Coronary artery ligation and reperfusion in rabbits made diabetic with alloxan

1987 ◽  
Vol 112 (1) ◽  
pp. 43-49 ◽  
Author(s):  
S. Bhimji ◽  
D. V. Godin ◽  
J. H. McNeill
Keyword(s):  
Coronary Artery ◽  
Left Ventricular Pressure ◽  
Clinical Situation ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Coronary Artery Ligation ◽  
Mitochondrial Atpase ◽  
Artery Ligation ◽  
Functional Changes

ABSTRACT The biochemical and functional changes associated with ligation (40 min) of the left circumflex coronary artery and subsequent reperfusion (60 min) in the rabbit made diabetic with alloxan were studied and compared with those of control animals. Measurement of haemodynamic parameters revealed that both left ventricular pressure and mean arterial pressure were significantly (P < 0·05) decreased after ligation and reperfusion in the diabetic animals compared with controls. Analysis of subcellular organelle enzyme markers from the ischaemic tissue revealed that sarcolemmal Na+,K+-ATPase, mitochondrial ATPase and sarcoplasmic reticulum ATPase activities were decreased after ligation to the same extent in the diabetic and control animals. However, upon reperfusion, the recovery of mitochondrial ATPase activity was significantly (P < 0·05) less in the diabetic animals than in the controls. Ion measurements revealed a significant (P < 0·05) depletion of Mg in diabetic hearts before ligation, and this was augmented during reperfusion. In contrast, a significantly (P < 0·05) higher calcium accumulation was observed upon reperfusion in the hearts of diabetic animals. Similarly, both tissue ATP levels and the ability of the mitochondria to generate ATP were depressed to a greater degree in the diabetic animals. Our results indicate, therefore, a greater susceptibility of the diabetic myocardium to ischaemic/reperfusion injury which in the clinical situation would exacerbate the problems associated with atherosclerosis and possibly contribute to the high mortality from cardiovascular complications in diabetic patients. J. Endocr. (1987) 112, 43–49

Abstract 132: Cardiomyocyte Specific Conditional Overexpression Of Stromal Cell Derived Factor 1 Facilitates Cardiac Regeneration After Permanent Coronary Artery Ligation In Mice.

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Detlef Obal ◽  
Kenneth Brittian ◽  
Michael Book ◽  
Aruni Bhatnagar ◽  
Yiru Guo ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Stromal Cell ◽  
Cardiac Regeneration ◽  
Left Ventricular ◽  
Border Zone ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Casein Kinase 1 ◽  
Coronary Ligation ◽  
Stromal Cell Derived Factor

Background: Interruption of cardiac stromal cell derived factor 1 (SDF1)-CXCR4 axis by chronic AMD3100 administration increased myocardial injury after permanent coronary artery ligation demonstrating the important role of this chemokine in cardiac regeneration. Hypothesis: Cardiomyocyte specific conditional overexpression of SDF1 prevents heart failure after permanent coronary ligation and facilitates cardiac regeneration. Methods and Results: Tetracycline-controlled, αMyHC promoter directed overexpression of cardiac SDF1, resulted in a significant increase of SDF1 expression (SDF1: 8.1 ng/mg protein) compared to littermate WT mice (0.02 ng/mg protein) four weeks after doxycycline withdraw. SDF1 overexpression increased AKT and casein kinase 1 levels in the heart. Although there was no difference in cardiac function and scar size 1 week after infarction, SDF1 overexpression improved left ventricular (LV) ejection fraction (SDF1 [n=13]: 47±5% [mean±SEM] vs. WT [n=15]: 29±4%, p<0.05) decreased end-diastolic volume (78±10 vs. 158±30, p<0.05) and reduced infarct size measured by trichrome staining (13±3% vs. 23±3% of LV wall, p<0.05) 4 weeks after permanent ligation. Bromodeoxyuridine (BrdU) staining revealed increased regeneration indicated by a 5-fold increase in BrdU + cardiomyocyte (CM) nuclei in the borderzone of the infarct (22±3% vs. 5±1% CM nuclei, p<0.01). Increased proliferation in SDF1 mice was confirmed by a higher number of KI67 + cells compared to WT mice. Cardiomyocyte cross sectional area in the border zone was significantly reduced in SDF1 mice (365±13 μm 2 vs. 434±10 μm 2 , p<0.001) while capillary density was unchanged (2348±151/ mm 2 vs. 2498±153/ mm 2 ) compared to WT mice. Conclusion: This study demonstrates for the first time that cardiac specific overexpression of SDF1 increases myocardial regeneration and improves LV function 4 weeks after permanent coronary ligation.

Comparison of Myocardial Infarction with Sequential Ligation of the Left Anterior Descending Artery and Its Diagonal Branch in Dogs and Sheep

2003 ◽  
Vol 26 (4) ◽  
pp. 351-357 ◽  
Author(s):  
W.G. Kim ◽  
Y.C. Shin ◽  
S.W. Hwang ◽  
C. Lee ◽  
C.Y. Na
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Pulmonary Artery ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Suitable Model ◽  
Artery Ligation ◽  
Diagonal Branch ◽  
Left Anterior Descending Artery ◽  
Arterial Blood

We report a comparison of the effects of myocardial infarction in dogs and sheep using sequential ligation of the left anterior descending artery (LAD) and its diagonal branch (DA), with hemodynamic, ultrasonographic and pathological evaluations. Five animals were used in each group. After surgical preparation, the LAD was ligated at a point approximately 40% of the distance from the apex to the base of the heart, and after one hour, the DA was ligated at the same level. Hemodynamic and ultrasonographic measurements were performed preligation, 30 minutes after LAD ligation, and 1 hour after DA ligation. As a control, two animals in each group were used for the simultaneous ligation of the LAD and the DA. Two months after the coronary ligation, the animals were evaluated as previously, and killed for postmortem examination of their hearts. All seven animals in the dog group survived the experimental procedures, while in the sheep group only animals with sequential ligation of the LAD and DA survived. Statistically significant decreases in systemic arterial blood pressure and cardiac output, and an increase in the pulmonary artery capillary wedge pressure (PACWP) were observed one hour after sequential ligation of the LAD and its DA in the sheep, while only systemic arterial pressures decreased in the dog. Ultrasonographic analyses demonstrated variable degrees of anteroseptal dyskinesia and akinesia in all sheep, but in no dogs. Data two months after coronary artery ligation showed significant increases in central venous pressure, pulmonary artery pressure, and PACWP in the sheep, but not in the dog. Left ventricular end-diastolic dimension and left ventricular end-systolic dimension in ultrasonographic studies were also increased only in the sheep. Pathologically, the well-demarcated thin-walled transmural anteroseptal infarcts with chamber enlargement were clearly seen in all specimens of sheep, and only-mild-to-moderate chamber enlargements with endocardial fibrosis were observed in the dog hearts. In conclusion, this study confirms that the dog is not a suitable model for myocardial infarction with failure by coronary artery ligation despite negligent operative mortality, when compared directly with an ovine model.

scholarly journals Mitigation of the progression of heart failure with sildenafil involves inhibition of RhoA/Rho-kinase pathway

2011 ◽  
Vol 300 (6) ◽  
pp. H2272-H2279 ◽  
Author(s):  
Vinh Q. Chau ◽  
Fadi N. Salloum ◽  
Nicholas N. Hoke ◽  
Antonio Abbate ◽  
Rakesh C. Kukreja
Keyword(s):  
Heart Failure ◽  
Coronary Artery ◽  
Rho Kinase ◽  
Inhibitory Effect ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Saline Treatment ◽  
Kinase Pathway ◽  
Fractional Shortening

Chronic inhibition of phosphodiesterase-5 with sildenafil immediately after permanent occlusion of the left anterior descending coronary artery was shown to limit ischemic heart failure (HF) in mice. To mimic a more clinical scenario, we postulated that treatment with sildenafil beginning at 3 days post-myocardial infarction (MI) would also reduce HF progression through the inhibition of the RhoA/Rho-kinase pathway. Adult male ICR mice with fractional shortening < 25% at day 3 following permanent left anterior descending coronary artery ligation were continuously treated with either saline (volume matched, ip, 2 times/day) or sildenafil (21 mg/kg, ip, 2 times/day) for 25 days. Echocardiography showed fractional shortening preservation and less left ventricular end-diastolic dilatation with sildenafil treatment compared with saline treatment at 7 and 28 days post-MI ( P < 0.05). Both fibrosis and apoptosis, determined by Masson's trichrome and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL), respectively, were attenuated in the sildenafil-treated mice ( P < 0.05 vs. saline). Western blot analysis showed enchanced Bcl-2-to-Bax ratio with sildenafil treatment ( P < 0.05 vs. saline). Activity assay showed sildenafil-mediated PKG activation 1 day after treatment ( P < 0.05 vs. sham and saline). PKG activation was associated with sildenafil-mediated inhibition of Rho kinase ( P < 0.05) compared with saline treatment, whereas PKG inhibition with KT-5823 abolished this inhibitory effect of sildenafil. In conclusion, for the first time, our findings show that chronic sildenafil treatment, initiated at 3 days post-MI, attenuates left ventricular dysfunction independent of its infarct-sparing effect, and this cardioprotection involves the inhibition of the RhoA/Rho-kinase pathway. Sildenafil may be a promising therapeutic tool for advanced HF in patients.

scholarly journals Clofibrate Treatment Decreases Inflammation and Reverses Myocardial Infarction-Induced Remodelation in a Rodent Experimental Model

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 270 ◽  
Author(s):  
Luz Ibarra-Lara ◽  
María Sánchez-Aguilar ◽  
Elizabeth Soria-Castro ◽  
Jesús Vargas-Barrón ◽  
Francisco Roldán ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Cardiac Remodeling ◽  
Ventricular Remodeling ◽  
Ex Vivo ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Cardiac Damage ◽  
Artery Ligation ◽  
Apoptotic Proteins

Myocardial infarction (MI) initiates an inflammatory response that promotes both beneficial and deleterious effects. The early response helps the myocardium to remove damaged tissue; however, a prolonged later response brings cardiac remodeling characterized by functional, metabolic, and structural pathological changes. Current pharmacological treatments have failed to reverse ischemic-induced cardiac damage. Therefore, our aim was to study if clofibrate treatment was capable of decreasing inflammation and apoptosis, and reverse ventricular remodeling and MI-induced functional damage. Male Wistar rats were assigned to (1) Sham coronary artery ligation (Sham) or (2) Coronary artery ligation (MI). Seven days post-MI, animals were further divided to receive vehicle (V) or clofibrate (100 mg/kg, C) for 7 days. The expression of IL-6, TNF-α, and inflammatory related molecules ICAM-1, VCAM-1, MMP-2 and -9, nuclear NF-kB, and iNOS, were elevated in MI-V. These inflammatory biomarkers decreased in MI-C. Also, apoptotic proteins (Bax and pBad) were elevated in MI-V, while clofibrate augmented anti-apoptotic proteins (Bcl-2 and 14-3-3ε). Clofibrate also protected MI-induced changes in ultra-structure. The ex vivo evaluation of myocardial functioning showed that left ventricular pressure and mechanical work decreased in infarcted rats; clofibrate treatment raised those parameters to control values. Echocardiogram showed that clofibrate partially reduced LV dilation. In conclusion, clofibrate decreases cardiac remodeling, decreases inflammatory molecules, and partly preserves myocardial diameters.

Changes in cardiac ANG II postmyocardial infarction in rats: effects of nephrectomy and ACE inhibitors

1999 ◽  
Vol 276 (1) ◽  
pp. H317-H325 ◽  
Author(s):  
Frans H. H. Leenen ◽  
Vaclav Skarda ◽  
Baoxue Yuan ◽  
Roselyn White
Keyword(s):  
Coronary Artery ◽  
Ace Inhibitors ◽  
Time Course ◽  
Cardiac Tissue ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Ang Ii ◽  
Artery Ligation ◽  
Conscious Rats ◽  
Postmyocardial Infarction

We evaluated in rats the time course of changes in cardiac versus plasma ANG I and II postmyocardial infarction (MI) and the effects of nephrectomy and angiotensin-converting enzyme (ACE) inhibitors on the early changes post-MI. Acute coronary artery ligation was induced in conscious rats using the two-stage model, and plasma and cardiac tissue were obtained shortly (6 h, 1 and 3 days) and chronically (1, 4, and 8–9 wk) after MI. In an additional group of rats, bilateral nephrectomy was performed 18 h before the coronary artery ligation, and samples were obtained at 6 h post-MI. Furthermore, in two additional groups of rats, treatment with enalapril and quinapril was started 3 days before the ligation, and samples were obtained at 1 or 3 days post-MI. In these groups of rats, plasma and left ventricular (LV) (infarct and infarct free) ANG I and II were measured by RIA after separation on HPLC. In control rats, plasma ANG I and II showed a clear increase at 6 h post-MI but subsequently only minor increases were observed. In contrast, LV ANG II showed major increases at 6 h and 1 day post-MI, which had returned to normal by 3 days in the infarct-free LV and after 1(–2) wk in the infarct LV. LV ANG I showed a more gradual increase and remained elevated in the infarct up to 8–9 wk. Nephrectomy preceding the MI lowered ANG I and II in plasma but enhanced their increases in the heart at 6 h post-MI. Both ACE inhibitors decreased plasma ANG II associated with large increases in plasma ANG I. They also inhibited the increases in LV ANG II in both the infarct and infarct-free LV at 1 and 3 days post-MI with however no significant increase in LV ANG I. In conclusion, induction of a MI in conscious rats leads to rapid and marked, but only short-lived, increases in cardiac tissue ANG II in both the infarct and infarct-free parts of the LV. Pretreatment with ACE inhibitors, but not nephrectomy, blocks this increase. Local production appears to play a major role in the increases in cardiac ANG II post-MI.

Midterm Surgical Outcomes for ALCAPA Repair in Infants and Children

2021 ◽  
Author(s):  
Renjie Hu ◽  
Wen Zhang ◽  
Xiafeng Yu ◽  
Hongbin Zhu ◽  
Haibo Zhang ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Mitral Valve ◽  
Mitral Valve Regurgitation ◽  
Left Ventricular ◽  
Surgical Correction ◽  
Circulatory Support ◽  
Lv Function ◽  
Coronary Artery Ligation ◽  
Artery Ligation

Abstract Background Surgical correction of an anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) has been associated with excellent survival during recent years. The purpose of this study was to evaluate the effectiveness of reimplantation of the coronary artery and to investigate the recovery of postoperative cardiac and mitral valve (MV) function. Methods From 2005 to 2015, 80 patients who had ALCAPA received surgical correction. Among them, 49 were infants. The median patient age was 7.8 months. Operative strategies included reimplantation of the coronary artery in 71 patients, the Takeuchi procedure in another 7 patients, and coronary artery ligation in the remaining 2 patients. Results There were 11 hospital deaths and 2 late deaths. Six patients required intraoperative or postoperative mechanical circulatory support. A significant improvement in the ejection fraction (EF) and shortening fraction (SF) was present in all surviving patients at discharge, at a 3-month follow-up and at a 1-year follow-up. MV function improved gradually after surgical repair with no late secondary intervention. Conclusions The repair of ALCAPA can be accomplished by establishment of a dual-coronary system, which offers an acceptable mortality rate and will rarely require a second surgery. Left ventricular (LV) recovery is a progressive process, especially for infants with impaired LV function. Concomitant MV annuloplasty is safe and reliable and can be performed as necessary in patients with moderate or severe mitral valve regurgitation.

Abstract 3659: High-Mobility Group Box 1 Restores Cardiac Dysfunction after Myocardial Infarction in Transgenic Mice

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Tatsuro Kitahara ◽  
Yasuchika Takeishi ◽  
Tetsuro Shishido ◽  
Satoshi Suzuki ◽  
Shigehiko Kato ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Cardiac Dysfunction ◽  
Nuclear Dna ◽  
Inflammatory Responses ◽  
High Mobility ◽  
Left Ventricular ◽  
High Mobility Group ◽  
Coronary Artery Ligation ◽  
Artery Ligation

High-mobility group box 1 (HMGB1) is a nuclear DNA-binding protein and is released from necrotic cells, inducing inflammatory responses and promoting tissue repair and angiogenesis. To test the hypothesis that HMGB1 enhances angiogenesis and restores cardiac dysfunction after myocardial infarction, we generated transgenic mouse with cardiac specific overexpression of HMGB1 (HMGB1-Tg) using α-myosin heavy chain (MHC) promoter. The left anterior descending coronary artery was ligated in HMGB1-Tg and wild-type littermate (Wt) mice. After coronary artery ligation, HMGB1 was released into circulation from the necrotic cardiomyocytes of HMGB1 overexpressing hearts. The size of myocardial infarction was smaller in HMGB1-Tg than in Wt mice (figure ). Echocardiography and cardiac catheterization demonstrated that cardiac remodeling and dysfunction after myocardial infarction were prevented in HMGB1-Tg mice compared to Wt mice. Furthermore, survival rate after myocardial infarction in HMGB1-Tg mice was higher than that in Wt mice (figure ). Immunohistochemical staining revealed that capillary and arteriole formations after myocardial infarction were enhanced in HMGB1-Tg mice. We demonstrated the first in vivo evidence that HMGB1 enhances angiogenesis, restores cardiac dysfunction, and improves survival after myocardial infarction. These results may provide a novel therapeutic approach for left ventricular dysfunction after myocardial infarction.

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