Large- and Medium-sized Arteries Remaining in Transmural Scar Distal to Permanent Coronary Ligation Undergo Neointimal Hyperplasia and Inward Remodeling

2021 ◽  
Vol 69 (5) ◽  
pp. 321-338
Author(s):  
Eduard I. Dedkov
Keyword(s):  
Structural Integrity ◽  
Neointimal Hyperplasia ◽  
Coronary Artery Ligation ◽  
Sprague Dawley ◽  
Artery Ligation ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Coronary Ligation ◽  
Extracellular Matrix Components ◽  
Vessel Integrity

This study aimed to investigate the structural integrity and dynamic changes in chronically occluded residual arteries found in post–myocardial infarction (MI) scar. A transmural MI was induced in middle-aged, male Sprague-Dawley rats by left coronary artery ligation. The rats were euthanized 3 days and 1, 2, 4, 8, and 12 weeks after MI, and their hearts were processed into paraffin for histology, immunohistochemistry, and quantitative morphometry. It has been found that large- and medium-sized arteries were able to survive inside the transmural scars for 12 post-MI weeks. Furthermore, most residual arteries preserved their structural integrity for up to 2 weeks post-MI, but gradually all disused vessels had undergone neointimal hyperplasia and inward remodeling at later time periods. In addition, the replacement of vascular smooth muscle cells in the wall of residual arteries by extracellular matrix components led to a disruption of the vessel integrity and progressive obliteration of their lumen between 4 and 12 post-MI weeks. Taken together, this study demonstrate that residual arteries in post-infarcted region were capable of maintaining their structural integrity, including the patent lumen, during two post-MI weeks, suggesting that during this period they can be used as potential conduits for conceivable reflow of arterial blood within the scarred region of the heart

Infarct size is increased in female post-MI rats treated with rapamycin

2009 ◽  
Vol 87 (6) ◽  
pp. 460-470 ◽  
Author(s):  
Claude Lajoie ◽  
Viviane El-Helou ◽  
Cindy Proulx ◽  
Robert Clément ◽  
Hugues Gosselin ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Female Rats ◽  
Coronary Artery Ligation ◽  
Female Rat ◽  
Sprague Dawley ◽  
Ischemic Insult ◽  
Fibrotic Response ◽  
Artery Ligation ◽  
Sprague Dawley Rats ◽  
Scar Healing

Rapamycin represents a recognized drug-based therapeutic approach to treat cardiovascular disease. However, at least in the female heart, rapamycin may suppress the recruitment of putative signalling events conferring cardioprotection. The present study tested the hypothesis that rapamycin-sensitive signalling events contributed to the cardioprotective phenotype of the female rat heart after an ischemic insult. Rapamycin (1.5 mg/kg) was administered to adult female Sprague–Dawley rats 24 h after complete coronary artery ligation and continued for 6 days. Rapamycin abrogated p70S6K phosphorylation in the left ventricle of sham rats and the noninfarcted left ventricle (NILV) of 1-week postmyocardial-infarcted (MI) rats. Scar weight (MI 0.028 ± 0.006, MI+rapamycin 0.064 ± 0.004 g) and surface area (MI 0.37 ± 0.08, MI+rapamycin 0.74 ± 0.03 cm2) were significantly larger in rapamycin-treated post-MI rats. In the NILV of post-MI female rats, rapamycin inhibited the upregulation of eNOS. Furthermore, the increased expression of collagen and TGF-β3 mRNAs in the NILV were attenuated in rapamycin-treated post-MI rats, whereas scar healing was unaffected. The present study has demonstrated that rapamycin-sensitive signalling events were implicated in scar formation and reactive fibrosis. Rapamycin-mediated suppression of eNOS and TGF-β3 mRNA in post-MI female rats may have directly contributed to the larger infarct and attenuation of the reactive fibrotic response, respectively.

Oxidative stress contributes to vascular endothelial dysfunction in heart failure

2001 ◽  
Vol 281 (4) ◽  
pp. H1767-H1770 ◽  
Author(s):  
Julia H. Indik ◽  
Steven Goldman ◽  
Mohamed A. Gaballa
Keyword(s):  
Heart Failure ◽  
Normal Control ◽  
Coronary Artery Ligation ◽  
No Production ◽  
Vascular Endothelial ◽  
Sprague Dawley ◽  
Artery Ligation ◽  
Sod Activity ◽  
Sprague Dawley Rats ◽  
Peripheral Arterial

Congestive heart failure (HF) is characterized by inadequate nitric oxide (NO) production in the vasculature. Because NO is degraded by oxygen radicals, we hypothesized that NO is degraded faster in HF from inadequate peripheral arterial antioxidant reserves. HF was induced in male Sprague-Dawley rats by left coronary artery ligation. Vascular endothelial function was evaluated by measuring the NO-mediated vasorelaxation response to acetylcholine (ACh; 10−9–10−4M) in excised aortas. This was repeated with the free radical generator pyrogallol (20 μM) and again with pyrogallol and superoxide dismutase (SOD; 60 U/ml). Aortic and myocardial SOD activity was also determined. ACh-induced vasorelaxation was reduced in HF ( n = 9) compared with normal control rats ( n = 11; P < 0.001). Pyrogallol further reduced vasorelaxation in HF: 74 ± 11% at 10−4M ACh versus 58 ± 10% in normal control rats ( P < 0.004). There was a trend ( P = 0.06) toward reduced SOD activity in HF aortas. In conclusion, altered NO-dependent vasorelaxation in HF is in part due to excessive degradation of NO and is likely related to reduced vascular SOD activity.

Modulating the Infarcted Ventricle’s Refractoriness with an Epicardial Biomaterial

2020 ◽  
pp. jim-2020-001486 ◽  
Author(s):  
Ikeotunye Royal Chinyere ◽  
Mathew Hutchinson ◽  
Talal Moukabary ◽  
Jen Watson Koevary ◽  
Elizabeth Juneman ◽  
...  
Keyword(s):  
Dermal Fibroblasts ◽  
Monophasic Action Potential ◽  
Coronary Artery Ligation ◽  
Sprague Dawley ◽  
Electrophysiologic Study ◽  
Artery Ligation ◽  
Reduced Ejection Fraction ◽  
Sprague Dawley Rats ◽  
Increased Risk ◽  
Reentrant Circuit

Patients diagnosed with heart failure with reduced ejection fraction (HFrEF) are at increased risk of monomorphic ventricular tachycardia (VT) and ventricular fibrillation. The presence of myocardial fibrosis provides both anatomical and functional barriers that promote arrhythmias in these patients. Propagation of VT in a reentrant circuit depends on the presence of excitable myocardium and the refractoriness of the circuit. We hypothesize that myocardial refractoriness can be modulated surgically in a model of HFrEF, leading to decreased susceptibility to VT.Male Sprague-Dawley rats were infarcted via permanent left coronary artery ligation. At 3 weeks post-infarction, engineered grafts composed of human dermal fibroblasts cultured into a polyglactin-910 biomaterial were implanted onto the epicardium to cover the area of infarction. Three weeks post-graft treatment, all rats underwent a terminal electrophysiologic study to compare monophasic action potential electroanatomic maps and susceptibility to inducible monomorphic VT.HFrEF rats (n=29) demonstrated a longer (p=0.0191) ventricular effective refractory period (ERP) and a greater (p=0.0394) VT inducibility compared with sham (n=7). HFrEF rats treated with the graft (n=12) exhibited no change in capture threshold (p=0.3220), but had a longer ventricular ERP (p=0.0029) compared with HFrEF. No statistically significant change in VT incidence was found between HFrEF rats treated with the graft and untreated HFrEF rats (p=0.0834).Surgical deployment of a fibroblast-containing biomaterial in a rodent ischemic cardiomyopathy model prolonged ventricular ERP as measured by programmed electrical stimulation. This hypothesis-generating study warrants additional studies to further characterize the antiarrhythmic or proarrhythmic effects of this novel surgical therapy.

scholarly journals Angiotensin II-mediated posttranslational modification of nNOS in the PVN of rats with CHF: role for PIN

2013 ◽  
Vol 305 (6) ◽  
pp. H843-H855 ◽  
Author(s):  
Neeru M. Sharma ◽  
Tamra L. Llewellyn ◽  
Hong Zheng ◽  
Kaushik P. Patel
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Molecular Mechanism ◽  
Neuronal Cell ◽  
Coronary Artery Ligation ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Artery Ligation ◽  
Sprague Dawley Rats ◽  
Catalytically Active

An increased sympathetic drive is an adverse characteristic in chronic heart failure (CHF). The protein expression of neuronal nitric oxide synthase (nNOS)- and hence nitric oxide (NO)-mediated sympathoinhibition is reduced in the paraventricular nucleus (PVN) of rats with CHF. However, the molecular mechanism(s) of nNOS downregulation remain(s) unclear. The aim of the study was to reveal the underlying molecular mechanism for the downregulation of nNOS in the PVN of CHF rats. Sprague-Dawley rats with CHF (6–8 wk after coronary artery ligation) demonstrated decreased nNOS dimer/monomer ratio (42%), with a concomitant increase in the expression of PIN (a protein inhibitor of nNOS known to dissociate nNOS dimers into monomers) by 47% in the PVN. Similarly, PIN expression is increased in a neuronal cell line (NG108) treated with angiotensin II (ANG II). Furthermore, there is an increased accumulation of high-molecular-weight nNOS-ubiquitin (nNOS-Ub) conjugates in the PVN of CHF rats (29%). ANG II treatment in NG108 cells in the presence of a proteasome inhibitor, lactacystin, also leads to a 69% increase in accumulation of nNOS-Ub conjugates immunoprecipitated by an antiubiquitin antibody. There is an ANG II-driven, PIN-mediated decrease in the dimeric catalytically active nNOS in the PVN, due to ubiquitin-dependent proteolytic degradation in CHF. Our results show a novel intermediary mechanism that leads to decreased levels of active nNOS in the PVN, involved in subsequent reduction in sympathoinhibition during CHF, offering a new target for the treatment of CHF and other cardiovascular diseases.

scholarly journals Increased superoxide levels in ganglia and sympathoexcitation are involved in sarafotoxin 6c-induced hypertension

2008 ◽  
Vol 295 (5) ◽  
pp. R1546-R1554 ◽  
Author(s):  
Melissa Li ◽  
Xiaoling Dai ◽  
Stephanie Watts ◽  
David Kreulen ◽  
Gregory Fink
Keyword(s):  
Blood Pressure ◽  
Sympathetic Innervation ◽  
Sympathetic Ganglia ◽  
Plasma Norepinephrine ◽  
Sprague Dawley ◽  
Surgical Ablation ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Induced Hypertension ◽  
Hypertension Development

Endothelin (ET) type B receptors (ETBR) are expressed in multiple tissues and perform different functions depending on their location. ETBR mediate endothelium-dependent vasodilation, clearance of circulating ET, and diuretic effects; all of these should produce a fall in arterial blood pressure. However, we recently showed that chronic activation of ETBR in rats with the selective agonist sarafotoxin 6c (S6c) causes sustained hypertension. We have proposed that one mechanism of this effect is constriction of capacitance vessels. The current study was performed to determine whether S6c hypertension is caused by increased generation of reactive oxygen species (ROS) and/or activation of the sympathetic nervous system. The model used was continuous 5-day infusion of S6c into male Sprague-Dawley rats. No changes in superoxide anion levels in arteries and veins were found in hypertensive S6c-treated rats. However, superoxide levels were increased in sympathetic ganglia from S6c-treated rats. In addition, superoxide levels in ganglia increased progressively the longer the animals received S6c. Treatment with the antioxidant tempol impaired S6c-induced hypertension and decreased superoxide levels in ganglia. Acute ganglion blockade lowered blood pressure more in S6c-treated rats than in vehicle-treated rats. Although plasma norepinephrine levels were not increased in S6c hypertension, surgical ablation of the celiac ganglion plexus, which provides most of the sympathetic innervation to the splanchnic organs, significantly attenuated hypertension development. The results suggest that S6c-induced hypertension is partially mediated by sympathoexcitation to the splanchnic organs driven by increased oxidative stress in prevertebral sympathetic ganglia.

Parathyroid Hormone- and Deoxycorticosterone Acetate-Induced Hypertension in the Rat

1980 ◽  
Vol 58 (5) ◽  
pp. 365-371 ◽  
Author(s):  
A. Berthelot ◽  
A. Gairard
Keyword(s):  
Parathyroid Hormone ◽  
Hormone Secretion ◽  
Sprague Dawley ◽  
Physiological Concentration ◽  
Deoxycorticosterone Acetate ◽  
Calcium Diet ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
High Calcium ◽  
High Calcium Diet

1. Hypertension induced by treatment with deoxycorticosterone acetate and sodium chloride was studied in male Sprague-Dawley rats and related to parathyroid hormone secretion. 2. Lack of parathyroid hormone (due to parathyroidectomy) or decreased parathormone secretion (due to a high-calcium diet) partially inhibited the development of arterial hypertension. 3. In contrast, in thyroparathyroidectomized rats supplemented with thyroxine, the administration of parathyroid hormone rapidly elevated arterial blood pressure. 4. Maintaining a physiological concentration of serum calcium in the absence of parathyroid hormone (by feeding a high-calcium diet to parathyroidectomized rats) was not sufficient to establish mineralocorticoid hypertension. 5. These results show that parathyroid hormone is necessary for the complete development of mineralocorticoid hypertension.

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.

Exercise training and its effects with renal hypertensive rats

1985 ◽  
Vol 59 (5) ◽  
pp. 1410-1415 ◽  
Author(s):  
K. D. Marcus ◽  
C. M. Tipton
Keyword(s):  
Blood Pressure ◽  
Exercise Training ◽  
Capillary Density ◽  
Heart Weight ◽  
Sprague Dawley ◽  
Vo2 Max ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Resting Blood Pressure ◽  
Renal Hypertensive Rats

The influence of endurance training on functional capacity [maximal O2 consumption (VO2 max)], caudal arterial blood pressure, and myocardial capillary density were investigated in normotensive rats and rats made hypertensive using the two-kidney one-clip approach (Goldblatt's hypertension). Male Sprague-Dawley rats were assigned to sham (N: 120–140 mmHg), moderately hypertensive (MH = 0.30-mm clips, 150–170 mmHg), or severely hypertensive (SH = 0.25-mm clips, 190–230 mmHg) groups. Rats designated to be runners (T) were exercised on a motor-driven treadmill equal to 50–70% of their VO2 max values for 8–12 wk. Compared with their nontrained (NT) controls, training was associated with significantly higher VO2 max values (12–15%) and muscle cytochrome-c oxidase activities (33–78%). Resting systolic blood pressure was not significantly changed in the N-and MH-T subgroups; however, it was 20–30 mmHg higher in the SH-T subgroup. Mean absolute heart weight for only the N-T group was significantly heavier than their NT controls. However, the mean predicted heart weights (heart wt = 0.639 X body wt of N-NT + 0.001 g) of the two SH groups were significantly higher than expected. The SH-T group had a lower (11%) subepicardial capillary density mean than its NT control and significantly fewer capillaries in the subendocardial region than the other five subgroups. It was concluded that moderate exercise training appeared to be detrimental to rats with severe hypertension because it increased resting blood pressure and decreased myocardial capillary density, even though it improved their functioning capacity.

Increased renal α-ENaC and NCC abundance and elevated blood pressure are independent of hyperaldosteronism in vasopressin escape

2006 ◽  
Vol 291 (1) ◽  
pp. F49-F57 ◽  
Author(s):  
Swasti Tiwari ◽  
Randall K. Packer ◽  
Xinqun Hu ◽  
Yoshihisa Sugimura ◽  
Joseph G. Verbalis ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Urine Volume ◽  
Sprague Dawley ◽  
Α Subunit ◽  
Water Load ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Solid Diet ◽  
Epithelial Sodium Channel Enac

Previously, we demonstrated that rats undergoing vasopressin escape had increased mean arterial blood pressure (MAP), plasma and urine aldosterone, and increased renal protein abundance of the α-subunit of the epithelial sodium channel (ENaC), the thiazide-sensitive Na-Cl cotransporter (NCC), and the 70-kDa band of γ-ENaC (Song J, Hu X, Khan O, Tian Y, Verbalis JG, and Ecelbarger CA. Am J Physiol Renal Physiol 287: F1076–F1083, 2004; Ecelbarger CA, Knepper MA, and Verbalis JG. J Am Soc Nephrol 12: 207–217, 2001). Here, we determine whether changes in these renal proteins and MAP require elevated aldosterone levels. We performed adrenalectomies (ADX) or sham surgeries on male Sprague-Dawley rats. Corticosterone and aldosterone were replaced to clamp these hormone levels. MAP was monitored by radiotelemetry. Rats were infused with 1-deamino-[8-d-arginine]-vasopressin (dDAVP) via osmotic minipumps (5 ng/h). At day 3 of dDAVP infusion, seven rats in each group were offered a liquid diet [water load (WL)] or continued on a solid diet (SD). Plasma aldosterone and corticosterone and urine aldosterone were increased by WL in sham rats. ADX-WL rats escaped, as assessed by early natriuresis followed by diuresis; however, urine volume and natriuresis were somewhat blunted. WL did not reduce the abundance or activity of 11-β-hydroxsteroid dehydrogenase type 2. Furthermore, the previously observed increase in renal aldosterone-sensitive proteins and escape-associated increased MAP persisted in clamped rats. The densitometry of immunoblots for NCC, α- and γ-70 kDa ENaC, respectively, were (% sham-SD): sham-WL, 159, 278, 233; ADX-SD, 69, 212, 171; ADX-WL, 116, 302, 161. However, clamping corticosteroids blunted the rise at least for NCC and γ-ENaC (70 kDa). Overall, the increase in aldosterone observed in vasopressin escape is not necessary for the increased expression of NCC, α- or γ-ENaC or increased MAP associated with “escape.”

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