Elevated Systemic Vascular Resistance Research Articles

Effect of systemic vascular resistance on the agreement between stroke volume by non-invasive pulse wave analysis and Doppler ultrasound in healthy volunteers.

Stroke volume can be estimated beat-to-beat and non-invasively by pulse wave analysis (PWA). However, its reliability has been questioned during marked alterations in systemic vascular resistance (SVR). We studied the effect of SVR on the agreement between stroke volume by PWA and Doppler ultrasound during reductions in stroke volume in healthy volunteers. In a previous study we simultaneously measured stroke volume by PWA (SVPWA) and suprasternal Doppler ultrasound (SVUS). We exposed 16 healthy volunteers to lower body negative pressure (LBNP) to reduce stroke volume in combination with isometric hand grip to elevate SVR. LBNP was increased by 20 mmHg every 6 minutes from 0 to 80 mmHg, or until hemodynamic decompensation. The agreement between SVPWA and SVUS was examined using Bland-Altman analysis with mixed regression. Within-subject limits of agreement (LOA) was calculated from the residual standard deviation. SVRUS was calculated from SVUS. We allowed for a sloped bias line by introducing the mean of the methods and SVRUS as explanatory variables to examine whether the agreement was dependent on the magnitude of stroke volume and SVRUS. Bias ± limits of agreement (LOA) was 27.0 ± 30.1 mL. The within-subject LOA was ±11.1 mL. The within-subject percentage error was 14.6%. The difference between methods decreased with higher means of the methods (-0.15 mL/mL, confidence interval (CI): -0.19 to -0.11, P<0.001). The difference between methods increased with higher SVRUS (0.60 mL/mmHg × min × L-1, 95% CI: 0.48 to 0.72, P<0.001). PWA overestimated stroke volume compared to Doppler ultrasound during reductions in stroke volume and elevated SVR in healthy volunteers. The agreement between SVPWA and SVUS decreased during increases in SVR. This is relevant in settings where a high level of reliability is required.

Monoclonal antibodies neutralizing alpha-hemolysin, bicomponent leukocidins, and clumping factor A protected against Staphylococcus aureus-induced acute circulatory failure in a mechanically ventilated rabbit model of hyperdynamic septic shock.

Patients with septic shock caused by Staphylococcus aureus have mortality rates exceeding 50%, despite appropriate antibiotic therapy. Our objectives were to establish a rabbit model of S. aureus septic shock and to determine whether a novel immunotherapy can prevent or halt its natural disease progression. Anesthetized rabbits were ventilated with lung-protective low-tidal volume, instrumented for advanced hemodynamic monitoring, and characterized for longitudinal changes in acute myocardial dysfunction by echocardiography and sepsis-associated biomarkers after S. aureus intravenous challenge. To demonstrate the potential utility of this hyperdynamic septic shock model for preclinical drug development, rabbits were randomized for prophylaxis with anti-Hla/Luk/ClfA monoclonal antibody combination that neutralizes alpha-hemolysin (Hla), the bicomponent pore-forming leukocidins (Luk) including Panton-Valentine leukocidin, leukocidin ED, and gamma-hemolysin, and clumping factor A (ClfA), or an irrelevant isotype-matched control IgG (c-IgG), and then challenged with S. aureus. Rabbits challenged with S. aureus, but not those with saline, developed a hyperdynamic state of septic shock characterized by elevated cardiac output (CO), increased stroke volume (SV) and reduced systemic vascular resistance (SVR), which was followed by a lethal hypodynamic state characterized by rapid decline in mean arterial pressure (MAP), increased central venous pressure, reduced CO, reduced SV, elevated SVR, and reduced left-ventricular ejection fraction, thereby reproducing the hallmark clinical features of human staphylococcal septic shock. In this model, rabbits pretreated with anti-Hla/Luk/ClfA mAb combination had 69% reduction in mortality when compared to those pretreated with c-IgG (P<0.001). USA300-induced acute circulatory failure-defined as >70% decreased in MAP from pre-infection baseline-occurred in only 20% (2/10) of rabbits pretreated with anti-Hla/Luk/ClfA mAb combination compared to 100% (9/9) of those pretreated with c-IgG. Prophylaxis with anti-Hla/Luk/ClfA mAb combination halted progression to lethal hypodynamic shock, as evidenced by significant protection against the development of hyperlactatemia, hypocapnia, hyperkalemia, leukopenia, neutropenia, monocytopenia, lymphopenia, as well as biomarkers associated with acute myocardial injury. These results demonstrate the potential utility of a mechanically ventilated rabbit model that reproduced hallmark clinical features of hyperdynamic septic shock and the translational potential of immunotherapy targeting S. aureus virulence factors for the prevention of staphylococcal septic shock.

Is Maternal Cardiovascular Performance Impaired in Altitude-Associated Fetal Growth Restriction?

Mundo, William, Lilian Toledo-Jaldin, Alexandrea Heath-Freudenthal, Jaime Huayacho, Litzi Lazo-Vega, Alison Larrea-Alvarado, Valquiria Miranda-Garrido, Rodrigo Mizutani, Lorna G. Moore, Any Moreno-Aramayo, Richard Gomez, Patricio Gutierrez, and Colleen G. Julian. Is maternal cardiovascular performance impaired in altitude-associated fetal growth restriction? High Alt Med Biol 00:000-000, 2022. Introduction: The incidence of fetal growth restriction (FGR) is elevated in high-altitude resident populations. This study aims to determine whether maternal central hemodynamics during the last trimester of pregnancy are altered in high-altitude FGR. Methods: In this cross-sectional study of maternal-infant pairs (FGR, n = 27; controls, n = 26) residing in La Paz, Bolivia, maternal heart rate, cardiac output (CO), stroke volume, and systemic vascular resistance (SVR) were assessed using continuous-wave Doppler ultrasound. Transabdominal Doppler ultrasound was used for uterine artery (UtA) resistance indices and fetal measures. Maternal venous soluble fms-like tyrosine kinase-1 (sFlt1) levels were measured. Results: FGR pregnancies had reduced CO, elevated SVR and UtA resistance, fetal brain sparing, and increased maternal sFlt1 versus controls. Maternal SVR was positively associated with UtA resistance and inversely associated with middle cerebral artery resistance and birth weight. Maternal sFlt1 was greater in FGR than controls and positively associated with UtA pulsatility index. Women with elevated sFlt1 levels also tended to have lower CO and higher SVR. Conclusion: Noninvasive assessment of maternal cardiovascular function may be an additional method for detecting high-risk pregnancies at high altitudes, thereby informing the need for increased surveillance and appropriate allocation of resources to minimize adverse outcomes.

The cardiac-fetal-placental unit: fetal umbilical vein flow rate is linked to the maternal cardiac profile in fetal growth restriction

The functional maternal-fetal hemodynamic unit includes fetal umbilical vein flow and maternal peripheral vascular resistance. This study investigated the relationships between maternal and fetal hemodynamics in a population with suspected fetal growth restriction. This was a prospective study of normotensive pregnancies referred to our outpatient clinic for a suspected fetal growth restriction. Maternal hemodynamics measurement was performed, using a noninvasive device (USCOM-1A) and a fetal ultrasound evaluation to assess fetal biometry and velocimetry Doppler parameters. Comparisons among groups were performed with 1-way analysis of variance with Student-Newman-Keuls correction for multiple comparisons and with Kruskal-Wallis test where appropriate. The Spearman rank coefficient was used to assess the correlation between maternal and fetal hemodynamics. Pregnancies were observed until delivery. A total of 182 normotensive pregnancies were included. After the evaluation, 54 fetuses were classified as growth restricted, 42 as small for gestational age, and 86 as adequate for gestational age. The fetus with fetal growth restriction had significantly lower umbilical vein diameter (P<.0001), umbilical vein velocity (P=.02), umbilical vein flow (P<.0001), and umbilical vein flow corrected for fetal weight (P<.01) than adequate-for-gestational-age and small-for-gestational-age fetuses. The maternal hemodynamic profile in fetal growth restriction was characterized by elevated systemic vascular resistance and reduced cardiac output. The umbilical vein diameter was positively correlated to maternal cardiac output (rs=0.261), whereas there was a negative correlation between maternal systemic vascular resistance (rs=-0.338) and maternal potential energy-to-kinetic energy ratio (rs=-0267). The fetal umbilical vein time averaged max velocity was positively correlated to maternal cardiac output (rs=0.189) and maternal inotropy index (rs=0.162), whereas there was a negative correlation with maternal systemic vascular resistance (rs=-0.264) and maternal potential energy-to-kinetic energy ratio (rs=-0.171). The fetal umbilical vein flow and the flow corrected for estimated fetal weight were positively correlated with maternal cardiac output (rs=0.339 and rs=0.297) and maternal inotropy index (rs=0.217 and r=0.336), whereas there was a negative correlation between maternal systemic vascular resistance (rs=-0.461 and rs=-0.409) and maternal potential energy-to-kinetic energy ratio (rs=-0.336 and rs=-0.408). Maternal and fetal hemodynamic parameters were different in the 3 groups of fetuses: fetal growth restriction, small for gestational age, and adequate for gestational age. Maternal hemodynamic parameters were closely and continuously correlated with fetal hemodynamic features. In particular, a maternal hemodynamic profile with high systemic vascular resistance, low cardiac output, reduced inotropism, and hypodynamic circulation was correlated with a reduced umbilical vein flow and increased umbilical artery pulsatility index. The mother, placenta, and fetus should be considered as a single cardiac-fetal-placental unit. The correlations of systemic vascular resistance, cardiac output, and inotropy index with umbilical artery impedance indicate the key role of these 3 parameters in placental vascular tree development. The umbilical vein flow rate and, therefore, the placental perfusion seems to be influenced not only by these three parameters but also by the maternal cardiovascular kinetic energy.

Abstract 17241: The Impact of Overweight and Obesity on End-Organ Function in Fontan Patients

Introduction: Patients with Fontan circulation often develop multiorgan dysfunction. Obesity is a risk factor for systemic complications in the general population, but the impact of obesity in Fontan circulation is unclear. This study investigates the impact of increased BMI on end-organ function in Fontan survivors. Methods: Single center data from patients 13 years and older with Fontan circulation were retrospectively collected from June 2018 to May 2020. Weight at clinic visit was categorized as normal or overweight/obese by WHO BMI-for-age classifications. End-organ function between normal and overweight patients was assessed. The relationship between overweight and measures of end-organ function were modeled via multivariable regression analyses controlling for age, sex, race, heterotaxy, time since Fontan, ventricular function, and atrioventricular valve (AVV) regurgitation. Results: Among 75 patients (median age 18 [15, 26] years), 24 (32%) were overweight or obese. Age, race, duration since Fontan, oxygen saturation, and dominant ventricle did not differ between groups. There were significantly more overweight females (p= 0.02). Overweight patients had significantly lower GFR (p= 0.01), lower predicted peak VO2 (p= 0.02), and higher systemic vascular resistance (SVR) (p= 0.02) than normal weight patients. Duration since Fontan (β= 0.38, p = 0.02) and overweight (β= -0.35, p = 0.03) were independently associated with GFR. Female sex (β= -0.42, p &lt; 0.01) and overweight were independently associated with lower predicted peak VO2. Overweight was independently associated with presence of high SVR (OR = 7.5, p= 0.03). Other tested variables for hepatic (MELD-XI score, liver stiffness), cardiovascular (cardiac index, Fontan pressure, ventricular and AVV function), pulmonary, bone, and hematologic function did not significantly differ between groups. Conclusions: Overweight/obese BMI is common in aging Fontan patients and is significantly associated with worse renal function, exercise capacity, and elevated SVR. These findings suggest a possible relationship between weight, vascular changes, and renal perfusion. Further studies are needed to investigate this mechanism and the impact on Fontan patient outcome.

Sex differences in the prevalence and hemodynamic profiles of hypertensive phenotypes: the HELIUS study

Abstract Background Based on systolic (SBP) and diastolic blood pressure (DBP), patients with hypertension can be classified into different phenotypes. Earlier studies have shown clear sex-differences in the relation between phenotype and cardiovascular outcomes, but large studies addressing underlying sex-differences in hemodynamics are lacking. Purpose To examine sex differences in the prevalence and underlying hemodynamic profile of different hypertensive phenotypes. Methods We used cross-sectional data of 22.112 individuals, 57.8% female, aged between 18–70 years from the HEalthy LIfe in an Urban Setting (HELIUS) study, an ongoing large multi-ethnic prospective cohort study. Based on office BP patients were classified as having: normal (NBP; SBP &amp;lt;140 mmHg and DBP &amp;lt;90 mmHg), isolated systolic hypertension (ISH; SBP ≥140 and DBP &amp;lt;90 mmHg), isolated diastolic hypertension (IDH; SBP &amp;lt;140 and DBP ≥90mmHg) or combined systolic diastolic hypertension (SDH; SBP ≥140 and DBP ≥90 mmHg). We explored sex differences in the prevalence hypertension and the distribution of phenotypes using chi-squared tests after stratification for age (young: &amp;lt;50, old: ≥50 years). In a subgroup of 11.046 participants, continuous non-invasive measurements of cardiac output (CO), stroke volume (SV), systemic vascular resistance (SVR) and mean arterial pressure (MAP) were obtained during 3–5 minutes with finger photoplethysmography in the supine position (Nexfin, Edwards Lifesciences, Irvine, CA, USA). Sex-differences between hemodynamic parameters were assessed using ANOVA tests of linear regression models correcting for age. Results In young participants, the overall prevalence of hypertension was significantly higher in men (19.7%) compared to women (11.4%), with a different distribution of phenotypes (both p&amp;lt;0.001). Amongst young hypertensive participants, SDH was the most prevalent phenotype in both men (46%) and women (52%), ISH had a prevalence of respectively 23% in men and 26% in women. In older subjects, overall prevalence of hypertension was 40.2% in men and 35.9% in women (p&amp;lt;0.001), with a different phenotypical distribution (p&amp;lt;0.001). SDH was the most predominant phenotype in men (50%), whilst ISH was the most prevalent phenotype in women (55%). Both young and old participants with ISH showed an elevated cardiac output, ranging from 0.38–0.47 ml/min compared to normotensives. Older men with SDH and IDH had both elevated SVR and CO, while older women had only an elevation in SVR (Figure 1). Conclusions There are important age-dependent sex-differences in the prevalence of hypertension, which translate into a different hemodynamic profile. The pattern of cardiac output alterations across phenotypes was different between older men and women, suggesting sex differences in the underlying pathophysiology of elevated blood pressure. These findings contribute to a better understanding of the pathogenesis of hypertension and could impact treatment responses. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): The Academic Medical Center (AMC) of Amsterdam and the Public Health Service of Amsterdam (GGD Amsterdam) provided core financial support for HELIUS. The HELIUS study is also funded by research grants of the Dutch Heart Foundation (Hartstichting; grant no. 2010T084), the Netherlands Organization for Health Research and Development (ZonMw; grant no. 200500003), the European Integration Fund (EIF; grant no. 2013EIF013) and the European Union (Seventh Framework Programme, FP-7; grant no. 278901).

Euthyroid sick syndrome in paediatric and adult patients requiring extracorporeal circulatory support and the role of thyroid hormone supplementation: a review.

Non-thyroid disorders may modify thyroid hormone metabolism, resulting in an 'euthyroid sick syndrome'. Studies determining the association of cardiopulmonary bypass to thyroid function showed changes in line with this euthyroid sick syndrome. In some cases, cardiovascular dysfunction after cardiac surgery with cardiopulmonary bypass is comparable to that noticed in hypothyroidism associated with low cardiac output and elevated systemic vascular resistance. Numerous lines of research have proposed that triiodothyronine can behave acutely as a positive inotropic and vasodilator agent. The aim of this review is to present an update on the current literature about in what clinical situations the use of thyroid supplementation during the perioperative period of extracorporeal circulation in the adult and paediatric populations may impact outcome to any appreciable degree. The contribution of thyroid function in patients undergoing a ventricular assist device implantation is additionally reviewed and future study directions are proposed. This is a narrative review, where the search strategy consisted on retrieving the articles through an extensive literature search performed using electronic databases from January 1978 up to September 2019. All controlled trials randomly allocating to perioperative thyroid hormone administration in children and adults undergoing extracorporeal circulation for cardiac surgery were considered. Thyroid hormone supplementation may be recommended particularly in selected paediatric sub-populations. There is currently no firm evidence regarding the benefits of routine use of thyroid hormone administration in cardiac adult patients. Further studies are required to assess the beneficial effect of thyroid hormone on patients with end-stage heart failure supported by ventricular assist devices.

Wave reflections and systemic vascular resistance are stronger determinants of pulse pressure amplification than aortic stiffness in drug-naïve hypertensives

ABSTRACTBackground: Aortic-to-brachial pulse pressure (PP) amplification is a novel biomarker that prognosticates the cardiovascular risk above and beyond central aortic and brachial blood pressure. This phenomenon is modulated by left ventricular contractility and chronotrophy, large-artery stiffness and reflecting properties of microcirculation. However, the relative importance of these parameters as hemodynamic determinant of PP amplification remains elusive.Methods: A total of 88 consecutive drug-naïve hypertensives underwent a non-invasive assessment of central and peripheral hemodynamics via impedance cardiography and pulse wave analysis. Participants were classified into tertiles according to the magnitude of PP amplification. Hemodynamic determinants of low PP amplification were explored in univariate and multivariate regression analysis.Results: Compared with the high tertile, patients within the low PP amplification tertile were older and more commonly female and had lower height, weight and heart rate. Augmentation index (AIx) and systemic vascular resistance index (SVRI) were higher among patients within the low PP amplification tertile, whereas aortic pulse wave velocity (PWV) did not differ among groups. In multivariate analysis, higher AIx (OR: 1.27; 95% CI: 1.09–1.48) and higher SVRI were independently associated with higher odds for low PP amplification, whereas higher heart rate was the only parameter related to lower odds for low PP amplification (OR: 0.84; 95% CI: 0.71–0.99).Conclusion: This study shows that among newly-diagnosed drug-naïve hypertensives, elevated wave reflections and systemic vascular resistance are stronger determinants of PP amplification than aortic stiffness.

Predictors of Hemodynamic Response to Intra-Aortic Balloon Pump Therapy in Patients with Acute Decompensated Heart Failure and Cardiogenic Shock

Introduction There is renewed interest in the utility of the intra-aortic balloon pump (IABP) for short-term and durable support in patients with chronic systolic heart failure (HF) who present with acute decompensation and cardiogenic shock (CS). However, the clinical characteristics of IABP-responders and non-responders remain incompletely defined. We sought to identify predictors of early IABP response to guide optimal use of IABP therapy in this population. Methods We retrospectively analyzed the records of chronic systolic HF patients who presented at our institution between 2011-2018 with acute decompensated HF with hemodynamic evidence of CS and underwent IABP placement. IABP-responder was defined as having an immediate increase in cardiac output (CO) and an immediate decrease in mean pulmonary artery pressure (MPAP) above the median values of the cohort. Logistic regression was used to identify predictors of hemodynamic response. Results During the study period, 218 chronic systolic HF patients underwent IABP insertion for acute decompensation with CS. The mean age was 59.4 ±13.4 years, 79.8% were men, and 38.5% had ischemic cardiomyopathy (ICM). The average hemodynamic response to IABP in the whole cohort was a CO increase of 0.57 ±0.85L/min and a MPAP reduction of 5.1 ±7.6mmHg; IABP-responders had a CO increase of 1.21 ±0.87L/min and a MPAP reduction of 12.1 ±5.9mmHg (figure). Univariable predictors of IABP-response were ICM, presence of severe mitral regurgitation, baseline heart rate, elevated MPAP, and elevated systemic vascular resistance (SVR). Following multivariable logistic regression, independent predictors of IABP-response were elevated baseline SVR (OR 2.05, 95% CI 1.01 - 4.17; p=0.047) and elevated MPAP (OR 2.47, 95% CI 1.23 - 5.00; p=0.01). MPAP reduction decreased the odds of death or need for escalation to another short-term circulatory support device while CO increase did not [OR 0.52 (0.28 - 0.97; p=0.04) vs. 0.83 (0.45 - 1.54; p=0.56)]. Conclusions A subset of chronic systolic HF patients had a robust hemodynamic response to IABP insertion with CO augmentation and MPAP reduction. Elevated baseline SVR and MPAP are predictors of robust response following device insertion. These parameters may be used to identify patients who may respond favorably to IABP counterpulsation therapy.

Disturbed Cardiorespiratory Adaptation in Preeclampsia: Return to Normal Stress Regulation Shortly after Delivery?

Women with pregnancies complicated by preeclampsia appear to be at increased risk of metabolic and vascular diseases in later life. Previous research has also indicated disturbed cardiorespiratory adaptation during pregnancy. The aim of this study was to follow up on the physiological stress response in preeclampsia several weeks postpartum. A standardized laboratory test was used to illustrate potential deviations in the physiological stress responding to mildly stressful events of the kind and intensity in which they regularly occur in further everyday life after pregnancy. Fifteen to seventeen weeks postpartum, 35 women previously affected by preeclampsia (19 mild, 16 severe preeclampsia), 38 women after uncomplicated pregnancies, and 51 age-matched healthy controls were exposed to a self-relevant stressor in a standardized stress-reactivity protocol. Reactivity of blood pressure, heart rate, stroke index, and systemic vascular resistance index as well as baroreceptor sensitivity were analyzed. In addition, the mutual adjustment of blood pressure, heart rate, and respiration, partitioned for influences of the sympathetic and the parasympathetic branches of the autonomic nervous system, were quantified by determining their phase synchronization. Findings indicated moderately elevated blood pressure levels in the nonpathological range, reduced stroke volume, and elevated systemic vascular resistance in women previously affected by preeclampsia. Despite these moderate abnormalities, at the time of testing, women with previous preeclampsia did not differ from the other groups in their physiological response patterns to acute stress. Furthermore, no differences between early, preterm, and term preeclampsia or mild and severe preeclampsia were observed at the time of testing. The findings suggest that the overall cardiovascular responses to moderate stressors return to normal in women who experience a pregnancy with preeclampsia a few weeks after delivery, while the operating point of the arterial baroreflex is readjusted to a higher pressure. Yet, their regulation mechanisms may remain different.

Caring Practices May Save a Life.

Caring Practices May Save a Life.

Adverse influence of bisoprolol on central blood pressure in the upright position: a double-blind placebo-controlled cross-over study

Treatment with beta-blockers is characterized by inferior reduction of central versus peripheral blood pressure. We examined changes in blood pressure, cardiac function, and vascular resistance after 3 weeks of bisoprolol treatment (5 mg/day) during passive head-up tilt in 16 never-treated Caucasian males with grade I–II primary hypertension. A double-blind, randomized, placebo-controlled cross-over design was applied, and hemodynamics were recorded using continuous tonometric pulse wave analysis and whole-body impedance cardiography. Bisoprolol decreased blood pressure in the aorta (~8/10 mmHg, p ≤ 0.032) and radial artery (~10/9 mmHg, p ≤ 0.037), but upright aortic systolic blood pressure was not significantly reduced (p = 0.085). Bisoprolol reduced heart rate and left cardiac work, and increased subendocardial viability index in supine and upright positions (p ≤ 0.044 for all). Bisoprolol increased stroke volume in the supine (~11 ml, p = 0.02) but not in the upright position, while only upright (~1 l/min, p = 0.007) but not supine cardiac output was reduced. Upright elevation in systemic vascular resistance was increased 2.7-fold (p = 0.002), while upright pulse pressure amplification was decreased by ~20% (p = 0.002) after bisoprolol. Aortic augmentation index, augmentation pressure, and pulse pressure were not changed in the supine position but were increased in the upright position (from 9% to 17%, 3–6 mmHg, and 30–34 mmHg, respectively, p ≤ 0.016 for all). In conclusion, although bisoprolol treatment reduced peripheral blood pressure, central systolic blood pressure in the upright position was not decreased. Importantly, the harmful influences of bisoprolol on central pulse pressure and pressure wave reflection were manifested in the upright position.

Non-invasive characterization of hemodynamics in adult out-of-hospital cardiac arrest patients soon after return of spontaneous circulation

BackgroundLittle is known about hemodynamics in adult, out-of-hospital (OHCA) patients following return of spontaneous circulation (ROSC). A 1994 study when “high-dose epinephrine” use was common showed consistently elevated systemic vascular resistance (SVR) lasting ≥6 h in 49 adult patients after return of spontaneous circulation (ROSC). Study aimTo characterize hemodynamic abnormalities in adult OHCA patients soon after ROSC. Our hypothesis was that, unlike the consistently high SVR values reported when “high-dose” epinephrine was in common use, there would be a more heterogenous distribution of SVR values using current adrenergic therapy. MethodsWe included adult, OHCA patients transported by paramedics to the Emergency Department (ED) post-ROSC. Children, prisoners, pregnant women, and those with ongoing CPR or arrest due to traumatic injury were excluded. Hemodynamics were recorded non-invasively as soon as feasible after ED arrival but were not used to influence therapy, which was guided by clinical judgment of treating ED physicians. ResultsHemodynamics were recorded on 30 patients 20 [16,25] minutes after ED arrival: 50% had a normal SVR, 30% had a high SVR, and 20% had a low SVR. There was no difference in survival to admission among groups, although there was a difference among groups in survival to discharge. Comparing the low SVR group vs the combined normal and high group revealed a trend for fewer 0/6 (0%) low vs. 10/24 (42%) normal or high SVR patients surviving to hospital discharge (p = .053). ConclusionA heterogeneous range of hemodynamic states exist post-ROSC rather than consistent vasoconstriction. Adequately powered, randomized clinical trials will be needed to determine whether noninvasively-derived, hemodynamic-directed therapy can play a role in improving neurologically-intact survival following OHCA in adults.

Exercise Training Attenuates Sympathetic Activity and Improves Morphometry of Splenic Arterioles in Spontaneously Hipertensive Rats.

BackgroundAlterations in the structure of resistance vessels contribute to elevated systemic vascular resistance in hypertension and are linked to sympathetic hyperactivity and related lesions in target organs.ObjectiveTo assess the effects of exercise training on hemodynamic and autonomic parameters, as well as splenic arteriolar damages in male Wistar Kyoto (WKY) and Spontaneously Hypertensive Rats (SHR).MethodsNormotensive sedentary (WKYS) and trained (WKYT) rats, and hypertensive sedentary (SHRS) and trained (SHRT) rats were included in this study. After 9 weeks of experimental protocol (swimming training or sedentary control), arterial pressure (AP) and heart rate (HR) were recorded in freely moving rats. We assessed the autonomic control of the heart by sympathetic and vagal autonomic blockade. Morphometric analyses of arterioles were performed in spleen tissues. The statistical significance level was set at p < 0.05.ResultsResting bradycardia was observed in both trained groups (WKYT: 328.0 ± 7.3 bpm; SHRT: 337.0 ± 5.2 bpm) compared with their respective sedentary groups (WKYS: 353.2 ± 8.5 bpm; SHRS: 412.1 ± 10.4 bpm; p < 0.001). Exercise training attenuated mean AP only in SHRT (125.9 ± 6.2 mmHg) vs. SHRS (182.5 ± 4.2 mmHg, p < 0.001). The WKYT showed a higher vagal effect (∆HR: 79.0 ± 2.3 bpm) compared with WKYS (∆HR: 67.4 ± 1.7 bpm; p < 0.05). Chronic exercise decreased sympathetic effects on SHRT (∆HR: -62.8 ± 2.8 bpm) in comparison with SHRS (∆HR: -99.8 ± 9.2 bpm; p = 0.005). The wall thickness of splenic arterioles in SHR was reduced by training (332.1 ± 16.0 µm2 in SHRT vs. 502.7 ± 36.3 µm2 in SHRS; p < 0.05).ConclusionsExercise training attenuates sympathetic activity and AP in SHR, which may be contributing to the morphological improvement of the splenic arterioles.

Patients with hypertensive responses to exercise or dobutamine stress testing differ in resting hypertensive phenotype

Little is known of the importance of echocardiographic measures of resting systemic vascular resistance (SVR), cardiac output, and diastolic function in the development of a hypertensive response during dobutamine stress echocardiography. We performed a retrospective review of 325 subjects who underwent stress echocardiography and a resting echocardiogram on the same day. Logistical regressions were performed to determine associations between hypertensive response to each type of stress test and clinical and hemodynamic measurements obtained by transthoracic echocardiography. Patients with a hypertensive response to dobutamine or exercise stress modalities had Stage 1 hypertension. Those with a hypertensive response to dobutamine had a significantly elevated SVR and a lower cardiac output compared to those with a hypertensive response to exercise or a nonhypertensive response to dobutamine. An SVR ≥2000 dynes × sec/cm5 showed excellent discrimination between patients who did and did not have a hypertensive response to dobutamine (c = 0.80). A hypertensive response to both stress modalities showed an association with measures of diastolic dysfunction. The hemodynamic and echocardiographic phenotypes of individuals with a hypertensive response to exercise differ from those with a hypertensive response to dobutamine. Further work is necessary to understand and guide antihypertensive therapy when a hypertensive response to stress testing is discovered and to inform choice of stress modality when resting hypertension is present.

Voluntary liquorice ingestion increases blood pressure via increased volume load, elevated peripheral arterial resistance, and decreased aortic compliance

We investigated the haemodynamic effects of two-week liquorice exposure (glycyrrhizin dose 290–370 mg/day) in 22 healthy volunteers during orthostatic challenge. Haemodynamics were recorded during passive 10-minute head-up tilt using radial pulse wave analysis, whole-body impedance cardiography, and spectral analysis of heart rate variability. Thirty age-matched healthy subjects served as controls. Liquorice ingestion elevated radial systolic (p < 0.001) and diastolic (p = 0.018) blood pressure and systemic vascular resistance (p = 0.037). During orthostatic challenge, heart rate increased less after the liquorice versus control diet (p = 0.003) and low frequency power of heart rate variability decreased within the liquorice group (p = 0.034). Liquorice intake increased central pulse pressure (p < 0.001) and augmentation index (p = 0.002) supine and upright, but in the upright position the elevation of augmentation index was accentuated (p = 0.007). Liquorice diet also increased extracellular fluid volume (p = 0.024) and aortic to popliteal pulse wave velocity (p = 0.027), and aortic characteristic impedance in the upright position (p = 0.002). To conclude, in addition to increased extracellular fluid volume and large arterial stiffness, two weeks of liquorice ingestion elevated systemic vascular resistance and augmentation index. Measurements performed at rest may underestimate the haemodynamic effects of liquorice ingestion, as enhanced central wave reflection and reduced chronotropic response were especially observed in the upright position.

Myocardial and haemodynamic responses to two fluid regimens in African children with severe malnutrition and hypovolaemic shock (AFRIM study)

BackgroundFluid therapy in severely malnourished children is hypothesized to be deleterious owing to compromised cardiac function. We evaluated World Health Organization (WHO) fluid resuscitation guidelines for hypovolaemic shock using myocardial and haemodynamic function and safety endpoints.MethodsA prospective observational study of two sequential fluid management strategies was conducted at two East African hospitals. Eligible participants were severely malnourished children, aged 6–60 months, with hypovolaemic shock secondary to gastroenteritis. Group 1 received up to two boluses of 15 ml/kg/h of Ringer’s lactate (RL) prior to rehydration as per WHO guidelines. Group 2 received rehydration only (10 ml/kg/h of RL) up to a maximum of 5 h. Comprehensive clinical, haemodynamic and echocardiographic data were collected from admission to day 28.ResultsTwenty children were enrolled (11 in group 1 and 9 in group 2), including 15 children (75%) with kwashiorkor, 8 (40%) with elevated brain natriuretic peptide >300 pg/ml, and 9 (45%) with markedly elevated median systemic vascular resistance index (SVRI) >1600 dscm-5/m2 indicative of severe hypovolaemia. Echocardiographic evidence of fluid-responsiveness (FR) was heterogeneous in group 1, with both increased and decreased stroke volume and myocardial fractional shortening. In group 2, these variables were more homogenous and typical of FR. Median SVRI marginally decreased post fluid administration (both groups) but remained high at 24 h. Mortality at 48 h and to day 28, respectively, was 36% (4 deaths) and 81.8% (9 deaths) in group 1 and 44% (4 deaths) and 55.6% (5 deaths) in group 2. We observed no pulmonary oedema or congestive cardiac failure on or during admission; most deaths were unrelated to fluid interventions or echocardiographic findings of response to fluids.ConclusionBaseline and cardiac response to fluid resuscitation do not indicate an effect of compromised cardiac function on response to fluid loading or that fluid overload is common in severely malnourished children with hypovolaemic shock. Endocrine response to shock and persistently high SVRI post fluid-therapy resuscitation may indicate a need for further research investigating enhanced fluid volumes to adequately correct volume deficit. The adverse outcomes are concerning, but appear to be unrelated to immediate fluid management.

Impact of mild orthostatic stress on aortic-cerebral hemodynamic transmission: insight from the frequency domain.

High cerebral pressure and flow fluctuations could be a risk for future cerebrovascular disease. This study aims to determine whether acute systemic vasoconstriction affects the dynamic pulsatile hemodynamic transmission from the aorta to the brain. We applied a stepwise lower body negative pressure (LBNP) (-10, -20, and -30 mmHg) in 15 young men to induce systemic vasoconstriction. To elucidate the dynamic relationship between the changes in aortic pressure (AoP; estimated from the radial arterial pressure waveforms) and the cerebral blood flow velocity (CBFV) at the middle cerebral artery (via a transcranial Doppler), frequency-domain analysis characterized the beat-to-beat slow oscillation (0.02-0.30 Hz) and the intra-beat rapid change (0.78-9.69 Hz). The systemic vascular resistance gradually and significantly increased throughout the LBNP protocol. In the low-frequency range (LF: 0.07-0.20 Hz) of a slow oscillation, the normalized transfer function gain of the steady-state component (between mean AoP and mean CBFV) remained unchanged, whereas that of the pulsatile component (between pulsatile AoP and pulsatile CBFV) was significantly augmented during -20 and -30 mmHg of LBNP (+28.8% and +32.4% vs. baseline). Furthermore, the relative change in the normalized transfer function gain of the pulsatile component at the LF range correlated with the corresponding change in systemic vascular resistance (r = 0.41, P = 0.005). Regarding the intra-beat analysis, the normalized transfer function gain from AoP to CBFV was not significantly affected by the LBNP stimulation (P = 0.77). Our findings suggest that systemic vasoconstriction deteriorates the dampening effect on the pulsatile hemodynamics toward the brain, particularly in slow oscillations (e.g., 0.07-0.20 Hz).NEW & NOTEWORTHY We characterized the pulsatile hemodynamic transmission from the heart to the brain by frequency-domain analysis. The low-frequency transmission was augmented with a mild LBNP stimulation partly due to the elevated systemic vascular resistance. A systemic vasoconstriction deteriorates the dampening effect on slow oscillations of pulsatile hemodynamics toward the brain.

Role of VA ECMO in septic shock: Does it work?

The use of mechanical circulatory assistance remains controversial during refractory septic shock in adults. 1 However, a profound myocardial dysfunction can occur during bacterial septic shock. 2–4 In this context, extracorporeal membrane oxygenation (ECMO) is highly effective as salvage therapy for children with refractory septic shock. 5,6 We reported the largest cohort of adults who received VA-ECMO for refractory cardiovascular dysfunction in the context of severe bacterial septic shock. 5 Despite multiorgan failure at ECMO initiation and simplified acute physiology score (SAPS) 3-predicted mortality of 79%, >70% of these patients survived with complete recovery of cardiac function. The hemodynamic profile we describe herein (low cardiac index, elevated filling pressure, profound myocardial depression, and elevated systemic vascular resistance) is certainly a rare entity in the spectrum of septic shock, which resembles that of the classic paradigm of cardiogenic shock. In this setting, the infusion o...

The Fontan Operation is Not the End of the Road.

The purpose of essay is to increase the awareness on what patients, families and those involved in the treatment and follow-up can face in the long run regarding the survivors of the Fontan operation (FO) and to provide some clues to diminish the deleterious effects of the single ventricle (SV) physiology. Although a significant number of patients survive and are initially asymptomatic, most probably due to adaptation to their limitations, an active approach without being pessimistic is needed in order to prevent problems and thereby improve the long-term prognosis of these patients. When William Harvey described the circulation he stated: Those who believe that one ventricle can drive blood full of spirit into the body and the lungs likewise, are heretics. They forget that nature, being divine, never gave a heart to any where there was no need. When Fontan and Baudet published their procedure they advised us that this procedure is not an anatomical correction, which would require the creation of a right ventricle, but a way of physiological pulmonary blood flow restoration, with suppression of right and left blood flow mixing.1 They also described the Ten commandments, a list of precise recommendations regarding the indications for surgery.2 Some of the problems that we see today are the result of not following their guidelines. Although they clearly defined the main purpose of procedure, they could not anticipate the long-term implications of improvement. More than forty years later, we are witnessing the consequences of not having a sub-pulmonary ventricle. Although clinical experience shows that to survive we do not need a pumping chamber to drive blood into the lungs, the non-pulsatile flow of both vena cava directly connected to the pulmonary circulation results in the following unintended consequences: 1) elevated central venous pressure, and 2) suboptimal cardiac output, relative to the normal two-ventricle state due to: a) impaired chronotropic response to exercise; b) decreased capability to transport a normal blood volume across the pulmonary vascular bed, resulting in reduced ventricular filling and low stroke volume; c) inability to adequately increase stroke volume during periods of increased demand; and, d) elevated systemic vascular resistance with deprived tissue perfusion and anaerobic metabolism.