Increased left ventricular mass after thoracotomy and pericardiotomy. A role for relief of pericardial constraint?

Tischler, Marc D.; Rowan, Michaelanne; LeWinter, Martin M.

doi:10.1161/01.cir.87.6.1921

Cited by 25 publications

(12 citation statements)

References 43 publications

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“…To our knowledge, no studies have investigated the effect of thoracotomy in the mouse on hemodynamic function at two time points. An effect of relief of pericardial constraint after pericardectomy could play a role, as it has been described that LV dilation and hypertrophy occurs in humans after pericardectomy (22). However, in the present study, no LV remodeling was observed in the sham group at 8 wk and no significant differences were observed between sham and control animals at 8 wk.…”

Section: Discussioncontrasting

confidence: 67%

A novel model of cryoinjury-induced myocardial infarction in the mouse: a comparison with coronary artery ligation

Bos

Mees

Waard

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

121

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The most commonly applied model is coronary artery ligation. However, coronary ligation often gives rise to apical aneurysmatic infarcts of variable size. Other infarct models include cryoinfarction, which produces reproducible infarcts of the anterior wall. Thus far, this model has not been extensively described in mice. Therefore, we developed a murine cryoinfarction model and compared it with coronary ligation. Studies were performed under isoflurane anesthesia with a follow-up of 4 and 8 wk. Cryoinfarction was induced using a 2-or 3-mm cryoprobe. Two-dimensional guided M-mode echocardiography was used to assess fractional shortening and left ventricular (LV) dimensions at baseline and end point. At end point, hemodynamics were assessed using a 1.4-Fr Millar catheter. Pressure-diameter relations were constructed by combining echocardiography and hemodynamic data. Histological and morphometric analyses of infarct and remote areas were performed. At 4 wk, 3-mm cryoinfarction resulted in decreased LV fractional shortening as well as decreased global LV contractility and relaxation, which was comparable with coronary ligation. No adverse remodeling was observed at this time point, in contrast with the ligation model. However, progressive LV remodeling occured between 4 and 8 wk after cryoinfarction with a further decline in hemodynamic parameters and LV pump function. Histologically, cryoinfarction resulted in highly reproducible, transmural, coneshaped infarcts with reperfusion at the macrovascular level. These results indicate that the cryoinfarction model represents the anterior myocardial infarct with modest adverse remodeling and may thus be representative for infarcts encountered in clinical practice. heart function; cardiac remodeling; echocardiography WITH THE ACCUMULATING AVAILABILITY of various models of genetically modified mice, there is a growing interest in murine models of myocardial infarction (MI) for the study of cardiac remodeling (18). The most widely studied model of murine MI is permanent ligation of the left anterior descending coronary artery (LAD) (12, 16). Although highly representative of ischemic cell death as occurs in humans, the ligation model is inherently associated with infarcts of variable size, requiring large group numbers of mice in studies that evaluate antiremodeling therapies. Even more importantly, LAD ligation in the mouse heart typically leads to apical infarcts with large aneurysm formation causing a particular ventricular geometry. Ligation-induced infarcts in the mouse heart appear therefore less representative for infarcts encountered in clinical practice, where acute LAD occlusion followed by aggressive reperfusion therapy often leads to moderately sized infarcts of the anterior free wall.Several alternative models of MI have been proposed and studied over the years in various animal models, including infarction by freeze-thaw injury, or cryoinjury (2, 20). In the last years, cryoinjury has been mainly applied in studies on intracardiac cell transplantation (9,14,1...

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Section: Discussioncontrasting

confidence: 67%

A novel model of cryoinjury-induced myocardial infarction in the mouse: a comparison with coronary artery ligation

Bos

Mees

Waard

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

121

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“…In our study we have shown that there was significant decrease of scar tissue, a corresponding increase in viable tissue and an increase in regional contractile performance (as measured by both systolic wall thickening and tissue tagging), which together yielded a significant increase of global LVEF. The seemingly paradoxical simultaneous increase in EDV and LVEF, which is well described in other trials post-CABG 24, 25, 32 , is attributable to the interactions of an intact pericardium (or the lack thereof post-surgery) and the ventricular hemodynamics 33 without directly affecting the contractile performance 32, 34 .…”

Section: Discussionmentioning

confidence: 64%

Autologous Mesenchymal Stem Cells Produce Concordant Improvements in Regional Function, Tissue Perfusion, and Fibrotic Burden When Administered to Patients Undergoing Coronary Artery Bypass Grafting

Karantalis

DiFede

Gerstenblith

et al. 2014

Circulation Research

320

235

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Rationale While accumulating data support the efficacy of intramyocardial cell-based therapy to improve LV function in patients with chronic ischemic cardiomyopathy undergoing CABG, the underlying mechanism and impact of cell injection site remain controversial.Mesenchymal stem cells (MSCs) improve LV structure and function through several effects including: reducing fibrosis, neoangiogenesis and neomyogenesis. Objective To test the hypothesis that the impact on cardiac structure and function following intramyocardial injections of autologous MSCs results from a concordance of pro-recovery phenotypic effects. Methods and Results Six patients were injected with autologous MSCs into akinetic/hypokinetic myocardial territories not receiving bypass graft for clinical reasons. MRI was used to measure scar, perfusion, wall thickness and contractility at baseline, 3, 6 and 18 months and to compare structural and functional recovery in regions that received MSC injections alone, revascularization alone, or neither. A composite score of MRI variables was used to assess concordance of antifibrotic effects, perfusion, and contraction at different regions. After 18 months, subjects receiving MSCs exhibited increased LVEF (+9.4±1.7%, p=0.0002) and decreased scar mass (-47.5±8.1%; p<0.0001) compared to baseline. MSC-injected segments had concordant reduction in scar size, perfusion and contractile improvement (concordant score: 2.93±0.07), whereas revascularized (0.5±0.21) and non-treated segments (-0.07±0.34) demonstrated non-concordant changes (p<0.0001 vs. injected segments). Conclusions Intramyocardial injection of autologous MSCs into akinetic yet non-revascularized segments produces comprehensive regional functional restitution, which in turn drives improvement in global LV function. These findings, although inconclusive due to lack of placebo group, have important therapeutic and mechanistic hypothesis-generating implications.

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“…17 Pericardial resection in animals and humans is associated with mild, balanced increases in LV dimension and mass. 17, 30 This modest increase in chamber size, if confirmed in chronic animal studies and in humans, would be expected to improve forward stroke volume and cardiac output, which limit exercise capacity in many patients with HFpEF. 6 …”

Section: Discussionmentioning

confidence: 95%

Percutaneous Pericardial Resection

Borlaug

Carter

Melenovský

et al. 2017

Circ: Heart Failure

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Background People with heart failure and preserved ejection fraction (HFpEF) develop increases in left ventricular (LV) end-diastolic pressures (LVEDP) during exercise that contribute to dyspnea. In normal open-chest animal preparations, the pericardium restrains LV filling when central blood volume increases. We hypothesized that resection of the pericardium using a minimally-invasive epicardial approach would mitigate the increase in LVEDP that develops during volume loading in normal and diseased hearts with the chest intact. Methods and Results Invasive hemodynamic assessment was performed at baseline and following saline load before and after pericardial resection in normal canines with open (n=3) and closed chest (n=5) and in a pig model with features of human HFpEF with sternum intact (n=4). In closed-chest animals, pericardiotomy was performed using a novel subxiphoid procedure. In both experimental preparations of normal dogs, pericardiotomy blunted the increase in LVEDP with saline infusion, while enhancing the saline-mediated increase in LV end-diastolic volume (LVEDV). With chest intact in the pig model, percutaneous pericardial resection again blunted the increase in LVEDP secondary to volume expansion (+4±3 vs +13±5 mmHg, p=0.014) while enhancing the saline-mediated increase in LVEDV (+17±1 vs +10±2 ml, p=0.016). Conclusions This proof of concept study demonstrates that pericardial resection through a minimally-invasive percutaneous approach mitigates the elevation in LV filling pressures with volume loading in both normal animals and a pig model with diastolic dysfunction. Further study is warranted to determine whether this method is safe and produces similar acute and chronic hemodynamic benefits in people with HFpEF.

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Increased left ventricular mass after thoracotomy and pericardiotomy. A role for relief of pericardial constraint?

Abstract: Background. Myocardial stretch and increased ventricular filling can lead to increased rates of myocardial protein synthesis. In animal studies, left ventricular mass increases after pericardiectomy,

Cited by 25 publications

References 43 publications

A novel model of cryoinjury-induced myocardial infarction in the mouse: a comparison with coronary artery ligation

A novel model of cryoinjury-induced myocardial infarction in the mouse: a comparison with coronary artery ligation

Autologous Mesenchymal Stem Cells Produce Concordant Improvements in Regional Function, Tissue Perfusion, and Fibrotic Burden When Administered to Patients Undergoing Coronary Artery Bypass Grafting

Percutaneous Pericardial Resection

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