Pressor Effect Research Articles

PENGARUH PEMBERIAN KUNYIT DAN MADU TERHADAP PENURUNAN NYERI HAID (DYSMENORRHAE) PADA REMAJA PUTRI DI KECAMATAN MEDAN AMPLAS KOTA MEDAN TAHUN 2022

Abstract Dysmenorrhea is lower abdominal pain during menstruation that can interfere with daily activities. Pain arises due to increased levels of prostaglandins. Prostaglandins have an effect that can increase the contractility of the uterine muscle and prostaglandins also have a vasoconstrictive effect that can cause ischemia in the uterine muscle and can cause pain. Research on the effect of giving turmeric and honey on the reduction of menstrual pain (dysmenorrhea) in adolescent girls was conducted in the Medan Amplas sub-district. A decoction of turmeric and honey is given 3 times a day as much as 150 mL for 2 days. Pain intensity was measured using the Numeric Rating Scale (NRS) before and after giving turmeric and honey. Data were collected using Questionnaires and Observation sheets. The number of samples in this study was 15 young women. The sampling technique used was accidental sampling. Analysis of the data used is the Paired T-test. The results of this study showed that the intensity of pain before being given boiled honey turmeric water which had a moderate pain scale was 10 people (66%). The intensity of pain after being given boiled honey turmeric water which has a mild scale of 12 people (80%), namely with a value of p = 0.000 (p <0.05), which means that there is an effect of giving honey turmeric water decoction to decrease the intensity of menstrual pain in Teenage girl.

Oxygen Saturation During Dental Surgery with Local Anesthesia Alone and in Combination with Sedation in Medically Compromised Patients

Objective. The aim of this study was to determine which specific operative events are associated with change in SaO2 and blood pressure and heart rate in patients undergoing exodontia or minor oral surgery with local anaesthetic Medically compromised patients with Local anaesthesia alone or in combination with sedation. Methods. Arterial oxygen saturation (SaO2) with Heart rate and blood pressure was measured in 60 patients divided into two equal groups. Group I consisted of 30 patients receiving LA alone and undergoing simple extraction minor oral surgery, group II 30 patients receiving LA with oral midazolam and undergoing simple extraction or minor oral surgery. Results. There was a decrease in SaO2 from the baseline in 10% of group I patients, represented in 3 patients, 2 of them asthmatic and one anxious patient who the BP and HR raised slightly during LA admiration. There was a fall in SaO2 from the baseline in 53% of patients in group II, represented in 16 patients, the majority of them asthmatic and anxious patients, 6 patients with history of ischemic heart disease. The majority of these decreases in SaO2 or raining in BP or HR were associated with breath holding, in response to fear or emotional stress, during administration of LA due to vasoconstrictor effect or during elevation of teeth. The patients in group II showed a significantly (P<0. 001) greater maximum decrease in SaO2 from the baseline value compared to group I. The length of the operating time was longer in group II than that in group I, and the patients of group II were more anxious than the patients in group I. Conclusion. It was concluded that during simple extraction and minor oral surgery under LA alone or in combination with sedation procedures such as elevation of the tooth or administration of the LA may as a result of Breath holding cause reduction in SaO2 or raising in BP or HR. In fit patients this may be of little consequence, however patients with existing airway disease or Medically compromised patients may suffer significant falls in SaO2 or alter the Blood Pressure and Heart Rate. Therefor Monitoring of vital signs and oxygen saturation recommended during simple extraction dental surgery procedure and sedation as premedication for cardiac patients would be recommended.

Local thermal non-equilibrium bioheat transfer model for interstitial hyperthermia treatment of tumour cell: A numerical approach

Cancer treatment is achieved by destroying the damaged tissue with precise heating, which may be internally or externally on a human body. Thus, tracking the temperature at the targeted site during thermal therapy is essential to avoid unnecessary damage to the neighbouring tissues. Therefore, to avoid difficulties in the experimental in-vivo analysis of the human body, more and more priority has been given to computational modelling. Dual-phase lag bioheat transfer modelling is one that pioneers the biological heat transfer problem to a new horizon where the non-Fourier approach makes the model near realistic. The present paper has developed a numerical model based on the Local Thermal Non-Equilibrium Bioheat Transfer model, as the phase lag values directly depend on the biological tissues' thermophysical properties. Besides the effect of vasodilation and vasoconstriction, metabolic heat generation, as well as muscle shivering, are also considered in the present numerical model. A modified spatial Gaussian heat distribution function has been adapted to model the external heat source and destroy the targeted tissue inside the skin layers. A numerical code is developed using MATLAB in a finite difference approach, which can evaluate the temperature data in an anisotropic medium like human skin. A detailed 2D analysis has been done in different therapeutic conditions, various levels of doses, and different body positions during interstitial hyperthermia treatment. Analysis of biological tissue using the LTNE DPL bioheat transfer equation has not been reported for thermal therapy. Outcomes of the present study give an overview of the range of thermal dose, environmental effect on the treatment of cancer cells, and, most notably, the comparison with Fourier and Local Thermal Equilibrium Non-Fourier models.

Selective gene expression profiling contributes to a better understanding of the molecular pathways underlying the histological changes observed after RHMVL

BackgroundIn previous studies, five vasoactive drugs were investigated for their effect on the recovery process after extended liver resection without observing relevant improvements. We hypothesized that an analysis of gene expression could help to identify potentially druggable pathways and could support the selection of promising drug candidates.MethodsLiver samples obtained from rats after combined 70% partial hepatectomy and right median hepatic vein ligation (n = 6/group) sacrificed at 0 h, 24 h, 48 h, and 7days were selected for this study. Liver samples were collected from differentially perfused regions of the median lobe (obstruction-zone, border-zone, normal-zone). Gene expression profiling of marker genes regulating hepatic hemodynamics, vascular remodeling, and liver regeneration was performed with microfluidic chips. We used 3 technical replicates from each sample. Raw data were normalized using LEMming and differentially expressed genes were identified using LIMMA.ResultsThe strongest differences were found in obstruction-zone at 24 h and 48 h postoperatively compared to all other groups. mRNA expression of marker genes from hepatic hemodynamics pathways (iNOS,Ptgs2,Edn1) was most upregulated.ConclusionThese upregulated genes suggest a strong vasoconstrictive effect promoting arterial hypoperfusion in the obstruction-zone. Reducing iNOS expression using selective iNOS inhibitors seems to be a promising approach to promote vasodilation and liver regeneration.

Effects of Psidium guajava L. leaves extract on blood pressure control and IL-10 production in salt-dependent hypertensive rats

Psidium guajava (guava) leaves extract displays anti-hypertensive properties by mechanisms not yet fully understood. Here, we investigated whether sympathetic drive and immune signaling mechanisms are involved with the antihypertensive effect of the guava extract in a model of salt-dependent hypertension. Raw guava extract (rPsE) was characterized by colorimetric and UPLC-MS techniques. Two doses of rPsE (100 and 200 mg/kg) were evaluated for anti-hypertensive effect using a suspension system (PsE). Weaned male Wistar rats were put on a high-salt diet (HSD, 0.90 % Na+) for 16 weeks and received gavages of PsE for the last 4 weeks. Blood pressure (BP) was measured at the end of treatment in conscious rats. The neurogenic pressor effect was assessed by ganglionic blockade with hexamethonium. Autonomic modulation of heart rate was evaluated by spectral analysis. The effects of orally administered PsE on lumbar sympathetic nerve activity (LSNA) were assessed in anesthetized rats. Blood IL-10, IL-17A, and TNF were measured. The increased neurogenic pressor effect of HSD rats was reduced by PsE 100 mg/kg, but not by 200 mg/kg. PsE (200 mg/kg) administration in anesthetized rats produced a greater fall in BP of HSD rats compared to standard salt diet (SSD) rats. PsE hypotensive response elicited an unproportionable increase in LSNA of HSD rats compared to SSD rats. PsE (200 mg/kg) increased plasma concentrations of IL-10 but had no effect on TNF or IL-17A. Our data indicate that the antihypertensive effects of PsE may involve autonomic mechanisms and immunomodulation by overexpression of IL-10 in salt-dependent hypertensive rats.

Role of endothelial dysfunction in the severity of COVID‑19 infection (Review).

COVID-19 patients with severe infection have been observed to have elevated auto-antibodies (AAs) against angiotensin II receptor type 1 (AT1R) and endothelin (ET) 1 receptor type A (ETAR), compared with healthy controls and patients with favorable (mild) infection. AT1R and ETAR are G protein-coupled receptors, located on vascular smooth muscle cells, fibroblasts, immune and endothelial cells, and are activated by angiotensin II (Ang II) and ET1 respectively. AAs that are specific for these receptors have a functional role similar to the natural ligands, but with a more prolonged vasoconstrictive effect. They also induce the production of fibroblast collagen, the release of reactive oxygen species and the secretion of proinflammatory cytokines (including IL-6, IL-8 and TNF-α) by immune cells. Despite the presence of AAs in severe COVID-19 infected patients, their contribution and implication in the severity of the disease is still not well understood and further studies are warranted. The present review described the major vascular homeostasis systems [ET and renin-angiotensin-aldosterone system (RAAS)], the vital regulative role of nitric oxide, the AAs, and finally the administration of angiotensin II receptor blockers (ARBs), so as to provide more insight into the interplay that exists among these components and their contribution to the severity, prognosis and possible treatment of COVID-19.

Morphological changes in retinochoroidal microvasculature after caffeinated versus decaffeinated coffee consumption

BackgroundTo investigate changes in retinochoroidal microvascular morphology after caffeinated versus decaffeinated coffee consumption in age- and gender-matched healthy individuals using optical coherence tomography (OCT) and OCT angiography (OCTA). MethodsIn this prospective, randomized clinical study, a staff member in charge of record keeping randomly assigned 48 healthy volunteers to two groups: caffeinated coffee consumers (24 eyes) and decaffeinated coffee consumers (24 eyes). Participants' ages and genders were recorded before consumption, and a comprehensive ophthalmologic exam was performed, followed by OCT and OCTA analyses before, 30 min, one, six, and 24 h after blindly consuming either of the coffees. ResultsCaffeinated and decaffeinated coffee consumers had mean ages of 23.45 ± 0.92 and 22.73 ± 1.13, respectively (p = 0.407). The following parameters changed significantly in caffeinated coffee consumers 30 min and 1 h post-consumption (pre-consumption versus 30 min versus one hour post-consumption; p < 0.05): a) parafoveal superficial capillary plexus vessel density (%): 54.45 versus 51.8 versus 51.92, b) parafoveal deep capillary plexus vessel density (%): 55.16 versus 52.45 versus 52.83, c) outer retinal flow area (%): 8.87 ± 1.91 versus 8.03 ± 1.88 versus 8.11 ± 1.93, d) choriocapillaris flow area (mm2): 20.95 ± 0.98 versus 19.82 ± 1.20 a versus 19.62 ± 0.95, and e) sub-foveal choroidal thickness (µm): 295.06 ± 5.45 versus 277.08 ± 5.33 versus 260.71 ± 58.61. No significant differences in any OCT and OCTA parameters were found between consecutive measurements in decaffeinated coffee consumers (p > 0.05). ConclusionsCaffeinated coffee appears to transiently reduce parafoveal vessel density, capillary flow area, and sub-foveal choroidal thickness. Lack of these microvascular morphological changes in decaffeinated coffee suggests a potential caffeine-induced vasoconstrictive effect.

S1325 Association of Alcohol Consumption With Diastolic Hypertension in Patients With Mild Liver Stiffness: Analysis of the National Health and Nutrition Examination Survey 2017-2020

Introduction: While excessive alcohol consumption is associated with arterial hypertension. Cirrhotic patient’s risk for hypertension remains unclear due to both vasodilatation and vasoconstriction effect. We aim to examine the association between alcohol consumption and hypertension in patients with different degrees of liver fibrosis. Methods: A cross-sectional study using the National Health and Nutrition Examination Survey (NHANES) 2017 to March 2020 included adult participants. Association between alcohol consumption and both systolic and diastolic hypertension (SHTN and DHTN) defined as SBP and DBP ≥120 and ≥80 mmHg, respectively were analyzed by multivariate logistic regression. Prespecified subgroup analyses were performed to investigate potential effect modifiers. Results: A total of 9,693 patients were identified (mean age 50±19 years old; 51% female; 35% white). Among the participants with Fibroscan results, they were stratified into 3 groups based on the number of alcohol drinks per day (0-1 drink per day (G1), 2,126 [36%]; 1-4 drinks per day (G2), 2,612 [45%]; > 4 drinks per day (G3), 1,125 [20%]). After controlling for age, race, gender, body mass index, diabetic status, hyperlipidemic status, serum creatinine, urinary albumin:creatinine ratio, and fibrotic liver stage (< F2 = mild and ≥F2 = significant with fibrosis scores of < 7.5 and ≥7.5 kPa, respectively), the G2 and G3 had greater the odds of having SHTN but not statistically significant. (ORG21.26; P 0.155; 95%CI 0.9076, 1.760; ORG3 1.30, P 0.180, 95%CI 0.886, 1.909). Both G2 and G3 were significantly more likely to develop DHTN (ORG2 1.53, P 0.018, 95%CI 1.076, 2.172; OR3G3 1.88, P0.002 95%CI 1.259, 2.802). Subgroup analysis revealed a significant increased odds of developing DHTN in G2 and G3 only for those with mild fibrosis (< F2; ORG2 1.45, P 0.048, 95%CI 1.004, 2.151; OR G3 1.83, P 0.006, 95%CI 1.186, 2.833). The magnitude and direction of the association were similar for participants with significant fibrosis (≥F2; ORG21.64, P 0.363, 95%CI 0.566, 4.728; OR G3 1.86, P 0.308, 95%CI 0.564, 6.168; Figure A). The alcohol – SHTN association remains no statistical significance in all subgroups (Figure B). There was no effect modification observed between alcohol consumption and key covariates. Conclusion: In this study, there is an association between alcohol intake and DHTN in mild fibrotic liver patients. Longitudinal studies are required to further evaluate this association and possible underlying mechanisms.Figure 1.: Distribution of diastolic (A) and systolic (B) hypertension stratified by the amount of alcohol consumption per day and the severity of liver fibrosis

The search for novel biomarkers in sepsis-induced cardiomyopathy – A new challenge to overcome

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and it remains the most frequent cause of death amongst critically ill patients worldwide, despite recent medical advancements. The cardiac involvement in sepsis, better known as sepsis-induced cardiomyopathy, represents a form of cardiac dysfunction identified in septic patients, characterized by ventricular dilation, myocardial involvement, decreased ejection fraction and reversibility. Although the implications of cardiac involvement in sepsis can be extremely severe, this affliction has not been intensely debated in literature. Therefore, in order to better understand this affliction, we need to identify new markers. Two biomarkers, endothelin-1 (ET-1) and the soluble form of suppression of tumorigenicity 2 protein (sST2) have previously been linked to both sepsis and acute/chronic heart failure. Endothelin-1 is part of a family of amino acid peptides, that is mainly produced by endothelial cells and exerts a vasoconstrictive effect, but also causes fibrosis of the vascular cells, stimulates production of reactive oxygen species and induces proinflammatory mechanisms. During sepsis, it induces coronary vasoconstriction, decreased cardiac output, increased vascular resistance and permeability and increased fluid flux into the extravascular space on cardiac level, as well as affecting the contractility of myocardial myocytes. High values of serum ET-1 have also been identified in septic shock and in endotoxin-induced febrile responses in rats. The Suppression of tumorigenicity 2 protein (ST2) is a member of the interleukin-1 receptor family and is involved in T helper 2 cells-associated immune response. Recent studies identified a close link between ST2 and both inflammatory and heart diseases. Furthermore, it was recently approved by the Food and Drug Administration as a prognostic biomarker in heart failure and is recommended for the evaluation of additional cardiovascular risk.

Preclinical studies of NOS inhibitor T1059 vasopressor activity on the models of acute hemorrhagic shock in rats and dogs.

The development of new effective and safe vasopressors is one of the ways to increase the effectiveness of the treatment of hypotensive disorders, the severe forms of which remain a common cause of death in all countries of the world. Previously, we synthesized the original compound T1059, a selective inhibitor of eNOS/iNOS which has a pronounced vasoconstrictive effect. Here we show its vasopressor activity in models of the early stage of acute hemorrhagic shock in rats and dogs, as part of preclinical studies. The results indicate NOS inhibitor T1059 as a potent long-acting vasopressor. Its single parenteral administration in sufficiently safe doses (1/50–1/9 LD10), caused in rats and dogs a rapid increase in vascular tone, accompanied by a prolonged hypertensive effect (within 90–120 min in rats, and within 115 min in dogs). The repeated administration of T1059 at low doses (1/3 of the first dose) made it possible to considerably (by at least 60 min) prolong a significant vasopressor effect. In all schemes, T1059 administration considerably inhibited the development of threatening cardiorespiratory disorders and significantly (p = 0.0026–0.0098) increased the short-term survival of experimental animals, formally extending the duration of the “golden hour” by 2 times. These data indicate that NOS inhibitors and, in particular, compound T1059, are able to create new opportunities in the treatment of hypotensive disorders, including the provision of assistance at the prehospital stage of treatment of such pathologies.

Immediate pressor response to oral salt and its assessment in the clinic: a time series clinical trial

BackgroundHigh blood pressure (BP) is associated with high-salt consumption especially in sub-Saharan Africa. Although the pressor effect of salt is viewed as a chronic effect, some studies suggest that a salty meal may increase BP immediately in some individuals, and that this effect may cause endothelial dysfunction. Therefore, the aim of our research was to study the immediate pressor response to oral salt (IPROS) and its determinants, with the expectation that a simple methodology may be devised to diagnose it in the clinic or in low-resource environments.MethodsWe conducted a time series trial at Livingstone Central Hospital. We present data in 127 normotensive participants who ingested 2 g of sodium chloride; their BP was monitored for 120 minutes in intervals of 10 minutes. Sociodemographic and clinical data were collected. Descriptive and inferential statistics were used for analyses of data.ResultsMedian age was 30 years (interquartile range, 22–46 years) and 52% were female patients. An increase of ≥10 mmHg in mean arterial pressure (MAP), considered a clinically significant IPROS, was present in 62% of participants. Systolic BP 30 minutes after the salt load was a significant predictor of IPROS, avoiding the need to calculate MAP in the clinic setting.ConclusionsWe confirm the presence of an IPROS in a high proportion (62%) of otherwise normotensive participants. The average time course for this response was 30 minutes and its duration was sustained for the 120-minutes period of study in most of the participants. Prediction of IPROS by ∆SBP (change in systolic blood pressure) at 30 minutes allows for easy assessment of possible responder status in the clinic. Our data indicate that the IPROS to oral salt-loads in the range currently consumed by the Western world and African populations in single meals may increase the 24-hour BP load, which is a risk factor for hypertension and target organ damage. The relevance of our findings indicates the need to include dietary sodium assessment in the diagnosis, prevention, and management of high BP.

Vasoconstrictor and hemodynamic effects of a methanolic extract from Rhinella marina toad poison

Rhinella marina toad is abundant in Brazil. Its poison contains cardiac glycosides called bufadienolides, which are extensively investigated for their bioactivity. Our aim was to characterize the vasoactivity of Rhinella marina poison (RmP) on the aorta of male Wistar rats. For this, the RmP was first collected and processed to obtain an alcoholic extract. To determine cardiovascular effects of RmP, we performed in vivo tests by administering RmP intravenously in doses of 0.1–0.8 mg/kg. Vascular reactivity was also performed through concentration-response curves to RmP (10 ng/mL to 200 μg/mL) in aortic segments with and without endothelium. RmP induced a concentration-dependent contraction in rat aorta which was partly endothelium-mediated. Nitric oxide contributes with this response in view that incubation with L-NAME increased the contractile response. Additionally, treatment with indomethacin [cyclooxygenase, (COX) inhibitor], nifedipine (L-type voltage-gated calcium channels blocker), and BQ-123 (ETA receptors antagonist) decreased maximum response, and ketanserin (5-HT2 receptors antagonist) decreased pEC50, suggesting active participation of these pathways in the contractile response. On the other hand, apocynin (NADPH oxidase inhibitor) did not alter contractility. Incubation with prazosin (α1-adrenergic receptor antagonist) abolished the contractile response, suggesting that the RmP-induced contraction is dependent on the adrenergic pathway. In the Na+/K+ ATPase protocol, a higher Emax was observed in the RmP experimental group, suggesting that RmP potentiated Na+/K+ATPase hyperpolarizing response. When this extract was injected (i.v.) in vivo, increase in blood pressure and decrease in heart rate were observed. The results were immediate and transitory, and occurred in a dose-dependent manner. Overall, these data suggest that the poison extract of R. marina toad has an important vasoconstrictor action and subsequent vasopressor effects, and its use can be investigated to some cardiovascular disorders.

Cocaine’s cerebrovascular vasoconstriction is associated with astrocytic Ca2+ increase in mice

Human and animal studies have reported widespread reductions in cerebral blood flow associated with chronic cocaine exposures. However, the molecular and cellular mechanisms underlying cerebral blood flow reductions are not well understood. Here, by combining a multimodal imaging platform with a genetically encoded calcium indicator, we simultaneously measured the effects of acute cocaine on neuronal and astrocytic activity, tissue oxygenation, hemodynamics and vascular diameter changes in the mouse cerebral cortex. Our results showed that cocaine constricted blood vessels (measured by vessel diameter Φ changes), decreasing cerebral total blood volume (HbT) and temporally reducing tissue oxygenation. Cellular imaging showed that the mean astrocytic Ca2+ dependent fluorescence (Delta {F/F}_{{{{rm{Ca}}}^{2+}}{mbox{-}{{{rm{G(A)}}}}}}) increase in response to cocaine was weaker but longer lasting than the mean neuronal Ca2+ dependent fluorescence (Delta {F/F}_{{{{rm{Ca}}}^{2+}}{mbox{-}{{{rm{G(N)}}}}}}) changes. Interestingly, while cocaine-induced Delta {F/F}_{{{{rm{Ca}}}^{2+}}{mbox{-}{{{rm{G(N)}}}}}} increase was temporally correlated with tissue oxygenation change, the Delta {F/F}_{{{{rm{Ca}}}^{2+}}{mbox{-}{{{rm{G(A)}}}}}} elevation after cocaine was in temporal correspondence with the long-lasting decrease in arterial blood volumes. To determine whether the temporal association between astrocytic activation and cocaine induced vasoconstriction reflected a causal association we inhibited astrocytic Ca2+ using GFAP-DREADD(Gi). Inhibition of astrocytes attenuated the vasoconstriction resulting from cocaine, providing evidence that astrocytes play a critical role in cocaine’s vasoconstrictive effects in the brain. These results indicate that neurons and astrocytes play different roles in mediating neurovascular coupling in response to cocaine. Our findings implicate neuronal activation as the main driver of the short-lasting reduction in tissue oxygenation and astrocyte long-lasting activation as the driver of the persistent vasoconstriction with cocaine. Understanding the cellular and vascular interaction induced by cocaine will be helpful for future putative treatments to reduce cerebrovascular pathology from cocaine use.

Correlation of rosacea with hot beverage intake.

In this report, we correlated the incidence of rosacea with coffee (regular and decaffeinated) and tea consumption in a large cohort of middle-aged men and women living within the United Kingdom. Caffeinated coffee drinkers had lower odds for rosacea diagnosis compared to non-coffee drinkers. We hypothesize that the vasoconstrictive effects of caffeine in regular coffee overpower the vasodilatory effects associated with hot beverages and support it to be protective against rosacea.

Efficacy of Combination Therapy with Epinephrine Local Injection and Hemostatic Clips on Active Diverticular Bleeding.

Epinephrine local injection is a hemostatic procedure used in active diverticular bleeding that elicits vasoconstriction and tamponade effects. We compared the additional benefit of combination therapy with HSE-C (hypertonic saline epinephrine injection with clipping) to clipping monotherapy. Retrospective data on diverticular bleeding between 2011 and 2016 was reviewed. Those with an active bleeding source confirmed by colonoscopy (excluding non-bleeding vessels and adherent clots) who received either HSE-C or clipping were evaluated. Endpoints were rates of successful primary hemostasis, recurrent bleeding, and surgical intervention during hospitalization. A total of 320 patients with diverticular bleeding were evaluated, on which either HSE-C (n = 35) or clipping monotherapy (n = 18) was performed. Rates of successful primary hemostasis (91.4% vs. 66.7%, p = 0.048) and direct placement of endoclips (60.0% vs. 16.7%, p = 0.004) were significantly higher in the HSE-C group. Although not statistically significant, the HSE-C group had a higher rate of early rebleeding (18.8% vs. 8.3%, p = 0.653), while no difference was seen in the number of patients requiring surgery (11.4% vs. 5.5%, p = 0.651). HSE-C is associated with a higher rate of successful primary hemostasis for severe active diverticular bleeding but has no significant difference in reducing early recurrent bleeding or the number of patients requiring surgery, suggesting that hemostatic effects may be temporary.

Reflex Sympathetic Vasoconstriction And Functional Sympatholysis In Patients With Heart Failure With Preserved Ejection Fraction.

INTRODUCTION: Vascular impairments resulting in blood flow limitations to exercising muscle likely contribute to marked exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF). Blood flow to exercising muscle is modulated by the interaction of sympathetic nervous system (SNS)-mediated vasoconstriction and factors related to muscle contraction that counteract this vasoconstriction, so-called “functional sympatholysis”. While there is emerging evidence for SNS overactivity during exercise in patients with HFpEF, functional sympatholysis has not been assessed in this patient group. PURPOSE: To determine the effect of SNS-mediated vasoconstriction on exercising muscle blood flow and the efficacy of functional sympatholysis in HFpEF vs. age-matched control (CON) subjects. METHODS: 4 CON (2 male, 70 ± 2 yrs) and 5 Class II/III patients with HFpEF (2 male, 70 ± 4 yrs) participated in this study. Forearm blood flow (FBF, ultrasound Doppler), mean arterial blood pressure (MAP, Finometer), and forearm vascular conductance (FVC) were evaluated at rest and during rhythmic handgrip exercise (30% maximum voluntary contraction, 3-min bout, 1 Hz) before and after SNS activation evoked by lower body negative pressure (LBNP -20 mmHg). Hemodynamic changes (%Δ) in response to LBNP at rest and during exercise were compared between groups, and the magnitude of functional sympatholysis was calculated as the difference between LBNP-induced %Δ FVC from rest to exercise. RESULTS: At rest, %Δ FBF in response to LBNP was similar between CON vs. HFpEF (-24 ± 4% vs. 17 ± 5%), while %Δ FVC was significantly greater in CON vs. HFpEF (-23 ± 4% vs. -10 ± 3%, P < 0.05). During exercise, LBNP reduced FBF (-1 ± 2% vs. -6 ± 3%) and FVC (-1 ± 3% vs. -6 ± 3%) to a similar degree between groups. However, the magnitude of sympatholysis was significantly greater in CON vs. HFpEF (-23 ± 4% vs. -3 ± 4%, P < 0.05). LBNP-induced changes in MAP were not different between CON vs. HFpEF at rest (-1 ± 2% vs. -3 ± 1%) or during exercise (0 ± 2% vs. 1 ± 2%). CONCLUSION: These data suggest impaired functional sympatholysis in HFpEF, indicating that SNS-mediated vasoconstriction may contribute to blood flow limitations underpinning exercise intolerance in HFpEF

Abstract 125: Modified Angiotensin II Has Lower Vasoconstrictive Effect Than Angiotensin II

Introduction: The renin-angiotensin-aldosterone system (RAAS) is involved in the regulation of the blood pressure, water- and electrolyte balance. Pathophysiologically, this system is essential for the development and pathogenesis of both cardiovascular and renal diseases. Angiotensin II, a component of the RAAS, is the best-known vasoconstrictive and hypertensive peptide in the human organism. This peptide consists of 8 amino acids (asp-arg-val-tyr-ile-his-pro-phe). The first amino acid, aspartic acid, is converted to pyruvamide in the presence of pyridoxal-5’-phosphate (PLP). The influence of pyruvamide-angiotensin II on the blood pressure is not yet clarified. Hypothesis: We assessed the hypothesis that the transformation of angiotensin II to pyruvamide-angiotensin II by PLP leads to lowering the blood pressure. Methods: To clarify the influence of pyruvamide-angiotensin II on blood pressure ex vivo experiments were performed. Angiotensin II as well as pyruvamide-angiotensin II was tested in isolated perfused rat kidney. Further, in vivo experiments were performed. Wistar Kyoto rats (WKY) and Spontaneously Hypertensive Rats (SHR) were treated with angiotensin II in the absence and presence of PLP. The blood pressure was measured at different time. Results: Pressure in isolated perfused rat kidney increases by 50.11 ± 4.57 mmHg after injecting angiotensin II, whereas pressure increases by 38.40 ± 4.31 mmHg after injecting pyruvamide-angiotensin II. Data are shown as mean ± SEM of triplicate measurements from three independent experiments. Further, blood pressure of SHR treated with PLP decreases from 171/139 ± 5 mmHg to 129/98 ± 2 mmHg after three days. Blood pressure of WKY treated with angiotensin II increases to 167/133 ± 3 mmHg, whereas blood pressure of WKY treated with angiotensin II and PLP decreases to 129/99 ± 2 mmHg. Data are shown as mean ± SEM from five independent experiments. Conclusions: In conclusion, pyruvamide-angiotensin II has a lower vasoconstrictive effect than angiotensin II. Furthermore, PLP decreases the blood pressure in SHR and WKY.

Smoking Affects Bone Healing and Blood Perfusion

Nicotine is the primary component in cigarettes that is responsible for the negative effects that tobacco has on the body. Nicotine is also the primary component responsible for the addiction that can develop from smoking. Tobacco addiction is also primarily caused by nicotine, which is another component of tobacco. Aim: The effect that nicotine has on the rate at which bones can recover after being shattered is still a topic of ongoing debate. The study of bone repair and regeneration is made a great deal easier by the utilisation of a model that is known as distraction osteogenesis. The mandibular extension of a rabbit model is serving as the subject of the inquiry that is now being conducted. Duration &amp; Place of Study: October 2018 to March 2021 Rashid Latif medical college Lahore Method: Using the rabbit as a test subject, the purpose of this study is to evaluate the influence that nicotine has on blood perfusion, angiogenesis, and bone formation. There were a total of forty rabbits, and they were distributed among the control group, which received no nicotine, and the nicotine group, which received nicotine. The bunnies were distributed to the several groups in a haphazard manner. It was discovered that each rat had been exposed to nicotine or a placebo for a total of seven weeks during the course of the experiment. After a period of consolidation time ranging from two to four weeks post osteotomy, the animals were slaughtered and their mandibles were removed. After this, there was a lag time of three days, and then there was active distraction for eleven days. Utilizing the techniques of Laser Doppler monitoring and Collagen IV immunohistochemical labelling, respectively, allowed for the assessment of both vascularization and blood perfusion. Studies that were radiographic, histological, and immunohistochemical in nature were carried out in order to investigate the development of bone. Result : According to the findings, being exposed to nicotine led to an increase in the density of microvessels, but it had a detrimental effect on the flow of blood and the development of bones. In addition to this, it was found that the expression of bone morphogenetic protein (BMP)-2 in osteoblasts was lower than it had been in the past. In the process of distraction regeneration, ischemia and a low oxygen tension were both present, and the creation of cartilage islands on a consistent basis was a sign of both of these circumstances. Result: As a result of our investigation, we got to the realisation that nicotine consumption slows down the process of bone regeneration. We hypothesise that this takes place as a result of the fact that nicotine leads to ischemia and has an effect that is directly inhibitory on osteoblastic cells. It has been demonstrated that nicotine causes an increase in angiogenesis; however, this improvement is not adequate to compensate for the harmful effect of vasoconstriction caused by nicotine.

New Oral Drugs for Migraine.

Migraine is a common and disabling neurological disorder, with several manifestations, of which pain is just one. Despite its worldwide prevalence, there remains a paucity of targeted and effective treatments for the condition, leaving many of those affected underserved by available treatments. Work over the last 30+ years has recently led to the emergence of the first targeted acute and preventive treatments in our practice since the triptan era in the early 1990s, which are changing the landscape of migraine treatment. These include the monoclonal antibodies targeting calcitonin gene-related peptide or its receptor. Evolving work on novel therapeutic targets, as well as continuing to exploit drugs used in other disorders that may also have a therapeutic effect in migraine, is likely to lead to more and more treatments being able to be offered to migraineurs. Future work involves the development of agents that lack vasoconstrictive effects, such as lasmiditan, do not contribute to medication overuse, such as the gepants, and do not interact with other drugs that may be used for the disorder, as well as agents that can act both acutely and preventively, thereby utilising the quantum between acute and preventive drug effects which has been demonstrated with different migraine drugs before. Here we discuss the evolution of oral migraine treatments over the last 5 years, including those that have gained regulatory approval and reached clinical practice, those in development and potential other targets for the future.

Lung perfusion disturbances in nonhospitalized post-COVID with dyspnea-A magnetic resonance imaging feasibility study.

BackgroundDyspnea is common after COVID‐19. Though the underlying mechanisms are largely unknown, lung perfusion abnormalities could contribute to lingering dyspnea.ObjectivesTo detect pulmonary perfusion disturbances in nonhospitalized individuals with the post‐COVID condition and persistent dyspnea 4–13 months after the disease onset.MethodsIndividuals with dyspnea and matched healthy controls were recruited for dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI), a 6‐min walk test, and an assessment of dyspnea. The DCE‐MRI was quantified using two parametric values: mean time to peak (TTP) and TTP ratio, reflecting the total lung perfusion resistance and the fraction of lung with delayed perfusion, respectively.ResultsTwenty‐eight persons with persistent dyspnea (mean age 46.5 ± 8.0 years, 75% women) and 22 controls (mean age 44.1 ± 10.8 years, 73% women) were included. There was no systematic sex difference in dyspnea. The post‐COVID group had no focal perfusion deficits but had higher mean pulmonary TTP (0.43 ± 0.04 vs. 0.41 ± 0.03, p = 0.011) and TTP ratio (0.096 ± 0.052 vs. 0.068 ± 0.027, p = 0.032). Post‐COVID males had the highest mean TTP of 0.47 ± 0.02 and TTP ratio of 0.160 ± 0.039 compared to male controls and post‐COVID females (p = 0.001 and p < 0.001, respectively). Correlations between dyspnea and perfusion parameters were demonstrated in males (r = 0.83, p < 0.001 for mean TTP; r = 0.76, p = 0.003 for TTP ratio), but not in females.ConclusionsDCE‐MRI demonstrated late contrast bolus arrival in males with post‐COVID dyspnea, suggestive of primary vascular lesions or secondary effects of hypoxic vasoconstriction. Since this effect was not regularly observed in female patients, our findings suggest sex differences in the mechanisms underlying post‐COVID dyspnea, which warrants further investigation in dedicated trials.