Rise In Cardiac Output Research Articles

Adrenoceptors and Hypertension.

Hypertension is a very prevalent condition associated with high mortality and morbidity, secondary to changes resulting in blood vessels and resultant end-organ damage. Haemodynamic changes, including an initial rise in cardiac output followed by an increase in total peripheral resistance, denote the early changes associated with borderline or stage 1 hypertension, especially in young men. Increased sodium reabsorption leading to kidney damage is another mechanism proposed as one of the initial triggers for essential hypertension. The underlying pathophysiological mechanisms include catecholamine-induced α1- and ß1-adrenoceptor stimulation, and renin-angiotensin-aldosterone system activation leading to endothelial dysfunction which is believed to lead to persistent blood pressure elevation.α1 blockers, α2 agonists, and ß blockers were among the first oral anti-hypertensives. They are no longer first-line therapy after outcome trials did not demonstrate any benefits over and above other agents, despite similar blood pressure reductions. Angiotensin-converting enzyme inhibitors(or angiotensin receptor blockers), calcium channel blockers, and thiazide-like diuretics are now considered the first line of therapy, although adrenoceptor agents still have a role as second- or third-line therapy. The chapter also highlights hypertension in specific medical conditions such as pregnancy, phaeochromocytoma, hyperthyroidism, portal hypertension, pulmonary arterial hypertension, and ocular hypertension, to provide an overview for clinicians and researchers interested in the role of adrenoceptors in the pathophysiology and management of hypertension.

The Elusive Hypertrophy of the Python Heart.

The Burmese python, one of the world's largest snakes, has reached celebrity status for its dramatic physiological responses associated with digestion of enormous meals. The meals elicit a rapid gain of mass and function of most visceral organs, particularly the small intestine. There is also a manyfold elevation of oxygen consumption that demands the heart to deliver more oxygen. It therefore made intuitive sense when it was reported that the postprandial response entailed a 40% growth of heart mass that could accommodate a rise in stroke volume. Many studies, however, have not been able to reproduce the 40% growth of the heart. We collated published values on postprandial heart mass in pythons, which include several instances of no change in heart mass. On average, the heart mass is only 15% greater. The changes in heart mass did not correlate to the mass gain of the small intestine or peak oxygen consumption. Hemodynamic studies show that the rise in cardiac output does not require increased heart mass but can be fully explained by augmented cardiac filling and postprandial tachycardia. Under the assumption that hypertrophy is a contingent phenomenon, more recent experiments have employed two interventions such as feeding with a concomitant reduction in hematocrit. The results suggest that the postprandial response of the heart can be enhanced, but the 40% hypertrophy of the python heart remains elusive.

Comparison of Cardiac Indices Using Two Different Concentrations of Topical Adrenaline during Endoscopic Transsphenoidal Pituitary Surgery: A Prospective Randomized Observational Study.

Introduction Adrenaline-soaked wicks are often employed to decongest nasal mucosa during transsphenoidal pituitary surgeries to ensure proper hemostasis and visibility of the operating field. Considerable debate exists regarding the optimum concentration of adrenaline that strikes a balance between hemostasis as well as the hemodynamic side effects of adrenaline. This study assessed cardiac indices like cardiac output and cardiac index using a FloTrac Vigileo cardiac output monitor to compare two different concentrations of adrenaline used for topical instillation. Materials and Methods 60 adult patients undergoing transsphenoidal pituitary surgery were randomly assigned to receive cotton wicks soaked in adrenaline solution (either 1:100,000 or 1:200,000) for nasal decongestion. Following a standardized anesthetic regime, a FloTrac Vigileo cardiac output monitor was attached with the invasive arterial line for precise monitoring and recording of cardiac indices (cardiac output and cardiac index). Additionally, quality of surgical field (as reported by the operating surgeon) blood loss, incidences of adverse hemodynamic events, and rescue drug usage were recorded. Results No difference in cardiac outputs and cardiac indexes of the patients was observed during baseline to 55 minutes and at 80 minutes and onward, whereas difference rose to statistical significance at the time points of 60 minutes and 70 minutes ( p < 0.05). Other parameters like stroke volume, stroke volume variation, and hemodynamic parameters were similar. Quality of the surgical fields (as reported by the surgeon), intraoperative bleeding, incidences of adverse effects, and frequency of rescue drugs usage were similar. Conclusion Instillation of 1:100,000 dilution of adrenaline solution compared with 1:200,000 for nasal decongestion is associated with significant rise in cardiac output and cardiac index at 60 and 70 minutes of the surgery with similar blood loss and hemodynamic variables. Therefore, the lower concentration of adrenaline can be recommended for usage during transsphenoidal pituitary surgeries.

#4606 INNOVATIVE METHOD TO EVALUATE MATURATION OF NEWLY CREATED ARTERIO-VENOUS FISTULAS: INSIGHTS FROM A QUALITY IMPROVEMENT PROJECT

Abstract Background and Aims Recently, we introduced central-venous oxygen saturation (ScvO2) and estimated upper-body blood flow (eUBBF) to monitor the maturation of newly created arterio-venous fistulas (AVF) in hemodialysis (HD) patients [1]. The approach was implemented in a clinical quality improvement project (QIP). Method The QIP involved two Renal Research Institute dialysis centers in New York City that use the Crit-Line monitor (CLM, Fresenius Medical Care, Waltham, MA, USA) as part of the standard of care. CLM measures automatically and non-invasively hematocrit and oxygen saturation (i.e., ScvO2 in patients with central venous catheter as vascular access). eUBBF was computed as described previously [1]. Patients with a with a newly created AVF were included, irrespective of their HD vintage. The QIP team comprised a registered nurse per clinic, two research physicians, and two data analysts. The team met weekly to assess the AVF maturation progress based on eUBBF and ScvO2 data that were displayed on a specific dashboard. Successful AVF maturation is typically accompanied by a rise in cardiac output and eUBBF that starts immediately after AVF creation. However, it is unknown what degree of eUBBF increase indicates a subsequently successful AVF maturation. To identify predictive eUBBF thresholds, we correlated eUBBF changes with the progress of AVF maturation in the six weeks following AVF creation. We defined maturation as unsuccessful when the newly created AVF required an intervention (e.g., angioplasty) or was abandoned. Results We studied 39 patients (age 56 ±18 years; 25 males). Twenty-eight of them were incident patients. Two patients had a second AVF created. In 15 patients AVF maturation was unsuccessful. In these patients, eUBBF increased to an average of 119.2% (SD 35.2) compared to pre-AFV creation. In patients with successful AFV maturation (N = 24), eUBBF increased to an average of 153.7% (SD 31.6) (Figure 1). The difference between the groups is 34.4 percentage points (95% CI: 12.4 to 56.4; p = 0.003). Using eUBBF as a diagnostic measure to discriminate successful vs. failed AVF maturation, an area under the receiver operating characteristics curve of 0.824 (95% CI: 0.673 to 0.925; p&amp;lt;0.0001) was obtained. An eUBBF increase of 25% had a sensitivity of 59% and a specificity of 92% to predict AVF maturation outcomes. Conclusion Computation of eUBBF provides a simple and non-invasive means to track AVF maturation and predict its outcomes.

Abstract 13228: Cannabis Inhalation Reduces Muscle Sympathetic Nerve Activity in Humans

Introduction: Despite widespread use, the neuro-cardiovascular responses associated with cannabis use remain incompletely understood. Acute increases in heart rate, which are abolished under beta-adrenoreceptor blockade, suggest cannabis increases cardiac sympathetic activity; however, its effects on peripheral sympathetic outflow have not been measured. The objective of this work was to quantify direct recordings of efferent post-ganglionic muscle sympathetic nerve activity (MSNA) following cannabis inhalation. Hypothesis: MSNA would be increased following cannabis inhalation. Methods: Blood pressure (BP), heart rate, and MSNA measured from the fibular nerve, were recorded in seventeen young, healthy participants (22±3y: 8F) for a 10-minute epoch before and after inhalation of aerosolized dry cannabis flower (100mg, 13.6% THC). Cardiac output was estimated from finger photoplethysmography (Modelflow method). Arterial baroreflex control of MSNA was quantified using the slope of the weighted linear regression between diastolic BP and MSNA. Results: Mean BP (79±7 vs. 84±8mmHg), heart rate (61±7 vs. 81±14bpm), cardiac output (4.8±1.1 vs. 6.8±2.5L/min), and total vascular conductance (50±11 vs. 71±26mL/min/mmHg) were increased, while MSNA burst frequency (17±7 vs. 8±6bursts/min), incidence (29±11 vs. 11±9bursts/100hb), and amplitude (38.6±6.4% vs. 23.8±8.3%), and sympathetic baroreflex sensitivity (-3.9±1.8 vs. -1.5±1.5bursts/100hb/mmHg) were decreased following cannabis inhalation (all P &lt;0.01). The rise in cardiac output was negatively associated with the reduction in MSNA burst frequency (r 2 =0.40; P &lt;0.01). Conclusions: These data demonstrate that MSNA is reduced following acute cannabis inhalation in humans and is mediated, in part, through a baroreflex mechanism.

Cerebral and systemic hemodynamic effect of recurring seizures

The increase in neuronal activity induced by a single seizure is supported by a rise in the cerebral blood flow and tissue oxygenation, a mechanism called neurovascular coupling (NVC). Whether cerebral and systemic hemodynamics are able to match neuronal activity during recurring seizures is unclear, as data from rodent models are at odds with human studies. In order to clarify this issue, we used an invasive brain and systemic monitoring to study the effects of chemically induced non-convulsive seizures in sheep. Despite an increase in neuronal activity as seizures repeat (Spearman’s ρ coefficient 0.31, P < 0.001), ictal variations of cerebral blood flow remained stable while it progressively increased in the inter-ictal intervals (ρ = 0.06, P = 0.44 and ρ = 0.22; P = 0.008). We also observed a progressive reduction in the inter-ictal brain tissue oxygenation (ρ = − 0.18; P = 0.04), suggesting that NVC was unable to compensate for the metabolic demand of these closely repeating seizures. At the systemic level, there was a progressive reduction in blood pressure and a progressive rise in cardiac output (ρ = − 0.22; P = 0.01 and ρ = 0.22; P = 0.01, respectively), suggesting seizure-induced autonomic dysfunction.

Effects of aerospace environments on the cardiovascular system.

Certain physical and physiological changes occur in the atmospheric levels where flight and space activities take place. Air pressure decreases with increasing altitude and the partial pres¬sure of O2 decreases in parallel with the atmospheric pressure drop and creates hypoxia in the flight crew and in the passen¬gers. In case of acute hypobaric hypoxia, blood is redistributed to the brain and the heart, whereas blood supply to internal organs, such as kidney and skin is reduced. Peripheral cyanosis can be observed on the fingertips and the lips during hypoxia-induced blood redistribution. Tachycardia develops, but the stroke volume does not change. The coronary blood flow increases in parallel with the rise of cardiac output; however, the presence of severe hypoxia leads to myocardial depression. Coronary reflex vasoconstriction is followed by cardiac arrest. Another important pathology caused by low pressure is decompression sickness. In this disease, immediate reduction of the environmental pressure leads to the dissolved nitrogen transforms into gas, and nitrogen bubbles form in the tissue and in the blood. These bubbles interfere the perfusion of the blood and cause ischemia. Symptoms and signs of cardiac decompression sicknesses are dyspnea, tachypnea, chest pain, cough, hemoptysis, cyanosis, retrosternal discomfort, and rarely, shock. Air embolism of coronary vessels manifests as rhythm disturbances, myocardial infarction, and circulatory collapse. The physical forces that occur because of aircraft move¬ment and affect both the pilot and the aircraft, are called acceleration (G) forces. The basic physical effect of G forces is weight increments and motion restriction. During high +Gz, blood pressure decreases in the brain and increases in the lower extremities. Blood forced to move into the lower parts of the body and lower extremities. Thus, brain perfusion cannot be achieved, and loss of consciousness occurs at approximately +4 Gz acceleration levels. Earth also applies an acceleration force to the objects on or around the world. Therefore, gravitational force is also applied to orbiting spacecraft by Earth. The centrifugal force and the gravitational force are in an equilibrium, weightlessness is created inside the orbiting spacecraft, and this is called microgravity. Blood redistributed to the neck and head veins, and astronauts feel nasal fullness, and bulging around the eyes during space missions. As the time spent in the space progresses, a 22% decrease in plasma volume is observed in the cardiovascular system within 1 week owing to increased venous return, and this causes a temporary hemoconcentration. After staying one week in space, cardiac output increases by 22% whereas peripheral resistance decreases by 14%. Rhythm disturbances are also seen during activities performed in space is and thought to be caused by electrolyte imbalance or stress. There is an increasing demand for high altitude and space travel nowadays. These trips cause several physical and physiological effects on both passenger and flight crew. Therefore, it is necessary to take precautionary measures to carry out these activities safely.

Potential role of the corpus luteum in maternal cardiovascular adaptation to pregnancy and preeclampsia risk

Studies in the gravid rat model revealed a key role for the corpus luteal hormone, relaxin, in the maternal circulatory changes of early pregnancy epitomized by profound systemic vasodilation and increased arterial compliance. To determine whether the corpus luteum may play a similar role in human pregnancy, women who conceived by invitro fertilization were studied. Implementation of artificial (programmed) cycles for embryo transfers, which precluded the formation of a corpus luteum, was associated with notable attenuation of the gestational rise in cardiac output and fall in carotid-femoral pulse wave velocity (reflecting impairment of arterial dilation and increased compliance, respectively) and deficiencies in other cardiovascular changes normally observed during the first trimester. Cardiac output and carotid-femoral pulse wave velocity were restored after the first trimester of pregnancy, consistent with rescue by placental vasodilators, such as placental growth factor. In addition, a potential role of corpus luteal factors in reducing the risk of developing preeclampsia was hypothesized. In most single and multiple center, prospective and retrospective cohort (and registry) studies, the risk of developing preeclampsia and preeclampsia with severe features was increased specifically in women undergoing autologous frozen embryo transfer in artificial cycles without the formation of a corpus luteum relative to natural, modified natural, stimulated, or controlled ovarian stimulation cycles and spontaneous pregnancies-all associated with the formation of at least 1 corpus luteum. Taken together, these observational studies are sufficiently compelling to warrant randomized clinical trials comparing preeclampsia risk in autologous frozen embryo transfer in natural vs artificial cycles. Impaired endometrial function because of suboptimal hormonal administration is an alternative but not mutually exclusive explanation for increased preeclampsia risk in autologous frozen embryo transfer in artificial cycles. Potential mechanisms by which the corpus luteum may reduce the risk of developing preeclampsia and whether autologous frozen embryo transfer in artificial cycles is associated with increased risk of preterm preeclampsia, term preeclampsia, or both are discussed. Last, suggestions for future investigations are noted.

Invasive assessment of fluid therapy in hypotensive patients of postinferior wall myocardial infarction complicated by right ventricular infarction

Background: Management of such patients with inferior wall myocardial infarction (IWMI) complicated by right ventricular myocardial infarction (RVMI) requires volume replacement along with the standard therapy. However, the optimum amount of fluid needed to maintain systolic blood pressure (SBP) ≥90 mmHg in such patients has not been reported yet. This study evaluates the role of graded fluid infusion in improving the hemodynamic parameters in patients of IWMI with RVMI in hypotension or shock and also optimizes the amount of fluid needed to maintain SBP ≥ 90 mmHg. Materials and Methods: In this single-center, prospective observational study, patients with first episode of acute coronary syndrome diagnosed as IWMI complicated by RVMI and SBP &lt;90 mmHg were included. The hemodynamic parameters such as heart rate, SBP, cardiac output, cardiac index, and pulmonary capillary wedge pressure (PCWP) were measured at the baseline and after each 500 ml normal saline over 15 min until SBP ≥ 90 mmHg was attained. The primary objective was to study the change in cardiac output, cardiac index, and PCWP with response to fluid. The amount of fluid needed for ≥ 10 rise in cardiac output and to maintain SBP ≥ 90 mmHg was also evaluated. The secondary objectives were to study the need for inotropic support, complications such as inhospital mortality, acute pulmonary edema, and local site bleeding. Further, the predictors of early responders (&lt;2 L of fluid) were also evaluated. Results: Among all 16 patients, 3 (18.7%) were excluded and the rest received graded fluid therapy. Invasively monitored and graded fluid therapy resulted a significant rise in cardiac output (2.1 ± 0.7 L/min vs. 3.7 ± 0.7 L/min), cardiac index (1.3 ± 0.3 L/min/m2 vs. 2.4 ± 0.76 L/min/m2), and PCWP (8.4 ± 3.0 mmHg vs. 17.6 ± 1.5 mmHg) in comparison to baseline parameters. On an average, 865 ± 462 mL fluid infusion was required for 10% improvement in CO from baseline. However, 2192 ± 560 mL fluid was needed for consistent maintenance of SBP ≥ 90 mmHg. The effect of fluid therapy was not significantly correlated with baseline clinical and hemodynamic parameters. There were no procedure- and therapy-related complications reported during the study. Conclusions: Early response to fluid therapy within 2 L of normal saline occurred independently of baseline hemodynamic parameters. However, more studies with larger number of patients would be needed to confirm the same.

Cardiovascular control during heat stress in older adults: time for an update.

It is generally accepted that older adults display an impaired cardiovascular response to heat stress, and it has been suggested that this impaired response contributes to their increased risk of mortality during extreme heat events. Seminal studies have shown that cutaneous vasodilation, the redistribution of blood flow from visceral organs, and the increase in cardiac output are blunted in older adults during passive heating. The blunted rise of cardiac output was initially attributed to an inability to maintain stroke volume, suggesting that cardiac systolic and/or diastolic function does not adequately respond to the constraints of heat stress in older adults. Recent studies evaluated potential mechanisms underlying these seminal findings and their results challenge some of these initial observations. Notably, stroke volume is maintained during heat exposure in older adults and studies have provided evidence for preserved cardiac systolic and diastolic functions in this population. Nonetheless, a blunted increase in cardiac output during heat exposure remains a consistent observation in older adults, although it is now attributed to a blunted increase in heart rate. Recent studies have also evaluated the possibility that the attenuated capacity of aged skin to vasodilate contributes to a blunted increase in cardiac output during heat stress. The objective of this Mini-Review is to highlight these recent advances and challenge the long-standing view that the control of stroke volume during heat exposure is compromised in older adults. By doing so, our intent is to stimulate future studies to evaluate several unanswered questions in this area of research.

Restrictive cardiac phenotype as primary cause of impaired aerobic capacity in Afro-Caribbean patients with val122ile variant transthyretin amyloid cardiomyopathy

Background: Impaired aerobic capacity in cardiac amyloidosis patients may be related to limited inotropic myocardial reserve and heart rate (HR) response limiting cardiac output rise. This study sought to investigate whether chronotropic incompetence (CI) and blunted HR recovery would be prevalent in patients with mutant transthyretin (ATTRv) cardiomyopathy.Methods and results: Eighteen ATTRv (Val122Ile) patients (72 ± 8-year) and 15 age-matched controls (73 ± 3-year) were prospectively enrolled. Patients' medical records, pulmonary function and cardiopulmonary exercise testing, including non-invasive cardiac hemodynamics and chronotropic response were studied. Compared with age-matched controls, maximal workload (91 ± 8 vs. 65 ± 20 watts) and peak VO2 (19.5 ± 3.0 vs. 14.4 ± 4.1 mL.kg−1.min−1) were lower in ATTRv patients. Despite reaching similar age-predicted maximal HR, ATTRv patients displayed smaller changes in stroke volume (SV) index relative to change in VO2 (49 ± 26 vs. 67 ± 18%). Adequate chronotropic-metabolic index was prevalent in ATTRv patients. HR recovery, as percent decrease in peak HR at 1 and 3-min, was blunded ATTv patients.Conclusions: In Val122Ile ATTRv patients, chronotropic response was appropriate relative to exercise intensity with only few patients displaying CI. HR response to exercise was further characterised by blunted HR recovery in ATTRv patients suggesting lower parasympathetic activity and greater sympathetic stimulation compared with controls.

Percutaneous balloon valvuloplasty of pulmonary valve stenosis: state of the art and future prospects

This study is aimed to delineate readers with an overview of percutaneous balloon pulmonary valvuloplasty (PBPV) of pulmonary valve stenosis (PVS) and highlighting outcome based on influential and recent studies. It has been four decades since Kan et al first introduce PBPV. Since then, PBPV has recognized as a gold standard therapy for PVS of all ages. Nowadays, PBPV is practiced for a broad range of indication such as PVS, PV dysplasia and pulmonary atresia. Typically, PBPV is recommended when gradient across the PV is &gt;50 mmHg. The procedure involves the placement of one or more balloon catheters across the stenotic PV with the guidance of a guidewire; thereafter, inflation of the balloons is done by pressure, thus producing valvotomy. Nowadays, PBPV is done by echocardiographic guidance, but previously, it was done by fluoroscopic guidance. The main disadvantage of fluoroscopy was the radiation injury of patients. The recently recommended balloon/annulus ratio is 1.2 to 1.25. Following the procedure, the dramatic reduction of pressure gradient, free motion of the PV leaflets with less doming, the rise of cardiac output have been noted, whereas complications may occur but are unusual and minimal. Significant predictors of restenosis include balloon/annulus ratio &lt;1.2 and immediate post-PBPV gradient ≥30 mmHg. Only a few percentages of patients needed repeat PBPV. Long-term follow-up results are surprisingly excellent. In conclusion, it is our opinion that PBPV is equally successful in patients of all ages, while worldwide recognized studies prove the safety, feasibility, and effectiveness. However, for early detection of any complication, life-long clinical follow-up is mandatory.

SYNTHETIC CANNABINOIDS: A LESS UNDERSTOOD CAUSE OF ACUTE CORONARY SYNDROME

SESSION TITLE: Monday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM PURPOSE: Current research suggests there is an association between natural cannabinoid use and acute coronary syndrome (ACS). Via an extensive literature review we will describe how synthetic marijuana can cause ACS in patients lacking typical cardiac risk factors. METHODS: Cardiology, critical care, and emergency medicine journals were searched for keywords including marijuana, tetrahydrocannabinol (THC), K2/spice in addition to ACS, myocardial infarction and sudden death. Inclusion criteria were topic relevance, peer review, and recent publication. RESULTS: A Norwegian study revealed THC as the only drug present in six postmortem patients with unexplained sudden death. Another larger study identified a 4.8-fold increase in acute myocardial infarction risk within an hour of marijuana use. Multiple case reports have linked synthetic derivatives, known as K2/spice, with ACS in young patients with no known health issues including three cases of myocardial infarction in teenage boys as well as several ACS events in healthy adults. CONCLUSIONS: An active component of both natural and synthetic marijuana is THC. It blocks parasympathetic pathways via norepinephrine release and is thought to be the cause of most cardiovascular effects. One study found a 6-53% increase in heart rate and a 4-9% rise in cardiac output after smoking marijuana, while another found a 30% increase in cardiac output and a dose-dependent increased heart rate of 20-100%. Both factors can lead to oxygen demand/delivery mismatch, which marijuana exacerbates further by increasing carboxyhemoglobin. THC can also disrupt oxygen delivery via vasospasm of the coronary vessels, increased shear stress of the arterial walls, and by forming a procoagulant state due to increased tissue factor expression in monocytic cells. Cannabinoid receptor type 1 (CB1R) is one of two receptors found abundantly in the central and peripheral nervous systems. When bound by THC, CB1R triggers autonomic responses which directly affect the vascular endothelial and smooth muscles, myocardium, and circulating erythrocytes. A recent study found CB1R leads to p38 and JNK mitogen-activated protein kinase (MAPK) activation. This increases reactive oxygen species (ROS) generation and contributes to endothelial and cardiomyocyte cell dysfunction or death. Synthetic cannabinoids are mixtures of several synthetic CB1R agonists. They can be up to 170-times more potent, leading to severe cardiac outcomes. CLINICAL IMPLICATIONS: More research is needed to fully understand effects of synthetic cannabinoids on the cardiovascular system, as synthetic marijuana may be much more dangerous than natural cannabis. It is paramount for both emergency and critical care physicians to be cognizant of the possible detrimental effects of synthetic marijuana in order to prevent ACS related events in the future. DISCLOSURES: No relevant relationships by Gary Esper, source=Web Response No relevant relationships by Peter Nesbitt, source=Web Response No relevant relationships by Ravi Patel, source=Web Response No relevant relationships by Heidi Storer, source=Web Response No relevant relationships by O'Rell Williams, source=Web Response No relevant relationships by Thijs Wolf, source=Web Response

Low activation threshold of juxtapulmonary capillary (J) receptors of the lung

Respiratory reflexes arising from stimulating juxtapulmonary capillary (J) receptors by increasing doses of phenyl diguanide (PDG) were examined in 18 spontaneously breathing cats. In 60% an immediate and four-fold increase in breathing frequency (fR) was produced by doses as small as 5.1 ± μg/kg (range: 3.5–7.5) thus establishing that a significant increase in fR is produced by J receptors by stimulating them with minimal or threshold doses of PDG. In response to similar minimal doses of PDG J receptor afferent activity increased accompanied by acceleration of breathing rate.The response to supra threshold doses was either an apnoea followed by rapid shallow breathing (rsb) or to an apnoea preceded by rsb or only to rsb. Respiratory excursions counted from high-speed run records of intrapleural pressure revealed that the apnoeic response obtained in some cases was a phase of high-frequency breathing and not its suspension.These findings using a chemical stimulus demonstrate that J receptors, with some variability, have a very low threshold for stimulation resulting in notable respiratory acceleration. Thus their afferent output could increase significantly at low intensities of their physiological stimuli such as rise in cardiac output and incipient pulmonary congestion that are generated with mild exercise, to give rise to augmented breathing which is consequently seen.

A novel prediction of simulated fluid responsiveness by echocardiography assessment of tricuspid annulus tissue velocity with passive leg raising

Background: Fluid responsiveness can be predicted by the effect of passive leg raising on cardiac output. Objectives: This research aimed to compare the changes in cardiac output and the peak systolic velocity values of Tricuspid annulus velocity at the free wall (S’) before and after passive leg raising in healthy volunteers. Methods: The study was approved by ethical commission. The desired sample size was 28, and 57 volunteers were included after they signed informed consent. The first measurements, including vital signs, S’, and cardiac output, were taken with the participants lying supine and were performed in the morning after 12 h fast. The participants were then asked to lie in a semirecumbent position for 3 min. After 3 min, the head of the bed was lowered to the supine position and the participants’ legs were elevated at 45°. Secondary measurements were repeated in this position. The differences between vital signs, cardiac output, and S’ measurements before and after passive leg raising were statistically compared. The level of significance was set as p &lt; 0.05. Results: The mean values of cardiac output and S’ before passive leg raising was 9.59 L/min and 11.57 cm/s, respectively; however, those increased to 11.44 L/min and 13.72 cm/s after passive leg raising. The average increases were 16.17% for cardiac output and 15.67% for S’. The changes of cardiac output and S’ were statistically significant. The changes of vital signs before and after passive leg raising were statistically insignificant. Conclusion: This study has demonstrated the concordance of rise in cardiac output with S’ change by passive leg raising in healthy subjects. Further studies are needed to validate the use of S’ values in critically ill subjects.

The Effect of Maximal Exercise on Echocardiographic Pulmonary to Left Atrial Ratio in 1,000 Patients Undergoing Treadmill Stress Echocardiography

Background: Exercise results in a rise in cardiac output, with proportionally less effect on the pulmonary pressures, owing to reduced vascular resistance. Echocardiography readily estimates cardiac output and right heart pressures non–invasively. The echocardiographic pulmonary to left atrial ratio (ePLAR; tricuspid velocity maximum velocity [TRVmax]/mitral E/e′) is a new measurement for differentiating causes of elevated right heart pressures. The effect on ePLAR with exercise has not yet been evaluated. This study was designed to estimate the effect of exercise on right ventricular systolic pressure (RVSP) and ePLAR.

Role of endothelial nitric oxide in control of peripheral vascular conductance during muscle metaboreflex activation.

The muscle metaboreflex is a powerful pressor reflex induced by the activation of chemically sensitive muscle afferents as a result of metabolite accumulation. During submaximal dynamic exercise, the rise in arterial pressure is primarily due to increases in cardiac output, since there is little systemic vasoconstriction. Indeed, in normal animals, we have often shown a small, but significant, peripheral vasodilation during metaboreflex activation, which is mediated, at least in part, by release of epinephrine and activation of vascular β2-receptors. We tested whether this vasodilation is in part due to increased release of nitric oxide caused by the rise in cardiac output eliciting endothelium-dependent flow-mediated vasodilation. The muscle metaboreflex was activated via graded reductions in hindlimb blood flow during mild exercise with and without nitric oxide synthesis blockade [NG-nitro-l-arginine methyl ester (l-NAME); 5 mg/kg]. We assessed the role of increased cardiac output in mediating peripheral vasodilation via the slope of the relationship between the rise in nonischemic vascular conductance (conductance of all vascular beds excluding hindlimbs) vs. the rise in cardiac output. l-NAME increased mean arterial pressure at rest and during exercise. The metaboreflex-induced increases in mean arterial pressure were unaltered by l-NAME, whereas the increases in cardiac output and nonischemic vascular conductance were attenuated. However, the slope of the relationship between nonischemic vascular conductance and cardiac output was not affected by l-NAME, indicating that the rise in cardiac output did not elicit vasodilation via increased release of nitric oxide. Thus, although nitric oxide is intrinsic to the vascular tonus, endothelial-dependent flow-mediated vasodilation plays little role in the small peripheral vasodilation observed during muscle metaboreflex activation.

Haemodynamic changes during labour: continuous minimally invasive monitoring in 20 healthy parturients

BackgroundThere are few studies on maternal haemodynamic changes during labour. None have used continuous cardiac output monitoring during all labour stages. In this observational study, we monitored haemodynamic variables continuously during the entire course of labour in healthy parturients. MethodsContinuous haemodynamic monitoring with the LiDCOplus technique was performed in 20 healthy parturients during spontaneous labour, vaginal delivery and for 15minutes postpartum. Cardiac output, stroke volume, heart rate, systemic vascular resistance, and systolic arterial pressure were measured longitudinally at baseline (periods between/without contractions) and during contractions in early and late stage 1, stage 2, during delivery, and postpartum, and were analysed with marginal linear models. ResultsTwenty parturients were included. In early stage 1, baseline cardiac output was 6.3L/min (95% CI 5.7 to 6.9). Baseline values were similar across both labour stages and postpartum for all haemodynamic variables. During stage 2 contractions, cardiac output decreased by 32%, stroke volume decreased by 44%, heart rate increased by 52%, systemic vascular resistance increased by 88%, and systolic arterial pressure increased by 36% compared to baseline. During stage 1 contractions, haemodynamic changes were less profound and less uniform than during stage 2. ConclusionProgression of labour had no major effect on haemodynamic baseline values. Haemodynamic stress during contractions was substantial in both labour stages, yet most pronounced during the second stage of labour. The absence of an increase in stroke volume and cardiac output postpartum questions the common belief in an immediate rise in cardiac output after delivery due to autotransfusion from the contracted uterus.

Role of endothelial nitric oxide in control of peripheral vascular conductance during muscle metaboreflex activation

The muscle metaboreflex is a powerful pressor reflex induced by the activation of chemically sensitive muscle afferents as a result of metabolite accumulation. During submaximal dynamic exercise, the rise in arterial pressure is primarily due to increases in cardiac output as there is little systemic vasoconstriction. Indeed, in normal animals we have shown a small, but significant, peripheral vasodilation during metaboreflex activation which is mediated at least in part by release of epinephrine and activation of vascular β2 receptors (Kaur et al., Am. J. Physiol. Heart Circ., 2015). We tested whether this vasodilation is in part due to increased release of nitric oxide caused by the rise in cardiac output eliciting endothelium‐dependent flow‐mediated vasodilation. The muscle metaboreflex was activated via graded reductions in hindlimb blood flow during mild exercise with and without nitric oxide synthesis blockade (L‐nitroarginine methyl ester (L‐NAME); 5mg/kg). We accessed the role of increased cardiac output in mediating peripheral vasodilation via the slope of the relationship between the rise in non‐ischemic vascular conductance (conductance of all vascular beds excluding hindlimbs) vs. the rise in cardiac output. L‐NAME increased mean arterial pressure at rest and during exercise. The metaboreflex‐induced increases in mean arterial pressure were unaltered by L‐NAME; whereas, the increases in cardiac output and non‐ischemic vascular conductance were attenuated. However, the slope of the relationship between non‐ischemic vascular conductance and cardiac output was not affected by L‐NAME indicating that the rise in cardiac output did not elicit vasodilation via increased release of nitric oxide. Thus, although nitric oxide is intrinsic to the vascular tonus, endothelial‐dependent flow‐mediated vasodilation plays little role in the small peripheral vasodilation observed during muscle metaboreflex activation.Support or Funding Information(NIH HL55473)

Comprehensive assessment of the global and regional vascular responses to food ingestion in humans using novel rapid MRI.

Ingestion of food is known to increase mesenteric blood flow. It is not clear whether this increased flow demand is compensated by a rise in cardiac output (CO) alone or by redistribution of blood flow from other organs. We used a new comprehensive imaging method to assess the human cardiovascular response to food ingestion. Following a 12-h fast, blood flow in segments of the aorta and in organ-specific arteries, and ventricular volumes were assessed in 20 healthy adults using MRI at rest and following ingestion of a high-energy liquid meal. Systemic vascular resistance (SVR) fell substantially and CO rose significantly. Blood pressure remained stable. These changes were predominantly driven by a rapid fall in mesenteric vascular resistance, resulting in over four times more intestinal blood flow. Renal vascular resistance also declined but less dramatically. No changes in blood flow to the celiac territory, the brain, or the limbs were observed. In conclusion, this is the first study to fully characterize systemic and regional changes in vascular resistance after food ingestion in humans. Our findings show that the postprandial drop in SVR is fully compensated for by increased CO and not by redistribution of blood from other organs. With the exception of a modest increase in renal blood flow, there was no evidence of altered blood flow to nondigestive organs. The proposed oral food challenge protocol can be applied safely in an MRI environment and may be useful for studying the involvement of the gut in systemic or cardiovascular disease.