Magnetic resonance imaging and multi-detector computed tomography assessment of extracellular compartment in ischemic and non-ischemic myocardial pathologies

Myocardial pathologies are major causes of morbidity and mortality worldwide. Early detection of loss of cellular integrity and expansion in extracellular volume(ECV) in myocardium is critical to initiate effective treatment. The three compartments in healthy myocardium are: intravascular(approximately 10% of tissue volume), interstitium(approximately 15%) and intracellular(approximately 75%). Myocardial cells, fibroblasts and vascular endothelial/smooth muscle cells represent intracellular compartment and the main proteins in the interstitium are types Ⅰ/Ⅲ collagens. Microscopic studies have shown that expansion of ECV is an important feature of diffuse physiologic fibrosis(e.g., aging and obesity) and pathologic fibrosis [heart failure, aortic valve disease, hypertrophic cardiomyopathy, myocarditis, dilated cardiomyopathy, amyloidosis, congenital heart disease, aortic stenosis, restrictive cardiomyopathy(hypereosinophilic and idiopathic types), arrythmogenic right ventricular dysplasia and hypertension]. This review addresses recent advances in measuring of ECV in ischemic and non-ischemic myocardial pathologies. Magnetic resonance imaging(MRI) has the ability to characterize tissue proton relaxation times(T1, T2, and T2*). Proton relaxation times reflect the physical and chemical environments of water protons in myocardium. Delayed contrast enhanced-MRI(DE-MRI) and multi-detector computed tomography(DE-MDCT) demonstrated hyper-enhanced infarct, hypo-enhanced microvascular obstruction zone and moderately enhanced peri-infarct zone, but are limited for visualizing diffuse fibrosis and patchy microinfarct despite the increase in ECV. ECV can be measured on equilibrium contrast enhanced MRI/MDCT and MRI longitudinal relaxation time mapping. Equilibrium contrast enhanced MRI/MDCT and MRI T1 mapping is currently used, but at a lower scale, as an alternative to invasive sub-endomyocardial biopsies to eliminate the need for anesthesia, coronary catheterization and possibility of tissue sampling error. Similar to delayed contrast enhancement, equilibrium contrast enhanced MRI/MDCT and T1 mapping is completely noninvasive and may play a specialized role in diagnosis of subclinical and other myocardial pathologies. DE-MRI and when T1-mapping demonstrated sub-epicardium, sub-endocardial and patchy mid-myocardial enhancement in myocarditis, Behcet's disease and sarcoidosis, respectively. Furthermore, recent studies showed that the combined technique of cine, T2-weighted and DE-MRI technique has high diagnostic accuracy for detecting myocarditis. When the tomographic techniques are coupled with myocardial perfusion and left ventricular function they can provide valuable information on the progression of myocardial pathologies and effectiveness of new therapies.

Reduced cardiac output is associated with decreased mitochondrial efficiency in the non-ischemic ventricular wall of the acute myocardial-infarcted dog

Cardiogenic shock is the leading cause of death among patients hospitalized with acute myocardial infarction （MI）. Understanding the mechanisms for acute pump failure is therefore important. The aim of this study is to examine in an acute MI dog model whether mitochondrial bio-energetic function within non-ischemic wall regions are associated with pump failure. Anterior MI was produced in dogs via ligation of left anterior descending （LAD） coronary artery, that resulted in an infract size of about 30% of the left ventricular wall. Measurements ofhemodynamic status, mitochondrial function, free radical production and mitochondrial uncoupling protein 3 （UCP3） expression were determined over 24 h period. Hemodynamic measurements revealed a 〉 50% reduction in cardiac output at 24 h post infarction when compared to baseline. Biopsy samples were obtained from the posterior non-ischemic wall during acute infarction. ADP/O ratios for isolated mitochondria from non-ischemic myocardium at 6 h and 24 h were decreased when compared to the ADP/O ratios within the same samples with and without palmitic acid （PA）. GTP inhibition of （PA）-stimulated state 4 respiration in isolated mitochondria from the non-ischemic wall increased by 7% and 33% at 6 h and 24 h post-infarction respectively when compared to sham and pre-infarction samples. This would suggest that the mitochondria are uncoupled and this is supported by an associated increase in UCP3 expression observed on western blots from these same biopsy samples. Blood samples from the coronary sinus measured by electron paramagnetic resonance （EPR） methods showed an increase in reactive oxygen species （ROS） over baseline at 6 h and 24 h post-infarction. In conclusion, mitochondrial bio-energetic ADP/O ratios as a result of acute infarction are abnormal within the non-ischemic wall. Mitochondria appear to be energetically uncoupled and this is associated with declining pump function. Free radical production may be associated with the induction of uncoupling proteins in the mitochondria.

Clinical Study of Sulfotanshinone Sodium Injection in Treating Non-Ischemic Retinal Vein Occlusion

Objectives: To study the effect of sulfotanshinone sodium (SS) injection in the treatment of non-ischemic retinal vein occlusion (RVO). Methods: Sixty-two RVO patients treated in our hospital between Jan. 2013 and Oct. 2014 were randomly divided into Control Group (30 patients;Bendazol tablets) and Treatment Group (32 patients, Bendazol tablets + SS injections), each with a follow-up period of 6 months. Statistical analysis was then performed on changes in visual acuity, central retinal thickness (CRT) and retinal circulation time (RCT) before and after the treatment. Results: After treatment, both Control Group and Treatment Group witnessed an improvement on visual acuity (Control Group: t = 2.103, p = 0.044;Treatment Group: t = 8.021, p = 0.000). Visual acuity could be greatly improved in Treatment Group when compared with Control Group, with significant differences (p < 0.01). Macular edema could be greatly relieved in Treatment Group measured by CRT (t = 2.571, p = 0.007) while the difference was of no statistical significance in Control Group (t = 1.016, p = 0.070). RCT were remarkably shortened in both groups (Control Group: t = 43.83, p = 0.000;Treatment Group: t = 27.34, p = 0.000), and when compared with Control group, the changes in Treatment Group were more significant (p < 0.05). Conclusion: SS injection could effectively improve the therapeutic effect in patients with non-ischemic retinal vein occlusion.

Non-ischemic complications of dermal fillers

Dermal fillers have been commonly used for the filling of facial rhytids.As the use of dermal fillers has grown,so has the incidence of non-ischemic complications.These complications range from edema,bruising,and erythema to more complex conditions such as delayed hypersensitivity nodules and biofilms.This article sought to review the causes of various non-ischemic complications,discuss their risk factors,and review management techniques.Certain predisposing factors to delayed hypersensitivity nodules,such as Vycross technology,a history of viral illness,or coronavirus disease 19(COVID-19)infections,are discussed in detail in this review.Prevention techniques such as patient counseling,elucidating certain patient history(viral illness,dental procedures),the use of aseptic technique,and procedural factors are also discussed.Understanding appropriate management for these complications can also help in treatment.Imaging,such as ultrasound,computed tomography(CT)and magnetic resonance imaging(MRI),has taken on a larger role in the management of non-ischemic complications.

Vitreous hemorrhage and fibrovascular proliferation after laser-induced chorioretinal venous anastomosis

·AIM:To describe a case in which vitrectomy was required for vitreous hemorrhage and fibrovascular proliferation after laser-induced chorioretinal venous anastomosis (LCVA) for non-ischemic central retinal vein occlusion (CRVO).·METHODS:Observational case report.·RESULTS:A 72-year-old man complained of central scotoma in the left eye,and was diagnosed as suffering from non-ischemic CRVO.LCVA was performed in another hospital.Although favorable visual function was briefly maintained postoperatively,severe vitreous hemorrhage developed in his left eye,necessitating vitrectomy.·CONCLUSION:Considering that LCVA carries a risk of serious complications,we must apply this treatment with caution,especially in ethnic groups,such as the Japanese,in whom pigmentation reacts to photocoagulation excessively.·

Cardiac Remote Conditioning and Clinical Relevance:All Together Now!

Acute myocardial infarction （AMI） is the leading cause of death and disability worldwide. Timely reperfusion is the standard of care and results in decreased infarct size, improving patient survival and prognosis. However, 25% of patients proceed to develop heart failure （HF） after myocardial infarction （MI） and 50% of these will die within five years. Since the size of the infarct is the major predictor of the outcome, including the development of HF, therapies to improve myocardial salvage have great potential. Over the past three decades, a number of stimuli have been discovered that activate endogenous cardioprotective pathways. In ischemic preconditioning （IPC） and ischemic postconditioning, ischemia within the heart initiates the protection. Brief reversible episodes of ischemia in vascular beds remote from the heart can also trigger cardioprotection when applied before, during, or immediately after myocardial ischemia-- known as remote ischemic pre-, per-, and post-conditioning, respectively. Although the mechanism of remote ischemic preconditioning （RIPC） has not yet been fully elucidated, many mechanistic components are shared with IPC. The discovery of RIPC led to research into the use of remote non-ischemic stimuli including nerve stimulation （spinal and vagal）, and electroacupuncture （EA）. We discovered and, with others, have elucidated mechanistic aspects of a non- ischemic phenomenon we termed remote preconditioning of trauma （RPCT）. RPCT operates via neural stimulation of skin sensory nerves and has similarities and differences to nerve stimulation and EA conducted at acupoints. We show herein that RPCT can be mimicked using electrical stimulation of the abdominal midline （EA-like treatment） and that this modality of activating cardioprotection is powerful as both a preconditioning and a postconditioning stimulus （when applied at reperfusion）. Investigations of these cardioprotective phenomena have led to a more integrative understanding of mechanisms related to cardioprotection, and in the last five to ten years, it has become clear that the mechanisms are similar, whether induced by ischemic or non-ischemic stimuli. Taking together much of the data in the literature, we propose that all of these cardioprotective ＂conditioning＂ phenomena represent activation from different entry points of a cardiac conditioning network that converges upon specific mediators and effectors of myocardial cell survival, including NF-KB, Stat3/5, protein kinase C, bradykinin, and the mitoKA^P channel. Nervous system pathways may represent a novel mechanism for initiating conditioning of the heart and other organs. IPC and RIPC have proven difficult to translate clinically, as they have associated risks and cannot be used in some patients. Because of this, the use of neural and nociceptive stimuli is emerging as a potential non-ischemic and non-traumatic means to initiate cardiac conditioning. Clinical relevance is underscored by the demonstration of postconditioning with one of these modalities, supporting the conclusion that the development of pharmaceuticals and electroceuticals for this purpose is an area ripe for clinical development.