Cardiovascular reflex contributions to sympathetic inhibition during low intensity dynamic leg exercise in healthy middle-age.

Aging augments resting muscle sympathetic nerve activity (MSNA) and sympatho-inhibition during mild dynamic 1-leg exercise. To elucidate which reflexes elicit exercise-induced inhibition, we recruited 19 (9 men) healthy volunteers (mean age 56 ± 9 SD years), assessed their peak oxygen uptake (VO2peak ), and, on another day, measured heart rate (HR), blood pressure (BP) and MSNA (microneurography) at rest and during 1-leg cycling (2 min each at 0 load and 30%-40% VO2peak ), 3 times: (1) seated +2 min of postexercise circulatory occlusion (PECO) (elicit muscle metaboreflex); (2) supine (stimulate cardiopulmonary baroreflexes);and (3) seated, breathing 32% oxygen (suppress peripheral chemoreceptor reflex). While seated, MSNA decreased similarly during mild and moderate exercise (p < 0.001) with no increase during PECO (p = 0.44). Supine posture lowered resting MSNA (main effect p = 0.01) BP and HR. MSNA fell further (p = 0.04) along with diastolic BP and HR during mild, not moderate, supine cycling. Hyperoxia attenuated resting (main effect p = 0.01), but not exercise MSNA. In healthy middle-age, the cardiopulmonary baroreflex and arterial chemoreflex modulate resting MSNA, but contrary to previous observations in young subjects, without counter-regulatory offset by the sympatho-excitatory metaboreflex, resulting in an augmented sympatho-inhibitory response to mild dynamic leg exercise.

Emergent catheter ablation for atrial fibrillation in a patient with acute decompensated heart failure on a mechanical haemodynamic support: a case report.

BACKGROUND: Atrial fibrillation (AF) is associated with the exacerbation of heart failure (HF). Although AF ablation has become an established treatment for patients with HF, it is usually an elective procedure. Here, we present a case of acute decompensated heart failure (ADHF) exacerbated by refractory AF, which was successfully treated with emergent AF ablation. CASE SUMMARY: A 53-year-old, obese man with a history of myocardial infarction presented to our hospital. Heart function deteriorated with an ejection fraction of 9.8%, and he was repeatedly hospitalized due to worsening HF. This time, the patient was emergently admitted due to ADHF associated with persistent AF. Atrial fibrillation was refractory to electrical cardioversion. Despite optimized medical support, the patient developed haemodynamic collapse and multiple organ failure. Intra-aortic balloon pump (IABP) and mechanical ventilation were initiated in addition to intravenous catecholamines. Emergent AF ablation was performed. Following pulmonary vein isolation, sinus rhythm was restored and the patient's haemodynamic status dramatically improved. The IABP and mechanical ventilation were withdrawn within a few days, and the catecholamine dose was reduced. After cardiac rehabilitation, the patient was discharged. DISCUSSION: Our case suggests that an emergent AF ablation is feasible and effective even in a patient with severe ADHF. An emergent AF ablation could be a therapeutic option to treat a critically unwell patient who has deteriorated due to a vicious cycle of AF and HF.

Lung-to-finger circulation time can be measured stably with high reproducibility by simple breath holding method in cardiac patients.

Lung to finger circulation time (LFCT) has been used to estimate cardiac function. We developed a new LFCT measurement device using a laser sensor at fingertip. We measured LFCT by measuring time from re-breathing after 20 s of breath hold to the nadir of the difference of transmitted red light and infrared light, which corresponds to percutaneous oxygen saturation. Fifty patients with heart failure were enrolled. The intrasubject stability of the measurement was assessed by the intraclass correlation coefficient (ICC). The ICC calculated from 44 cases was 0.85 (95% confidence interval: 0.77-0.91), which means to have "Excellent reliability." By measuring twice, at least one clear LFCT value was obtained in 89.1% of patients and the overall measurability was 95.7%. We conducted all LFCT measurements safely. High ICCs were obtained even after dividing patients according to age, cardiac index (CI); 0.85 and 0.84 (≥ 75 or < 75 years group, respectively), 0.81 and 0.84 (N = 26, ≥ or < 2.2 L/min/M2). These results show that our new method to measure LFCT is highly stable and feasible for any type of heart failure patients.

Early follow-up at outpatient care after discharge improves long-term heart failure readmission rate and prognosis.

AIMS: It has been reported that congestive heart failure (CHF) readmission has not decreased in the last decade. It is also reported that CHF readmission is likely to occur shortly after discharge. We investigated whether an early follow-up at outpatient care within 2 weeks after discharge affects the long-term readmission rate and prognosis. METHODS AND RESULTS: We reviewed consecutive 1002 patients admitted to our hospital due to CHF. Two-hundred and fifty-nine patients who died in-hospital or were transferred to another hospital or readmitted within 2 weeks were excluded and 743 of discharged patients were analysed. We extracted contributing variables associated with heart failure (HF) readmission and the composite adverse outcome (all cause death or HF readmissions) by univariate and multivariate analysis. Multivariate analysis showed that the early follow-up was independently associated with freedom from HF readmission and the composite outcome. We divided these patients into two groups, with/without early follow-up and performed a propensity score-matching analysis (n = 259 each). HF readmission during 2 year follow-up was significantly less in the early follow-up group [P = 0.02, hazard ratio (HR) = 0.647, 95% confidence interval (CI) = 0.447-0.935] as well as the composite outcome was less in the early follow-up group (P = 0.01, HR = 0.643, 95% CI = 0.456-0.908). Medication adjustments were done in only 33.2% of the patients. Rates of HF readmissions were comparable regardless of whether or not medication adjustment was done at the early follow-up (P = 0.505, HR = 1.208, 95% CI = 0.692-2.106). CONCLUSIONS: The present study demonstrates that an early follow-up approach after discharge in CHF patients may improve the long-term prognosis. These results may not depend on medication adjustment but rather on modifying patient factors early after discharge.

Changes in lung to finger circulation time measured via cardiopulmonary polygraphy in patients with varying types of heart disease.

Cardiopulmonary polygraphy (PG) demonstrates not only parameters for sleep disordered breathing (SDB) but also hemodynamics. We previously developed a software that detects lung to fingertip circulation time (LFCT) derived from PG dataset and reported that those LFCT reflected the cardiac output. The purpose of this study is to investigate how the LFCT changes during clinical course and whether reflects the impact of in-hospital treatment on cardiac function. Consecutive patients (N = 89) who admitted to the cardiovascular division, underwent PG at the early and late phase of admission. Parameters for SDB and LFCT were compared between an acute decompensated heart failure (ADHF) group (n = 51) and non-ADHF group (n = 38). ADHF group was further divided into subgroups: preserved ejection fraction (pEF) (EF > 40%) and reduced EF (rEF) (EF ≤ 40%). Using our original algorithm, we obtained LFCT values from all of the patients, though 29.4% of ADHF and 44.7% of non-ADHF had no or mild SDB. LFCT significantly shortened in the ADHF-rEF group, in contrast to ADHF-pEF group or non-ADHF group (ADHF-rEF group: 26.9 ± 7.6 to 24.2 ± 6.1 s, p = 0.01; ADHF-pEF group: 25.3 ± 7.3 to 25.3 ± 6.9 s, p = 0.98; non-ADHF group: 21.5 ± 5.5 to 21.9 ± 5.0 s, p = 0.65). The respiratory disorder index in the ADHF group improved after treatment, irrespective of EF (pEF: 26.9 ± 16.1 to 15.8 ± 11.9/h, p < 0.01; rEF: 27.0 ± 16.5 to 20.7 ± 13.6/h, p = 0.03). Automatic detection of LFCT was feasible in almost all cardiac patients. LFCT value changed according to the heart failure treatment in ADHF-rEF patients and reflected cardiac function. LFCT might be a useful indicator of effective cardiac disease treatment.

Local temperature control improves the accuracy of cardiac output estimation using lung-to-finger circulation time after breath holding.

As timely measurement of the cardiac index (CI) is one of the key elements in heart failure management, a noninvasive, simple, and inexpensive method of estimating CI is keenly needed. We attempted to develop a new device that can estimate CI from the data of lung-to-finger circulation time (LFCT) obtained after a brief breath hold in the awake state. First, we attempted to estimate CI from the LFCT value by utilizing the correlation between 1/LFCT and CI estimated with MRI. Although we could obtain LFCT from 45 of 53 patients with cardiovascular diseases, we could not find the anticipated relation between 1/LFCT and CI. However, we realized that when we adopted only LFCT from patients with a finger temperature of ≥31°C, we could obtain a consistent and clear correlation with CI (correlation coefficient, r = .81). Thus, we next measured LFCT before and after warming the forearm. We found that LFCT decreased after the local temperature increased (from 27.5 ± 13.6 to 18.4 ± 5.3 s, p < 0.01). The correlation between the inverse of LFCT and CI improved after warming (1/LFCT vs. CI, from r = .69 to r = .82). The final Bland-Altman analysis between the measured and estimated CI values revealed that the bias and precision were -0.05 and 0.37 L min-1  m-2 , respectively, and the percentage error was 34.3%. This study clarified that estimating CI using a simple measurement of LFCT is feasible in most patients and a low fingertip temperature strongly affects the CI-1/LFCT relationship, causing an error that can be corrected by proper local warming.

Blood Oxygen, Sleep Disordered Breathing, and Respiratory Instability in Patients With Chronic Heart Failure　- PROST Subanalysis.

Background: Respiratory stability index (RSI), a semi-quantitative measure of respiratory instability, was found to reflect congestive and other clinical status of acutely decompensated heart failure in the PROST study. Given that the association between RSI and another important factors affecting respiration, such as peripheral oxygen saturation (SpO2), and the influence of oxygen inhalation on this association were undetermined, and that the association between common sleep-disordered breathing (SDB) parameters and RSI was unknown, we performed a subanalysis using PROST data. Methods and Results: Correlation analyses were performed to evaluate the relationships between RSI, SpO2, and other SDB parameters (3% oxygen desaturation index [3%ODI], respiratory disturbance index [RDI]) using Spearman's rank correlation. RSI and overnight mean SpO2 were not significantly correlated either after admission (n=38) or before discharge (n=36; r=0.27, P=0.10 and r=0.05, P=0.76, respectively). This correlation was also not affected by presence or absence of oxygen inhalation. 3%ODI, RDI and RSI were significantly and inversely correlated both after admission and before discharge. Conclusions: RSI and blood oxygen level were not significantly correlated irrespective of oxygen inhalation, while the SDB parameters were significantly correlated, suggesting that RSI reflects lung congestion independently of blood oxygen concentration and, thus, can be a useful indicator of the non-invasive assessment of lung congestion.

Multicenter, Prospective Study on Respiratory Stability During Recovery From Deterioration of Chronic Heart Failure.

BACKGROUND: The respiratory instability frequently observed in advanced heart failure (HF) is likely to mirror the clinical status of worsening HF. The present multicenter study was conducted to examine whether the noble respiratory stability index (RSI), a quantitative measure of respiratory instability, reflects the recovery process from HF decompensation. Methods and Results: Thirty-six of 44 patients hospitalized for worsening HF completed all-night measurements of RSI both at deterioration and recovery phases. Based on the signs, symptoms, and laboratory data during hospitalization, the Central Adjudication Committee identified 22 convalescent patients and 14 patients with less extent of recovery in a blinded manner without any information on RSI or other respiratory variables. The all-night RSI in the convalescent patients was increased from 27.8±18.4 to 34.6±15.8 (P<0.05). There was no significant improvement of RSI, however, in the remaining patients with little clinical improvement. Of the clinical and laboratory variables, on stepwise linear regression modeling, body weight, peripheral edema, and lung congestion were closely related to the RSI of recovered patients and accounted for 56% of the changes in RSI (coefficient of determination, R2=0.56). CONCLUSIONS: All-night RSI, a quantitative measure of respiratory instability, could faithfully reflect congestive signs and clinical status of HF during the recovery process from acute decompensation.

The impact of volume loading-induced low pressure baroreflex activation on arterial baroreflex-controlled sympathetic arterial pressure regulation in normal rats.

Although low pressure baroreflex (LPB) has been shown to elicit various cardiovascular responses, its impact on sympathetic nerve activity (SNA) and arterial baroreflex (ABR) function has not been fully elucidated. The aim of this study was to clarify how volume loading-induced acute LPB activation impacts on SNA and ABR function in normal rats. In 20 anesthetized Sprague-Dawley rats, we isolated bilateral carotid sinuses, controlled carotid sinus pressure (CSP), and measured central venous pressure (CVP), splanchnic SNA, and arterial pressure (AP). We infused blood stepwise (3 mL/kg/step) to activate volume loading-induced LPB. Under the ABR open-loop condition, stepwise volume loading markedly increased SNA by 76.8 ± 21.6% at CVP of 3.6 ± 0.2 mmHg. In contrast, further volume loading suppressed SNA toward the baseline condition. Bilateral vagotomy totally abolished the changes in SNA by volume loading. To assess the impact of LPB on ABR function, we changed CSP stepwise. Low volume loading (CVP = 3.6 ± 0.4 mmHg) significantly shifted the sigmoidal CSP-SNA relationship (central arc) upward from baseline, whereas high volume loading (CVP = 5.4 ± 0.4 mmHg) returned it to the baseline level. Volume loading shifted the linear SNA-AP relationship (peripheral arc) upward without significant changes in slope. In conclusions, volume loading-induced acute LPB activation evoked two-phase changes, an initial increase followed by decline from baseline value, in SNA via resetting of the ABR central arc. LPB may contribute greatly to stabilize AP in response to volume status.

Improved Diastolic Function Is Associated With Higher Cardiac Output in Patients With Heart Failure Irrespective of Left Ventricular Ejection Fraction.

BACKGROUND: Little is known regarding the impact of diastolic function on cardiac output (CO) in patients with heart failure, particularly in patients with lower ejection fraction. This study aimed to evaluate the impact of end-diastolic pressure-volume relationship (EDPVR) on CO and end-diastolic pressure (EDP). METHODS AND RESULTS: We retrospectively analyzed 1840 consecutive patients who underwent heart catheterization. We divided patients into 8 groups according to ejection fraction (EF) (35-45%, 46-55%, 56-65%, and 66-75%) and EDP (>16 or ≤16 mm Hg). We estimated EDPVR from single measurements in the catheterization data set. Then, we replaced EDPVRs of high-EDP groups with those of normal-EDP groups and compared CO before and after EDPVR replacement. Normalized EDPVR significantly increased CO at EDP=10 mm Hg regardless of EF (EF 35-45%, from 4.5±1.6 to 4.9±1.0; EF 46-55%, 4.6±1.3 to 5.1±1.1; EF 56-65%, 4.9±1.5 to 5.2±1.0; EF 66-75%, 4.9±1.5 to 5.2±1.1). Changes in CO were similar across EF groups. CONCLUSIONS: Diastolic function normalization was associated with higher CO irrespective of EF. Diastolic dysfunction plays an important role in determining CO irrespective of EF in heart failure patients.

Marked ST-segment elevation during permanent pacemaker implantation.

Some acute complications are known during permanent pacemaker implantation such as pneumothorax, lead perforation, lead dislodgement, and hemorrhage. ST-segment elevation in electrocardiogram during implantation is rare, but it might indicate critical complication like myocardial ischemia or ventricular perforation. Physicians should pay attention about ST-segment change during pacemaker implantation.

Baroreflex failure increases the risk of pulmonary edema in conscious rats with normal left ventricular function.

In heart failure with preserved ejection fraction (HFpEF), the complex pathogenesis hinders development of effective therapies. Since HFpEF and arteriosclerosis share common risk factors, it is conceivable that stiffened arterial wall in HFpEF impairs baroreflex function. Previous investigations have indicated that the baroreflex regulates intravascular stressed volume and arterial resistance in addition to cardiac contractility and heart rate. We hypothesized that baroreflex dysfunction impairs regulation of left atrial pressure (LAP) and increases the risk of pulmonary edema in freely moving rats. In 15-wk Sprague-Dawley male rats, we conducted sinoaortic denervation (SAD, n = 6) or sham surgery (Sham, n = 9), and telemetrically monitored ambulatory arterial pressure (AP) and LAP. We compared the mean and SD (lability) of AP and LAP between SAD and Sham under normal-salt diet (NS) or high-salt diet (HS). SAD did not increase mean AP but significantly increased AP lability under both NS (P = 0.001) and HS (P = 0.001). SAD did not change mean LAP but significantly increased LAP lability under both NS (SAD: 2.57 ± 0.43 vs. Sham: 1.73 ± 0.30 mmHg, P = 0.01) and HS (4.13 ± 1.18 vs. 2.45 ± 0.33 mmHg, P = 0.02). SAD markedly increased the frequency of high LAP, and SAD with HS prolonged the duration of LAP > 18 mmHg by nearly 20-fold compared with Sham (SAD + HS: 2,831 ± 2,366 vs. Sham + HS: 148 ± 248 s, P = 0.01). We conclude that baroreflex failure impairs volume tolerance and together with salt loading increases the risk of pulmonary edema even in the absence of left ventricular dysfunction. Baroreflex failure may contribute in part to the pathogenesis of HFpEF.

Recurrent paroxysmal atrial fibrillation induced by marked hypoxia during sleep-disordered breathing.

Sleep-disordered breathing (SDB) has a big impact on autonomic nervous activity and thus induces or deteriorates various cardiovascular diseases. We here describe a typical but rarely documented case which clearly indicates a strong link between SDB and cardiovascular disease. A 68-year-old woman complaining of frequent palpitations was referred to our institute. An electrocardiogram (ECG) at a previous clinic had shown atrial fibrillation, although it had already returned to sinus rhythm on arrival at our institute. Her body mass index was 32.5 kg/m2 and she had a history of loud snoring. Simultaneous examinations of Holter ECG monitoring and ambulatory polysomnography (PSG) showed onset of paroxysmal atrial fibrillation following marked oxygen desaturation at midnight. In-hospital PSG revealed severe obstructive sleep apnea. A new device with desaturation triggered ambulatory blood pressure monitoring system performed 1 week later again showed a midnight onset of paroxysmal atrial fibrillation coincided with surge of blood pressure with marked desaturation. Her recurrence of palpitations had obviously decreased by continuous positive airway pressure therapy thereafter. .

Exercise-induced pneumomediastinum.

BACKGROUND: A sudden onset of chest pain, which often reflects a life-threatening disease, requires prompt diagnosis in the emergency department. FINDINGS: A 12-year-old boy presented with sustained chest pain and dyspnea after diving into a swimming pool and was transferred to our emergency department. A chest examination noted a crunching and rasping sound at the precordium, synchronous with the heartbeat. Chest radiography showed lucent streaks and the mediastinal pleura at the left cardiac outline. Additionally, computed tomography showed massive pneumomediastinum surrounding the heart. Thus, he was diagnosed with spontaneous pneumomediastinum. CONCLUSIONS: Spontaneous pneumomediastinum should be considered in the differential diagnosis of chest pain. In addition to medical history-taking, careful physical examination, which can identify the characteristic finding of a friction sound synchronous with the heartbeat (Hamman's sound), will help in the immediate diagnosis of spontaneous pneumomediastinum.

Changes in vascular properties, not ventricular properties, predominantly contribute to baroreflex regulation of arterial pressure.

Baroreflex modulates both the ventricular and vascular properties and stabilizes arterial pressure (AP). However, how changes in those mechanical properties quantitatively impact the dynamic AP regulation remains unknown. We developed a framework of circulatory equilibrium, in which both venous return and cardiac output are expressed as functions of left ventricular (LV) end-systolic elastance (Ees), heart rate (HR), systemic vascular resistance (R), and stressed blood volume (V). We investigated the contribution of each mechanical property using the framework of circulatory equilibrium. In six anesthetized dogs, we vascularly isolated carotid sinuses and randomly changed carotid sinus pressure (CSP), while measuring the LV Ees, aortic flow, right and left atrial pressure, and AP for at least 60 min. We estimated transfer functions from CSP to Ees, HR, R, and V in each dog. We then predicted these parameters in response to changes in CSP from the transfer functions using a data set not used for identifying transfer functions and predicted changes in AP using the equilibrium framework. Predicted APs matched reasonably well with those measured (r2=0.85-0.96, P<0.001). Sensitivity analyses indicated that Ees and HR (ventricular properties) accounted for 14±4 and 4±2%, respectively, whereas R and V (vascular properties) accounted for 32±4 and 39±4%, respectively, of baroreflex-induced AP regulation. We concluded that baroreflex-induced dynamic AP changes can be accurately predicted by the transfer functions from CSP to mechanical properties using our framework of circulatory equilibrium. Changes in the vascular properties, not the ventricular properties, predominantly determine baroreflex-induced AP regulation.

Cardiac phase-targeted dynamic load on left ventricle differentially regulates phase-sensitive gene expressions and pathway activation.

The heart has remarkable capacity to adapt to mechanical load and to dramatically change its phenotype. The mechanism underlying such diverse phenotypic adaptations remains unknown. Since systolic overload induces wall thickening, while diastolic overload induces chamber enlargement, we hypothesized that cardiac phase-sensitive mechanisms govern the adaptation. We inserted a balloon into the left ventricle (LV) of a Langendorff perfused rat heart, and controlled LV volume (LVV) using a high performance servo-pump. We created isolated phasic systolic overload (SO) by isovolumic contraction (peak LV pressure >170mmHg) at unstressed diastolic LVV [end-diastolic pressure (EDP)=0mmHg]. We also created pure phasic diastolic overload (DO) by increasing diastolic LVV until EDP >40mmHg and unloading completely in systole. After 3hours under each condition, the myocardium was analyzed using DNA microarray. Gene expressions under SO and DO conditions were compared against unloaded control condition using gene ontology and pathway analysis (n=4 each). SO upregulated proliferation-related genes, whereas DO upregulated fibrosis-related genes (P<10(-5)). Both SO and DO upregulated genes related functionally to cardiac hypertrophy, although the gene profiles were totally different. Upstream regulators confirmed by Western blot indicated that SO activated extracellular signal-regulated kinase 1/2, c-Jun NH2-terminal kinase, and Ca(2+)/calmodulin-dependent protein kinase II (3.2-, 2.0-, and 4.7-fold versus control, P<0.05, n=5), whereas DO activated p38 (2.9-fold, P<0.01), which was consistent with the downstream gene expressions. In conclusion, pure isolated systolic and diastolic overload permits elucidation of cardiac phase-sensitive gene regulation. The genomic responses indicate that mechanisms governing the cardiac phase-sensitive adaptations are different.

Bionic baroreceptor corrects postural hypotension in rats with impaired baroreceptor.

BACKGROUND: Impairment of the arterial baroreflex causes orthostatic hypotension. Arterial baroreceptor sensitivity degrades with age. Thus, an impaired baroreceptor plays a pivotal role in orthostatic hypotension in most elderly patients. There is no effective treatment for orthostatic hypotension. The aims of this investigation were to develop a bionic baroreceptor (BBR) and to verify whether it corrects postural hypotension. METHODS AND RESULTS: The BBR consists of a pressure sensor, a regulator, and a neurostimulator. In 35 Sprague-Dawley rats, we vascularly and neurally isolated the baroreceptor regions and attached electrodes to the aortic depressor nerve for stimulation. To mimic impaired baroreceptors, we maintained intracarotid sinus pressure at 60 mm Hg during activation of the BBR. Native baroreflex was reproduced by matching intracarotid sinus pressure to the instantaneous pulsatile aortic pressure. The encoding rule for translating intracarotid sinus pressure into stimulation of the aortic depressor nerve was identified by a white noise technique and applied to the regulator. The open-loop arterial pressure response to intracarotid sinus pressure (n=7) and upright tilt-induced changes in arterial pressure (n=7) were compared between native baroreceptor and BBR conditions. The intracarotid sinus pressure-arterial pressure relationships were comparable. Compared with the absence of baroreflex, the BBR corrected tilt-induced hypotension as effectively as under native baroreceptor conditions (native, -39±5 mm Hg; BBR, -41±5 mm Hg; absence, -63±5 mm Hg; P<0.05). CONCLUSIONS: The BBR restores the pressure buffering function. Although this research demonstrated feasibility of the BBR, further research is needed to verify its long-term effect and safety in larger animal models and humans.

Impact of baroreflex on venous return surface.

BACKGROUND: Although Guyton's concept of venous return (VR) revolutionized circulatory physiology, the pulmonary circulation is invisible in its original framework. Since the pulmonary circulation is critical in left heart failure, we characterized the VR as a surface described by right (P(RA)) and left atrial (P(LA)) pressures and demonstrated that the VR surface was capable of representing mechanics of pulmonary as well as systemic circulation. However how baroreflex impacts the VR surface remains unknown. METHODS/RESULTS: In 8 dogs, we isolated the carotid sinuses and replaced both ventricles with pumps. We varied cardiac output, shifted blood distribution between the systemic and pulmonary circulation at carotid sinus pressures (CSP) of 100 or 140 mmHg. The coefficient of determination of the VR surface ranged 0.96-0.99 indicating how flat the surface is. Increasing CSP decreased maximum VR (233 ± 27 vs. 216 ± 33 ml/kg/min, p<0.05), whereas did not change the slopes of VR along P(RA) or P(LA) axes. CONCLUSIONS: Baroreflex parallel shifts the VR surface, thereby stressed volume, without changing its slopes.

Artificial baroreflex system restores volume tolerance in the absence of native baroreflex.

The arterial baroreflex stabilizes arterial pressure by modulating the mechanical properties of cardiovascular system. We previously demonstrated that the baroreflex impairment makes the circulatory system extremely sensitive to volume overload and predisposes to pulmonary edema irrespective of left ventricular systolic function. To overcome the volume intolerance, we developed an artificial baroreflex system by directly stimulating the carotid sinus nerves in response to changes in arterial pressure. The artificial baroreflex system precisely reproduced the native arterial pressure response and restored physiological volume buffering function. We conclude that the artificial baroreflex system would be an attractive tool in preventing pulmonary edema in patients with impaired baroreflex function.