Influence of Prolonged Serotonin and Ergovaline Pre-Exposure on Vasoconstriction Ex Vivo

Ergot alkaloid mycotoxins interfere in many functions associated with serotonergic neurotransmitters. Therefore, the objective was to evaluate whether the association of serotonin (5-hydroxytryptamine, 5-HT) and ergot alkaloids during a 24 h pre-incubation could affect the vascular contractile response to ergot alkaloids. To evaluate the effects of 24 h exposure to 5-HT and ergot alkaloids (ergovaline, ERV), two assays were conducted. The first assay determined the half-maximal inhibitory concentration (IC50) following the 24 h pre-exposure period, while the second assay evaluated the effect of IC50 concentrations of 5-HT and ERV either individually or in combination. There was an interaction between previous exposure to 5-HT and ERV. Previous exposure to 5-HT at the IC50 concentration of 7.57 × 10−7 M reduced the contractile response by more than 50% of control, while the exposure to ERV at IC50 dose of 1.57 × 10−10 M tended to decrease (p = 0.081) vessel contractility with a response higher than 50% of control. The 24 h previous exposure to both 5-HT and ERV did not potentiate the inhibitory response of blood vessels in comparison with incubation with each compound alone. These results suggest receptor competition between 5-HT and ERV. More studies are necessary to determine the potential of 5-HT to treat toxicosis caused by ergot alkaloids.

Fetal Sex and Fetal Environment Interact to Alter Diameter, Myogenic Tone, and Contractile Response to Thromboxane Analog in Rat Umbilical Cord Vessels

Fetal growth needs adequate blood perfusion from both sides of the placenta, on the maternal side through the uterine vessels and on the fetal side through the umbilical cord. In a model of intrauterine growth restriction (IUGR) induced by reduced blood volume expansion, uterine artery remodeling was blunted. The aim of this study is to determine if IUGR and fetus sex alter the functional and mechanical parameters of umbilical cord blood vessels. Pregnant rats were given a low sodium (IUGR) or a control diet for the last 7 days of pregnancy. Umbilical arteries and veins from term (22 day) fetal rats were isolated and set-up in wire myographs. Myogenic tone, diameter, length tension curve and contractile response to thromboxane analog U46619 and serotonin (5-HT) were measured. In arteries from IUGR fetuses, myogenic tone was increased in both sexes while diameter was significantly greater only in male fetuses. In umbilical arteries collected from the control group, the maximal contraction to U46619 was lower in females than males. Compared to the control groups, the maximal response decreased in IUGR male arteries and increased in female ones, thus abolishing the sexual dimorphism observed in the control groups. Reduced contractile response to U46619 was observed in the IUGR vein of both sexes. No difference between groups was observed in response to 5HT in arteries. In conclusion, the change in parameters of the umbilical cord blood vessels in response to a mild insult seems to show adaptation that favors better exchange of deoxygenated and wasted blood from the fetus to the placenta with increased myogenic tone.

Effects of different vasopressors on the contraction of the superior mesenteric artery and uterine artery in rats during late pregnancy

Background Hypotension after neuraxial anaesthesia is one of the most common complications during caesarean section. Vasopressors are the most effective method to improve hypotension, but which of these drugs is best for caesarean section is not clear. We assessed the effects of vasopressors on the contractile response of uterine arteries and superior mesenteric arteries in pregnant rats to identify a drug that increases the blood pressure of the systemic circulation while minimally affecting the uterine and placental circulation. Methods Isolated ring segments from the uterine and superior mesenteric arteries of pregnant rats were mounted in organ baths, and the contractile responses to several vasopressor agents were studied. Concentration-response curves for norepinephrine, phenylephrine, metaraminol and vasopressin were constructed. Results The contractile response of the mesenteric artery to norepinephrine, as measured by the pEC50 of the drug, was stronger than the uterine artery (5.617 ± 0.11 vs. 4.493 ± 1.35, p = 0.009), and the contractile response of the uterine artery to metaraminol was stronger than the mesenteric artery (pEC50: 5.084 ± 0.17 vs. 4.92 ± 0.10, p = 0.007). There was no statistically significant difference in the pEC50 of phenylephrine or vasopressin between the two blood vessels. Conclusions In vitro experiments showed that norepinephrine contracts peripheral blood vessels more strongly and had the least effect on uterine artery contraction. These findings support the use of norepinephrine in mothers between the time of neuraxial anaesthesia and the delivery of the foetus.

Can SARS-CoV-2 Induce Uterine Vascular Anomalies and Poor Contractile Response?—A Case Report

We are reporting a case of a 36 year-old Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) positive hypertensive primigravida with postpartum uterine atony that required emergency subtotal hysterectomy at Saint John Hospital Bucur Maternity Bucharest. The maternity was designated as the Coronavirus Disease 2019 (COVID-19) Maternity for Bucharest and Ilfov County since March 2020. The patient was mildly symptomatic for SARS-CoV-2, infection confirmed with reverse transcription polymerase chain reaction (RT-PCR). The caesarean section was performed and a live male fetus was born, 2630 g and Apgar Score of 9 (the male fetus was negative for SARS-CoV-2). Postpartum hysterectomy with adnexal preservation was performed because of uterine atony. The postoperative evolution was favorable. The patient was discharged with her baby 10 days after birth. Given the limited resources, the placenta, the umbilical cord and the uterus were not tested for SARS-CoV-2. The pathology exam revealed that on the maternal side there were specific uterine atony lesions as well as endometrial and miometrial ischaemia. The placenta had nonspecific findings: chronic ischemic lesions with small villi, fibrin deposits in the materno-fetal interface. The peculiarity of the case is that we report the morphological findings of the placenta and uterus resulted from intrapartum uterine atonia in a patient with gestational arterial hypertension, premature birth and COVID-19. Further studies are required to characterize the pattern of such intricate conditions.

Tensiomyographic Neuromuscular Response of the Peroneus Longus and Tibialis Anterior with Chronic Ankle Instability

This study aimed to investigate the muscle contractile response of the peroneus longus (PL) and tibialis anterior (TA) in groups with and without chronic ankle instability (CAI) using tensiomyography. Twenty-three adults, 12 with CAI and 11 healthy participants, participated in this study. All subjects underwent a tensiomyographic assessment of the PL and TA to measure delay time, contraction time and maximal displacement. The ankle evertor and invertor normalized peak torques, maximum work done and muscle thickness of the PL and TA were calculated. The delay time and contraction time of the PL in the CAI side were significantly higher than those in the healthy group (p < 0.05); however, no significant difference could be detected in the TA between groups. Furthermore, there was no significant difference in the normalized peak torques, maximum work done and muscle thickness of the PL and TA between groups. The CAI side demonstrated a delayed muscle contractile response of the PL when compared with the healthy group although there was no difference in muscle strength and muscle size. Clinicians should consider the muscle contractile response of the PL for rehabilitation of the ankle evertor with CAI.

The Effects of Low-dose Empagliflozin on Cardiac Function in a Rat Model of Streptozotocin-induced Diabetes

Purpose: Diabetes mellitus is a metabolic disorder leading to cardiovascular complications. Both in vivo cardiac function and β-adrenoceptor (β-AR) mediated responsiveness have been demonstrated to be blunted in the diabetic heart. Sodium glucose co-transporter-2 (SGLT2) inhibitors, such as empagliflozin (EMPA) have shown cardioprotective effects in patients and in some animal models. In this study, we aimed to investigate the effects of low-dose EMPA (10 mg/kg/day) on in vivo cardiac function and β-AR-mediated contractile response in streptozotocin (STZ)-induced diabetic rats. Methods: 11-12 week old male Sprague Dawley rats were divided into 4 groups; control, EMPA-treated control, diabetic, EMPA-treated diabetic. Diabetes was induced by STZ injection (40 mg/kg, i.p.). After 13-16 weeks, some of the diabetic and control rats were treated with a low dose of EMPA (10 mg/kg/day, oral gavage, once a day) or vehicle for another 8 weeks. At study end, in vivo cardiac function was evaluated by pressure-volume loop analysis. β-AR mediated contractile response was determined using isoprenaline in papillary muscle preparations. Results: EMPA did not change cardiac function in control rats. Diabetic rats had a reduced heart rate, cardiac output, stroke work, +dp/dt and -dp/dt and increased isovolumic relaxation, whereas in vitro responses were reduced to a minor extent. Treatment with EMPA showed a trend for improvement of some but not all parameters. Conclusion: Our results indicate that low dose EMPA treatment had limited effects on cardiac impairment although it reduced blood glucose. Future studies with a higher dose and greater sample sizes could help to clarify the possible benefits of EMPA on the diabetic heart.