Inhibition of cyclooxygenase-2 improves cardiac function after myocardial infarction in the mouse

2004 ◽  
Vol 286 (4) ◽  
pp. H1416-H1424 ◽  
Author(s):  
Margot C. LaPointe ◽  
Mariela Mendez ◽  
Alicia Leung ◽  
Zhenyin Tao ◽  
Xiao-Ping Yang
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Infarct Size ◽  
Left Ventricular ◽  
Cross Sectional Area ◽  
Collagen Content ◽  
Vehicle Group ◽  
Sectional Area ◽  
Cross Sectional ◽  
Cox 2

Cyclooxygenase (COX)-2 is expressed in the heart in animal models of ischemic injury. Recent studies have suggested that COX-2 products are involved in inflammatory cell infiltration and fibroblast proliferation in the heart. Using a mouse model, we questioned whether 1) myocardial infarction (MI) in vivo induces COX-2 expression chronically, and 2) COX-2 inhibition reduces collagen content and improves cardiac function in mice with MI. MI was produced by ligation of the left anterior descending coronary artery in mice. Two days later, mice were treated with 3 mg/kg NS-398, a selective COX-2 inhibitor, or vehicle in drinking water for 2 wk. After the treatment period, mice were subjected to two-dimensional M-mode echocardiography to determine cardiac function. Hearts were then analyzed for determination of infarct size, interstitial collagen content, brain natriuretic peptide (BNP) mRNA, myocyte cross-sectional area, and immunohistochemical staining for transforming growth factor (TGF)-β and COX-2. COX-2 protein, detected by immunohistochemistry, was increased in MI versus sham hearts. MI resulted in increased left ventricular systolic and diastolic dimension and decreased ejection fraction, fractional shortening, and cardiac output. NS-398 treatment partly reversed these detrimental changes. Myocyte cross-sectional area, a measure of hypertrophy, was decreased by 30% in the NS-398 versus vehicle group, but there was no effect on BNP mRNA. The interstitial collagen fraction increased from 5.4 ± 0.4% in sham hearts to 10.4 ± 0.9% in MI hearts and was decreased to 7.9 ± 0.6% in NS-398-treated hearts. A second COX-2 inhibitor, rofecoxib (MK-0966), also decreased myocyte cross-sectional area and interstitial collagen fraction. TGF-β, a key regulator of collagen synthesis, was increased in MI hearts. NS-398 treatment reduced TGF-β immunostaining by 40%. NS-398 treatment had no effect on infarct size. These results suggest that COX-2 products contribute to cardiac remodeling and functional deficits after MI. Thus selected inhibition of COX-2 may be a therapeutic target for reducing myocyte damage after MI.

scholarly journals Cardiomyocyte remodeling in ischemic heart disease

Medicina ◽  
2008 ◽  
Vol 44 (11) ◽  
pp. 848 ◽  
Author(s):  
Dalia Pangonytė ◽  
Elena Stalioraitytė ◽  
Reda Žiuraitienė ◽  
Danutė Kazlauskaitė ◽  
Jolita Palubinskienė ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Left Ventricular ◽  
Cross Sectional Area ◽  
Ischemic Heart ◽  
Cardiomyocyte Hypertrophy ◽  
Control Group ◽  
Sectional Area ◽  
Cross Sectional

Objective. The aim of the study was to detect changes in left ventricular cardiomyocyte size and shape in response to chronic ischemia and loss of cardiac tissue (myocardial infarction) during the course of ischemic heart disease (IHD). Material and methods. Left ventricular cardiomyocyte dimensions (diameter and length) were estimated histomorphometrically, and their cross-sectional area and volume were assessed in 85 males who died suddenly out of hospital (within 6 hours of the onset of the terminal event) due to the acute first (preinfarction IHD group, n=53, aged 48.6±2.9 years) or repeated (postinfarction IHD group, n=32, aged 51.7±2.9 years) IHD attack, and had no other causes for the increased heart load. Twenty-nine males of similar age (mean age, 46.0±3.1 years) who succumbed to external causes served as controls. Results. We have found cardiomyocyte hypertrophy in the preinfarction IHD group already. The cardiomyocyte volume was increased by 32.0% in comparison with the same index in the control group, and cross-sectional area and length – by 17.2 and 12.5%, respectively. In postinfarction IHD group, all studied cardiomyocyte parameters did not differ significantly from the analogous indices in the preinfarction IHD group (P>0.05). Cardiomyocyte hypertrophy was related to the increase in left ventricular cardiomyocyte parameters. Conclusions. Left ventricular cardiomyocyte hypertrophy occurs before the first myocardial infarction. In postinfarction myocardium, cardiomyocyte dimensions do not differ significantly at least prior to the appearance of congestive heart failure syndrome.

GH replacement fails to improve ventricular function in hypophysectomized rats with myocardial infarction

1996 ◽  
Vol 271 (5) ◽  
pp. H1721-H1727 ◽  
Author(s):  
Y. T. Shen ◽  
R. T. Wiedmann ◽  
J. J. Lynch ◽  
W. Grossman ◽  
R. G. Johnson
Keyword(s):  
Myocardial Infarction ◽  
Body Weight ◽  
Cardiac Function ◽  
Infarct Size ◽  
Recovery Period ◽  
Left Ventricular ◽  
Vehicle Group ◽  
Gh Treatment ◽  
Gh Replacement ◽  
Hypophysectomized Rats

To determine whether growth hormone (GH) replacement improves cardiac function, GH-deficient hypophysectomized rats with moderate myocardial infarction (MI) were studied after 3 wk of treatment with either recombinant rat GH (3.2 mg.kg-1.day-1 sc) or vehicle. The serum insulin-like growth factor I level in rats after GH treatment was approximately 10-fold greater than in vehicle-treated rats. GH replacement prevented a decrease in body weight at 1 wk (+5 +/- 6 vs. -26 +/- 4 g in vehicle group, P < 0.01) and increased body weight at 3 wk (+40 +/- 5 vs. -30 +/- 4 g in vehicle group, P < 0.01) after MI. Infarct size, expressed as a percentage of left ventricular (LV) perimeter, was similar for GH-treated (21 +/- 3%) and vehicle-treated (23 +/- 3%) rats. Basal LV systolic pressure, LV end-diastolic pressure, LV dP/dt, mean arterial pressure and heart rate, and the changes in these parameters in response to isoproterenol and norepinephrine were similar for these two groups. Although GH replacement tended to prevent depression in myocardial contractility during the recovery period after maximal stimulation either by the largest dose of isoproterenol (0.8 microgram/kg iv) or by acute volume loading, differences between the two groups were not statistically significant. In addition, to determine the effects of excess GH treatment in a severe state of cardiac dysfunction, nonhypophysectomized rats with larger infarcts (i.e., > 45% of the LV) were studied after 4 wk of treatment. There were no differences either in hemodynamic indexes or in infarct size between the GH- and vehicle-treated groups, whereas body weight had increased (P < 0.01) in the GH-treated group. Thus, although GH treatment effectively prevents the loss of body weight after MI, neither GH replacement nor excess GH treatment plays an important role in preserving cardiac function in rats with moderate or large MI.

Cardioprotection with esmolol-based cardioplegia for non-infarcted and infarcted rat hearts

2021 ◽  
Author(s):  
Alexander B Veitinger ◽  
Audrey Komguem ◽  
Lena Assling-Simon ◽  
Martina Heep ◽  
Julia Schipke ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Lactate Production ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
Cardioplegic Arrest ◽  
Blood Cardioplegia ◽  
Rat Hearts

Abstract OBJECTIVES Esmolol-based cardioplegic arrest offers better cardioprotection than crystalloid cardioplegia but has been compared experimentally with blood cardioplegia only once. We investigated the influence of esmolol crystalloid cardioplegia (ECCP), esmolol blood cardioplegia (EBCP) and Calafiore blood cardioplegia (Cala) on cardiac function, metabolism and infarct size in non-infarcted and infarcted isolated rat hearts. METHODS Two studies were performed: (i) the hearts were subjected to a 90-min cardioplegic arrest with ECCP, EBCP or Cala and (ii) a regional myocardial infarction was created 30 min before a 90-min cardioplegic arrest. Left ventricular peak developed pressure (LVpdP), velocity of contractility (dLVP/dtmax), velocity of relaxation over time (dLVP/dtmin), heart rate and coronary flow were recorded. In addition, the metabolic parameters were analysed. The infarct size was determined by planimetry, and the myocardial damage was determined by electron microscopy. RESULTS In non-infarcted hearts, cardiac function was better preserved with ECCP than with EBCP or Cala relative to baseline values (LVpdP: 100 ± 28% vs 86 ± 11% vs 57 ± 7%; P = 0.002). Infarcted hearts showed similar haemodynamic recovery for ECCP, EBCP and Cala (LVpdP: 85 ± 46% vs 89 ± 55% vs 56 ± 26%; P = 0.30). The lactate production with EBCP was lower than with ECCP (0.6 ± 0.7 vs 1.4 ± 0.5 μmol/min; P = 0.017). The myocardial infarct size and (ECCP vs EBCP vs Cala: 16 ± 7% vs 15 ± 9% vs 24 ± 13%; P = 0.21) the ultrastructural preservation was similar in all groups. CONCLUSIONS In non-infarcted rat hearts, esmolol-based cardioplegia, particularly ECCP, offers better myocardial protection than Calafiore. After an acute myocardial infarction, cardioprotection with esmolol-based cardioplegia is similar to that with Calafiore.

Relation between Coronary Artery Cross Sectional Area and Left Ventricular Wall Mass

1990 ◽  
Vol 20 (4) ◽  
pp. 748
Author(s):  
Doo Hong Choi ◽  
Hak Sun Kim ◽  
Sun Ho Chang ◽  
Joo Young Cho ◽  
Sung Gu Kim ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Left Ventricular ◽  
Cross Sectional Area ◽  
Left Ventricular Wall ◽  
Ventricular Wall ◽  
Sectional Area ◽  
Cross Sectional ◽  
Wall Mass

scholarly journals Cardiac surgery in acute myocardial infarction: crystalloid versus blood cardioplegia – an experimental study

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Andreas Boening ◽  
Maximilian Hinke ◽  
Martina Heep ◽  
Kerstin Boengler ◽  
Bernd Niemann ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Cardiac Surgery ◽  
Cardiac Function ◽  
Infarct Size ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Cardioplegic Arrest ◽  
Blood Cardioplegia ◽  
Cardioplegia Solution

Abstract Background Because hearts in acute myocardial infarction are often prone to ischemia-reperfusion damage during cardiac surgery, we investigated the influence of intracellular crystalloid cardioplegia solution (CCP) and extracellular blood cardioplegia solution (BCP) on cardiac function, metabolism, and infarct size in a rat heart model of myocardial infarction. Methods Following euthanasia, the hearts of 50 rats were quickly excised, cannulated, and inserted into a blood-perfused isolated heart apparatus. A regional myocardial infarction was created in the infarction group (18 hearts) for 120 min; the control group (32 hearts) was not subjected to infarction. In each group, either Buckberg BCP or Bretschneider CCP was administered for an aortic clamping time of 90 min. Functional parameters were recorded during reperfusion: coronary blood flow, left ventricular developed pressure (LVDP) and contractility (dp/dt max). Infarct size was determined by planimetry. The results were compared between the groups using analysis of variance or parametric tests, as appropriate. Results Cardiac function after acute myocardial infarction, 90 min of cardioplegic arrest, and 90 min of reperfusion was better preserved with Buckberg BCP than with Bretschneider CCP relative to baseline (BL) values (LVDP 54 ± 11% vs. 9 ± 2.9% [p = 0.0062]; dp/dt max. 73 ± 11% vs. 23 ± 2.7% [p = 0.0001]), whereas coronary flow was similarly impaired (BCP 55 ± 15%, CCP 63 ± 17% [p = 0.99]). The infarct in BCP-treated hearts was smaller (25% of myocardium) and limited to the area of coronary artery ligation, whereas in CCP hearts the infarct was larger (48% of myocardium; p = 0.029) and myocardial necrosis was distributed unevenly to the left ventricular wall. Conclusions In a rat model of acute myocardial infarction followed by cardioplegic arrest, application of BCP leads to better myocardial recovery than CCP.

Left ventricular wave speed

2001 ◽  
Vol 91 (6) ◽  
pp. 2531-2536 ◽  
Author(s):  
Jiun-Jr Wang ◽  
Kim H. Parker ◽  
John V. Tyberg
Keyword(s):  
Wave Speed ◽  
Pulse Generator ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Cross Sectional ◽  
Pressure Transducers ◽  
Pressure Area ◽  
Axis Length

Left ventricular (LV) wave speed (LVWS) was studied experimentally and confirmed in theory. Combining the definition of elastance (E) with the equations for the conservation of mass and momentum shows that LVWS is proportional to the square root of E LA, where L is long-axis length and A is the cross-sectional area, and the density of the blood. (We defined E LA = γ, where γ is compressibility.) We studied nine open chest, anesthetized dogs, three of which were studied during caval constriction when LV end-diastolic pressure was ≤0 mmHg. The hearts were paced at ∼90 beats/min, and LV cross-sectional area was measured by using two pairs of ultrasonic crystals; E was calculated from the LV pressure-area loop. A pulse generator was connected to the LV apex, and LVWS was measured by using two pressure transducers: one near the apex and the other near the base. Their distance was measured roentgenographically and compared with the diameter of a reference ball. LVWS ranged from ∼1 m/s during diastole to ∼10 m/s during systole. The slope of the log c(where c is wave speed) vs. log γ was 0.546, which is in agreement with theory (0.5). When γ ≤ 0, LVWS was ∼1.5 m/s.

scholarly journals HGF Treatment Promotes Cardiac Function and Cardiac Repair: Meta-analysis of Pig Models With Myocardial Infarction

2020 ◽  
Author(s):  
Chong Du ◽  
Xiao-Wen Chen ◽  
Ze-Mu Wang ◽  
Hao-Yu Meng ◽  
Ya-Fei Li ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Growth Factor ◽  
Cardiac Function ◽  
Infarct Size ◽  
Meta Analysis ◽  
Left Ventricular ◽  
Cardiac Repair ◽  
Control Group ◽  
Hepatocyte Growth ◽  
Better Than

Abstract Background: Previous studies reported that hepatocyte growth factor (HGF) could promote angiogenesis and cardiac function after myocardial infarction (MI) in pigs. However, the results of these studies were controversial. To clarify the therapeutic efficacy of local HGF administration after MI, we performed a systematic review and meta-analysis of data from the pig models, which could provide evidence for the feasibility of clinical HGF application.Methods: PubMed, EMBASE, and China National Knowledge Infrastructure were searched for randomized studies that correspond to our subject. The search terms included (hepatocyte growth factor OR HGF) AND (heart failure OR HF OR myocardial infarction OR MI OR AMI OR coronary heart disease OR CHD). The primary endpoint indicators were identified as the left ventricular ejection fraction (LVEF) and capillaries density. Other parameters reflecting cardiac function and ventricular remodeling were analyzed as secondary indicators, including ventricular volume, infarct size, apoptotic index and others.Results: In total, 9 studies were finally included in the meta-analysis. On comparing the cardiac function indexes, the HGF group was found to be better than the control group in regard to LVEF, stroke volume, left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV). However, no statistically significant differences were found in heart rate. Furthermore, HGF treatment promotes angiogenesis in ischemic areas, which is manifested by increased capillary density. In addition, the HGF group was found to be better than the control group when it comes to infarct size, arteriole densities, and other indicators of cardiac remodeling.Conclusions: HGF treatment can effectively promote cardiac function and cardiac repair including angiogenesis, and this strategy is a promising cardio-protective approach that merits further clinical studies.

Left atrial cross-sectional area is a novel measure of atrial shape associated with cardioembolic strokes

Heart ◽  
2020 ◽  
Vol 106 (15) ◽  
pp. 1176-1182
Author(s):  
Timothy C Tan ◽  
Maria Carmo Pereira Nunes ◽  
Mark Handschumacher ◽  
Octavio Pontes-Neto ◽  
Yong-Hyun Park ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Flow Velocity ◽  
Left Atrial ◽  
Velocity Profiles ◽  
Left Ventricular ◽  
Cross Sectional Area ◽  
Left Ventricular Ejection ◽  
Sectional Area ◽  
Cross Sectional

ObjectiveCardioembolic (CE) stroke carries significant morbidity and mortality. Left atrial (LA) size has been associated with CE risk. We hypothesised that differential LA remodelling impacts on pathophysiological mechanism of major CE strokes.MethodsA cohort of consecutive patients hospitalised with ischaemic stroke, classified into CE versus non-CE strokes using the Causative Classification System for Ischaemic Stroke were enrolled. LA shape and remodelling was characterised by assessing differences in maximal LA cross-sectional area (LA-CSA) in a cohort of 40 prospectively recruited patients with ischaemic stroke using three-dimensional (3D) echocardiography. Flow velocity profiles were measured in spherical versus ellipsoidal in vitro models to determine if LA shape influences flow dynamics. Two-dimensional (2D) LA-CSA was subsequently derived from standard echocardiographic views and compared with 3D LA-CSA.ResultsA total of 1023 patients with ischaemic stroke were included, 230 (22.5%) of them were classified as major CE. The mean age was 68±16 years, and 464 (45%) were women. The 2D calculated LA-CSA correlated strongly with the LA-CSA measured by 3D in both end-systole and end-diastole. In vitro flow models showed shape-related differences in mid-level flow velocity profiles. Increased LA-CSA was associated with major CE stroke (adjusted relative risk 1.10, 95% CI 1.04 to 1.16; p<0.001), independent of age, gender, atrial fibrillation, left ventricular ejection fraction and CHA2DS2-VASc score. Specifically, the inclusion of LA-CSA in a model with traditional risk factors for CE stroke resulted in significant improvement in model performance with the net reclassification improvement of 0.346 (95% CI 0.189 to 0.501; p=0.00001) and the integrated discrimination improvement of 0.013 (95% CI 0.003 to 0.024; p=0.0119).ConclusionsLA-CSA is a marker of adverse LA shape associated with CE stroke, reflecting importance of differential LA remodelling, not simply LA size, in the mechanism of CE risk.

Sign in / Sign up

Export Citation Format

Share Document