High Peripheral Vascular Resistance Research Articles

Comparison of baseline non- invasive hemodynamic evaluation among patients with advanced conduction disorders based on high Vs. low peripheral vascular resistance reserve

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Patients with advanced conduction disorders can have various hemodynamic presentation ranging from cardiovascular shock to an excessive hypertension state. The peripheral vascular resistance has an important role in the physiology of compensation mechanisms related to reduced heart rate. We aimed to compare baseline characteristics among patients with advanced conduction disorders based on high versus low peripheral vascular resistance reserve. Methods We performed a non-invasive hemodynamic study using the NicaS system (whole-body bio-impedance monitoring system) in 47 patients who presented with advanced conduction disorder and required pacemaker implantation. Non-invasive hemodynamic parameters including total peripheral resistance index (TPRI) were measured before and after pacemaker implantation. TPRI reserve was defined as the change between the two TPRI measurements. Patients were categorized to have high or low TPRI reserve. We compared baseline characteristics based on high vs. low TPRI reserve. Results There were 27 (56%) patients presented with complete AV block and 21 (44%) with other advanced conduction disorders. The average heart rate at presentation was 38.5±5.3 with cardiac output of 2.5±0.6 and cardiac index of 1.4±0.3. Twenty-three patients were categorized with high TPRI reserve. The mean age of patients with high and low TPRI reserve was 77 ± 11 years and 75 ± 16 years, respectively. The systolic blood pressure at presentation for patients with high TPRI reserve was 176 ± 25 mmHg vs. 156 ± 29 mmHg among patients with low TPRI reserve (p-value=0.016). The diastolic blood pressure was similar among patients having high and low TPRI. High TPRI reserve was not correlated with history of hypertension, lower heart rate, lower cardiac output or cardiac index at presentation. Conclusion High systolic blood pressure at presentation of patients with advanced heart conduction disorders is associated with higher peripheral resistance reserve.

Sympathetic and hemodynamic responses to exercise in heart failure with preserved ejection fraction.

Excessive sympathetic activity during exercise causes heightened peripheral vasoconstriction, which can reduce oxygen delivery to active muscles, resulting in exercise intolerance. Although both patients suffering from heart failure with preserved and reduced ejection fraction (HFpEF and HFrEF, respectively) exhibit reduced exercise capacity, accumulating evidence suggests that the underlying pathophysiology may be different between these two conditions. Unlike HFrEF, which is characterized by cardiac dysfunction with lower peak oxygen uptake, exercise intolerance in HFpEF appears to be predominantly attributed to peripheral limitations involving inadequate vasoconstriction rather than cardiac limitations. However, the relationship between systemic hemodynamics and the sympathetic neural response during exercise in HFpEF is less clear. This mini review summarizes the current knowledge on the sympathetic (i.e., muscle sympathetic nerve activity, plasma norepinephrine concentration) and hemodynamic (i.e., blood pressure, limb blood flow) responses to dynamic and static exercise in HFpEF compared to HFrEF, as well as non-HF controls. We also discuss the potential of a relationship between sympathetic over-activation and vasoconstriction leading to exercise intolerance in HFpEF. The limited body of literature indicates that higher peripheral vascular resistance, perhaps secondary to excessive sympathetically mediated vasoconstrictor discharge compared to non-HF and HFrEF, drives exercise in HFpEF. Excessive vasoconstriction also may primarily account for over elevations in blood pressure and concomitant limitations in skeletal muscle blood flow during dynamic exercise, resulting in exercise intolerance. Conversely, during static exercise, HFpEF exhibit relatively normal sympathetic neural reactivity compared to non-HF, suggesting that other mechanisms beyond sympathetic vasoconstriction dictate exercise intolerance in HFpEF.

Longitudinal maternal cardiac function in hypertensive disorders of pregnancy

Compared with gestational hypertension, preeclampsia has traditionally been considered the worse end of the spectrum of hypertensive disorders of pregnancy. It is associated with worse pregnancy outcomes and future cardiovascular morbidities. Both hypertensive disorders may be associated with cardiac maladaptation in pregnancy. However, previous studies were limited by small numbers and a paucity of longitudinal data and unaccounted for the contribution of maternal characteristics that can affect hemodynamics. This study aimed to assess, in an unselected population, the maternal cardiac adaptation in normotensive and hypertensive pregnancies after controlling for important maternal characteristics that affect maternal cardiac function and the interaction among these covariates. This was a prospective, multicenter longitudinal study of maternal hemodynamics, assessed by a noninvasive bioreactance technology, measured at 11 0/7 to 13 6/7, 19 0/7 to 24 0/7, 30 0/7 to 34 0/7, and 35 0/7 to 37 0/7 weeks of gestation in 3 groups of women. Group 1 was composed of women with preeclampsia (n=45), group 2 was composed of women with gestational hypertension (n=61), and group 3 was composed of normotensive women (n=1643). A multilevel linear mixed-effects model was performed to compare the repeated measures of hemodynamic variables controlling for maternal age, height, weight, weight gain, race, previous obstetrical history, and birthweight. After adjusting for confounders that significantly affect maternal hemodynamics, both group 1 and group 2, compared with group 3, had pathologic cardiac adaptation. Group 1, compared with group 3, demonstrated hyperdynamic circulation with significantly higher cardiac output driven by greater stroke volume in the first trimester of pregnancy. As the pregnancies progressed to after 20 0/7 weeks of gestation, this hyperdynamic state transitioned to hypodynamic state with low cardiac output and high peripheral vascular resistance. Group 2, compared with group 3, had no significant differences in cardiac output, stroke volume, and heart rate before 20 0/7 weeks of gestation but thereafter demonstrated a continuous decline in cardiac output and stroke volume, similar to group 1. Both groups 1 and 2, compared with group 3, had persistently elevated mean arterial pressure and uterine artery pulsatility index throughout pregnancy. After adjusting for confounders that affect maternal hemodynamics in an unselected pregnant population, women with preeclampsia and gestational hypertension, compared with normotensive women, demonstrated similar cardiac maladaptation. This pathologic profile was evident after 20 0/7 weeks of gestation and at least 10 weeks before the clinical manifestation of the disease.

Effect of race on longitudinal central hemodynamics in pregnancy.

To compare central hemodynamics between white, black and Asian women in pregnancy. This was a prospective, longitudinal study of maternal central hemodynamics in white, black and Asian women with a singleton pregnancy, assessed using a bioreactance method at 11 + 0 to 13 + 6, 19 + 0 to 24 + 0, 30 + 0 to 34 + 0 and 35 + 0 to 37 + 0 weeks' gestation. At each visit, cardiac output (CO), stroke volume (SV), heart rate (HR), peripheral vascular resistance (PVR) and mean arterial pressure were recorded. Multilevel linear mixed-effects analysis was performed to compare the repeated measures of the cardiac variables between white, black and Asian women, controlling for maternal characteristics, medical history and medication use. The study population included 1165 white, 247 black and 116 Asian women. CO increased with gestational age to a peak at 32 weeks and then decreased; the highest CO was observed in white women and the lowest in Asian women. SV initially increased after the first visit but subsequently declined with gestational age in white women, decreased with gestational age in black women and remained static in Asian women. In all three study groups, HR increased with gestational age until 32 weeks and then remained constant; HR was highest in black women and lowest in white women. PVR showed a reversed pattern to that of CO; the highest values were in Asian women and the lowest in white women. The least favorable hemodynamic profile, which was observed in black and Asian women, was reflected in higher rates of a small-for-gestational-age infant. There are race-specific differences in maternal cardiac adaptation to pregnancy. White women have the most favorable cardiac adaptation by increasing SV and HR, achieving the highest CO and lowest PVR. In contrast, black and Asian women have lower CO and higher PVR than do white women, with CO increasing through a rise in HR due to declining or static SV. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Cardiac Imaging in Liver Transplantation Candidates: Current Knowledge and Future Perspectives.

Cardiovascular dysfunction in cirrhotic patients is a recognized clinical entity commonly referred to as cirrhotic cardiomyopathy. Systematic inflammation, autonomic dysfunction, and activation of vasodilatory factors lead to hyperdynamic circulation with high cardiac output and low peripheral vascular resistance. Counter acting mechanisms as well as direct effects on cardiac cells led to systolic or diastolic dysfunction and electromechanical abnormalities, which are usually masked at rest but exposed at stress situations. While cardiovascular complications and mortality are common in patients undergoing liver transplantation, they cannot be adequately predicted by conventional cardiac examination including transthoracic echocardiography. Newer echocardiography indices and other imaging modalities such as cardiac magnetic resonance have shown increased diagnostic accuracy with predictive implications in cardiovascular diseases. The scope of this review was to describe the role of cardiac imaging in the preoperative assessment of liver transplantation candidates with comprehensive analysis of the future perspectives anticipated by the use of newer echocardiography indices and cardiac magnetic resonance applications.

Posterior Approach Popliteal Artery Endarterectomy Combined with Above Knee Bypass Versus Below Knee Bypass Surgery for Long Occlusions of the Superficial and Popliteal Arteries: Long-term Results

Introduction - Long occlusion of the superficial and popliteal arteries causing limb ischemia often presents a treatment dilemma, especially when autologous vein is absent. Femoropopliteal bypass below-knee position has significant disadvantages: small diameter of popliteal artery doesn’t always corresponds with blood flow from femoral artery due to high peripheral vascular resistance, while collateral arteries surrounding knee joint are excluded from circulation. Therefore, we developed a novel approach to treatment popliteal artery occlusive disease including consecutive endarterectomy using direct posterior approach in prone position and above knee femoropopliteal bypass (E+FemPop bypass) in supine position (Patent RF 2601698). Long-term results of retrospective study will be presented. Methods - The study included 58 patients: 34 underwent E+FemPop bypass (I group), and 24 - distal femoropopliteal bypass (II group). Indications for surgery were claudication in 20, rest pain in 19 and tissue loss in 19. All patients had TASC D lesions affecting superficial femoral artery and P1, P2 or all segments of popliteal artery. At least 1 crural artery was patent from origin to at least 8 cm distally. Results - Primary patency after 74 months of follow-up was 42,05% for E+FemPop bypass and 15,5% for distal bypass (p = 0,0184, log-rank test), and secondary patency was 57,8% and 19,15% (p = 0.00298), respectively. Limb salvage after 74 months was 93,41% after E+FemPop bypass and 44,93% after femoropopliteal bypass below knee surgery (p = 0,0097): 10 amputations in I group (40% major), 9 amputations in II group (100% major). Cumulative primary, secondary patency and limb salvage after 133 months in I group were 37,85%, 52,95% and 30,81% respectively. Conclusion - E+FemPop bypass is a good option for surgical repair in superficial femoral and popliteal arteries occlusions, with better primary and secondary patency rates then distal bypass surgery. If the saphenous vein is not applicable, E+FemPop should be considered.

Association of Vitamin D Insufficiency and Peripheral Vascular Resistance

Abstract Background Vitamin D insufficiency is prevalent worldwide. Recently, the role of vitamin D substitution in hypertensive vitamin D deficient and insufficient patients has been studied by many investigators worldwide. In this observational study, the peripheral vascular resistance (PVR) of patients with vitamin D insufficiency or deficiency was analyzed. Objective The main purpose of this article is the assessment of PVR in vitamin D deficient subjects and in that any gender variation. Methods Subjects who were not known hypertensives, and who were free of other comorbidities, were included. Diabetic subjects were excluded. Serum vitamin D3 levels of all the subjects were recorded. Thirty-three subjects with serum vitamin D3 levels in insufficiency or deficiency range were included in our study. AGEDIO peripheral resistance calculator was used to calculate arterial stiffness indices, PVR, stroke volume, cardiac output, and cardiac index. Augmentation pressure (AG) is the contribution that wave reflection makes to systolic arterial pressure. Augmentation index (AI) is an indirect measure of arterial stiffness and is calculated as AG divided by pulse pressure ×100. Results The total number of subjects studied was 33, of whom 18 were males, and 15 were females. The mean serum vitamin D3 levels were 19.28 nanograms/mL. In this study, it was observed that the mean AI was 21.42 ± 12.6%, and mean pulse wave velocity was 6.9 ± 1.2 m/s. Among central hemodynamic measures, mean PVR was found to be 1733 ± 201.1dyn*s/cm5, mean cardiac output was 4.3 ± 0.5 L/min, and mean cardiac index was 2.56 +/– 0.33 L/mi*L/m2). Twenty-five (76%) patients showed increased PVR. Even though in patients with normal PVR, there is female preponderance, but in patients with high PVR, there was no gender difference. Conclusions This study has shown that the PVR was significantly high in vitamin D deficient and insufficient subjects (without hypertension or diabetes mellitus) with no significant gender difference for high PVR, even though AG and AI were not significantly different among subjects.

Smooth Muscle PPARgamma Mutation Causes Impaired Renal Blood Flow and Salt‐Sensitive Hypertension

Failure to vasodilate the systemic and renal vasculature in response to salt loading is a hallmark of salt sensitive hypertension (HT). Human subjects carrying dominant negative mutations in PPARgamma (PPARG) exhibit early onset HT while global PPARG activation consistently lowers blood pressure (BP). To determine whether tissue‐specific actions of PPARG regulate systemic and renal vascular function, salt sensitivity and BP, we studied mice specifically expressing a human HT‐causing mutation in PPARG P467L in smooth muscle (S‐P467L). S‐P467L transgenic mice and non‐transgenic controls (NT) were fed regular diet (0.4% salt) or high salt (HS) diet containing 4% salt for 4 weeks. Salt induced marked elevations in systolic BP in S‐P467L mice (135 ± 2 mmHg HS vs 121 ± 4 mmHg regular diet), but not in NT mice (121 ± 5 mmHg HS vs 118 ± 3 mmHg regular diet). S‐P467L and NT animals exhibited identical cardiac output at baseline and under chronic HS; thus the pressor effect of salt intake in S‐P467L mice was not due to a larger fluid volume, but likely higher peripheral vascular resistance. In keeping with this, HS‐consuming S‐P467L mice, but not NT controls, exhibited severe impairment in acetylcholine‐ and sodium nitroprusside‐induced vasorelaxation in carotid artery (Maximal relaxation at 30 μM acetylcholine: S‐P467L 35 ± 4% vs. NT 90 ± 2%), basilar artery (S‐P467L −3 ± 9% vs. NT 70 ± 5%), and first order renal arteries branches (S‐P467L 34 ± 4% vs. NT 76 ± 4%). Importantly, salt‐induced vascular dysfunction rapidly developed in S‐P467L mice after receiving HS diet for only 3 days, preceding the BP elevation. In line with the impaired renovascular relaxation, S‐P467L mice failed to adapt their renal blood flow (RBF) to HS (HS‐induced increases in RBF: S‐P467L 3 μL/min/g vs. NT 20 μL/min/g). The impaired renovascular dilation and blunted RBF was not caused by differences in circulating renin‐angiotensin levels or renal sympathetic nerve activity between the two strains. In the 3rd week of HS diet, S‐P467L mice produced 31% less nitrate/nitrite in 24 hour urine compared to NT controls, which was indicative of blunted renal bioavailability of nitric oxide, a potent inhibitor of Na‐K‐2Cl cotransporter (NKCC2). These changes were associated with a declined capacity of HS‐fed S‐P467L mice to excrete excess sodium and volume challenge, which was rescued by an NKCC2 inhibitor furosemide, but not by the Na‐Cl‐cotransporter inhibitor thiazide. Further supporting a role of NKCC2, a single dose of furosemide (20 mg/kg) induced a larger decrease in systolic BP in salt‐consuming S‐P467L mice (S‐P467L HS −16 ± 3 mmHg, S‐P467L regular diet −5 ± 2 mmHg, NT HS −6 ± 2 mmHg, and NT regular diet −6 ± 2 mmHg), while thiazide did not. Our data support the novel concept that smooth muscle PPARG regulates systemic and renal vascular resistance, renal perfusion and tubular sodium transport, and loss of these protective actions of PPARG predisposes to salt sensitivity and hypertension.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Maternal hemodynamics in normal pregnancy and in pregnancy affected by pre-eclampsia.

To determine if, in a high-risk group of women in the first half of pregnancy, those who develop pre-eclampsia (PE) with fetal growth restriction (FGR) demonstrate distinct hemodynamics compared with those with PE in the absence of FGR (PE only). Cardiac output (CO), peripheral vascular resistance (PVR) and mean arterial pressure (MAP) were measured at the first hospital visit at 9-24 weeks' gestation in 69 women who had chronic hypertension and 67 who had had a hypertensive disorder in a previous pregnancy. These women were divided into five groups according to pregnancy outcome. In total, 19 subsequently developed PE only, 22 developed PE with FGR, 17 developed pregnancy-induced hypertension, 39 had chronic hypertension without PE or FGR and 39 had had a hypertensive disorder in a previous pregnancy without PE, pregnancy-induced hypertension or FGR in the index pregnancy. The hemodynamic values in each of these groups were compared with those in a cohort of 300 low-risk women with normal pregnancy. In all the high-risk groups, PVR and MAP were higher than in women with a normal pregnancy, but CO was lower in the group of women with PE and FGR, whereas in the other high-risk groups, it was not significantly different from normal. In women who develop PE, there is evidence of high PVR and MAP from the first half of pregnancy, whilst PE and FGR are associated with failure in physiological expansion of CO. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Abstract 094: Smooth Muscle PPARγ Mutation Causes Impaired Renal Blood Flow and Salt-Sensitive Hypertension

Mutations in PPARγ cause hypertension (HT) while PPARγ activation lowers blood pressure (BP) in humans. To determine if vascular smooth muscle (VSM) PPARγ regulates salt sensitivity, we studied transgenic mice selectively expressing a HT-causing PPARγ mutant in VSM (S-P467L) and non-transgenic littermates (NT) fed a 4% high salt (HS) diet for 4 weeks. Salt equally suppressed plasma renin in both strains, but S-P467L mice exhibited increased systolic BP (S-P467L 136±3 mmHg vs NT 124±2 mmHg, p<0.01) and pulse wave velocity (3.1±0.1 vs 2.7±0.1 m/s, p<0.01) in response to HS. The salt-induced HT was not associated with changes in diastolic BP, sympathetic nerve activity, heart rate, or cardiac output. Thus, the pressor effect of HS was likely due to higher peripheral vascular resistance. HS-fed S-P467L mice developed impaired acetylcholine (ACh)- and sodium nitroprusside (SNP)-induced vasorelaxation in carotid (Max ACh relaxation: 31±4.9% vs 90±1.8%, p<0.01; Max SNP relaxation: 38±2.8% vs 89±2.6%, p<0.01) and basilar artery (Max ACh relaxation: -3.2±9.3% vs 57±5.9%, p<0.01). The impaired vasodilation rapidly developed after 3-day HS diet, preceding salt-induced BP elevation. Pre-incubation with a cyclooxygenase inhibitor indomethacin normalized ACh/SNP relaxation responses, and preliminary mass spectrometry indicated HS increased prostaglandin E2 in S-P467L aortas. HS-fed S-P467L mice had smaller renal artery luminal diameter (322±21 vs 389±22 μm, p<0.05) and blunted renal blood flow (36±3.6 vs. 50±6.4 μL/min/g, p<0.05). During the 4 th week of HS diet, S-P467L mice produced 31% less nitrate/nitrite in 24 hour urine compared to NT controls (2.2±0.3 vs 3.2±0.4 μmol, p<0.05), suggesting blunted renal bioavailability of nitric oxide, a potent inhibitor of Na-K-2Cl cotransporter (NKCC2). This was associated with a declined capacity of HS-fed S-P467L mice to excrete an acute volume/Na + load, which was rescued by an NKCC2 inhibitor furosemide, but not by the Na-Cl-cotransporter inhibitor hydrochlorothiazide. Our data support the novel concept that smooth muscle PPARγ regulates systemic vascular resistance, renal perfusion and tubular sodium transport, and loss of these protective actions of PPARγ predisposes to salt sensitivity and hypertension.

PECULIARITIES OF THE FUNCTIONAL STATE OF THE MOTHER-PLACENTA–FETUS SYSTEM IN PREGNANT WOMEN WITH PLACENTAL DYSFUNCTION

Among the causes that lead to antenatal affliction of the fetus, namely its hypoxia, hypotrophy, ante- and intranatal distress, is placental dysfunction (PD). Perinatal mortality in PDs is 10.3‰ in newborn infants, 49 ‰ – in preterm infants. Perinatal morbidity with PD reaches 70‰, and mortality rate – 20%. Objective. To investigate the functional state of the fetoplacental complex (FPС) in pregnant women with PD. Material and methods. The functional status of the FPC in 104 patients with PD (main group) and in 136 women with uncomplicated pregnancy and delivery (control group) using ultrasound placentalography, Dopplerometry was examined. Research results. The ultrasound characteristics of the placental dysfunction were the following: discrepancy between the degree of maturity of the placenta of the gestation period, true thickening of the placenta, its hypoplasia, reduction of echogenicity of the placenta, oligohydramnios. Dopplerometric signs of disorder of the utero-placental blood flow were high peripheral vascular resistance, both in dominant and in subdominant UA, asymmetry of blood flow in UA. Hemodynamics of fetal-placental circulation against the ground of PD was characterized by a decrease in the final diastolic blood flow velocity, which was manifested by an increase resistance in the peripheral vascular of the fetal part of the placenta, decrease in placental coefficient. The peculiarity of fetal blood flow in pregnant women with PD was the decrease in the mean value of vascular resistance indices in the middle cerebral artery of the fetus and a significant decrease in the cerebral-umbilical index. Conclusions. In pregnant women with placental dysfunction hemodynamic changes in the utero-placental complex are associated with decrease in the intensity of placental-fetal blood flow and in 16.3% of cases by centralization of the fetal circulation. Timely Dopplerometry is important both in the diagnosis of the compensatory capabilities of the FPK, and during determination of reasonable suggested obstetrical tactics.

Smooth Muscle PPARγ Mutation Causes Impaired Renal Blood Flow and Salt‐Sensitive Hypertension

Failure to vasodilate in systemic and renal vasculature in response to salt loading is a hallmark of salt sensitivity in hypertensive humans and experimental models. Human subjects carrying dominant negative mutations in PPARγ exhibit hypertension while global PPARγ activation consistently lowers blood pressure (BP). To determine whether tissue‐specific actions of PPARγ regulate vascular function, salt sensitivity and BP, we studied mice specifically expressing a human hypertension‐causing mutation in PPARγ (P467L) selectively in smooth muscle (S‐P467L). S‐P467L transgenic mice and non‐transgenic littermate controls (NT) were fed regular diet (0.4% salt) or high salt (HS) diet containing 4% salt for 4 weeks. Salt induced marked elevations in systolic BP in S‐P467L mice (136±4 mmHg salt n=6 vs 121±3 mmHg regular diet n=7, p<0.01, two‐way ANOVA), but not in NT mice (121±4 mmHg salt n=4 vs 116±4.0 mmHg regular diet n=5). Because salt induced similar increases in cardiac output in S‐P467L and NT animals, the pressor effect of salt intake in S‐P467L mice was not due to a larger fluid volume, but likely higher peripheral vascular resistance. In keeping with this, HS‐fed S‐P467L mice, but not NT controls, exhibited severe impairment in acetylcholine (ACh)‐ and sodium nitroprusside (SNP)‐induced vasorelaxation in carotid artery (Maximal relaxation at 30 μM ACh: S‐P467L 31±4.9% n=4 vs. NT 90±1.8% n=6, p<0.01; Maximal relaxation to 30 μM SNP: S‐P467L 38±2.8% n=4 vs. NT 89±2.6% n=6, p<0.01, two‐way ANOVA Repeated Measurements) and in cerebral basilar artery (Maximal relaxation at 100 μM ACh: S‐P467L ‐3.2±9.3% n=7 vs. NT 57±5.9% n=5, p<0.01). Importantly, salt‐induced vascular dysfunction rapidly developed in S‐P467L mice after receiving HS diet for only 3 days, preceding BP elevations. The impaired vasorelaxation in HS‐fed S‐P467L mice was associated with smaller renal artery diameter (S‐P467L 322±21 μm n=6 vs NT 389±22 μm n=5, p<0.05 two‐way ANOVA) and blunted renal blood flow (S‐P467L 36±3.6 μL/min/g n=6 vs. NT 50±6.4 μL/min/g n=5, p<0.05). These changes were not caused by differences in circulating renin‐angiotensin levels or renal sympathetic nerve activity between the two strains. Preliminary data indicated that during the 3rd week of HS diet, S‐P467L mice produced 36% less nitrate/nitrite in 24 hour urine compared to NT controls, which suggested blunted renal bioavailability of nitric oxide, a potent inhibitor of Na‐K‐2Cl cotransporter (NKCC2). This was associated with a declined capacity of HS‐fed S‐P467L mice to excrete an acute volume challenge, which was rescued by an NKCC2 inhibitor furosemide, but not by the Na‐Cl‐cotransporter inhibitor hydrochlorothiazide. Our data support the novel concept that smooth muscle PPARγ regulates systemic vascular resistance, renal perfusion and tubular sodium transport, and loss of these protective actions of PPARγ predisposes to salt sensitivity and hypertension.Support or Funding InformationDr. Jing Wu is supported by an American Heart Association Postdoctoral Fellowship (17POST33660685). This project is funded by R01 HL125603 and R01 HL131689 to Dr. Curt Sigmund.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Early and late preeclampsia are characterized by high cardiac output, but in the presence of fetal growth restriction, cardiac output is low: insights from a prospective study

Preeclampsia and fetal growth restriction are considered to be placentally mediated disorders. The clinical manifestations are widely held to relate to gestation age at onset with early- and late-onset preeclampsia considered to be phenotypically distinct. Recent studies have reported conflicting findings in relation to cardiovascular function, and in particular cardiac output, in preeclampsia and fetal growth restriction. We conducted this study to examine the possible relation between cardiac output and peripheral vascular resistance in preeclampsia and fetal growth restriction. We investigated maternal cardiovascular function in relation to clinical subtype in 45 pathological pregnancies (14 preeclampsia only, 16 fetal growth restriction only, 15 preeclampsia and fetal growth restriction) and compared these with 107 healthy person observations. Cardiac output was the primary outcome measure and was assessed using an inert gas-rebreathing method (Innocor), from which peripheral vascular resistance was derived; arterial function was assessed by Vicorder, a cuff-based oscillometric device. Cardiovascular parameters were normalized for gestational age in relation to healthy pregnancies using Z scores, thus allowing for comparison across the gestational range of 24-40 weeks. Compared with healthy control pregnancies, women with preeclampsia had higher cardiac output Z scores (1.87 ± 1.35; P= .0001) and lower peripheral vascular resistance Z scores (-0.76 ± 0.89; P= .025); those with fetal growth restriction had higher peripheral vascular resistance Z scores (0.57 ± 1.18; P= .04) and those with both preeclampsia and fetal growth restriction had lower cardiac output Z scores (-0.80 ± 1.3 P= .007) and higher peripheral vascular resistance Z scores (2.16 ± 1.96; P= .0001). These changes were not related to gestational age of onset. All those affected by preeclampsia and/or fetal growth restriction had abnormally raised augmentation index and pulse wave velocity. Furthermore, in preeclampsia, low cardiac output was associated with low birthweight and high cardiac output with high birthweight (r= 0.42, P= .03). Preeclampsia is associated with high cardiac output, but if preeclampsia presents with fetal growth restriction, the opposite is true; both conditions are nevertheless defined by hypertension. Fetal growth restriction without preeclampsia is associated with high peripheral vascular resistance. Although early and late gestation preeclampsias are considered to be different diseases, we show that thehemodynamic characteristics of preeclampsia were unrelated to gestational age at onset but were strongly associated with the presence or absence of fetal growth restriction. Fetal growth restriction more commonly coexists with preeclampsia at early gestation, thus explaining the conflicting results of previous studies. Furthermore, antihypertensive agents act by reducing cardiac output or peripheral vascular resistance and are administered without reference to cardiovascular function in preeclampsia. The underlying pathology (preeclampsia, fetal growth restriction, preeclampsia and fetal growth restriction) defines cardiovascular phenotype, providing a rational basis for choice of therapy in which high or low cardiac output or peripheral vascular resistance is the predominant feature.

Kv7(KCNQ)-K+-Channels Influence Total Peripheral Resistance in Female but Not Male Rats, and Hamper Catecholamine Release in Hypertensive Rats of Both Sexes.

K+-channels of the Kv7/KCNQ-family hyperpolarize and stabilize excitable cells such as autonomic neurons and vascular smooth muscle cells (VSMC). Kv7 may therefore play a role in blood pressure (BP) homeostasis, and prevent a high total peripheral vascular resistance (TPR), a hallmark of hypertensive disease. The present study analyzed if Kv7 channels influence catecholamine release and TPR in normotensive (WKY) and spontaneously hypertensive rats (SHR), and if they may contribute to the antihypertensive protection seen in young, female SHR. Tyramine-stimulated norepinephrine release evokes an adrenergic cardiovascular response, and also allows modulation of release to be reflected in the overflow to plasma. The experiment itself activated some secretion of epinephrine. The results show: (1) XE-991 (Kv7.1-7.4-inhibitor), but not chromanol 293B (Kv7.1-inhibitor), increased tyramine-stimulated norepinephrine overflow and epinephrine secretion in both sexes in SHR, but not WKY. (2) Surprisingly, the Kv7-openers retigabine (Kv7.2-7.5) and ICA-27243 (Kv7.2-7.3-preferring) increased catecholamine release in female SHR. (3) The rise in TPR following tyramine-stimulated norepinephrine release was increased by XE-991 but not chromanol in the female WKY only. (4) Retigabine and ICA-27243 reduced the TPR-response to tyramine in the female SHR only. These results suggested: (1) Up-regulation of Kv7.2-7.3 function in sympathetic neurons and chromaffin cells hampered catecholamine release in SHR of both sexes. (2) The increase catecholamine release observed after channel openers in the female SHR may possibly involve reduced transmission in cholinergic neurons which hamper catecholamine release. These two mechanisms may serve to counter-act the hyperadrenergic state in SHR. (3) Kv7.4, most likely in the vasculature, opposed the tension-response to norepinephrine in the female WKY. (4) Vascular Kv7.4-7.5 could be stimulated and then opposed norepinephrine-induced vasoconstriction in the female SHR. (5) Vascular Kv7 channels did not counter-act norepinephrine induced vasoconstriction in male rats, possibly due to different Kv7 channel regulation. Kv7 channels may represent a novel target for antihypertensive therapy.

Lower limb revascularization in chronic critical ischemia

The article presents the results of examination and treatment of 92 patients with obliterating atherosclerosis under chronic critical ischemia. Based on imaging methods patients were divided into 3 groups with the isolation of a leading occlusive and stenotic segment and the choice of surgical approach accordingly. To ensure the functioning of the popliteal-posterotibial autovenous shunt with high peripheral vascular resistance, a method is provided of end-to-side anastomosis of the distal segment of autovenous shunt with arteriovenous fistula. Based on the determination of intradermal blood flow of the rear of the foot in patients with chronic critical limb ischemia, the effects of revascularization operations were predicted.

Longitudinal maternal hemodynamics in pregnancies affected by fetal growth restriction.

Fetal growth restriction (FGR) is a powerful determinant of poor perinatal outcome. From our previous work in pregnancies at high risk of development of hypertension we found impaired cardiovascular adaptation early in gestation in those destined to deliver growth-restricted infants. In this study, we monitored serially maternal hemodynamics from the first to third trimester in a similar high-risk cohort, in order to determine whether this distinct hemodynamic profile found at presentation persisted throughout pregnancy in those complicated by FGR. This was a prospective observational study based at a specialist antenatal hypertension clinic at a tertiary hospital in London. Maternal hemodynamics were evaluated serially using a non-invasive bioreactance method in pregnant women referred to the clinic with a history of chronic hypertension or a history of hypertensive disorder in a previous pregnancy. Differences in maternal hemodynamic parameters were compared between women who delivered a baby with a birth weight ≥ 10th vs < 10th percentile and ≥ 5th vs < 5th percentile. Eighty-four pregnant women were included in the study. Mean gestational age at presentation was 14.3 weeks. Sixteen women delivered babies with a birth weight < 10th percentile and 11 with a birth weight < 5th percentile. In pregnancies with a birth weight ≥ 10th percentile, longitudinal maternal hemodynamics showed a pattern consistent with well-established physiological changes in pregnancy, i.e. a reduction in vascular resistance and an increase in cardiac output with advancing gestation until mid-pregnancy. However, women who delivered babies with a birth weight < 10th percentile showed a static pattern with no change during gestation and lower cardiac output and higher peripheral vascular resistance. Similar differences were seen when the 5th percentile was used to discriminate between appropriately-grown and growth-restricted babies. Serial assessment of maternal hemodynamics in high-risk women identifies distinctive trends associated with pregnancies destined to deliver babies with birth weights < 10th and < 5th percentiles. These pregnancies have a suppressed and static maternal cardiac output and stroke volume, and have consistently raised peripheral vascular resistance. This suggests that, in women with chronic hypertension or a history of hypertensive disorder in a previous pregnancy, FGR is associated with a primary and persistent failure of maternal cardiovascular adaptation in pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Cerebral blood flow indices in children and adolescents with hypertension and metabolic syndrome

A total of 141 patients aged 10 to 17 years were examined. Doppler ultrasonography was carried out to assess blood flow in the intracranial (basilar and middle cerebral arteries) and extracranial (common and internal carotid arteries, vertebral arteries) cerebral arteries and cerebral vein (tentorial venous sinus) and the velocity characteristics of the flow and the level of peripheral vascular resistance were analyzed in all the children. Normal weight children with stable hypertension were found to have high peripheral vascular resistance in the beds of intracranial (basilar and right middle cerebral arteries) and extracranial arteries with the phenomena of hyperperfusion in the bed of the common carotid artery. Obese children having different stages of hypertension were, on the contrary, observed to have lowered peripheral resistance in the intracranial arteries and increased peak systolic blood flow velocity in the tentorial venous sinus. The found cerebral hemodynamic differences may suggest that obese children have secondary hypertension.

Methylene Blue Is Effective to Reverse Refractory Hemodynamic Instability due to Dimethoate Poisoning

Background:Organophosphates are commercially available agrochemicals for pest control, but may be abused for deliberate self-poisoning. We report a case of suicidal ingestion of dimethoate, a moderately toxic organophosphate insecticide, which can cause refractory hemodynamic instability, and the successful use of methylene blue (MB) for counteracting this complication. Case Presentation: An unconscious 47-year-old man was referred to emergency department with history of dimethoate ingestion. He rapidly developed hypotension that was refractory to antidotes, resuscitative hydration and multiple vasopressors including norepinephrine, epinephrine and vasopressin. Pulmonary artery catheterization revealed high cardiac output and low peripheral vascular resistance consistent with distributive shock, a complication previously reported in the setting of acute dimethoate toxicity. MB was initiated for the patient and improved hemodynamic status (increased MAP, systolic and diastolic blood pressures) and seized vasopressor requirement. Laboratory tests revealed that on-admission plasma cholinesterase level and dimethoate serum level were 2247 U and 56 μg/mL, respectively. The patient required 2 week ICU course with eventual tracheotomy for ventilation and later transferred to step down level of care. Discussion:Although MB therapy has been reported to be useful in managing sepsis-induced hypotension, there has been no similar report of its use in organophosphate poisoning. Our patient had no objective evidence for sepsis, and MB infusion improved hemodynamics within 6 hours and the effect was continued even after discontinuation of the therapy. The underlying mechanism of dimethoate-induced hypotension might be related to increase in nitric oxide (NO) formation. MB is effective to inhibit NO synthase. Conclusion:MB treatment was effective to reverse hypotension and restore hemodynamic instability caused by dimethoate poisoning. This index case may pave way to further investigation of MB therapy for OP-induced hemodynamic instabilities.

Prediction of pulmonary hypoplasia in mid‐trimester preterm prelabor rupture of membranes: research or clinical practice?

Prediction of pulmonary hypoplasia in mid‐trimester preterm prelabor rupture of membranes: research or clinical practice?

Racial Difference in Central Stiffness and Arterial Structure following Aerobic Exercise Training

African‐Americans (AA) have higher prevalence of hypertension than Caucasians (CA) in the United States. In addition, AA have stiffer central arteries (carotid and aortic) and higher peripheral vascular resistance. These factors are known to directly contribute to end‐organ damage. The purpose of this study was to examine the effects of aerobic exercise training on carotid and central stiffness in young white and African American individuals. 24 AA (8 men and 16 women) and 32 CA (17 men and 15 women) between the ages of 18–35 volunteered for the study, and completed a 8 week aerobic exercise training period (30–60 min of exercise at 60–90% of maximal heart rate, 3 times/week). Women were tested during menses. Carotid and aortic blood pressures were measured using applanation tonometry. Carotid maximum diameter increased significantly following training in CA (7.2 ± 0.1 to 7.4 ± 0.1) as compared to AA (7.5 ± 0.1 to 7.4 ± 0.2). In addition, carotid minimum diameter increased significantly following training in CA as compared to AA (6.5 ± 0.1 to 6.9 ± 0.1 vs. 6.9 ± 0.1 to 6.9 ± 0.2). Carotid SBP, DBP, MAP, Carotid/aortic stiffness or augmentation index showed no changes following training (data not shown, p&lt;0.05). These data suggest that even though 8 weeks of aerobic training had no effect on carotid BP and carotid/aortic stiffness in normotensive CA and AA there is significant arterial remodeling in CA as opposed to AA.