesophageal echocardiography (TEE) and GWI evaluation as a novel non-invasive measurement. MethodsIn 10 pigs, iCPR was initiated following electrically-induced CA and 10min of untreated ventricular fibrillation (VF). Pigs were randomized to either 20ppm (20ppm, n=5) or 0ppm (0ppm, n=5) of iNO in addition to therapeutic hypothermia for 5h following ROSC. All animals received TEE at five pre-specified time-points and invasive hemodynamic monitoring. ResultsLV end-diastolic volume (LVEDV) increased significantly in both groups following CA. iCPR alone led to significant LV unloading at 5h post-ROSC with LVEDV values reaching baseline values in both groups (20ppm: 68.2±2.7 vs. 70.8±6.1 mL, p=0.486; 0ppm: 70.8±1.3 vs. 72.3±4.2 mL, p=0.813, respectively). LV global longitudinal strain (GLS) increased in both groups following CA. LV-GLS recovered significantly better in the 20ppm group at 5h post-ROSC (20ppm: -18±3% vs. 0ppm: -13±2%, p=0.025). LV-GWI decreased in both groups after CA with no difference between the groups. Within 0ppm group, LV-GWI decreased significantly at 5h post-ROSC compared to baseline (1,125±214 vs. 1,835±305 mmHg%, p=0.011). RV-GWI was higher in the 20ppm group at 3h and 5h post-ROSC (20ppm: 189±43 vs. 0ppm: 108±22 mmHg%, p=0.049 and 20ppm: 261±54 vs. 0ppm: 152±42 mmHg%, p=0.041). The blood flow calculated by the Impella controller following iCPR initiation correlated well with the pulsed-wave Doppler (PWD) derived pulmonary flow (PWD vs. controller: 1.8±0.2 vs. 1.9±0.2L/min, r=0.85, p=0.012). ConclusionsiCPR after CA provided sufficient unloading and preservation of the LV systolic function by improving LV-GWI recovery. The addition of iNO to iCPR enabled better preservation of the RV-function as determined by better RV-GWI. Additionally, Impella-derived flow provided an accurate measure of total flow during iCPR.

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Section: Discussionsupporting

confidence: 77%

Inhaled Nitric Oxide Preserves Ventricular Function During Resuscitation Using a Percutaneous Mechanical Circulatory Support Device in a Porcine Cardiac Arrest Model – An Echocardiographic Myocardial Work Analysis

Nix

Zayat

Ebeling

et al. 2020

Preprint

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“…A similar experiment performed by Sun et al using surgically implanted Impella 5.0 pumps showed comparable findings [40]. Finally, a recent analysis by Swain and Kapur further identified that LV unloading with an Impella CP reduces mitochondrial damage associated with reperfusion injury [22]. By protecting mitochondrial function, heart muscle cells are more likely to recover function over time [40].…”

Section: Preclinical Studiesmentioning

confidence: 66%

“…One important mechanism to highlight is an improvement in coronary perfusion by reducing LV wall stress. The concept of functional or gentle reperfusion whereby LV unloading improves collateral flow to the ischemic myocardium has been shown to be an important mechanism to limit infarct size in canine models [20][21][22][23]. In sum, cardioprotective strategies, their mechanisms and the amelioration of reperfusion injury, remain an area of great scientific and clinical interest.…”

Section: Reperfusion Injurymentioning

confidence: 99%

Door-to-unload: Left Ventricular Unloading Before Reperfusion in ST-elevation Myocardial Infarction

et al. 2021

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ST-elevation myocardial infarction treatment in the modern era has focused on minimizing time of ischemia by reducing door-to-balloon time to limit infarct size and improve survival. Although there have been significant improvements in minimizing time to coronary reperfusion, the incidence of heart failure following a myocardial infarction has remained high. Preclinical studies have shown that unloading the left ventricle for 30 min prior to coronary reperfusion can reduce infarct size and promote myocardial recovery. The DTU-STEMI randomized prospective trial will test the hypothesis that left ventricular unloading for at least 30 min prior to coronary reperfusion will improve infarct size and heart failure-related events as compared with the current standard of care.

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“…However, the mechanism of myocardial I/R injury is very complex (5). Myocardial I/R injury has become a major obstacle in the clinical treatment of ischemic cardiomyopathy (6). Therefore, it is very important to clarify the mechanism of myocardial I/R and to find drugs against myocardial I/R injury for the treatment of ischemic cardiomyopathy.…”

Section: Introductionmentioning

confidence: 99%

Galanthamine improves myocardial ischemia-reperfusion-induced cardiac dysfunction, endoplasmic reticulum stress-related apoptosis, and myocardial fibrosis by suppressing AMPK/Nrf2 pathway in rats

Hou

Kang

et al. 2019

Ann. Transl. Med.

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Background: Myocardial ischemia/reperfusion (I/R) injury is an important cause of myocardial infarction and heart failure after cardiovascular surgery. Galanthamine (Gal) is an important Amaryllidaceae alkaloid with anti-acetylcholinesterase and anti-inflammatory activity. The purpose of this study was to investigate the role of Gal in myocardial I/R injury.Methods: In this study, an animal model of myocardial I/R injury was constructed, and the rats were divided into five groups (n=10): the sham, I/R model, I/R + Gal (1 mg/kg), I/R + Gal (3 mg/kg), and I/R + Aspirin (20 mg/kg) groups. The expression of related proteins was detected by Western blotting and Immunohistochemistry, and Histological lesion was detected by HE staining. Results: Results showed that Gal improves I/R-induced cardiac dysfunction in rats. Moreover, Gal inhibits I/R-induced endoplasmic reticulum stress (ERS)-related apoptosis by suppressing the expression of CHOP, Cleaved caspase 12, and caspase 3, and promoting the expression of CADD34 and BiP in rats. Furthermore, Gal mitigates I/R-induced myocardial fibrosis through restraining the expression of α-SMA and Collagen I in rats. Mechanically, Gal promoted the expression of AMPKα1, Nrf2 and HO-1. However, AMPK inhibitor Compound C exhibited the opposite effects. Collectively, this finding suggests that Gal improves I/R-induced cardiac dysfunction, ERS-related apoptosis, and myocardial fibrosis by activating AMPK/Nrf2 pathway in myocardial I/R rats.Conclusions: Given this evidence, Gal may be a potential therapeutic drug for the treatment of I/R injury.

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Mechanical Left Ventricular Unloading to Reduce Infarct Size During Acute Myocardial Infarction: Insight from Preclinical and Clinical Studies

Cited by 19 publications

References 35 publications

Inhaled Nitric Oxide Preserves Ventricular Function During Resuscitation Using a Percutaneous Mechanical Circulatory Support Device in a Porcine Cardiac Arrest Model – An Echocardiographic Myocardial Work Analysis

Inhaled Nitric Oxide Preserves Ventricular Function During Resuscitation Using a Percutaneous Mechanical Circulatory Support Device in a Porcine Cardiac Arrest Model – An Echocardiographic Myocardial Work Analysis

Door-to-unload: Left Ventricular Unloading Before Reperfusion in ST-elevation Myocardial Infarction

Galanthamine improves myocardial ischemia-reperfusion-induced cardiac dysfunction, endoplasmic reticulum stress-related apoptosis, and myocardial fibrosis by suppressing AMPK/Nrf2 pathway in rats

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