Vascular Reactivity to Hypercapnia Is Impaired in the Cerebral and Retinal Vasculature in the Acute Phase After Experimental Subarachnoid Hemorrhage

Objective: Impaired cerebral blood flow (CBF) regulation, such as reduced reactivity to hypercapnia, contributes to the pathophysiology after aneurysmal subarachnoid hemorrhage (SAH), but temporal dynamics in the acute phase are unknown. Featuring comparable molecular regulation mechanisms, the retinal vessels participate in chronic and subacute stroke- and SAH-associated vessel alterations in patients and can be studied non-invasively. This study is aimed to characterize the temporal course of the cerebral and retinal vascular reactivity to hypercapnia in the acute phase after experimental SAH and compare the potential degree of impairment.Methods: Subarachnoid hemorrhage was induced by injecting 0.5 ml of heparinized autologous blood into the cisterna magna of male Wistar rats using two anesthesia protocols [isoflurane/fentanyl n = 25 (Sham + SAH): Iso—Group, ketamine/xylazine n = 32 (Sham + SAH): K/X—Group]. CBF (laser speckle contrast analysis) and physiological parameters were measured continuously for 6 h. At six predefined time points, hypercapnia was induced by hypoventilation controlled via blood gas analysis, and retinal vessel diameter (RVD) was determined non-invasively.Results: Cerebral reactivity and retinal reactivity in Sham groups were stable with only a slight attenuation after 2 h in RVD of the K/X—Group. In the SAH Iso—Group, cerebral and retinal CO2 reactivity compared to baseline was immediately impaired starting at 30 min after SAH (CBF p = 0.0090, RVD p = 0.0135) and lasting up to 4 h (p = 0.0136, resp. p = 0.0263). Similarly, in the K/X—Group, cerebral CO2 reactivity was disturbed early after SAH (30 min, p = 0.003) albeit showing a recovery to baseline after 2 h while retinal CO2 reactivity was impaired over the whole observation period (360 min, p = 0.0001) in the K/X—Group. After normalization to baseline, both vascular beds showed a parallel behavior regarding the temporal course and extent of impairment.Conclusion: This study provides a detailed temporal analysis of impaired cerebral vascular CO2 reactivity starting immediately after SAH and lasting up to 6 h. Importantly, the retinal vessels participate in these acute changes underscoring the promising role of the retina as a potential non-invasive screening tool after SAH. Further studies will be required to determine the correlation with functional outcomes.

High Frequency of Microvascular Dysfunction in US Outpatient Clinics: A Sign of High Residual Risk? Data from 7,105 Patients

Previous studies have linked peripheral microvascular dysfunction measured by arterial tonometry to high residual risk in on-statin patients. Digital thermal monitoring (DTM) of microvascular function is a new and simplified technique based on fingertip temperature measurements that has been correlated with the burden of atherosclerosis and its risk factors. Here, we report analyses of DTM data from two large US registries: Registry-I (6,084 cases) and Registry-II (1,021 cases) across 49 US outpatient clinics. DTM tests were performed using a VENDYS device during a 5-minute arm-cuff reactive hyperemia. Fingertip temperature falls during cuff inflation and rebounds after deflation. Adjusted maximum temperature rebound was reported as vascular reactivity index (VRI). VRI distributions were similar in both registries, with mean ± SD of 1.58 ± 0.53 in Registry-I and 1.52 ± 0.43 in Registry-II. In the combined dataset, only 18% had optimal VRI (≥2.0) and 82% were either poor (<1.0) or intermediate (1.0-2.0). Women had slightly higher VRI than men ( 1.62 ± 0.56 vs. 1.54 ± 0.47 , p < 0.001 ). VRI was inversely but mildly correlated with age ( r = − 0.19 , p < 0.001 ). Suboptimal VRI was found in 72% of patients <50 years, 82% of 50-70 years, and 86% of ≥70 years. Blood pressure was not correlated with VRI. In this largest registry of peripheral microvascular function measurements, suboptimal scores were highly frequent among on-treatment patients, possibly suggesting a significant residual risk. Prospective studies are warranted to validate microvascular dysfunction as an indicator of residual risk.

Dietary Fibers and Nutraceuticals in Prevention of Hypertension

Hypertension is the major cause of mortality amongst many cardiovascular risk factors causing 7.5 million deaths annually. Macronutrient and micronutrient deficiencies are very common in general population and have broad-ranging physiological effects in-vivo which lessen inflammatory cascades and vascular reactivity. A recent trend is to perform nutritional epidemiological studies linking overall diet pattern to the lifestyle, examining the link between food and nutrients of diet to risk of chronic diseases. This chapter would deal with pharmacological and pathological basis of hypertension, utilization of dietary fibers, functional foods, nutraceuticals for hypertensive populations as well as to those with increased cardiovascular risks.

Cerebrovascular Accident Complicating Diabetic Ketoacidosis in a Nigerian Adolescent: A Case Report and Review of the Literature

Cerebrovascular accident (CVA) is a rare neurological complication of diabetic ketoacidosis (DKA) in the paediatric population. The risk of developing CVA in DKA patients is often increased due to abnormalities in coagulation factors, platelet activation, blood volume and flow, and vascular reactivity. Cerebral oedema, the most common neurological complication of DKA, may also predispose to CVA. We report the case of a -12-year-old adolescent with DKA complicated by CVA. She developed features of right hemispheric CVA while on admission and had radiological confirmation of an ischaemic CVA. This report highlights that cerebrovascular accidents in DKA can easily be missed or confused with cerebral oedema.

Efficacy of Pulsatile Flow Perfusion in Adult Cardiac Surgery: Hemodynamic Energy and Vascular Reactivity

Background: The role of pulsatile (PP) versus non-pulsatile (NP) flow during a cardiopulmonary bypass (CPB) is still debated. This study’s aim was to analyze hemodynamic effects, endothelial reactivity and erythrocytes response during a CPB with PP or NP. Methods: Fifty-two patients undergoing an aortic valve replacement were prospectively randomized for surgery with either PP or NP flow. Pulsatility was evaluated in terms of energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE). Systemic (SVRi) and pulmonary (PVRi) vascular resistances, endothelial markers levels and erythrocyte nitric-oxide synthase (eNOS) activity were collected at different perioperative time-points. Results: In the PP group, the resultant EEP was 7.3% higher than the mean arterial pressure (MAP), which corresponded to 5150 ± 2291 ergs/cm3 of SHE. In the NP group, the EEP and MAP were equal; no SHE was produced. The PP group showed lower SVRi during clamp-time (p = 0.06) and lower PVRi after protamine administration and during first postoperative hours (p = 0.02). Lower SVRi required a higher dosage of norepinephrine in the PP group (p = 0.02). Erythrocyte eNOS activity results were higher in the PP patients (p = 0.04). Renal function was better preserved in the PP group (p = 0.001), whereas other perioperative variables were comparable between the groups. Conclusions: A PP flow during a CPB results in significantly lower SVRi, PVRi and increased eNOS production. The clinical impact of increased perioperative vasopressor requirements in the PP group deserves further evaluation.

Food Restriction Augmented Alpha1 Adrenergic Mediated Contraction in Mesenteric Arteries

Food restriction (FR) enhances the sensitivity to cardiopulmonary reflexes and alpha1 adrenoreceptors in the female, despite hypotension. The effect of male FR on cardiopulmonary and systemic vascular function is not well understood. This study examines the effects of FR on cardiopulmonary, isolated mesenteric arterial function and potential underlying mechanisms. We hypothesized that FR decreased eNOS activity in mesenteric arteries. Male Sprague Dawley (SD) rats were randomly divided into three groups: (1) control (n=30), (2) 20 percent of food reduction (FR20, n=30), and (3) 40 percent of food reduction (FR40, n=30) for five weeks. Non-invasive blood pressure was measured twice a week. Pulmonary arterial pressure (PAP) was measured using isolated/perfused lungs in rats. The isolated vascular reactivity was assessed in double-wire myograph. After five weeks, food restricted rats exhibited a lower mean arterial pressure and heart rate, however, only FR40 groups exhibited statistically significant differences. The basal tone of PAP and various vasoconstrictors did not show significant differences in pulmonary circulation between each group. We observed that food restriction were enhanced the sensitivity (EC50) in response to α1-adrenoreceptors (phenylephrine, PhE)-induced vasoconstriction, but not to serotonin, U46619, and high K+ in the mesenteric arteries. FR reduced endothelium-dependent relaxation via decreased function of endothelial nitric oxide synthase (eNOS)-nitric oxide (NO) pathway in the mesenteric arteries. PhE-mediated vasoconstriction in mesenteric arteries was eliminated in the presence of eNOS inhibitor (L-NAME). In addition, incubation with NOX2/4 inhibitors (apocynin, GKT137831, VAS2870) and reactive oxygen species (ROS) scavenger inhibitor (Tiron) were eliminated the differences of PhE-mediated vasoconstriction but not to cyclooxygenase inhibitor (indomethacin) in the mesenteric artery. Augmentation of alpha1 adrenergic mediated contraction via inhibition of eNOS-NO pathway by increased activation of ROS through NOX2/4 in response to FR. Reduced eNOS-NO signaling might be a pathophysiological counterbalance to prevent hypovolemic shock in response to FR.

BBSome: a New Player in Hypertension and Other Cardiovascular Risks

The BBSome is an octameric protein complex involved in Bardet-Biedl syndrome (BBS), a human pleiotropic, autosomal recessive condition. Patients with BBS display various clinical features including obesity, hypertension, and renal abnormalities. Association studies have also linked the BBS genes to hypertension and other cardiovascular risks in the general population. The BBSome was originally associated with the function of cilia, a highly specialized organelle that extend from the cell membrane of most vertebrate cells. However, subsequent studies have implicated the BBSome in the control of a myriad of other cellular processes not related to cilia including cell membrane localization of receptors and gene expression. The development of animal models of BBS such as mouse lines lacking various components of the BBSome and associated proteins has facilitated studying their role in the control of cardiovascular function and deciphering the pathophysiological mechanisms responsible for the cardiovascular aberrations associated with BBS. These studies revealed the importance of the neuronal, renal, vascular, and cardiac BBSome in the regulation of blood pressure, renal function, vascular reactivity, and cardiac development. The BBSome has also emerged as a critical regulator of key systems involved in cardiovascular control including the renin-angiotensin system. Better understanding of the influence of the BBSome on the molecular and physiological processes relevant to cardiovascular health and disease has the potential of identifying novel mechanisms underlying hypertension and other cardiovascular risks.

603 Endothelial dysfunction is associated with hypertensive disorder during pregnancy

Aims Arterial hypertension (AH) is one of the main determinants of clinical disorders during pregnancy affecting 2% to 10% of pregnancies with a substantial public health impact. Both endothelial injury and increased vascular reactivity have been reported to be involved in the pathogenesis of pre-eclampsia syndrome. Abnormal patterns in brachial artery Doppler velocities have been shown to be predictive of pre-eclampsia in first trimester. The aim of this study is to investigate whether flow-mediated dilation (FMD) and Doppler flow derived-parameters can predict the occurrence of AH. Methods and results The study population consisted of pregnant women (mean age 32 years) who had been referred to the IRCCS Fondazione Ca’ Granda Policlinico of Milan. None of them had any medical issues and was taking any medications at the time of pregnancy. FMD was performed on left brachial artery according to expert recommendation. Measurements of brachial artery diameter and flow have been collected at rest, shortly before cuff release and then 5-, 15-, 30-, 60-, and 90-s during hyperaemia phase. Among Doppler measurements, systolic and diastolic velocity (Vs and Vd, respectively) as well as mean velocity (mean V) were considered. In addition, the pulsatility index (PI) and resistance index (RI) were calculated. A 3-months follow-up was planned in order to detect the presence of AH. All data were expressed as the median. U-test (Mann–Whitney analysis) was performed to test difference among hypertensives and non-hypertensives We recruited 48 women (median age 32 yeas) whose 4 (8.5%) developed AH during pregnancy. These latter had statistically significant higher systolic velocity measured at 5 s after the release of distal occlusion (126 cm/s vs. 173 cm/s; P &lt; 0.05). No other velocity Doppler data [diastolic velocity (Vd), mean velocity (mean V), PI, RI, TAMAX, and TAMEAN] showed a statistical significant association with AH development. Conclusions The present study suggests that the vascular assessment through Doppler during FMD procedure may foresee the development of hypertensive disorder in pregnancy. Our result provides the first evidence that the peak systolic velocity of brachial artery may represent a marker of early endothelial activation or damage, that can be directly involved in the pathophysiological mechanisms of the hypertensive disorders in pregnancy.

Effects of dipyridamole and its use in neurology

Dipyridamole has been on the pharmaceutical market since 1959 and, as a pyrimidyl-pyrimidine compound, has a variety of mechanisms of action. The very first action of dipyridamole was its antianginal effect. In subsequent years, attention was drawn to the antiplatelet properties of dipyridamole, which are related to inhibition of platelet phosphodiesterase as well as to blocking adenosine transport. Another important property of dipyridamole is its effect on the deformability of red blood cells, thereby improving microcirculation. Dipyridamole affects changes in the dynamics of platelet activity and vascular reactivity and causes improvement of cerebral perfusion. Due to its pronounced antiplatelet properties, the drug has been widely studied for the prevention of ischemic strokes and transient ischemic attacks, both as monotherapy and in combination with other drugs. Unlike other platelet antiaggregants, dipyridamole does not have a damaging effect on mucous membranes. Its antiplatelet effect is not accompanied with inhibition of cyclooxygenase activity and reduction of prostacyclin synthesis. In the treatment of cerebral circulation disorders, dipyridamole can be used to control the antithrombotic effect by selecting the optimal dose of the drug. Dipyridamole has antioxidant properties, enhances NO-mediated pathways, has indirect anti-inflammatory effects via adenosine and prostaglandin-2 as well as direct anti-inflammatory effects and several other effects. Dipyridamole is considered a safe drug based on decades of clinical experience. Its side effects are usually limited and transient. Given the diverse effects of dipyridamole, it can be used for a wide range of pathologies other than thrombosis prevention. Data on the efficacy and safety of dipyridamole in various diseases of the neurological spectrum are presented.