Ischemic Dysfunction Research Articles

USP15 as a Potential Therapeutic Target in Cerebral Ischemia: Modulation of Ferroptosis and Cognitive Dysfunction via the Nrf2/GPX4 Axis in Mice.

This study aimed to investigate the role of ubiquitin-specific peptidase 15 (USP15) in ischemic cognitive dysfunction using a mouse model and a cerebral ischemia (CI) cell model, its impact on ferroptosis and the underlying mechanisms. Oxygen-glucose deprivation/reoxygenation (OGD/ R)-induced HT-22 cells were used to establish the CI cell model, and mice induced with CI were used as the animal model for ischemic cognitive dysfunction. Cell damage was evaluated using Cell Counting Kit-8 (CCK-8), flow cytometry (FCM), immunoblotting, and immunofluorescence assays. Cognitive dysfunction in the CI mice was assessed through water maze experiments. Ferroptosis was examined with an iron detection kit and immunoblotting, oxidative stress was evaluated using 2',7'-dichlorofluorescin diacetate (DCF) and enzyme-linked immunosorbent assay (ELISA), and mechanistic experiments were performed via immunoblotting. USP15 knockdown alleviated OGD/ R-induced damage in HT-22 cells. In vivo, USP15 depletion mitigated brain injury in middle cerebral artery occlusion (MCAO) mice and improved learning and memory function. The absence of USP15 reduced oxidative stress in MCAO mice and attenuated ferroptosis by activating nuclear factor erythroid 2-related factor 2 (Nrf2). Mechanistic investigations confirmed that USP15 depletion ameliorated cognitive impairment and ferroptosis through the activation of the Nrf2/ GPX4 axis. USP15 is associated with ferroptosis and cognitive dysfunction in mice and could serve as a potential therapeutic target in CI.

Real-World safety and effectiveness of evolocumab in primary hypercholesterolemia and mixed dyslipidemia in Saudi Arabia

IntroductionEvolocumab’s short-term efficacy and safety were proven in phase-3 clinical trial, but its long-term safety and effectiveness in the Saudi population are yet to be studied. The aim of this study was to assess the long-term safety and effectiveness of evolocumab in Saudi patients with primary hypercholesterolemia or mixed dyslipidemia. MethodA retrospective cohort study evaluated adult patients who had newly been prescribed evolocumab for hypercholesterolemia or mixed dyslipidemia. Safety events included myocardial infarction, unstable angina, stroke, transient ischemic attack, heart failure, rhabdomyolysis, renal dysfunction, and myalgia. Effectiveness outcomes included changes in lipid profiles from baseline, assessed at 6-, 12-, 18-, and 24-month. ResultsThe study sample were 469 who newly prescribed evolocumab, from which 69.1 % being male, were included. The most prevalent comorbidities were coronary artery disease, diabetes, and hypertension. Statin was the most commonly used therapy. The most common adverse events at 6-month follow-up, based on the incidence rate per 1000 person-years, were coronary revascularization (63.20), myalgia (44.96), myocardial infarction (31.53), unstable angina (31.49), heart failure (26.94), rhabdomyolysis without renal dysfunction (8.93), transient ischemic attack (4.46), and rhabdomyolysis with renal dysfunction (4.46). Stroke incidence increased with follow-up length, from 8.87 per 1000 person-years at 6 months to 12.84 per 1000 person-years at 24 months. Evolocumab use significantly reduced LDL and total cholesterol levels at 6, 12, 18, and 24 months follow-up, while having no significant effect on HDL or triglycerides levels. ConclusionEvolocumab appeared to be safe and effective therapeutic option for patients with primary hypercholesterolemia or mixed dyslipidemia to potentially reduce LDL levels to therapeutic levels when statins are insufficient.

Soluble Epoxide Hydrolase Inhibitor Ameliorates Olfactory Dysfunction, Modulates Microglia Polarization, and Attenuates Neuroinflammation after Ischemic Brain Injury.

Olfactory bulb (OB) microglia activation and inflammation can lead to olfactory dysfunction, which often occurs after an ischemic stroke. Inhibition of soluble epoxide hydrolase (sEH) attenuates neuroinflammation in brain injuries by reducing the degradation of anti-inflammatory epoxyeicosatrienoic acids. However, whether sEH inhibitors can ameliorate olfactory dysfunction after an ischemic stroke remains unknown. Ischemic brain injury and olfactory dysfunction were induced by middle cerebral artery occlusion (MCAO) in Wistar Kyoto rats. The rats were administered 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), a selective sEH inhibitor. Olfactory function, cerebral infarct volume, and the degree of degeneration, microglial polarization and neuroinflammation in OB were evaluated. Following treatment with AUDA, rats subjected to MCAO displayed mild cerebral infarction and OB degeneration, as well as better olfactory performance. In OB, AUDA triggered a modulation of microglial polarization toward the M2 anti-inflammatory type, reduction in proinflammatory mediators, and enhancement of the antioxidant process. The effectiveness of AUDA in terms of anti-inflammatory, neuroprotection and anti-oxidative properties suggests that it may have clinical therapeutic implication for ischemic stroke related olfactory dysfunction.

Revascularization and outcomes in ischaemic left ventricular dysfunction after heart failure admission: The RevascHeart study.

Despite numerous trials on revascularization in patients with heart failure (HF) and ischaemic left ventricular (LV) dysfunction, its role remains unsettled. Guideline-directed medical therapy (GDMT) for HF has shown benefits on outcomes. This multicentre study aims to compare long-term mortality between revascularization and GDMT in patients with ischaemic LV dysfunction following admission for HF. Between 2012 and 2023, 408 patients admitted for HF with a LV ejection fraction (LVEF) of 40% or less and documented coronary artery disease (CAD) were included. Patients were categorized into two groups based on their initial treatment decision: revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG]) or GDMT. The primary outcome was rate of all-cause or cardiovascular mortality, and secondary outcomes included type of revascularization (PCI vs. CABG) and LV reverse remodelling. After a median 44.6-month follow-up, 100 patients (33%) died in the revascularization group, compared to 44 (43%) in the GDMT group. Multivariate analysis showed no significant benefit of revascularization on all-cause mortality (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.48-1.39, p = 0.45) or cardiovascular mortality (HR 0.97, 95% CI 0.62-1.52, p = 0.90) compared to GDMT. Neither CABG (HR 0.74, 95% CI 0.51-1.08, p = 0.13) nor PCI (HR 0.98, 95% CI 0.62-1.55, p = 0.93) demonstrated a mortality reduction compared to GDMT. Both groups experienced significant reductions in LV size and improvements in LVEF, greater in the revascularization group. Revascularization did not outperform GDMT in ischaemic LV dysfunction following HF admission in this retrospective analysis. Larger prospective studies are needed to clarify the potential role of revascularization in improving outcomes.

Brain perfusion alterations in patients and survivors of COVID‐19 infection using arterial spin labeling: A systematic review

AbstractCoronavirus disease (COVID‐19) has been shown to impact the central nervous system, leading to various neurological complications. Arterial spin labeling (ASL), a non‐invasive magnetic resonance imaging technique, enables the measurement of cerebral blood flow and perfusion abnormalities. This systematic review aims to synthesize ASL findings in patients with COVID‐19 and assess the potential role of ASL in diagnosing and managing neurological complications. A comprehensive search was conducted on PubMed and Scopus for studies related to ASL in individuals with COVID‐19 or post‐COVID‐19 syndrome published between December 2019 and August 2024. Extracted data encompassed study characteristics, ASL protocols, cognitive assessments, and principal findings. The most consistent observation across studies was hypoperfusion detected in various brain regions, particularly within the frontal lobes, which may correlate with cognitive impairment and olfactory dysfunction. Additionally, some investigations reported hyperperfusion localized to the leptomeninges. These results may reflect underlying mechanisms such as hypoxic–ischemic injury, inflammation, vascular dysfunction, and neuronal damage attributable to COVID‐19. In conclusion, ASL has emerged as a valuable tool for evaluating brain perfusion among patients affected by or recovering from COVID‐19 since it offers critical insights into cerebral hemodynamics and metabolism. Further research is warranted to validate these ASL findings and elucidate whether post‐COVID‐19 syndrome contributes to persistent brain perfusion issues.

Myocardial Strain Imaging: Theory, Current Practice, and the Future.

Myocardial strain imaging by echocardiography or cardiac magnetic resonance (CMR) is a powerful method to diagnose cardiac disease. Strain imaging provides measures of myocardial shortening, thickening, and lengthening and can be applied to any cardiac chamber. Left ventricular (LV) global longitudinal strain by speckle-tracking echocardiography is the most widely used clinical strain parameter. Several CMR-based modalities are available and are ready to be implemented clinically. Clinical applications of strain include global longitudinal strain as a more sensitive method than ejection fraction for diagnosing mild systolic dysfunction. This applies to patients suspected of having heart failure with normal LV ejection fraction, to early systolic dysfunction in valvular disease, and when monitoring myocardial function during cancer chemotherapy. Segmental LV strain maps provide diagnostic clues in specific cardiomyopathies, when evaluating LV dyssynchrony and ischemic dysfunction. Strain imaging is a promising modality to quantify right ventricular function. Left atrial strain may be used to evaluate LV diastolic function and filling pressure.

Mitochondria-containing extracellular vesicles from mouse vs. human brain endothelial cells for ischemic stroke therapy

Ischemic stroke-induced mitochondrial dysfunction in the blood-brain barrier-forming brain endothelial cells (BECs) results in long-term neurological dysfunction post-stroke. We previously reported data from a pilot study where intravenous administration of human BEC (hBEC)-derived mitochondria-containing extracellular vesicles (EVs) showed a potential efficacy signal in a mouse middle cerebral artery occlusion (MCAo) model of stroke. We hypothesized that EVs harvested from donor species homologous to the recipient species (e.g., mouse) may improve therapeutic efficacy, and therefore, use of mouse BEC (mBEC)-derived EVs may improve post-stroke outcomes in MCAo mice.We investigated potential differences in the mitochondria transfer of EVs derived from the same species as the recipient cell (mBEC-EVs and recipient mBECs or hBECs-EVs and recipient hBECs) vs. cross-species EVs and recipient cells (mBEC-EVs and recipient hBECs or vice versa). Our results showed that while both hBEC- and mBEC-EVs transferred EV mitochondria, mBEC-EVs outperformed hBEC-EVs in increasing ATP levels and improved recipient mBEC mitochondrial function via increasing oxygen consumption rates. mBEC-EVs significantly reduced brain infarct volume and neurological deficit scores compared to vehicle-injected MCAo mice. The superior therapeutic efficacy of mBEC-EVs in MCAo mice support the continued use of mBEC-EVs to optimize the therapeutic potential of mitochondria-containing EVs in preclinical mouse models.

Cardioprotective and antispasmodic effects of Humulus lupulus (Hops) in an oral subacute treatment in rats

Hops (Humulus lupulus) was used to treat menopausal symptoms because it contains phytoestrogens. Since these compounds prevent cardiac ischemic diseases, it was evaluated whether oral administration of an ethanol extract (Hops-T) to rats during a week could reduce cardiac post-ischemic dysfunction. Moreover, its effects on visceral peristaltism and the mechanisms of action were studied. Rat isolated hearts were perfused inside a calorimeter, left intraventricular pressure and calorimetrical signals were recorded during ischemia/reperfusion. The NO-synthases and mKATP channels roles were evaluated by respectively blocking them with L-NAME and 5-HD before ischemia. After the experiment, western-blots for cellular pathways (p-AKT, p-PKCϵ, GSK3b and BCL-2) were done. In isolated intestinal, bladder and uterine rat tissues, contractile carbachol concentration-response curves (CCh-CRCs) were performed. The HPLC-DAD mainly showed prenylated flavonoids, beta acids and isoflavones. Hops-T increased contractile and energetic recoveries more significantly in the male rat hearts compared to females, due to beneficial NO production and mitochondrial mKATP channels activation. However, the p-AKT, p-PKCϵ, GSK3b or BCL-2 expressions were not affected after reperfusion. Hops-T inhibited CCh-CRCs in intestinal, bladder and uterine tissues through a non-competitive mechanism. Additionally, it showed a non-competitive antagonism of the Ca2+-CRCs in bladder tissues, similar to the effects observed with verapamil. In conclusion, oral Hops-T prevented cardiac mitochondrial and contractile ischemic dysfunction, and it was a good visceral antispasmodic medicine by interfering with Ca2+ influx. This is a significant finding since it pre-clinically supports the use of hops extract for prevention of visceral spasms and cardiac diseases associated with coronary insufficiency.

Transcriptome Analysis of the Striatum of Electroacupuncture-treated Naïve and Ischemic Stroke Mice.

Electroacupuncture (EA) has been demonstrated to aid stroke recovery. However, few investigations have focused on identifying the potent molecular targets of EA by comparing EA stimulation between naïve and disease models. Therefore, this study was undertaken to identify the potent molecular therapeutic mechanisms underlying EA stimulation in ischemic stroke through a comparison of mRNA sequencing data obtained from EA-treated naïve control and ischemic stroke mouse models. Using both naïve control and middle cerebral artery occlusion (MCAO) mouse models, EA stimulation was administered at two acupoints, Baihui (GV20) and Dazhui (GV14), at a frequency of 2 Hz. Comprehensive assessments were conducted, including behavioral evaluations, RNA sequencing to identify differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction (PPI) network analysis, and quantitative real-time PCR. EA stimulation ameliorated the ischemic insult-induced motor dysfunction in mice with ischemic stroke. Comparative analysis between control vs. MCAO, control vs. control + EA, and MCAO vs. MCAO + EA revealed 4,407, 101, and 82 DEGs, respectively. Of these, 30, 7, and 1 were common across the respective groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed upregulated DEGs associated with the regulation of inflammatory immune response in the MCAO vs. MCAO + EA comparison. Conversely, downregulated DEGs in the control vs. control + EA comparison were linked to neuronal development. PPI analysis revealed major clustering related to the regulation of cytokines, such as Cxcl9, Pcp2, Ccl11, and Cxcl13, in the common DEGs of MCAO vs. MCAO + EA, with Esp8l1 identified as the only common downregulated DEG in both EA-treated naïve and ischemic models. These findings underscore the diverse potent mechanisms of EA stimulation between naïve and ischemic stroke mice, albeit with few overlaps. However, the potent mechanisms underlying EA treatment in ischemic stroke models were associated with the regulation of inflammatory processes involving cytokines.

In utero chronic intermittent nicotine aerosol exposure increases ischemic heart injury in adult offspring via programming of Angiotensin II receptor-derived TGFβ/ROS/Akt signaling pathway

BackgroundIn utero cigarette smoking/nicotine exposure during pregnancy significantly affects fetal development and increases the risk of cardiovascular disease late in life. However, the underlying molecular mechanisms remain largely unknown. We tested the hypothesis that fetal nicotine aerosol exposure reprograms ischemia-sensitive gene expressions, resulting in increased heart susceptibility to ischemic injury and cardiac dysfunction in adulthood. MethodsPregnant rats were exposed to chronic intermittent nicotine aerosol (CINA) or saline aerosol control from gestational day 4 to day 21. Experiments were performed on 6-month–old adult offspring. ResultsCINA exposure increased ischemia-induced cardiac injury and cardiac dysfunction compared to the control group, which was associated with over- expression of angiotensin II receptor (ATR) protein in the left ventricle (LV) of adult offspring. Meanwhile, CINA exposure up-regulated cardiac TGF-β/SMADs family proteins in the LV. In addition, CINA exposure enhanced cardiac reactive oxygen species (ROS) production and increased the DNA methylation level. The levels of phosphorylated-Akt were upregulated but LC3B-II/I protein abundances were downregulated in the hearts isolated from the CINA-treated group. ConclusionFetal nicotine aerosol exposure leads to cardiac dysfunction in response to ischemic stimulation in adulthood. Two molecular pathways are implicated. First, fetal CINA exposure elevates cardiac ATR levels, affecting the TGFβ-SMADs pathway. Second, heightened Angiotensin II/ATR signaling triggers ROS production, leading to DNA hypermethylation, p-Akt activation, and autophagy deficiency. These molecular shifts in cardiomyocytes result in the development of a heart ischemia-sensitive phenotype and subsequent dysfunction in adult offspring.

Impact of Anatomical and Viability-Guided Completeness of Revascularization on Clinical Outcomes in Ischemic Cardiomyopathy

BackgroundComplete revascularization of coronary artery disease has been linked to improved outcomes in patients with preserved left ventricular (LV) function. ObjectivesThis study sought to identify the impact of complete revascularization in patients with severe LV dysfunction. MethodsPatients enrolled in the REVIVED-BCIS2 (Revascularization for Ischemic Ventricular Dysfunction) trial were eligible if baseline/procedural angiograms and viability studies were available for analysis by independent core laboratories. Anatomical and viability-guided completeness of revascularization were measured by the coronary and myocardial revascularization indices (RIcoro and RImyo), respectively, where RIcoro = (change in British Cardiovascular Intervention Society Jeopardy score [BCIS-JS]) / (baseline BCIS-JS) and RImyo= (number of revascularized viable segments) / (number of viable segments supplied by diseased vessels). The percutaneous coronary intervention (PCI) group was classified as having complete or incomplete revascularization by median RIcoro and RImyo. The primary outcome was death or hospitalization for heart failure. ResultsOf 700 randomized patients, 670 were included. The baseline BCIS-JS and SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) scores were 8 (Q1-Q3: 6-10) and 22 (Q1-Q3: 15-29), respectively. In those patients assigned to PCI, median RIcoro and RImyo values were 67% and 85%, respectively. Compared with the group assigned to optimal medical therapy alone, there was no difference in the likelihood of the primary outcome in those patients receiving complete anatomical or viability-guided revascularization (HR: 0.90; 95% CI: 0.62-1.32; and HR: 0.95; 95% CI: 0.66-1.35, respectively). A sensitivity analysis by residual SYNTAX score showed no association with outcome. ConclusionsIn patients with severe LV dysfunction, neither complete anatomical nor viability-guided revascularization was associated with improved event-free survival compared with incomplete revascularization or treatment with medical therapy alone. (Revascularization for Ischemic Ventricular Dysfunction) [REVIVED-BCIS2]; NCT01920048)

Spectrum of COVID-19 induced liver injury: A review report.

The coronavirus disease 2019 (COVID-19) pandemic has caused changes in the global health system, causing significant setbacks in healthcare systems worldwide. This pandemic has also shown resilience, flexibility, and creativity in reacting to the tragedy. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection targets most of the respiratory tract, resulting in a severe sickness called acute respiratory distress syndrome that may be fatal in some individuals. Although the lung is the primary organ targeted by COVID-19 viruses, the clinical aspect of the disease is varied and ranges from asymptomatic to respiratory failure. However, due to an unorganized immune response and several affected mechanisms, the liver may also experience liver cell injury, ischemic liver dysfunction, and drug-induced liver injury, which can result in respiratory failure because of the immune system's disordered response and other compromised processes that can end in multisystem organ failure. Patients with liver cirrhosis or those who have impaired immune systems may be more likely than other groups to experience worse results from the SARS-CoV-2 infection. We thus intend to examine the pathogenesis, current therapy, and consequences of liver damage concerning COVID-19.

Nitrergic inhibition of sympathetic arteriolar constrictions in the female rodent urethra.

During the urine storage phase, tonically contracting urethral musculature would have a higher energy consumption than bladder muscle that develops phasic contractions. However, ischaemic dysfunction is less prevalent in the urethra than in the bladder, suggesting that urethral vasculature has intrinsic properties ensuring an adequate blood supply. Diameter changes in rat or mouse urethral arterioles were measured using a video-tracking system. Intercellular Ca2+ dynamics in arteriolar smooth muscle (SMCs) and endothelial cells were visualised using NG2- and parvalbumin-GCaMP6 mice, respectively. Fluorescence immunohistochemistry was used to visualise the perivascular innervation. In rat urethral arterioles, sympathetic vasoconstrictions were predominantly suppressed by α,β-methylene ATP (10μM) but not prazosin (1μM). Tadalafil (100nM), a PDE5 inhibitor, diminished the vasoconstrictions in a manner reversed by N-ω-propyl-l-arginine hydrochloride (l-NPA, 1μM), a neuronal NO synthesis (nNOS) inhibitor. Vesicular acetylcholine transporter immunoreactive perivascular nerve fibres co-expressing nNOS were intertwined with tyrosine hydroxylase immunoreactive sympathetic nerve fibres. In phenylephrine (1μM) pre-constricted rat or mouse urethral arterioles, nerve-evoked vasodilatations or transient SMC Ca2+ reductions were largely diminished by l-nitroarginine (l-NA, 10μM), a broad-spectrum NOS inhibitor, but not by l-NPA. The CGRP receptor antagonist BIBN-4096 (1μM) shortened the vasodilatory responses, while atropine (1μM) abolished the l-NA-resistant transient vasodilatory responses. Nerve-evoked endothelial Ca2+ transients were abolished by atropine plus guanethidine (10μM), indicating its neurotransmitter origin and absence of non-adrenergic non-cholinergic endothelial NO release. In urethral arterioles, NO released from parasympathetic nerves counteracts sympathetic vasoconstrictions pre- and post-synaptically to restrict arteriolar contractility. KEY POINTS: Despite a higher energy consumption of the urethral musculature than the bladder detrusor muscle, ischaemic dysfunction of the urethra is less prevalent than that of the bladder. In the urethral arterioles, sympathetic vasoconstrictions are predominately mediated by ATP, not noradrenaline. NO released from parasympathetic nerves counteracts sympathetic vasoconstrictions by its pre-synaptic inhibition of sympathetic transmission as well as post-synaptic arteriolar smooth muscle relaxation. Acetylcholine released from parasympathetic nerves contributes to endothelium-dependent, transient vasodilatations, while CGRP released from sensory nerves prolongs NO-mediated vasodilatations. PDE5 inhibitors could be beneficial to maintain and/or improve urethral blood supply and in turn the volume and contractility of urethral musculature.

Human-Induced Pluripotent Stem Cell-Derived Neural Progenitor Cells Showed Neuronal Differentiation, Neurite Extension, and Formation of Synaptic Structures in Rodent Ischemic Stroke Brains.

Ischemic stroke is a major cerebrovascular disease with high morbidity and mortality rates; however, effective treatments for ischemic stroke-related neurological dysfunction have yet to be developed. In this study, we generated neural progenitor cells from human leukocyte antigen major loci gene-homozygous-induced pluripotent stem cells (hiPSC-NPCs) and evaluated their therapeutic effects against ischemic stroke. hiPSC-NPCs were intracerebrally transplanted into rat ischemic brains produced by transient middle cerebral artery occlusion at either the subacute or acute stage, and their in vivo survival, differentiation, and efficacy for functional improvement in neurological dysfunction were evaluated. hiPSC-NPCs were histologically identified in host brain tissues and showed neuronal differentiation into vGLUT-positive glutamatergic neurons, extended neurites into both the ipsilateral infarct and contralateral healthy hemispheres, and synaptic structures formed 12 weeks after both acute and subacute stage transplantation. They also improved neurological function when transplanted at the subacute stage with γ-secretase inhibitor pretreatment. However, their effects were modest and not significant and showed a possible risk of cells remaining in their undifferentiated and immature status in acute-stage transplantation. These results suggest that hiPSC-NPCs show cell replacement effects in ischemic stroke-damaged neural tissues, but their efficacy is insufficient for neurological functional improvement after acute or subacute transplantation. Further optimization of cell preparation methods and the timing of transplantation is required to balance the efficacy and safety of hiPSC-NPC transplantation.

Effect of PCI on Health Status in Ischemic Left Ventricular Dysfunction: Insights From REVIVED-BCIS2

BackgroundIn the REVIVED-BCIS2 (Revascularization for Ischemic Ventricular Dysfunction) trial, percutaneous coronary intervention (PCI) did not reduce the incidence of death or hospitalization for heart failure (HHF). ObjectivesThis prespecified secondary analysis investigated the effect of PCI on health status measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ) combined with the primary outcome in a win ratio. MethodsParticipants with severe ischemic left ventricular dysfunction were randomized to either PCI in addition to optimal medical therapy (OMT) (PCI) or OMT alone (OMT). The primary outcome was a hierarchical composite of all-cause death, HHF, and KCCQ–Overall Summary Score (OSS) at 24 months analyzed using the unmatched win ratio. The key secondary endpoint was a KCCQ-OSS responder analysis. ResultsA total of 347 participants were randomized to PCI and 353 to OMT. Median age was 70.0 years (Q1-Q3: 63.3-76.1 years). Mean left ventricular ejection fraction was 27.0 ± 6.7%. PCI did not improve the primary endpoint (win ratio for PCI vs OMT: 1.05; 95% CI: 0.88-1.26; P = 0.58). PCI resulted in more KCCQ-OSS responders than OMT at 6 months (54.1% vs 40.7%; OR: 1.96; 95% CI: 1.41-2.71; P < 0.001) and fewer deteriorators (25.2% vs 31.4%; OR: 0.69; 95% CI: 0.47-1.00; P = 0.048). PCI did not impact KCCQ-OSS responders or deteriorators at 12 or 24 months. ConclusionsPCI did not improve the hierarchical composite of death, HHF, and health status at 2 years. PCI improved KCCQ-OSS at 6 months, but this benefit was not sustained to 1- or 2-year follow-up. (Revacularization for Ischemic Ventricular Dysfunction [REVIVED-BCIS2]; NCT01920048)

Limitations of Diagnosis of Ischemic Left Ventricular Dysfunction Using the Values of Strain, Twist and Untwist in Patients With Myocardial Infarction of Various Localization.

To compare capabilities for diagnosing regional and global myocardial dysfunction using the values of longitudinal and circular strain, left ventricular (LV) torsion and untwisting in patients with myocardial infarction (MI) of various locations. Patients included in the study (n=121) were divided into three groups: patients with unstable angina (n=30), patients with anterior MI (n=45), and patients with inferior MI (n=46). Clinical, laboratory and instrumental test were performed, including echocardiography. For a quantitative analysis of LV contractility, the maximum systolic peaks of regional and global longitudinal and circular strain, systolic and diastolic rotation, LV torsion and untwisting were measured. Anterior MI was characterized by injury of the LV apical segments, while inferior MI was characterized by injury of the basal segments. In anterior MI, the longitudinal strain was reduced less than 14.5% and circular strain less than 19.3% in the apical segment of the LV anteroseptal wall (ASW). In akinesia of the LV ASW apical segment, longitudinal and circular strains were reduced less than 10%. The magnitude of the circular strain of the LV ASW apical segment (diagnostic threshold 19.3%, sensitivity (Se) 87%, specificity (Sp) 90%) was superior to that of the longitudinal strain as a diagnostic marker for regional ischemic dysfunction in anterior MI. The magnitude of the circular strain of the basal segment of the LV inferior wall in inferior MI has a greater diagnostic value for identifying regional systolic dysfunction than the value of the longitudinal strain of this LV segment. The diagnostic threshold was 17.3%, Se 79%, Sp 80%. A decrease in the circular strain of the LV ASW less than 19.3% in the LV apical segment is more specific (Sp 90%) for diagnosing regional systolic dysfunction in anterior MI than a decrease in longitudinal strain. A circular strain value of less than 17.3% in the basal segment of the LV inferior wall is more specific (Sp 80%) than the longitudinal strain of this segment for diagnosing regional systolic dysfunction in inferior MI. Predominant injury to the LV apex in anterior MI can cause systolic and diastolic myocardial dysfunction, which is manifested by a decrease in LV circular deformation, torsion and untwisting.

Ayurvedic Management of Cervical Myelopathy

Cervical Myelopathy is a condition causing compression of the spinal cord at the cervical level of the spinal cord. It is mostly due to degenerative cervical spondylosis and is hence called Cervical Spondylotic Myelopathy. The spinal cord may directly experience compressive and ischemic dysfunction as a result of age-related spondylotic alterations. A 63-year-old male with complaints of gradually progressive weakness in the arms and hands along with numbness, tingling sensation, neck stiffness and pain around the neck region for the last 10 years came to the OPD of our hospital. The management offered by contemporary medicine is not satisfactory. Cervical myelopathy and Greevastambha can be co-related in this case, based on signs and symptoms. This case report demonstrates how the clinical and radiological symptoms of cervical spondylotic myelopathy were alleviated by an Ayurvedic intervention. To confirm these results and incorporate Ayurveda into conventional medicine for spinal cord injuries, more investigation and controlled trials are necessary.

Ischemia-Reperfusion Programming of Alzheimer's Disease-Related Genes-A New Perspective on Brain Neurodegeneration after Cardiac Arrest.

The article presents the latest data on pathological changes after cerebral ischemia caused by cardiac arrest. The data include amyloid accumulation, tau protein modification, neurodegenerative and cognitive changes, and gene and protein changes associated with Alzheimer's disease. We present the latest data on the dysregulation of genes related to the metabolism of the amyloid protein precursor, tau protein, autophagy, mitophagy, apoptosis, and amyloid and tau protein transport genes. We report that neuronal death after cerebral ischemia due to cardiac arrest may be dependent and independent of caspase. Moreover, neuronal death dependent on amyloid and modified tau protein has been demonstrated. Finally, the results clearly indicate that changes in the expression of the presented genes play an important role in acute and secondary brain damage and the development of post-ischemic brain neurodegeneration with the Alzheimer's disease phenotype. The data indicate that the above genes may be a potential therapeutic target for brain therapy after ischemia due to cardiac arrest. Overall, the studies show that the genes studied represent attractive targets for the development of new therapies to minimize ischemic brain injury and neurological dysfunction. Additionally, amyloid-related genes expression and tau protein gene modification after cerebral ischemia due to cardiac arrest are useful in identifying ischemic mechanisms associated with Alzheimer's disease. Cardiac arrest illustrates the progressive, time- and area-specific development of neuropathology in the brain with the expression of genes responsible for the processing of amyloid protein precursor and the occurrence of tau protein and symptoms of dementia such as those occurring in patients with Alzheimer's disease. By carefully examining the common genetic processes involved in these two diseases, these data may help unravel phenomena associated with the development of Alzheimer's disease and neurodegeneration after cerebral ischemia and may lead future research on Alzheimer's disease or cerebral ischemia in new directions.

Microsurgical penile revascularization for ischemic erectile dysfunction:Cumulative effective rate over time and factors affecting surgical outcomes.

This study aimed to clarify the cumulative effectiveness of microsurgical penile revascularization over time and factors that affect surgical outcomes. This study analyzed 114 men with a median age of 30.5 years. They had localized arterial lesions on the internal pudendal artery by angiography. They underwent the anastomosis of the distal end of the inferior epigastric artery to the dorsal artery of the penis with 11-0 sutures. The final cumulative effectiveness rate calculated by the Kaplan-Meier method was 92.5%. The 1- and 3-year cumulative effectiveness rates were 58.0% and 92.5%, respectively. Twenty-one patients were not cured during the study. Age was a factor significantly affecting the surgical outcomes (p=0.018), and the peak systolic and end-diastolic velocities on Doppler ultrasound, corporal veno-occlusive dysfunction, and venous ligation were less significant (p=0.290, p=0.559, p=0.054, and p=0.732, respectively). The final cumulative effectiveness rate of penile revascularization was 92.5%. Latency was observed until cure, half of the cases were cured in approximately 10 months. Cavernous function appears to be reversible and cavernous dysfunction was not a significant factor in surgical outcome. J. Med. Invest. 71 : 219-224, August, 2024.

РОЛЬ ИНСТРУМЕНТАЛЬНЫХ МЕТОДОВ ДИАГНОСТИКИ В ОЦЕНКЕ ЖИЗНЕСПОСОБНОСТИ МИОКАРДА У ПАЦИЕНТОВ СО СНИЖЕННОЙ КОНТРАКТИЛЬНОСТЬЮ ЛЕВОГО ЖЕЛУДОЧКА

Abstract. This review describes the most significant instrumental methods of diagnosis of viable myocardium in patients with reduced contractility of the left ventricle, since diagnosis of myocardial viability plays an important role in the management of patients with ischemic myocardial dysfunction.