-
Cardiovascular Engineering and... Feb 2022Sheep are the standard preclinical model for assessing safety of novel replacement heart valves, yet the anatomic and pathologic effects of invasive surgery, including...
PURPOSE
Sheep are the standard preclinical model for assessing safety of novel replacement heart valves, yet the anatomic and pathologic effects of invasive surgery, including those involving cardiopulmonary bypass (CPB), are unknown. Thus, we aimed to determine the gross, hematologic and biochemical effects of sham mitral and aortic replacement valve procedures in sheep to establish a useful control for evaluation of novel replacement valves.
METHODS
Six control sheep were examined without any surgical intervention. Six sham mitral valve replacements (MVR) and six sham aortic valve replacements (AVR) were performed on 12 sheep. Complete blood counts and serum biochemistry were performed throughout the study. Sheep were sacrificed with a necropsy performed at 90 days.
RESULTS
Renal infarcts (RIs) were the most frequently observed lesion, averaging 4.7 in control sheep, 2.5 with MVR and 5.8 with AVR. The number of infarcts strongly correlated with total estimated area of infarcted kidney (r = .84, p < .01). Additional cardiac interventions were significantly correlated with increased numbers of RIs (r = .85, p < .01). There was no correlation between number of RIs and time on CPB, or between AVR and MVR procedures.
CONCLUSION
The sheep model for AVR and MVR requires invasive surgery and CPB, which are associated with background anatomic and pathologic changes, especially in cases with additional surgical cardiac interventions. These findings serve as a critical control for future evaluation and development of novel replacement valves in order to distinguish device-related safety issues from expected outcomes of the surgical procedure and normal background changes in sheep.
Topics: Animals; Aortic Valve; Cardiac Surgical Procedures; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Infarction; Mitral Valve; Sheep
PubMed: 34263418
DOI: 10.1007/s13239-021-00563-6 -
Journal of the... Dec 2000Constitutive angiotensin-converting enzyme (ACE) is bound to endothelial cells where it serves to regulate circulating concentrations of angiotensin II (Ang II) that... (Review)
Review
Constitutive angiotensin-converting enzyme (ACE) is bound to endothelial cells where it serves to regulate circulating concentrations of angiotensin II (Ang II) that normally contribute to circulatory homeostasis. Recruitable ACE, bound to macrophage and myofibroblast cell membrane, regulates local concentrations of Ang II involved in tissue repair. De novo generation of Ang II modulates expression of TGF-beta1 whose autocrine/paracrine properties regulate collagen turnover at sites of fibrous tissue formation that appear in response to various forms of injury in diverse tissues. Persistent myofibroblasts and their ACE activity at the infarct site contribute to a sustained metabolic activity that can account for a progressive fibrosis at, and remote to, sites of myocardial infarction. Activation of the circulating renin-angiotensin-aldosterone system with sustained elevations in plasma Ang II and aldosterone induce a pro-inflammatory vascular phenotype of small arteries and arterioles. This further promotes the appearance of recruitable ACE bound to macrophages and myofibroblasts involved in vascular remodelling. Locally produced Ang II from these vascular sites leads to perivascular fibrosis of intramural coronary vasculature of non-infarcted myocardium. At these sites, remote to the infarct, such adverse structural remodelling by fibrous tissue eventuates in ICM, a major aetiologic factor involved in the appearance of chronic cardiac failure and contributes to its progressive nature.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Humans; Myocardial Infarction; Myocardium; Peptidyl-Dipeptidase A; Receptor, Angiotensin, Type 1; Reference Values; Wound Healing
PubMed: 11967815
DOI: 10.3317/jraas.2000.058 -
Brain and Behavior Aug 2023To explore the neural changes of brain activity in rats with circumscribed capsular infarcts to find a new therapeutic target for promoting the functional recovery.
BACKGROUND
To explore the neural changes of brain activity in rats with circumscribed capsular infarcts to find a new therapeutic target for promoting the functional recovery.
METHODS
A total of 18 capsular infarct rats and 18 normal rats were conducted in this study. All animal use procedures were strictly in accordance with the guide for the care and use of laboratory animals. After establishing the photothrombotic capsular infarct model, the functional magnetic resonance imaging (fMRI) data were collected and analyzed.
RESULTS
The fMRI results indicated that the passive movement would induce strong activation in caudate, putamen, frontal association somatosensory cortex, thalamus dorsolateral, and thalamus midline dorsal in control group, and the passive movement would only induce limited activation mostly in somatosensory cortex, thalamus dorsolateral, and thalamus midline dorsal in capsular infarct models. Capsular infarct makes the cortical activity weaken in sensory-related cortex and subcortical nuclei, including capsular area and thalamus.
CONCLUSIONS
Such findings imply that the posterior limb of internal capsule (PLIC) is connected to these structures in function, interacts together with them, and, accordingly, the lesion of PLIC manifests the related symptoms.
Topics: Humans; Rats; Animals; Stroke; Stroke Rehabilitation; Parietal Lobe; Internal Capsule; Magnetic Resonance Imaging; Infarction
PubMed: 37415300
DOI: 10.1002/brb3.3125 -
Journal of the American College of... Nov 2013This study sought to investigate the hypothesis that the favorable effects of mesenchymal stromal cells (MSCs) on infarct repair are mediated by macrophages.
OBJECTIVES
This study sought to investigate the hypothesis that the favorable effects of mesenchymal stromal cells (MSCs) on infarct repair are mediated by macrophages.
BACKGROUND
The favorable effects of MSC therapy in myocardial infarction (MI) are complex and not fully understood.
METHODS
We induced MI in mice and allocated them to bone marrow MSCs, mononuclear cells, or saline injection into the infarct, with and without early (4 h before MI) and late (3 days after MI) macrophage depletion. We then analyzed macrophage phenotype in the infarcted heart by flow cytometry and macrophage secretome in vitro. Left ventricular remodeling and global and regional function were assessed by echocardiography and speckle-tracking based strain imaging.
RESULTS
The MSC therapy significantly increased the percentage of reparative M2 macrophages (F4/80(+)CD206(+)) in the infarcted myocardium, compared with mononuclear- and saline-treated hearts, 3 and 4 days after MI. Macrophage cytokine secretion, relevant to infarct healing and repair, was significantly increased after MSC therapy, or incubation with MSCs or MSC supernatant. Significantly, with and without MSC therapy, transient macrophage depletion increased mortality 30 days after MI. Furthermore, early macrophage depletion produced the greatest negative effect on infarct size and left ventricular remodeling and function, as well as a significant incidence of left ventricular thrombus formation. These deleterious effects were attenuated with macrophage restoration and MSC therapy.
CONCLUSIONS
Some of the protective effects of MSCs on infarct repair are mediated by macrophages, which are essential for early healing and repair. Thus, targeting macrophages could be a novel strategy to improve infarct healing and repair.
Topics: Animals; Female; Heart; Macrophages; Mesenchymal Stem Cell Transplantation; Mice; Mice, Inbred BALB C; Myocardial Infarction; Regeneration
PubMed: 23973704
DOI: 10.1016/j.jacc.2013.07.057 -
Journal of Medical Case Reports Jun 2023Omental Infarction (OI) is uncommon and mimics common causes of acute abdomen. It is important to differentiate it from other abdominal conditions that require emergency...
BACKGROUND
Omental Infarction (OI) is uncommon and mimics common causes of acute abdomen. It is important to differentiate it from other abdominal conditions that require emergency management. It was first reported in literature in 1896 and about 400 cases have been reported till date.
CASE PRESENTATION
We reported on a 41 year-old Para 0 Ibo house wife who presented with 10 years history of supra-pubic mass and five months history of excessive menstrual flow. After physical examination, a diagnosis of symptomatic uterine fibroid was made. She had myomectomy and the raw surface created after the excision of the myomas was covered with omentum. Wound infection developed on the 8th post-operative day leading to a wound breakdown and later partial extrusion of infarcted omental tissue through the dehisced wound. During re-exploration, the infarcted omental tissue was extracted and the residual abdominal abscess was drained. Surgical site wound infection occurred on the 3rd day after re-operation and a sub-acute intestinal obstruction developed on the 4th day thereafter which responded to conservative management.
CONCLUSION
Careful surgical technique is imperative when utilizing the omentum for reconstructive abdominal surgery. Torsion of the omentum and creation of excess tension while using the omentum for reconstructive procedures should be avoided and increase awareness of this uncommon disease condition by the surgeon is also important. This case is to report a rare finding of omental infarction following myomectomy.
Topics: Female; Humans; Adult; Uterine Myomectomy; Peritoneal Diseases; Abdomen, Acute; Diagnosis, Differential; Omentum; Infarction
PubMed: 37337268
DOI: 10.1186/s13256-023-03924-y -
BMC Urology Apr 2022Segmental testicular infarction is a rare condition that often occurs in the upper pole of the left testicle and usually presents with acute onset of scrotal pain....
BACKGROUND
Segmental testicular infarction is a rare condition that often occurs in the upper pole of the left testicle and usually presents with acute onset of scrotal pain. Contrast-enhanced ultrasound and MR are essential for diagnosing and differentiating segmental testicular infarction in clinical practice, and conservative treatment can only be adopted after a definitive diagnosis. In the present case, after conservative treatment, the infarct volume was reduced, the blood flow around the infarct was increased, and blood flow signals appeared in the infarct. We performed a correlation analysis to investigate the causes of these changes.
CASE PRESENTATION
A 33-year-old male, without any specific disease history, was admitted to the hospital with a 5-day history of left testicular pain, and the imaging showed focal necrosis of the left testicle with hemorrhage. He was diagnosed with segmental testicular infarction after differentiating and excluding it from malignant tumors. Conservative medical treatment was given, and the symptoms of testicular pain were relieved after treatment. After discharge, regular reexamination at follow-ups showed that the infarct's size was reduced, the blood flow around the infarct was increased, and blood flow signals appeared in the infarct.
CONCLUSION
Conservative treatment has become the standard treatment currently adopted after confirming the diagnosis of segmental testicular infarction through contrast-enhanced ultrasound and MR. The blood flow changes in and around the focus of testicular infarction can be related to various factors. At present, relevant conclusions of the underlying mechanisms were mainly deduced from infarction studies of other related organs such as the heart and brain; thus, the specific pathological mechanism needs further experimental verification.
Topics: Acute Pain; Adult; Humans; Infarction; Male; Testicular Diseases; Testis; Ultrasonography
PubMed: 35382805
DOI: 10.1186/s12894-022-01006-7 -
NMR in Biomedicine May 2017To further understanding of the temporal evolution and pathophysiology of adverse ventricular remodeling over the first 60 days following a myocardial infarction (MI) in...
To further understanding of the temporal evolution and pathophysiology of adverse ventricular remodeling over the first 60 days following a myocardial infarction (MI) in both the infarcted and remote myocardium, we performed multi-parametric cardiac magnetic resonance (CMR) imaging in a closed-chest chronic Yucatan mini-pig model of reperfused MI. Ten animals underwent 90 min left anterior descending artery occlusion and reperfusion. Three animals served as controls. Multiparametric CMR (1.5T) was performed at baseline, Day 2, Day 30 and in four animals on Day 60 after MI. Left ventricular (LV) volumes and infarct size were measured. T and T mapping sequences were performed to measure values in the infarct and remote regions. Remote region collagen fractions were compared between infarcted animals and controls. Procedure success was 80%. The model created large infarcts (28 ± 5% of LV mass on Day 2), which led to significant adverse myocardial remodeling that stabilized beyond 30 days. Native T values did not reliably differentiate remote and infarct regions acutely. There was no evidence of remote fibrosis as indicated by partition coefficient and collagen fraction analyses. The infarct T values remained elevated up to 60 days after MI. Multiparametric CMR in this model showed significant adverse ventricular remodeling 30 days after MI similar to that seen in humans. In addition, this study demonstrated that remote fibrosis is absent and that infarct T signal remains chronically elevated in this model. These findings need to be considered when designing preclinical trials using CMR endpoints.
Topics: Algorithms; Animals; Computer Simulation; Image Enhancement; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging, Cine; Models, Biological; Models, Statistical; Multimodal Imaging; Myocardial Infarction; Myocardial Reperfusion Injury; Reproducibility of Results; Sensitivity and Specificity; Subtraction Technique; Swine; Swine, Miniature; Ventricular Remodeling
PubMed: 28164391
DOI: 10.1002/nbm.3693 -
Neurology Mar 2014Brain damage within the right middle cerebral artery (MCA) territory is particularly disruptive to mediolateral postural stabilization. The objective of this... (Comparative Study)
Comparative Study
OBJECTIVE
Brain damage within the right middle cerebral artery (MCA) territory is particularly disruptive to mediolateral postural stabilization. The objective of this cross-sectional study was to test the hypothesis that chronic right MCA infarcts (as compared to left) are associated with slower and more bilaterally asymmetrical gait. We further hypothesized that in those with chronic right MCA infarct, locomotor performance is more dependent on gray matter (GM) volumes within noninfarcted regions of the brain that are involved in motor control yet lie outside of the MCA territory.
METHODS
Gait speed was assessed in 19 subjects with right MCA infarct, 20 with left MCA infarct, and 108 controls. Bilateral plantar pressure and temporal symmetry ratios were calculated in a subset of the cohort. GM volumes within 5 regions outside of the MCA territory (superior parietal lobe, precuneus, caudate, putamen, and cerebellum) were quantified from anatomic MRIs.
RESULTS
Right and left infarct groups had similar poststroke duration (7.6 ± 6.0 years), infarct size, and functional independence. The right infarct group demonstrated slower gait speed and greater asymmetry compared to the left infarct group and controls (p < 0.05). In the right infarct group only, those with larger GM volumes within the cerebellum (r(2) = 0.32, p = 0.02) and caudate (r(2) = 0.56, p < 0.001) exhibited faster gait speed.
CONCLUSION
Individuals with chronic lesions within the right MCA territory, as compared to the left MCA territory, exhibit slower, more asymmetrical gait. For these individuals, larger GM volumes within regions outside of the infarcted vascular territory may help preserve locomotor control.
Topics: Aged; Aged, 80 and over; Brain; Cross-Sectional Studies; Female; Functional Laterality; Gait; Humans; Infarction, Middle Cerebral Artery; Locomotion; Magnetic Resonance Imaging; Male; Middle Aged; Movement Disorders; Retrospective Studies
PubMed: 24489132
DOI: 10.1212/WNL.0000000000000186 -
Matrix Biology : Journal of the... May 2021Tissue injury results in profound alterations in the collagen network, associated with unfolding of the collagen triple helix, proteolytic degradation and generation of...
Tissue injury results in profound alterations in the collagen network, associated with unfolding of the collagen triple helix, proteolytic degradation and generation of fragments. In the infarcted myocardium, changes in the collagen network are critically involved in the pathogenesis of left ventricular rupture, adverse remodeling and chronic dysfunction. We hypothesized that myocardial infarction is associated with temporally and spatially restricted patterns of collagen denaturation that may reflect distinct molecular mechanisms of collagen unfolding. We used a mouse model of non-reperfused myocardial infarction, and in vitro assays in fibroblast-populated collagen lattices. In healing infarcts, labeling with collagen hybridizing peptide (CHP) revealed two distinct patterns of collagen denaturation. During the inflammatory and proliferative phases of infarct healing, collagen denaturation was pericellular, localized in close proximity to macrophages and myofibroblasts. qPCR array analysis of genes associated with matrix remodeling showed that Membrane Type 1-Matrix Metalloproteinase (MT1-MMP) is markedly upregulated in infarct macrophages and fibroblasts, suggesting its involvement in pericellular collagen denaturation. In vitro, MT1-MMP-mediated pericellular collagen denaturation is involved in cardiac fibroblast migration. The effects of MT1-MMP on collagen denaturation and fibroblast migration involve the catalytic site, and require hemopexin domain-mediated actions. In contrast, during the maturation phase of infarct healing, extensive collagen denaturation was noted in the hypocellular infarct, in the infarct border zone and in the mitral valve annulus, in the absence of MT1-MMP. In vitro, mechanical tension in attached collagen lattices was sufficient to induce peripheral collagen denaturation. Our study suggests that in healing infarcts, early pericellular collagen denaturation may be important for migration of macrophages and reparative myofibroblasts in the infarct. Extensive denaturation of collagen fibers is noted in mature scars, likely reflecting mechanical tension. Chronic collagen denaturation may increase susceptibility of the matrix to proteolysis, thus contributing to progressive cardiac dilation and post-infarction heart failure.
Topics: Animals; Collagen; Matrix Metalloproteinase 14; Mice; Myocardial Infarction; Myocardium; Proteolysis
PubMed: 34048934
DOI: 10.1016/j.matbio.2021.05.005 -
British Medical Journal Jul 1953
Topics: Humans; Infarction; Myocardial Infarction
PubMed: 13051564
DOI: No ID Found