Chronic heart failure (CHF) is a growing global health concern characterized, in part, by progressive sympathetic overactivation, which exacerbates this condition. Accumulating evidence identifies oxidative stress as a key driver of sympatho-excitation, mediated by excess reactive oxygen species (ROS) and impaired antioxidant defenses. The redox-sensitive transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a central regulator of antioxidant gene expression, but its role in the peripheral sympathetic nervous system, particularly in the stellate ganglia, remains unclear. We hypothesized that Nrf2 signaling is disrupted in the stellate ganglia in CHF and that modulation of Nrf2 alters ROS levels and sympathetic responses. In rats, six weeks post myocardial infarction (MI), the stellate ganglia exhibited increased ROS levels in tyrosine hydroxylase-positive neurons along with reduced Nrf2 protein and mRNA expression; both changes were inversely associated with ejection fraction (EF). To determine the functional role of Nrf2, lentiviral vectors encoding GFP or GFP-Nrf2 were delivered to the stellate ganglia three weeks after MI. Nrf2 upregulation attenuated heart rate responses to stellate stimulation in sham rats but augmented responses in CHF rats. The increase in plasma norepinephrine levels was reduced following stellate stimulation in CHF rats that overexpressed Nrf2, while β1-adrenergic responsiveness to dobutamine was unchanged. This study demonstrates that CHF is associated with increased oxidative stress and reduced Nrf2 expression in the stellate ganglion. Nrf2 overexpression significantly modulated sympathetic regulation, altering heart rate responses and reducing plasma norepinephrine in CHF rats. These findings support the concept that impaired Nrf2 signaling contributes to ganglionic redox imbalance and dysregulated sympathetic nerve activity in CHF.

Heart failure with preserved ejection fraction (HFpEF) predominantly affects older individuals with multiple comorbidities. Although mitochondrial dysfunction appears to be a major contributor to diastolic dysfunction, the mechanisms underlying it during HFpEF remain unclear. We used a clinically relevant two-hit HFpEF model in aged mice to investigate remodeling of cardiomyocyte mitochondrial proteins and to determine whether mitochondrial dysfunction reflects impaired biogenesis or defective mitochondrial proteostasis. HFpEF was induced in aged (15-month-old) male and female mice using a high-fat diet combined with chronic nitric oxide synthase inhibition (L-NAME). This model recapitulated key features of human HFpEF, including preserved ejection fraction with diastolic dysfunction and impaired cardiac reserve in both sexes. Consistent with impaired energy reserve, mitochondrial respiratory capacity measured by high-resolution respirometry (Oroboros) was significantly reduced in left ventricular muscle fibers. To examine cardiomyocyte-intrinsic mechanisms, mitochondria were isolated from cardiomyocytes using Langendorff perfusion and analyzed by proteomics and pathway enrichment analysis. Proteomic profiling revealed broad suppression of mitochondrial proteins that support oxidative metabolism and organelle maintenance, including those involved in oxidative phosphorylation, carbohydrate metabolism, and the TCA cycle. In contrast, key regulators of mitochondrial biogenesis were preserved. Notably, mitochondrial chaperones and proteases for protein quality control were reduced, leading to increased accumulation of ubiquitinated mitochondrial proteins and impaired mitochondrial proteostasis. Together, these findings indicate that mitochondrial dysfunction in a 3-hit HFpEF model is characterized by reduced respiratory capacity and impaired mitochondrial proteostasis, rather than defective biogenesis, suggesting that impaired mitochondrial protein quality control may contribute to reduced cardiac reserve in HFpEF.

The objective of this prospective alternating crossover study was to compare quality of induction and recovery and cardiopulmonary function in horses administered guaifenesin or diazepam as co-induction drugs. Six healthy horses were anesthetized twice to undergo an MRI and surgical biopsies, with 5 wk between treatments. Horses were sedated intravenously (IV) with xylazine, 0.6 mg/kg BW, and IV induction started 4 min later. Group G received guaifenesin, 100 mg/kg BW, over 2 min and ketamine, 2 mg/kg BW, within 1 to 2 min of starting the guaifenesin. Group D received diazepam, 0.1 mg/kg BW, within 5 s and ketamine, 2 mg/kg BW, 0.5 to 1 min after and the quality of induction assessed. Horses were positioned on an MRI-compatible table, the trachea intubated, allowed to breathe spontaneously for the initial 10 min, then connected to a rebreathing circuit and anesthetic machine and mechanically ventilated under anesthesia [end-tidal isoflurane (FE'Isoflurane): 1.3 to 1.5%] during the MRI. Direct arterial blood pressure, heart rate, end-tidal CO2 (PE'CO2) and FE'Isoflurane were recorded at 10, 20, 30, and 40 min post-induction. Requirements for dobutamine and/or phenylephrine for arterial blood pressure support were recorded. A 2-way analysis of variance (ANOVA) was used to compare arterial blood pressure and a Wilcoxon matched-pairs signed rank test for comparing sedation, induction, and recovery scores (significance was set at P < 0.05). Arterial pressures were not significantly different between groups; however, systolic (P = 0.004), diastolic (P < 0.0001), and mean (P = 0.004) arterial pressures decreased significantly at 20, 30, and 40 min in Group D. Dose of dobutamine and/or phenylephrine was similar between groups. Sedation, induction, and recovery scores were similar. Induction scores were good to excellent [both groups: 0.5 (0, 2); median (range)]. In conclusion, guaifenesin and diazepam at the doses used in this study produced similar effects on arterial blood pressure and on the quality of induction and recovery.

Heart rate variability (HRV) is widely used as a noninvasive index of autonomic nervous system activity. The objective of this study was to determine whether the administration of sympathomimetic agents alters HRV indices during general anesthesia in Thoroughbred horses. Five healthy Thoroughbred horses were anesthetized with sevoflurane in oxygen. During 2-5 hr of general anesthesia, five treatments were administered to each horse in a randomized order. Two doses (µg·kg[-1]·min[-1]) of epinephrine (0.1 and 0.5), norepinephrine (0.5 and 1), dobutamine (1 and 5), dopamine (5 and 15), and saline (as a control) were infused for 7 min each. Electrocardiograms were recorded to assess HRV, and mean arterial pressure (MAP) was measured to evaluate hemodynamic responses. Data were analyzed using repeated-measures ANOVA. During general anesthesia, epinephrine at 0.5 µg·kg[-1]·min[-1] significantly increased low-frequency (LF) power, the LF/high-frequency (HF) ratio, and MAP. Norepinephrine at both doses significantly decreased heart rate and increased HF power and MAP. Dobutamine at 5 µg·kg[-1]·min[-1] significantly increased heart rate and MAP, without changing HRV indices, whereas dopamine did not induce significant changes in heart rate, MAP, or HRV indices. In conclusion, administration of sympathomimetic agents during general anesthesia induces distinct patterns of autonomic modulation in horses. Increases in LF power and the LF/HF ratio may reflect enhanced sympathetic modulation; however, these indices should be interpreted in the context of baroreflex-mediated autonomic regulation. Understanding the differential autonomic effects of sympathomimetic agents may aid in optimizing cardiovascular support during equine anesthesia.

Advanced heart failure (HF) may require complex palliative pharmacotherapy, including continuous home infusion of inotropes, diuretics, and opioids, together with careful management of infusion devices, injectable-drug quality, compatibility, and symptom monitoring. However, practical reports describing community pharmacist involvement in such care remain limited, particularly from the pre-discharge phase. We report a case of end-of-life pharmacotherapy and home infusion for advanced HF supported by an interdisciplinary team. A 76-year-old man with stage D HF and inotrope dependence chose home-based care after repeated hospitalizations for decompensated HF. Before discharge, the community pharmacist contributed to device-operation training, aseptic compounding procedures, cassette-exchange scheduling, and contingency planning for continuous dobutamine infusion. During home care, the pharmacist coordinated cassette preparation and exchange, proposed a lightweight disposable pump for high-dose continuous furosemide infusion, implemented light protection for furosemide, supported lumen separation to avoid incompatibility with dobutamine, and prepared a morphine cassette for continuous subcutaneous infusion. Home infusion was continued until the patient died peacefully at home on Day 45. This case highlights the multifaceted role of community pharmacists in supporting complex palliative pharmacotherapy and home infusion for advanced HF.

Chromatography remains a cornerstone technique in analyzing chiral compounds. The development and selection of chiral stationary phases （CSPs） are central to achieving high-resolution enantiomeric separation. This study presents a novel regeneration and functionalization strategy for the preparation of high-performance superficially porous particle （SPP）-CSP， offering a promising alternative to conventional fully porous particle （FPP）-CSP. First， bonded phases on the surface of spent chromatographic column silica packing materials were removed using ultraviolet light （λ=254 nm） and hydrogen peroxide solution （3%， mass fraction）， thereby obtaining sub-3 μm regenerated SPP. The regenerated SPP were then amino-functionalized. Subsequently， under mild reaction conditions， carbonyldiimidazole-activated （2-hydroxyethyl）-β-cyclodextrin （HE-β-CD） was bonded onto the surface of the amino-functionalized SPP to prepare the SPP-CSP. For comparative evaluation， a CSP based on 3 μm commercial FPPs was prepared. Additionally， a commercial （2-hydroxypropyl）-β-cyclodextrin （Hp-β-CD） chiral column with identical particle size and structure was selected as a reference. This commercial column was used to investigate the selectivity differences among different cyclodextrin derivatives. The enantioseparation and overall chromatographic performance of the CSPs were systematically evaluated under both supercritical fluid chromatography （SFC） and reversed-phase liquid chromatography （RPLC） modes. The evaluation was performed using ten chiral molecular probes： zopiclone， equol， 2-phenylpropionic acid， dobutamine， flutriafol， miconazole， folic acid， catechin， valacyclovir， and chlorphenamine. Results revealed that， under identical chromatographic conditions， the SPP-CSP consistently outperformed the FPP-CSP in terms of enantiomeric resolution， peak sharpness， theoretical plate number， and retention time efficiency. More importantly， the FPP-CSP exhibited a significant loss in resolution when chromatographic conditions were altered to yield equivalent analysis times. In contrast， the SPP-CSP showed only minor adverse effects on resolution when the flow rate was increased to shorten analysis time， highlighting its inherent suitability for ultrafast separations. Moreover， SFC and RPLC modes displayed complementary chiral recognition ranges. Within the overlapping separation scope of both modes， SFC mode achieved higher enantiomeric resolution and superior chromatographic performance. Notably， under RPLC mode， catechin showed high enantiomeric resolution on both CSPs， underscoring system-dependent selectivity differences. Multiple factors-including mobile phase composition （particularly the additive type）， and the stereochemical structure of the analytes-were found to significantly influence enantioseparation outcomes. Under SFC mode， none of the analytes could be eluted when acetonitrile was used as the mobile phase modifier， whereas alcohols effectively enabled elution， with weaker hydrophobicity correlating to stronger elution strength. Among the alcohols tested， methanol offered distinct advantages over isopropanol by maintaining lower backpressure and superior chromatographic performance without compromising resolution. Under RPLC mode， although isopropanol as a mobile phase component provided higher enantiomeric resolution， it resulted in relatively poorer chromatographic performance and higher column pressure drop. Using acetonitrile offered limited flexibility in adjusting elution strength. In both chromatographic modes， the influence trends of mobile phase additives on enantioseparation performance and overall column performance were generally consistent. Mobile phases with acidic additives were more suitable for analyzing acidic analytes such as 2-phenylpropionic acid and folic acid. Mobile phases with ammonium formate were better suited for analyzing basic analytes like chlorphenamine and flutriafol， as well as analytes with pKa values near 7， such as zopiclone. In contrast， NH3 as an additive yielded unsatisfactory results. Compared with the commercial Hp-β-CD chiral column of the same particle size and structure， the SPP-CSP exhibited different selectivity， which varied with the chromatographic mode. Under RPLC mode， the SPP-CSP showed higher resolution for zopiclone， dobutamine， and folic acid. Under SFC mode， it demonstrated higher resolution for equol， folic acid， and valacyclovir. Despite these advances， the study has certain limitations. To enhance compatibility with mass spectrometric detection， normal-phase mode was not investigated. Additives commonly used in chiral compound analysis， such as triethylamine and ammonium trifluoroacetate， were also not employed. Polar organic solvent mode was not investigated either. Additionally， peak symmetry and theoretical plate numbers on the SPP-CSP were generally inferior to those observed on the commercial Hp-β-CD chiral column across both chromatographic modes.

Severe adverse reactions induced by non-ionic contrast media remain an uncommon complication in veterinary medicine. This report describes the clinical manifestations and sequential computed tomography alterations indicative of acute shock captured during 2 min and 4 min delayed phases in a 10-year-old, castrated male Maltese dog. The patient, previously diagnosed with a cutaneous mast cell tumor on the lip exhibiting incomplete histopathological margins, underwent CT for metastatic evaluation. The patient had no clinical evidence of systemic disease, and no anesthetic adverse events were observed during past patellar luxation surgery. However, the 2 min delayed CT scan revealed suspected hepatic congestion, vascular collapse, marked esophageal wall edema, and intense intestinal mucosal contrast enhancement. Subsequently, the 4 min delayed CT scan demonstrated diffuse contrast medium stagnation within the cardiac chambers and renal parenchyma, accompanied by the absence of the renal excretory phase. During anesthetic recovery, severe hypotension and respiratory failure emerged, suggesting the development of hypersensitivity. Following immediate intervention with cardiopulmonary resuscitation, epinephrine, and dexamethasone, the patient temporarily exhibited facial edema, hematochezia, diarrhea, and transient ataxia. However, dobutamine administration successfully restored systemic blood pressure and tissue perfusion, returning the patient to a normal clinical status. Consequently, this case highlights potential pathophysiological mechanisms, key CT findings, and emergency management considerations for contrast-induced hypersensitivity. Notably, sequential CT imaging documented evolving shock-related changes before the onset of overt clinical deterioration, suggesting that these findings may represent early imaging indicators of contrast-induced hypersensitivity.

The application of triazole fungicides in agriculture has raised concerns regarding their potential deleterious effects on human health. Thus, the present study aimed to evaluate the in vivo cardiotoxicity of fungicides difenoconazole (DFZ) and prothioconazole (PRZ), in Wistar rats subjected to daily administration of 1 mg/kg/day, corresponding to the non-observed adverse effect level (NOAEL), by gavage over a period of 28 consecutive days. No significant alterations were observed in the weights of the heart, right atrium, left atrium, spleen, liver, and lungs of the animals. Histopathological analyses of the myocardium revealed no evidence of cardiac hypertrophy. Electrocardiographic assessments did not indicate significant changes in P wave duration, PR and QT intervals, QRS complex, or RR interval. Furthermore, during the cardiac stress tests induced by caffeine and dobutamine, DFZ and PRZ did not increase the likelihood of developing cardiac arrhythmias, nor did they augment the infarct area as measured by TTC/Evans Blue staining. Also, serum levels of the cardiac biomarkers CK-MB and LDH were comparable to those of the control group. Collectively, these results suggest that DFZ and PRZ, at the administered dose and time frame, do not induce structural or electrical alterations in the hearts of rats.