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American Journal of Veterinary Research Aug 2023To compare cardiac output (CO) measurements by transesophageal echocardiography (TEECO) and esophageal Doppler monitor (EDMCO) with pulmonary artery thermodilution...
Agreement of cardiac output measurements by esophageal Doppler and transesophageal echocardiography with intermittent pulmonary artery thermodilution during pharmacologic manipulation of hemodynamics in anesthetized dogs.
OBJECTIVE
To compare cardiac output (CO) measurements by transesophageal echocardiography (TEECO) and esophageal Doppler monitor (EDMCO) with pulmonary artery thermodilution (PATDCO) in anesthetized dogs subjected to pharmacological interventions. The effect of treatments on EDM-derived indexes was also investigated.
ANIMALS
6 healthy male dogs (10.8 ± 0.7 kg).
METHODS
Dogs were anesthetized with propofol and isoflurane, mechanically ventilated, and monitored with invasive mean arterial pressure (MAP), end-tidal isoflurane concentration (ETISO), PATDCO, TEECO, EDMCO, and EDM-derived indexes. Four treatments were administered to all dogs by randomization. Baseline data were collected before each treatment: (1) dobutamine infusion; (2) esmolol infusion; (3) phenylephrine infusion; and (4) ETISO > 3%. Data were collected after 10-minute stabilization and after 30 minutes of washout between treatments. Statistical tests were pairwise t test, Bland-Altman analysis, Lin's concordance correlation (ρc), and polar plot analysis with P < .05 set as significance.
RESULTS
The mean ± SD relative bias (limits of agreement) for TEECO was 0.35 ± 25.2% (-49.1% to 49.8%) and for EDMCO was -27.2 ± 22.5% (-71.4% to 17%) versus PATDCO. The percent error for TEECO and EDMCO was 27.6% and 44.1%, respectively. The ρc value was 0.82 for TEECO and 0.66 for EDMCO. TEECO and EDMCO showed good trending ability. EDM-derived indexes displayed significant changes specific to the drug administered (P < .001).
CLINICAL RELEVANCE
For minimally invasive CO monitoring, TEE may provide more favorable performance than EDM in clinical settings; however, EDM-derived indexes yield valuable hemodynamic information that reliably follows trends in CO, thus supporting critical decision-making in canine patients.
Topics: Male; Dogs; Animals; Pulmonary Artery; Cardiac Output; Echocardiography, Transesophageal; Isoflurane; Thermodilution; Hemodynamics; Reproducibility of Results
PubMed: 37385599
DOI: 10.2460/ajvr.23.05.0101 -
BMC Anesthesiology Mar 2024Tracking preload dependency non-invasively to maintain adequate tissue perfusion in the perioperative period can be challenging.The effect of phenylephrine on stroke... (Observational Study)
Observational Study
BACKGROUND
Tracking preload dependency non-invasively to maintain adequate tissue perfusion in the perioperative period can be challenging.The effect of phenylephrine on stroke volume is dependent upon preload. Changes in stroke volume induced by phenylephrine administration can be used to predict preload dependency. The change in the peripheral perfusion index derived from photoplethysmography signals reportedly corresponds with changes in stroke volume in situations such as body position changes in the operating room. Thus, the peripheral perfusion index can be used as a non-invasive potential alternative to stroke volume to predict preload dependency. Herein, we aimed to determine whether changes in perfusion index induced by the administration of phenylephrine could be used to predict preload dependency.
METHODS
We conducted a prospective single-centre observational study. The haemodynamic parameters and perfusion index were recorded before and 1 and 2 min after administering 0.1 mg of phenylephrine during post-induction hypotension in patients scheduled to undergo surgery. Preload dependency was defined as a stroke volume variation of ≥ 12% before phenylephrine administration at a mean arterial pressure of < 65 mmHg. Patients were divided into four groups according to total peripheral resistance and preload dependency.
RESULTS
Forty-two patients were included in this study. The stroke volume in patients with preload dependency (n = 23) increased after phenylephrine administration. However, phenylephrine administration did not impact the stroke volume in patients without preload dependency (n = 19). The perfusion index decreased regardless of preload dependency. The changes in the perfusion index after phenylephrine administration exhibited low accuracy for predicting preload dependency. Based on subgroup analysis, patients with high total peripheral resistance tended to exhibit increased stroke volume following phenylephrine administration, which was particularly prominent in patients with high total peripheral resistance and preload dependency.
CONCLUSION
The findings of the current study revealed that changes in the perfusion index induced by administering 0.1 mg of phenylephrine could not predict preload dependency. This may be attributed to the different phenylephrine-induced stroke volume patterns observed in patients according to the degree of total peripheral resistance and preload dependency.
TRIAL REGISTRATION
University Hospital Medical Information Network (UMIN000049994 on 9/01/2023).
Topics: Humans; Phenylephrine; Cardiac Output; Prospective Studies; Perfusion Index; Stroke Volume; Anesthesia, General; Fluid Therapy; Blood Pressure
PubMed: 38431582
DOI: 10.1186/s12871-024-02478-w -
Translational Vision Science &... Jun 2024To assess the impact of ocular confounding factors on aqueous humor (AH) proteomic and metabolomic analyses for retinal disease characterization.
PURPOSE
To assess the impact of ocular confounding factors on aqueous humor (AH) proteomic and metabolomic analyses for retinal disease characterization.
METHODS
This study recruited 138 subjects (eyes): 102 with neovascular age-related macular degeneration (nAMD), 18 with diabetic macular edema (DME), and 18 with cataract (control group). AH samples underwent analysis using Olink Target 96 proteomics and Metabolon's metabolomics platform Data analysis included correlation, differential abundance, and gene-set analysis.
RESULTS
In total, 756 proteins and 408 metabolites were quantified in AH. Total AH protein concentration was notably higher in nAMD (3.2-fold) and DME (4.1-fold) compared to controls. Pseudophakic eyes showed higher total AH protein concentrations than phakic eyes (e.g., 1.6-fold in nAMD) and a specific protein signature indicative of matrix remodeling. Unexpectedly, pupil-dilating drugs containing phenylephrine/tropicamide increased several AH proteins, notably interleukin-6 (5.4-fold in nAMD). Correcting for these factors revealed functionally relevant protein correlation clusters and disease-relevant, differentially abundant proteins across the groups. Metabolomics analysis, for which the relevance of confounder adjustment was less apparent, suggested insufficiently controlled diabetes and chronic hyperglycemia in the DME group.
CONCLUSIONS
AH protein concentration, pseudophakia, and pupil dilation with phenylephrine/tropicamide are important confounding factors for AH protein analyses. When these factors are considered, AH analyses can more clearly reveal disease-relevant factors.
TRANSLATIONAL RELEVANCE
Considering AH protein concentration, lens status, and phenylephrine/tropicamide administration as confounders is crucial for accurate interpretation of AH protein data.
Topics: Humans; Aqueous Humor; Female; Proteomics; Male; Aged; Metabolomics; Eye Proteins; Middle Aged; Cataract; Diabetic Retinopathy; Macular Edema; Wet Macular Degeneration; Aged, 80 and over
PubMed: 38913008
DOI: 10.1167/tvst.13.6.17 -
Pharmaceutical Biology Dec 2024The mechanisms of Traditional Chinese Medicine (TCM) Guizhi-Gancao Decoction (GGD) remain unknown.
Network pharmacology integrated with experimental validation to elucidate the mechanisms of action of the Guizhi-Gancao Decoction in the treatment of phenylephrine-induced cardiac hypertrophy.
CONTEXT
The mechanisms of Traditional Chinese Medicine (TCM) Guizhi-Gancao Decoction (GGD) remain unknown.
OBJECTIVE
This study explores the mechanisms of GGD against cardiac hypertrophy.
MATERIALS AND METHODS
Network pharmacology analysis was carried out to identify the potential targets of GGD. experiments, C57BL/6J mice were divided into Con, phenylephrine (PE, 10 mg/kg/d), 2-chloroadenosine (CADO, the stable analogue of adenosine, 2 mg/kg/d), GGD (5.4 g/kg/d) and GGD (5.4 g/kg/d) + CGS15943 (a nonselective adenosine receptor antagonist, 4 mg/kg/d). experiments, primary neonatal rat cardiomyocytes (NRCM) were divided into Con, PE (100 µM), CADO (5 µM), GGD (10 g/mL) and GGD (10 g/mL) + CGS15943 (5 µM). Ultrasound, H&E and Masson staining, hypertrophic genes expression and cell surface area were conducted to verify the GGD efficacy. Adenosine receptors (ADORs) expression were tested real-time polymerase chain reaction (PCR), western blotting and immunofluorescence analysis.
RESULTS
Network pharmacology identified ADORs among those of the core targets of GGD. experiments demonstrated that GGD attenuated PE-induced increased surface area (with an EC of 5.484 × 10 g/mL). data shown that GGD attenuated PE-induced ventricular wall thickening. and data indicated that GGD alleviated PE-induced hypertrophic gene expression (e.g., ANP, BNP and MYH7/MYH6), A1AR over-expression and A2aAR down-expression. Moreover, CADO exerts effects similar to GGD, whereas CGS15943 eliminated most effects of GGD.
DISCUSSION AND CONCLUSIONS
Our findings suggest the mechanism by which GGD inhibits cardiac hypertrophy, highlighting regulation of ADORs as a potential therapeutic strategy for HF.
Topics: Animals; Drugs, Chinese Herbal; Phenylephrine; Cardiomegaly; Mice, Inbred C57BL; Mice; Male; Rats; Myocytes, Cardiac; Network Pharmacology; Rats, Sprague-Dawley; Cells, Cultured; Disease Models, Animal; Medicine, Chinese Traditional
PubMed: 38773737
DOI: 10.1080/13880209.2024.2354335 -
Atherosclerosis May 2024Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce the risk of cardiovascular events independently of glycemic control. However, the...
BACKGROUND AND AIMS
Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce the risk of cardiovascular events independently of glycemic control. However, the possibility that SGLT2 inhibitors improve vascular restenosis is unknown. The aim of this study was to examine whether dapagliflozin could prevent neointima thickening following balloon injury and, if so, to determine the underlying mechanisms.
METHODS
Saline, dapagliflozin (1.5 mg/kg/day), or losartan (30 mg/kg/day) was administered orally for five weeks to male Wistar rats. Balloon injury of the left carotid artery was performed a week after starting the treatment and rats were sacrificed 4 weeks later. The extent of neointima was assessed by histomorphometric and immunofluorescence staining analyses. Vascular reactivity was assessed on injured and non-injured carotid artery rings, changes of target factors by immunofluorescence, RT-qPCR, and histochemistry.
RESULTS
Dapagliflozin and losartan treatments reduced neointima thickening by 32 % and 27 %, respectively. Blunted contractile responses to phenylephrine and relaxations to acetylcholine and down-regulation of eNOS were observed in the injured arteries. RT-qPCR investigations indicated an increased in gene expression of inflammatory (IL-1beta, VCAM-1), oxidative (p47phox, p22phox) and fibrotic (TGF-beta1) markers in the injured carotid. While these changes were not affected by dapagliflozin, increased levels of AT1R and NTPDase1 (CD39) and decreased levels of ENPP1 were observed in the restenotic carotid artery of the dapagliflozin group.
CONCLUSIONS
Dapagliflozin effectively reduced neointimal thickening. The present data suggest that dapagliflozin prevents restenosis through interfering with angiotensin and/or extracellular nucleotides signaling. SGLT2 represents potential new target for limiting vascular restenosis.
PubMed: 38879387
DOI: 10.1016/j.atherosclerosis.2024.117595 -
Investigative Ophthalmology & Visual... May 2024Earlier reports highlighted the predominant presence of aquaporin 4 (AQP4) in the duct cells of rabbit lacrimal glands (LGs). Whereas significant alterations in AQP4...
PURPOSE
Earlier reports highlighted the predominant presence of aquaporin 4 (AQP4) in the duct cells of rabbit lacrimal glands (LGs). Whereas significant alterations in AQP4 mRNA levels have been observed in experimental dry eye and during pregnancy, the impact of AQP4 in LG ductal fluid production remains unclear. In our recent work, the role of AQP4 in LG ductal fluid secretion was investigated utilizing wild type (WT) and AQP4 knock out (KO) mice.
METHODS
Tear production was assessed in both WT and KO animals. Immunostaining was used to identify AQP4 protein. Duct segments were harvested from LGs of WT and KO mice. Fluid secretion and filtration permeability (Pf) were quantified using video-microscopy. Ductal tear production, elicited by a cell-permeable cAMP analogue (8-bromo cAMP), carbachol, vasoactive intestinal peptide (VIP), and phenylephrine (PHE), were assessed in both WT and KO ducts.
RESULTS
A higher expression of AQP4 protein was noted in the duct cells from WT mice when compared to acinar cells. Pf did not show notable alterations between WT and AQP4 KO ducts. Carbachol elicited comparable secretory responses in ducts from both WT and KO animals. However, 8-bromo cAMP, VIP, and PHE stimulation resulted in decreased secretion in ducts from AQP4 KO LGs.
CONCLUSIONS
Our findings underscore the functional relevance of AQP4 in the fluid production of mouse LG ducts. AQP4 seems to play different roles in fluid secretions elicited by different secretagogues. Specifically, cAMP-mediated, and adrenergic agonist-related secretions were reduced in AQP4 KO ducts.
Topics: Animals; Mice; Lacrimal Apparatus; Tears; Mice, Knockout; Aquaporin 4; Mice, Inbred C57BL; Female
PubMed: 38771571
DOI: 10.1167/iovs.65.5.30 -
American Journal of Veterinary Research Dec 2023To assess the feasibility of isometric myography in pet dogs with myxomatous mitral valve disease (MMVD) to determine its use in quantifying endothelial dysfunction.
OBJECTIVE
To assess the feasibility of isometric myography in pet dogs with myxomatous mitral valve disease (MMVD) to determine its use in quantifying endothelial dysfunction.
ANIMALS
9 dogs euthanized for medical reasons.
METHODS
Femoral, renal, and mesenteric arteries were collected postmortem and stored in physiological saline solution at 4 °C for myography. Mitral valves were scored for myxomatous degeneration (grades 1 to 4). Sections of arteries were mounted in wells, immersed in physiological saline solution perfused with 95% O2 and 5% CO2 at 37 °C, and stretched to an internal circumference (IC) that generated the maximal difference between active and passive wall tension (IC1). Normalization factors were calculated by dividing the IC1 by the IC at which the passive wall tension was 100 mm Hg (IC100). Vasoconstriction to phenylephrine and vasodilation to acetylcholine (endothelial dependent) and sodium nitroprusside (endothelial independent) were assessed by cumulative dose-response curves.
RESULTS
Median MMVD grade was 3. Mean values of normalization factors were 1.00 ± 0.14 (renal, n = 15), 1.00 ± 0.10 (femoral, 8), and 1.05 ± 0.12 (mesenteric, 6). Responses to phenylephrine were similar between dogs (P = .14). Reduced responses to acetylcholine compared with sodium nitroprusside were identified in 15 arteries, suggesting endothelial dysfunction.
CLINICAL RELEVANCE
Isometric myography of arteries from pet dogs is feasible and can identify loss of endothelial-dependent relaxation in dogs with MMVD postmortem. Its use in further research can lead to a better understanding of the pathophysiology mechanisms of this disease.
Topics: Dogs; Animals; Mitral Valve; Acetylcholine; Nitroprusside; Saline Solution; Heart Valve Diseases; Myography; Phenylephrine; Dog Diseases
PubMed: 37709264
DOI: 10.2460/ajvr.23.06.0136 -
Antioxidants (Basel, Switzerland) Oct 2023Endothelium-derived nitric oxide (NO)-induced vasodilation is impaired in pregnancy hypertension. However, the role of perivascular adipose tissue (PVAT)-derived...
Vasodilator Responses of Perivascular Adipose Tissue-Derived Hydrogen Sulfide Stimulated with L-Cysteine in Pregnancy Hypertension-Induced Endothelial Dysfunction in Rats.
Endothelium-derived nitric oxide (NO)-induced vasodilation is impaired in pregnancy hypertension. However, the role of perivascular adipose tissue (PVAT)-derived hydrogen sulfide (HS), as an alternative for counteracting vascular dysfunction, is incompletely clear in hypertensive disorders of pregnancy. Therefore, PVAT-derived HS-induced vasodilation was investigated in pregnancy hypertension-induced endothelial dysfunction. Non-pregnant (Non-Preg) and pregnant (Preg) rats were submitted (or not) to the deoxycorticosterone (DOCA)-salt protocol and assigned as follows ( = 10/group): Non-Preg, Non-Preg+DOCA, Preg, and Preg+DOCA groups. Systolic blood pressure (SBP), angiogenesis-related factors, determinant levels of HS (PbS), NO (NOx), and oxidative stress (MDA) were assessed. Vascular changes were recorded in thoracic aortas with PVAT and endothelium (intact and removed layers). Vasorelaxation responses to the substrate (L-cysteine) for the HS-producing enzyme cystathionine-γ-lyase (CSE) were examined in the absence and presence of CSE-inhibitor DL-propargylglycine (PAG) in thoracic aorta rings pre-incubated with cofactor for CSE (pyridoxal-5 phosphate: PLP) and pre-contracted with phenylephrine. Hypertension was only found in the Preg+DOCA group. Preg+DOCA rats showed angiogenic imbalances and increased levels of MDA. PbS, but not NOx, showed increased levels in the Preg+DOCA group. Pre-incubation with PLP and L-cysteine elevated determinants of HS in PVAT and placentas of Preg-DOCA rats, whereas no changes were found in the aortas without PVAT. Aortas of Preg-DOCA rats showed that PVAT-derived HS-dependent vasodilation was greater compared to endothelium-derived HS, whereas PAG blocked these responses. PVAT-derived HS endogenously stimulated with the amino acid L-cysteine may be an alternative to induce vasorelaxation in endothelial dysfunction related to pregnancy hypertension.
PubMed: 38001772
DOI: 10.3390/antiox12111919 -
Kardiochirurgia I Torakochirurgia... Sep 2023The rat vascular ischaemia and reperfusion model is used to evaluate the molecular and functional effects of potential agents against ischaemia and reperfusion injury...
INTRODUCTION
The rat vascular ischaemia and reperfusion model is used to evaluate the molecular and functional effects of potential agents against ischaemia and reperfusion injury of autologous graft veins. However, there is no consensus on whether hypoxia, rather than ischaemia, is sufficient to induce vascular dysfunction.
AIM
To compare the effects of hypoxia and ischaemia, with or without reperfusion, on the vascular functions of isolated thoracic aortic rings of rats.
MATERIAL AND METHODS
Thoracic aortas of 12 male Sprague-Dawley rats (350-500 g, 18-24 months old) were isolated and divided into rings that were randomly allocated to control, ischaemia, hypoxia, ischaemia-reperfusion, and hypoxia-reperfusion groups. Aortic rings other than those of the control group were stored at 4°C for 24 h in saline. For ischaemia, saline was gassed with nitrogen. After 24 h, aortic rings in the ischaemia-reperfusion and hypoxia-reperfusion groups were incubated with 200 μM sodium hypochlorite for 30 min. Vascular and endothelial functions were tested in an organ bath set-up.
RESULTS
Vascular response to potassium chloride (80 mM) decreased in all experimental groups compared to the control group ( = 0.007), but phenylephrine-induced contraction (10 M) increased only in the ischaemia-reperfusion group ( < 0.0001). Acetylcholine (10-10 M)-induced endothelium-dependent vasorelaxations were impaired in all groups - particularly in the ischaemia-reperfusion group ( = 0.0011). Sodium nitroprusside (10-10 M)-induced endothelium-independent vasorelaxations were similar across all groups ( = 0.1258).
CONCLUSIONS
Ischaemia followed by reperfusion should be implanted to achieve maximum endothelial and contractile dysfunction , and to replicate ischaemia and reperfusion injury of autologous graft veins.
PubMed: 37937174
DOI: 10.5114/kitp.2023.131952 -
BMC Anesthesiology Aug 2023Hypotension frequently occurs after spinal anesthesia during cesarean delivery, and fluid loading is recommended for its prevention. We evaluated the efficacy of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Hypotension frequently occurs after spinal anesthesia during cesarean delivery, and fluid loading is recommended for its prevention. We evaluated the efficacy of subclavian vein (SCV) ultrasound (US)-guided volume optimization in preventing hypotension after spinal anesthesia during cesarean delivery.
METHODS
This randomized controlled study included 80 consecutive full-term parturients scheduled for cesarean delivery under spinal anesthesia. The women were randomly divided into the SCVUS group, with SCVUS analysis before spinal anesthesia with SCVUS-guided volume management, and the control group without SCVUS assessment. The SCVUS group received 3 mL/kg crystalloid fluid challenges repeatedly within 3 min with a 1-min interval based on the SCV collapsibility index (SCVCI), while the control group received a fixed dose (10 mL/kg). Incidence of post-spinal anesthetic hypotension was the primary outcome. Total fluid volume, vasopressor dosage, changes in hemodynamic parameters, maternal adverse effects, and neonatal status were secondary outcomes.
RESULTS
The total fluid volume was significantly higher in the control group than in the SCVUS group (690 [650-757.5] vs. 160 [80-360] mL, p < 0.001), while the phenylephrine dose (0 [0-40] vs. 0 [0-30] µg, p = 0.276) and incidence of post-spinal anesthetic hypotension (65% vs. 60%, p = 0.950) were comparable between both the groups. The incidence of maternal adverse effects, including nausea/vomiting and bradycardia (12.5% vs. 17.5%, p = 0.531 and 7.5% vs. 5%, p = 1.00, respectively), and neonatal outcomes (Apgar scores) were comparable between the groups. SCVCI correlated with the amount of fluid administered (R = 0.885, p < 0.001).
CONCLUSIONS
SCVUS-guided volume management did not ameliorate post-spinal anesthetic hypotension but reduced the volume of the preload required before spinal anesthesia. Reducing preload volume did not increase the incidence of maternal and neonatal adverse effects nor did it increase the total vasopressor dose. Moreover, reducing preload volume could relieve the heart burden of parturients, which has high clinical significance.
CLINICAL TRIAL REGISTRATION
The trial was registered with the Chinese Clinical Trial Registry at chictr.org.cn (registration number, ChiCTR2100055050) on December 31, 2021.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Subclavian Vein; Anesthesia, Spinal; Hypotension; Ultrasonography, Interventional; Anesthetics
PubMed: 37620761
DOI: 10.1186/s12871-023-02242-6