Hees JE, Cleveland WJ, Balzer C
… +1 more, Riess ML
Can J Physiol Pharmacol
· 2025 Jan · PMID 39378515
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During cardiopulmonary resuscitation, pulmonary vasoconstriction due to hypoxia and hypercarbia restricts blood flow from the right to the left heart, resulting in reduced cardiac output that further inhibits adequate ox...During cardiopulmonary resuscitation, pulmonary vasoconstriction due to hypoxia and hypercarbia restricts blood flow from the right to the left heart, resulting in reduced cardiac output that further inhibits adequate oxygenation and the ability to distribute oxygenated blood and medications. An inhaled pulmonary vasodilator could attenuate vasoconstriction and, therefore, increase cardiac output. We used rat isolated lungs to test if inhaled Argon leads to pulmonary vasodilation in phenylephrine-treated lungs. Lungs of 13 adult male Sprague-Dawley rats were isolated, ventilated, and perfused. Pulmonary artery and left atrium were cannulated and lungs perfused at constant flow with 4% albumin physiological saline solution. Controls ( = 6) were ventilated with 65% N, 5% CO, 30% O, and Argon lungs ( = 7) with 65% Argon, 5% CO, and 30% O. Pulmonary mean arterial pressure (pMAP) and airway pressure (AWP) were recorded continuously, and pulmonary vascular resistance (PVR) was calculated. Following baseline readings, phenylephrine, a pulmonary vasoconstrictor, was perfused at increasing concentrations from 10 to 10 mol/L every 5 min. Statistics: Student's test, α = 0.05. Argon led to significantly lower pMAPs and PVRs, independent of AWP. Thus, it significantly dilated pre-constricted pulmonary vessels in an ex vivo lung model. When given during resuscitation, this might aid to increase cardiac output.
Can J Physiol Pharmacol
· 2025 Mar · PMID 39374553
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The heterocyclic 2-aminothiazoles scaffolds are used in a wide range of therapeutic applications against various diseases for its antioxidant, anti-inflammatory, antimicrobial and anticancer actions. In this study, we sy...The heterocyclic 2-aminothiazoles scaffolds are used in a wide range of therapeutic applications against various diseases for its antioxidant, anti-inflammatory, antimicrobial and anticancer actions. In this study, we synthesized novel aniline aromatic ring-substituted 2-aminothiazole derivatives. Molecular docking was performed using Glide module of the Schrödinger Suite to fit compounds JG-49, JG-62, and KBA-18 against the Nicotinamide phosphoribosyl transferase (Nampt) enzyme, an intracellular regulator of nicotinamide adenine dinucleotide (NAD) redox cofactor involved in energy metabolism and epigenetics and are implicated in aging and metabolic diseases. The three compounds viz. JG-49, JG-62, and KBA-18 showed an increase in Nampt enzymatic activity in vitro. All three substituted derivatives of 2-aminothiazole showed no cytotoxicity with the mouse C2C12 myoblasts cultures assessed with the MTT cell viability assay. Moreover, the wound closure of the mouse C2C12 myoblasts in vitro displayed no significant difference between the treatment groups of the 2-aminothiazole derivatives compared with the control naïve and DMSO treated myoblasts cultures, except for the 2-aminothiazole substituted derivatives JG-62 and KBA-18, which showed a significant increase in the wound closure compared with the control cells at different concentrations. Taken together, we demonstrated that 2-aminothiazole substituted derivatives provide enhanced Nampt activity, wound closure, and no cytotoxic effects in vitro. Further studies will allow to improve the substitution of 2-aminothiazole derivatives and test their potential therapeutic applications.
Civelek E, Karaman EF, Özden S
… +3 more, Büyükpınarbaşılı N, Uydeş Doğan B, Kaleli Durman D
Can J Physiol Pharmacol
· 2025 Jan · PMID 39361973
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Perivascular adipose tissue (PVAT) plays an important role in many physiological and pathological processes, such as regulation of vascular tone. The aim of this study is to evaluate the effects of pioglitazone on functi...Perivascular adipose tissue (PVAT) plays an important role in many physiological and pathological processes, such as regulation of vascular tone. The aim of this study is to evaluate the effects of pioglitazone on functional, structural, and biochemical properties of PVAT in an experimental model of type-2 diabetes (T2DM). T2DM was induced by high-fat-diet/low-dose-streptozotocin in rats, and pioglitazone (20 mg/kg/p.o.) was administered for 6 weeks. Changes in biochemical parameters, PVAT-mass, vascular-reactivity in thoracic-aorta, as well as PVAT adipocytokine and -expression levels, and histopathology were evaluated. Pioglitazone administration improved blood glucose and lipid profiles in T2DM. Pioglitazone did not change the anticontractile effect of PVAT on aortic contractile reactivity and besides, had no influence on endothelium-dependent and -independent relaxation responses. Pioglitazone administration increased PVAT-mass and tumor necrotizing factor-α levels, while adiponectin, leptin, and interleukin-6 levels were unchanged. Also, a prominent increase was observed in -expression in T2DM-Pio group. Moreover, pioglitazone decreased liver steatosis, aortic wall thickening, and myocardial damage, whereas increased adipocyte size and adiposity in PVAT. Overall, pioglitazone treatment changed the mass and in part the inflammatory profile of PVAT but did not modify vasoreactivity in T2DM. This study provides novel findings in relationship with the adipogenic effect of pioglitazone and PVAT function.
Can J Physiol Pharmacol
· 2025 Jan · PMID 39361971
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Research on airway smooth muscle has traditionally focused on its putative detrimental role in asthma, emphasizing on how its shortening narrows the airway lumen, without much consideration about its potential role in su...Research on airway smooth muscle has traditionally focused on its putative detrimental role in asthma, emphasizing on how its shortening narrows the airway lumen, without much consideration about its potential role in subserving the function of the entire respiratory system. New experimental evidence on mice suggests that not only the smooth muscle is required to sustain life postnatally, but its stiffening effect on the lung tissue also protects against excessive airway narrowing and, most importantly, against small airway narrowing heterogeneity and closure. These results suggest that the smooth muscle plays an vital role in the lung periphery, essentially safeguarding alveolar ventilation by preventing small airway closure. These results also shed light on perplexing clinical observations, such as the long-standing doubts about the safety of bronchodilators. Since there seems to be an optimal level of smooth muscle contraction, at least in small airways, the therapeutic goal of maximizing the relaxation of the smooth muscle in asthma needs to be revisited. A bronchodilator with an excessive potency for inhibiting smooth muscle contraction, and that is still potent at concentrations reaching the lung periphery, may foster airway closure and air trapping, resulting in no net gain or even a decline in lung function.
Jesus CPS, Pimenta GF, de Oliveira MG
… +3 more, Dourado TMH, Antunes E, Tirapelli CR
Can J Physiol Pharmacol
· 2024 Dec · PMID 39270309
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Cyclophosphamide (CYP) is combined with cytoprotective agents to minimize its toxicity in the bladder, which is mediated by reactive oxygen species (ROS). Using multiple antioxidant mechanisms, nebivolol protects from ox...Cyclophosphamide (CYP) is combined with cytoprotective agents to minimize its toxicity in the bladder, which is mediated by reactive oxygen species (ROS). Using multiple antioxidant mechanisms, nebivolol protects from oxidative stress in distinctive conditions. We hypothesized that nebivolol would attenuate both molecular and functional alterations induced by CYP in the bladder. Male C57BL/6 were pretreated or not with nebivolol (10 mg/kg/day, gavage), which was given 5 days before a single injection of CYP (300 mg/kg; i.p.). Molecular and functional parameters were assessed at 24 h in the bladder. Nebivolol prevented increases in ROS generation and lipoperoxidation as well as reduction of superoxide dismutase activity induced by CYP. Increased voiding frequency, decreased voiding interval, and reduced bladder capacity were found in CYP-treated mice. These responses were prevented by nebivolol. An augmented number of urinary spots and smaller urinary volumes were detected in CYP-injected mice, and nebivolol partially prevented these responses. The reduction of ROS levels is the primary mechanism by which nebivolol attenuates the deleterious effects of CYP in the bladder. The association of nebivolol with other cytoprotective agents could be an option to prevent CYP-associated oxidative damage to the bladder during chemotherapy.
Braescu L, Sturza A, Sosdean R
… +8 more, Aburel OM, Lazar MA, Muntean D, Luca CT, Brie DM, Feier H, Crisan S, Mornos C
Can J Physiol Pharmacol
· 2024 Nov · PMID 39226407
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This study aimed to assess the utility of echocardiography-measured epicardial adipose tissue (EAT) thickness (EATT) as an independent predictor for coronary artery disease (CAD), examining its correlation with oxidative...This study aimed to assess the utility of echocardiography-measured epicardial adipose tissue (EAT) thickness (EATT) as an independent predictor for coronary artery disease (CAD), examining its correlation with oxidative stress levels in epicardial tissue and the complexity of the disease in patients undergoing open-heart surgery. This study included a total of 25 patients referred for cardiac surgery with 14 in the CAD group and 11 in the non-CAD group. Epicardial fat was sampled from patients subjected to open-heart surgery EATT was higher in the CAD group compared to the non-CAD group (8.15 ± 2.09 mm vs. 5.12 ± 1.8 mm, = 0.001). The epicardial reactive oxygen species level was higher in the CAD group compared to the non-CAD group (21.4 ± 2.47 nmol HO/g tisssue/h vs. 15.7 ± 1.55 nmol HO/g tisssue/h, < 0.001). EATT greater than 6.05 mm was associated with CAD, with a sensitivity of 86% and specificity of 73%. Echocardiographically measured EATT is a significant, independent predictor of CAD. Its relationship with increased EAT oxidative stress levels suggests a potential mechanistic link between EATT and CAD pathogenesis. These findings highlight the importance of EATT as a diagnostic tool in assessing the complexity of CAD in patients undergoing cardiac surgery.
Can J Physiol Pharmacol
· 2024 Nov · PMID 39189463
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Medicinal signaling cells (MSC) hold promise for regenerative medicine due to their ability to repair damaged tissues. However, their effectiveness can be affected by how long they are cultured in the lab. This study inv...Medicinal signaling cells (MSC) hold promise for regenerative medicine due to their ability to repair damaged tissues. However, their effectiveness can be affected by how long they are cultured in the lab. This study investigated how passage number influences key properties for regenerative medicine of pig bone marrow MSC. The medicinal signiling cells derived from pig bone marrow (BM-MSC) were cultured in D-MEM High Glucose supplemented with 15% foetal bovine serum until the 25th passage and assessed their growth, viability, ability to differentiate into different cell types (plasticity), and cell cycle activity. Our findings showed that while the cells remained viable until the 25th passage, their ability to grow and differentiate declined after the 5th passage. Additionally, cells in later passages spent more time in a resting phase, suggesting reduced activity. In conclusion, the number of passages is a critical factor for maintaining ideal MSC characteristics. From the 9th passage BM-MSC exhibit decline in proliferation, differentiation potential, and cell cycle activity. Given this, it is possible to suggest that the use of 5th passage cells is the most suitable for therapeutic applications.
Ali SR, Nkembo AT, Tipparaju SM
… +2 more, Ashraf M, Xuan W
Can J Physiol Pharmacol
· 2024 Dec · PMID 39186818
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Sarcopenia, a disorder marked by muscle loss and dysfunction, is a global health concern, particularly in aging populations. Sarcopenia is intricately related to various health conditions, including obesity, dysphagia, a...Sarcopenia, a disorder marked by muscle loss and dysfunction, is a global health concern, particularly in aging populations. Sarcopenia is intricately related to various health conditions, including obesity, dysphagia, and frailty, which underscores the complexity. Despite recent advances in metabolomics and other omics data for early detection and treatment, the precise characterization and diagnosis of sarcopenia remains challenging. In the present review we provide an overview of the complex metabolic mechanisms that underlie sarcopenia, with particular emphasis on protein, lipid, carbohydrate, and bone metabolism. The review highlights the importance of leucine and other amino acids in promoting muscle protein synthesis and clarifies the critical role played by amino acid metabolism in preserving muscular health. In addition, the review provides insights regarding lipid metabolism on sarcopenia, with an emphasis on the effects of inflammation and insulin resistance. The development of sarcopenia is largely influenced by insulin resistance, especially with regard to glucose metabolism. Overall, the review emphasizes the complex relationship between bone and muscle health by highlighting the interaction between sarcopenia and bone metabolism. Furthermore, the review outlines various therapeutic approaches and potential biomarkers for diagnosing sarcopenia. These include pharmacological strategies such as hormone replacement therapy and anabolic steroids as well as lifestyle modifications such as exercise, nutrition, and dietary changes.
Can J Physiol Pharmacol
· 2024 Dec · PMID 38968609
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Lysophosphatidic acid (LPA) is a bioactive lipid that is mainly produced by the secreted lysophospholipase D, autotaxin (ATX), and signals through at least six G protein-coupled receptors (LPA1-6). Extracellular LPA is d...Lysophosphatidic acid (LPA) is a bioactive lipid that is mainly produced by the secreted lysophospholipase D, autotaxin (ATX), and signals through at least six G protein-coupled receptors (LPA1-6). Extracellular LPA is degraded through lipid phosphate phosphatases (LPP1, LPP2, and LPP3) at the plasmamembrane, terminating LPA receptor signaling. The ATX-LPA-LPP3 pathway is critically involved in a wide range of physiological processes, including cell survival, migration, proliferation, angiogenesis, and organismal development. Similarly, dysregulation of this pathway has been linked to many pathological processes, including cardiovascular disease. This review summarizes and interprets current literature examining the regulation and role of the ATX-LPA-LPP3 axis in heart disease. Specifically, the contribution of altered LPA metabolism via ATX and LPP3 and resulting changes to LPA receptor signaling in obesity cardiomyopathy, cardiac mitochondrial dysfunction, myocardial infarction/ischemia-reperfusion injury, hypertrophic cardiomyopathy, and aortic valve stenosis is discussed.
The cardiac rehabilitation quality indicators (CRQIs) developed by the Canadian Cardiovascular Society provide a means to standardize program assessment and identify sex-related inequities. No formal evaluation of the CR...The cardiac rehabilitation quality indicators (CRQIs) developed by the Canadian Cardiovascular Society provide a means to standardize program assessment and identify sex-related inequities. No formal evaluation of the CRQIs has been conducted in Manitoba. An environmental scan for the CRQIs was performed using data in the electronic medical record at two cardiac rehabilitation (CR) sites in Winnipeg for 2016-2019 referrals. Of the 8116 referrals, 7758 (5491 males and 2267 females) had geographical access and were eligible for CR. The Manitoba Centre for Health Policy Data Quality Framework informed the data quality assessment. Thirteen CRQIs were available; four were considered high quality; nine demonstrated moderate to significant missing data. In addition to missing values, potential misclassification of risk (CR-4) and physiologically implausible and invalid dates were assessed and identified (CR-13 and CR-17). Each site had a physician medical director (CR-31) and a documented emergency response strategy (CR-32). Only high-quality data were evaluated for sex-related differences using chi-square and median tests. Women had lower enrollment (CR-3), and more women enrolled after the median of 41 days (CR-2b). Engagement with CR partners, including frontline staff, and utilizing strategies to assess and limit physiologically implausible values and dates will enhance data capture and quality.
Delgado Spicuzza J, Gosalia J, Studinski M
… +6 more, Armando C, Alipour E, Kim-Shapiro D, Flanagan M, Somani Y, Proctor D
Can J Physiol Pharmacol
· 2024 Nov · PMID 38901043
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Postmenopausal cardiovascular health is a critical determinant of longevity. Consumption of beetroot juice (BR) and other nitrate-rich foods is a safe, effective non-pharmaceutical intervention to increase systemic bioav...Postmenopausal cardiovascular health is a critical determinant of longevity. Consumption of beetroot juice (BR) and other nitrate-rich foods is a safe, effective non-pharmaceutical intervention to increase systemic bioavailability of the vasoprotective molecule, nitric oxide, through the exogenous nitrate (NO )-nitrite (NO )-nitric oxide (NO) pathway. We hypothesized that a single dose of nitrate-rich beetroot juice (BR 600 mg NO /140 mL, BR ∼ 0 mg/140 mL) would improve resting endothelial function and resistance to ischemia-reperfusion (IR) injury to a greater extent in early-postmenopausal (1-6 years following their final menstrual period (FMP), = 12) compared to late-postmenopausal (6+ years after FMP, = 12) women. Analyses with general linear models revealed a significant ( < 0.05) timetreatment interaction effect for brachial artery adjusted flow-mediated dilation (FMD). Pairwise comparisons revealed that adjusted FMD was significantly lower following IR-injury in comparison to all other time points with BR (early FMD 2.51 ± 1.18%, late FMD 1.30 ± 1.10, < 0.001) and was lower than post-IR with BR (early FMD 3.84 ± 1.21%, late FMD 3.21 ± 1.13%, = 0.014). A single dose of BR significantly increased resting macrovascular function in the late postmenopausal group only ( = 0.005). Considering the postmenopausal stage-dependent variations in endothelial responsiveness to dietary nitrate, we predict differing mechanisms underpin macrovascular protection against IR injury.
Can J Physiol Pharmacol
· 2024 Oct · PMID 38815593
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Cardiovascular disease is the leading indirect cause of maternal morbidity and mortality, accounting for nearly one third of maternal deaths during pregnancy. The burden of cardiovascular disease in pregnancy is increasi...Cardiovascular disease is the leading indirect cause of maternal morbidity and mortality, accounting for nearly one third of maternal deaths during pregnancy. The burden of cardiovascular disease in pregnancy is increasing, as are the incidence of maternal morbidity and mortality. Normal physiologic adaptations to pregnancy, including increased cardiac output and plasma volume, may unmask cardiac conditions, exacerbate previously existing conditions, or create de novo complications. It is important for care providers to understand the normal physiologic changes of pregnancy and how they may impact the care of patients with cardiovascular disease. This review outlines the physiologic adaptions during pregnancy and their pathologic implications for some of the more common cardiovascular conditions in pregnancy.
Bastiany A, Towns C, Kimmaliardjuk DM
… +2 more, Kalenga CZ, Burgess SN
Can J Physiol Pharmacol
· 2024 Aug · PMID 38815591
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Cardiovascular disease (CVD) remains the leading cause of death globally. Although the burden of CVD risk factors tends to be lower in women, they remain at higher risk of developing complications when affected by these...Cardiovascular disease (CVD) remains the leading cause of death globally. Although the burden of CVD risk factors tends to be lower in women, they remain at higher risk of developing complications when affected by these risk factors. There is still a lack of awareness surrounding CVD in women, both from a patient's and a clinician's perspective, especially among visible minorities. However, women who are informed about their heart health and who engage in decision-making with their healthcare providers are more likely to modify their lifestyle, and improve their CVD risk. A patient-centered care approach benefits patients' physical and mental health, and is now considered gold-standard for efficient patient care. Engaging women in their heart health will contribute in closing the gap of healthcare disparities between men and women, arising from sociocultural, socioeconomic, and political factors. This comprehensive review of the literature discusses the importance of engaging women in decision-making surrounding their heart health and offers tools for an effective and culturally sensitive patient-provider relationship.
Can J Physiol Pharmacol
· 2024 Oct · PMID 38781602
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Oral hormonal contraception (OHC) is a widely employed method in females for the prevention of unintended pregnancies, as well as for the treatment of menstrual disorders, endometriosis, and polycystic ovarian syndrome....Oral hormonal contraception (OHC) is a widely employed method in females for the prevention of unintended pregnancies, as well as for the treatment of menstrual disorders, endometriosis, and polycystic ovarian syndrome. However, it is believed that with OHCs use, some females may have higher risk of cardiovascular diseases, such as hypertension, diabetes, myocardial infarction, thrombosis, and heart failure. Although such risks are infrequently detected in healthy young females with the use of oral contraceptives, slightly elevated risks of cardiovascular diseases have been observed among reproductive-aged healthy females. However, prolonged use of OHC has also been claimed to have protective cardiac effects and may contribute to reduced risk of cardiovascular disease. In fact, the debate on whether OHC administration increases the risk of cardiovascular diseases has been ongoing with inconsistent and controversial viewpoints. Nevertheless, a great deal of work has been carried out to understand the relationship between OHC use and the occurrence of cardiovascular risk in females who use OHC for preventing the unwanted pregnancy or treatment of other disorders. Therefore, in this review we summarize the most recent available evidence regarding the association between the use of oral hormonal contraceptives and the risk for cardiovascular disease in females who are using OHC to prevent unintended pregnancy.