Overview of the 87th Annual Scientific Meeting of the Japanese Circulation Society (JCS2023)　- New Challenge With Next Generation.

The 87thAnnual Meeting of the Japanese Circulation Society (JCS2023) was held in March 2023 in Fukuoka, Japan, marking the first in-person gathering after the COVID-19 pandemic. With the theme of "New Challenge With Next Generation" the conference emphasized the development of future cardiovascular leaders and technologies such as artificial intelligence (AI). Notable sessions included the Mikamo Lecture on heart failure and the Mashimo Lecture on AI in medicine. Various hands-on sessions and participatory events were well received, promoting learning and networking. Post-event surveys showed high satisfaction among participants, with positive feedback on face-to-face interactions and the overall experience. JCS2023, attended by 17,852 participants, concluded successfully, marking a significant milestone in post-pandemic meetings, and advancing cardiovascular medicine.

Emphysematous pyelonephritis with ST elevation accompanied by reciprocal changes mimicking acute coronary syndrome.

Patients with infectious diseases including sepsis can develop ST segment changes on an electrocardiogram (ECG) in the absence of coronary artery disease. However, ST elevation with "reciprocal ST segment depression (RSTD)", which is recognized as a specific finding for ST-elevated myocardial infarction, is rare in such patients. Although a small number of cases have reported ST-segment elevation in gastritis, cholecystitis, and sepsis, regardless of coronary artery disease, none presented with reciprocal changes. Here, we describe a rare case of a patient with emphysematous pyelonephritis complicating septic shock who developed ST elevation accompanied by reciprocal changes with no coronary occlusion. Emergency physicians should consider the possibility of acute coronary syndrome mimicking, and choose non-invasive diagnostic procedures when investigating the causes of ECG abnormalities associated with critically ill patients.

Beneficial Effects of Pulmonary Vasodilators on Pre-Capillary Pulmonary Hypertension in Patients with Chronic Kidney Disease on Hemodialysis.

BACKGROUND: In patients with chronic kidney disease (CKD) on hemodialysis, comorbid pulmonary hypertension (PH) aggravates exercise tolerance and eventually worsens the prognosis. The treatment strategy for pre-capillary PH, including combined pre- and post-capillary PH (Cpc-PH), has not been established. OBJECTIVES: This study aimed to evaluate the impact of pulmonary vasodilators on exercise tolerance and pulmonary hemodynamics in patients with CKD on hemodialysis. METHODS AND RESULTS: The medical records of 393 patients with suspected PH who underwent right heart catheterization were reviewed. Of these, seven patients had isolated pre-capillary PH and end-stage CKD on hemodialysis. Pulmonary vasodilators decreased pulmonary vascular resistance from 5.9 Wood units (interquartile range (IQR), 5.5-7.6) at baseline to 3.1 Wood units (IQR, 2.6-3.3) post-treatment (p = 0.02) as well as increased pulmonary capillary wedge pressure from 10 mmHg (IQR, 7-11) to 11 mmHg (IQR, 8-16) (p = 0.04). Pulmonary vasodilators increased the World Health Organization functional class I or II from 0% to 100% (p = 0.0002) and the 6 min walk distance from 273 m (IQR, 185-365) to 490 m (IQR, 470-550) (p = 0.03). CONCLUSIONS: Pulmonary vasodilators for PH in patients with CKD on hemodialysis decrease pulmonary vascular resistance and eventually improve exercise tolerance. Pulmonary vasodilators may help hemodialysis patients with pre-capillary PH, although careful management considering the risk of pulmonary edema is required.

Increased Pulmonary Arterial Compliance after Balloon Pulmonary Angioplasty Predicts Exercise Tolerance Improvement in Inoperable CTEPH Patients with Lower Pulmonary Arterial Pressure.

BACKGROUND: Balloon pulmonary angioplasty (BPA) improved pulmonary arterial compliance (CPA) and exercise tolerance in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). OBJECTIVES: To investigate whether CPA is a useful index to indicate exercise tolerance improvement by BPA in CTEPH patients. METHODS: The correlation between changes in CPA and improvements in 6-minute walk distance (6MWD) by BPA was retrospectively analyzed in 70 patients (Analysis 1), and it was sequentially analyzed in 46 symptomatic patients who achieved mean pulmonary arterial pressure (mPAP)<30mmHg (Analysis 2). RESULTS: We enrolled 70 patients (female/male:57/13, mean age:59 years) who underwent a total of 352 BPA sessions which significantly increased CPA (1.5±0.8 vs. 3.0±1.0 mL/mmHg) and decreased pulmonary vascular resistance (PVR) (8.0 ± 3.9 vs. 3.6 ± 1.7 wood units). The correlation coefficient between improvement in 6MWD and changes in PVR and CPA were r=0.21 (p=0.09) and r=0.14 (p=0.26) (Analysis 1). In Analysis 2, those were r=0.32 (p=0.06) and r=0.38 (p=0.02), respectively. CONCLUSIONS: CPA can be a useful index to indicate the improvement in exercise tolerance by BPA in symptomatic patients with lower mPAP.

Flow Pattern of Outflow Graft is Useful for Detecting Pump Thrombosis in a Patient with Left Ventricular Assist Device.

Pump thrombosis (PT) is a serious complication after continuous-flow left ventricular assist device (LVAD) implantation. To detect PT, echocardiographic ramp test using left ventricular end-diastolic diameter (LVEDD) is known to be useful. However, this method has several limitations. In this study, we propose an alternative novel ramp test using the flow velocity of outflow graft (OG). A 46-year-old man underwent continuous-flow LVAD (HeartMate II, Abbott Laboratories, Lake Forest, IL, USA) implantation for advanced heart failure due to idiopathic dilated cardiomyopathy. About 2 years after implantation, he suffered from hemolysis and symptoms of heart failure, and PT was strongly suspected. The change in LVEDD was minimal with increase in pump speed (-0.06 cm/400 rotations per minute (rpm)), suggesting PT. The systolic to diastolic velocity (S/D) ratio of OG flow, which we proposed as a new indicator of PT, also showed minimal change (-0.07/400 rpm). His clinical symptoms improved with anticoagulation therapy, and the changing slope of the S/D ratio dramatically improved to -0.92/400 rpm. Although its consistency should be verified in many other cases, this novel method can be useful for detecting PT and evaluating its clinical course.

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.

Pulmonary arterial input impedance reflects the mechanical properties of pulmonary arterial remodeling in rats with pulmonary hypertension.

AIMS: Although pulmonary arterial remolding in pulmonary hypertension (PH) changes the mechanical properties of the pulmonary artery, most clinical studies have focused on static mechanical properties (resistance), and dynamic mechanical properties (compliance) have not attracted much attention. As arterial compliance plays a significant role in determining afterload of the right ventricle, we evaluated how PH changes the dynamic mechanical properties of the pulmonary artery using high-resolution, wideband input impedance (ZPA). We then examined how changes in ZPA account for arterial remodeling. Clarification of the relationship between arterial remodeling and ZPA could help evaluate arterial remodeling according to hemodynamics. MAIN METHODS: PH was induced in Sprague-Dawley rats with an injection of Sugen5416 (20 mg/kg) and 3-week exposure to hypoxia (10% oxygen) (SuHx). ZPA was evaluated from pulmonary artery pressure and flow under irregular pacing. Pulmonary histology was examined at baseline and 1, 3, and 8 weeks (n = 7, each) after Sugen5416 injection. KEY FINDINGS: SuHx progressively increased pulmonary arterial pressure. ZPA findings indicated that SuHx progressively increased resistance (baseline: 9.3 ±â€¯3.6, SuHx1W: 20.7 ±â€¯7.9, SuHx3W: 48.8 ±â€¯6.9, SuHx8W: 62.9 ±â€¯17.8 mm Hg/mL/s, p < 0.01) and decreased compliance (baseline: 11.9 ±â€¯2.1, SuHx1W: 5.3 ±â€¯1.7, SuHx3W: 2.1 ±â€¯0.7, SuHx8W: 1.9 ±â€¯0.6 × 10-3 mL/mm Hg, p < 0.01). The time constant did not significantly change. The progressive reduction in compliance was closely associated with wall thickening of small pulmonary arteries. SIGNIFICANCE: The finding that changes in resistance were reciprocally associated with those in compliance indicates that resistant and compliant vessels are anatomically inseparable. The analysis of ZPA might help evaluate arterial remodeling in PH according to hemodynamics.

Left Ventricular Mechanical Unloading by Total Support of Impella in Myocardial Infarction Reduces Infarct Size, Preserves Left Ventricular Function, and Prevents Subsequent Heart Failure in Dogs.

BACKGROUND: Acute myocardial infarction remains a leading cause of chronic heart failure. Excessive myocardial oxygen demand relative to supply is the fundamental mechanism of myocardial infarction. We thus hypothesized that left ventricular (LV) mechanical unloading by the total support of transvascular LV assist device Impella could minimize oxygen demand, thereby reducing infarct size and preventing subsequent heart failure. METHODS AND RESULTS: In 20 dogs, we ligated the left anterior descending coronary artery for 180 minutes and then reperfused. We introduced Impella from 60 minutes after the onset of ischemia to 60 minutes after reperfusion. In the partial support group, Impella supported 50% of total cardiac output. In the total support group, systemic flow totally depends on Impella flow. Four weeks after ischemia/reperfusion (I/R), we compared LV function and infarct size among 4 groups: sham (no I/R), I/R (no Impella support), partial support, and total support. Compared with I/R, total support lowered LV end-diastolic pressure (15.0±3.5 versus 4.7±1.7 mm Hg; P<0.001), increased LV end-systolic elastance (4.3±0.8 versus 13.9±5.1 mm Hg/mL; P<0.001), and decreased NT-proBNP (N-terminal pro-B-type natriuretic peptide) level (4081±1123 versus 1773±390 pg/mL; P<0.05). Furthermore, total support markedly reduced infarct size relative to I/R, whereas partial support decreased infarct size to a lesser extent (I/R, 16.3±2.6; partial support, 8.5±4.3; and total support, 2.1±1.6%; P<0.001). CONCLUSIONS: LV mechanical unloading by the total support of Impella during the acute phase of myocardial infarction reduced infarct size and prevented subsequent heart failure in dogs.

Three nights leg thermal therapy could improve sleep quality in patients with chronic heart failure.

Sleep quality is often impaired in patients with chronic heart failure (HF), which may worsen their quality of life and even prognosis. Leg thermal therapy (LTT), topical leg warming, has been shown to improve endothelial function, oxidative stress, and cardiac function in patients with HF. However, its short-term influence to sleep quality has not been evaluated in HF patients. Eighteen of 23 patients with stable HF received LTT (15 min of warming at 45 °C and 30 min of insulation) at bedtime for 3 consecutive nights and 5 patients served as control. Subjective sleep quality was evaluated by St. Mary's Hospital Sleep Questionnaire, Oguri-Shirakawa-Azumi Sleep Inventory, and Epworth sleepiness scale, and also objectively evaluated by polysomnography. LTT significantly improved subjective sleep quality indicated by depth of sleep (p < 0.01), sleep duration (p < 0.05), number of awaking (p < 0.01), nap duration (p < 0.01), sleep quality (p < 0.05), and sleep satisfaction (p < 0.05). It was also objectively affirmed by a slight but significant decrease of sleep stage N1 (p < 0.01), and increase in sleep stage N2 (p < 0.05). No significant changes occurred in the controls. Hence, the short-term LTT could improve subjective and objective sleep quality in patients with HF. LTT can be a complimentary therapy to improve sleep quality in these patients.

Central chemoreflex activation induces sympatho-excitation without altering static or dynamic baroreflex function in normal rats.

Central chemoreflex activation induces sympatho-excitation. However, how central chemoreflex interacts with baroreflex function remains unknown. This study aimed to examine the impact of central chemoreflex on the dynamic as well as static baroreflex functions under open-loop conditions. In 15 anesthetized, vagotomized Sprague-Dawley rats, we isolated bilateral carotid sinuses and controlled intra-sinus pressure (CSP). We then recorded sympathetic nerve activity (SNA) at the celiac ganglia, and activated central chemoreflex by a gas mixture containing various concentrations of CO2 Under the baroreflex open-loop condition (CSP = 100 mmHg), central chemoreflex activation linearly increased SNA and arterial pressure (AP). To examine the static baroreflex function, we increased CSP stepwise from 60 to 170 mmHg and measured steady-state SNA responses to CSP (mechanoneural arc), and AP responses to SNA (neuromechanical arc). Central chemoreflex activation by inhaling 3% CO2 significantly increased SNA irrespective of CSP, indicating resetting of the mechanoneural arc, but did not change the neuromechanical arc. As a result, central chemoreflex activation did not change baroreflex maximum total loop gain significantly (-1.29 ± 0.27 vs. -1.68 ± 0.74, N.S.). To examine the dynamic baroreflex function, we randomly perturbed CSP and estimated transfer functions from 0.01 to 1.0 Hz. The transfer function of the mechanoneural arc approximated a high-pass filter, while those of the neuromechanical arc and total (CSP-AP relationship) arcs approximated a low-pass filter. In conclusion, central chemoreflex activation did not alter the transfer function of the mechanoneural, neuromechanical, or total arcs. Central chemoreflex modifies hemodynamics via sympatho-excitation without compromising dynamic or static baroreflex AP buffering function.

Carotid Body Denervation Markedly Improves Survival in Rats With Hypertensive Heart Failure.

BACKGROUND: Hypertension is a major cause of heart failure. Excessive sympathoexcitation in patients with heart failure leads to poor prognosis. Since carotid body denervation (CBD) has been shown to reduce sympathetic nerve activity in animal models of hypertension and heart failure, we examined if bilateral CBD attenuates the progression of hypertensive heart failure and improves survival. METHODS: We randomly allocated Dahl salt-sensitive rats fed a high-salt diet from 6 weeks of age into CBD (n = 31) and sham-operation (SHAM; n = 50) groups, and conducted CBD or SHAM at 7 weeks of age. We examined the time course of 24-hour urinary norepinephrine (uNE) excretion, blood pressure (BP) and the percent fractional shortening assessed by echocardiography, and estimated the pressure-natriuresis relationship at 14 weeks of age. Finally, we assessed hemodynamics, histological findings, and survival at 16 weeks of age. RESULTS: Compared to SHAM, CBD significantly reduced 24-hour uNE at 12, 14, and 16 weeks of age, shifted the pressure-natriuresis relationship leftward without changing its slope, and attenuated the increase in BP. CBD preserved percent fractional shortening (34.2 ± 1.2 vs. 29.1 ± 1.3%, P < 0.01) and lowered left ventricular end-diastolic pressure (5.0 ± 0.9 vs. 9.0 ± 1.4 mm Hg, P < 0.05). Furthermore, CBD significantly attenuated myocardial hypertrophy (P < 0.01) and fibrosis (P < 0.01). Consequently, CBD markedly improved survival (relative risk reduction: 64.8%). CONCLUSIONS: CBD attenuated the progression of hypertension and worsening of heart failure possibly through sympathoinhibition, and markedly improved survival in a rat model of hypertensive heart failure.

Intravenous electrical vagal nerve stimulation prior to coronary reperfusion in a canine ischemia-reperfusion model markedly reduces infarct size and prevents subsequent heart failure.

BACKGROUND: Reducing myocardial damage is a prerequisite to prevent chronic heart failure after acute myocardial infarction (AMI). Although vagal nerve stimulation (VNS) has been repeatedly demonstrated to have potent anti-infarct effect, technical difficulties have precluded its clinical application. We developed a novel therapeutic strategy of intravenous VNS (iVNS) and examined whether iVNS administered prior to coronary reperfusion in a canine AMI model reduces infarct size and prevents heart failure. METHODS AND RESULTS: In 35 mongrel dogs, we induced ischemia by ligating the left anterior descending coronary artery and then reperfused 3h later (I/R). We transvenously placed a catheter electrode in the superior vena cava and adjusted the stimulation intensity to a level that induced bradycardia but maintained stable hemodynamics (continuous, 5.1±2.1V, 10Hz). We administered iVNS from onset (iVNS-0, n=7) or 90min after onset (iVNS-90, n=7) of ischemia until one hour after reperfusion. Four weeks after ischemia-reperfusion, iVNS markedly reduced infarct size (iVNS-0: 2.4±2.1%, p<0.05 and iVNS-90: 4.5±4.5%, p<0.05) compared with I/R control (I/R: 13.3±2.5%), and improved cardiac performance and hemodynamics. Atrial pacing (n=7) to abolish iVNS-induced bradycardia significantly attenuated the beneficial effects of iVNS. CONCLUSIONS: Short-term iVNS delivered prior to coronary reperfusion markedly reduced infarct size and preserved cardiac function one month after AMI. The bradycardic effect plays an important role in the beneficial effect of iVNS. How other mechanisms contribute to the reduction of infarct size remains to be studied.

Prediction of hemodynamics under left ventricular assist device.

Left ventricular assist device (LVAD) saves lives in patients with severe left ventricular (LV) failure. However, predicting how much LVAD boosts total cardiac output (CO) remains difficult. This study aimed to develop a framework to quantitatively predict the impact of LVAD on hemodynamics. We adopted the circulatory equilibrium framework and incorporated LVAD into the integrated CO curve to derive the circulatory equilibrium. In anesthetized dogs, we ligated left coronary arteries to create LV failure and inserted a centrifugal pump as LVAD. Using CO and right (PRA) and left atrial pressure (PLA) measured before LVAD support, we predetermined the stressed volume (V) and logarithmic slope of right heart CO curve (SR). Next, we initiated LVAD at maximum level and then decreased LVAD flow stepwise while monitoring hemodynamic changes. We predicted LVAD-induced CO and PRA for given PLA from the predetermined SR and V and compared with those measured experimentally. The predicted CO [r2 = 0.907, SE of estimate (SEE) = 5.59 ml·min-1·kg-1, P < 0.001] and PRA (r2 = 0.967, SEE = 0.307 mmHg, P < 0.001) matched well with measured values indicating the validity of the proposed framework. We further conducted simulation using the validated framework to analyze the impact of LVAD on PRA under various right ventricular (RV) functions. It indicated that PRA is relatively insensitive to changes in RV end-systolic elastance or pulmonary arterial resistance, but sensitive to changes in V. In conclusion, the circulatory equilibrium framework predicts quantitatively the hemodynamic impact of LVAD. This knowledge would contribute to safe management of patients with LV failure undergoing LVAD implantation. NEW & NOTEWORTHY: Hemodynamic response to left ventricular assist device (LVAD) has not been quantitatively investigated. This is the first report of quantitative prediction of the hemodynamics on LVAD using circulatory equilibrium framework. The validated framework allows us to simulate the impact of LVAD on right atrial pressure under various right ventricular functions.

Optimal Titration Is Important to Maximize the Beneficial Effects of Vagal Nerve Stimulation in Chronic Heart Failure.

BACKGROUND: Although vagal nerve stimulation (VNS) benefits patients with chronic heart failure (CHF), the optimal dose of VNS remains unknown. In clinical trials, adverse symptoms limited up-titration. In this study, we evaluated the impact of various voltages of VNS which were titrated below symptom threshold on cardiac function and CHF parameters in rat myocardial infarction (MI) models. METHODS AND RESULTS: We randomly allocated MI rats to vagal (VNS; n = 41) and sham (Sham; n = 16) stimulation groups. We stimulated the right vagal nerve with 20 Hz at 3 different voltages for 4 weeks. We defined Max as the highest voltage that did not evoke any symptom, Half as one-half of Max, and Quarter as one-fourth of Max. All 3 VNS groups significantly reduced biventricular weight compared with Sham (P < .05). In contrast, only Half decreased left ventricular (LV) end-diastolic pressure (Half: 17.5 ± 2.0 mm Hg; Sham: 24.2 ± 1.2 mm Hg; P < .05) and increased LV ejection fraction (Half: 37.9 ± 3.1%; Sham: 28.4 ± 2.3%,-P < .05) and LV maximum +dP/dt (Half: 5918.6 ± 2.0 mm/Hg/s; Sham: 5001.2 ± 563.2 mm Hg/s; P < .05). The number of large vagal nerve fibers was reduced with Max (Max: 163.1 ± 43.0 counts/bundle; Sham: 360.0 ±61.6 counts/bundle; P < .05), indicating significant neural damage by VNS. CONCLUSION: The optimal titration of VNS would maximize benefits for CHF and minimize adverse effects.

Total Mechanical Unloading Minimizes Metabolic Demand of Left Ventricle and Dramatically Reduces Infarct Size in Myocardial Infarction.

BACKGROUND: Left ventricular assist device (LVAD) mechanically unloads the left ventricle (LV). Theoretical analysis indicates that partial LVAD support (p-LVAD), where LV remains ejecting, reduces LV preload while increases afterload resulting from the elevation of total cardiac output and mean aortic pressure, and consequently does not markedly decrease myocardial oxygen consumption (MVO2). In contrast, total LVAD support (t-LVAD), where LV no longer ejects, markedly decreases LV preload volume and afterload pressure, thereby strikingly reduces MVO2. Since an imbalance in oxygen supply and demand is the fundamental pathophysiology of myocardial infarction (MI), we hypothesized that t-LVAD minimizes MVO2 and reduces infarct size in MI. The purpose of this study was to evaluate the differential impact of the support level of LVAD on MVO2 and infarct size in a canine model of ischemia-reperfusion. METHODS: In 5 normal mongrel dogs, we examined the impact of LVAD on MVO2 at 3 support levels: Control (no LVAD support), p-LVAD and t-LVAD. In another 16 dogs, ischemia was induced by occluding major branches of the left anterior descending coronary artery (90 min) followed by reperfusion (300 min). We activated LVAD from the beginning of ischemia until 300 min of reperfusion, and compared the infarct size among 3 different levels of LVAD support. RESULTS: t-LVAD markedly reduced MVO2 (% reduction against CONTROL: -56 ± 9%, p<0.01) whereas p-LVAD did less (-21 ± 14%, p<0.05). t-LVAD markedly reduced infarct size compared to p-LVAD (infarct area/area at risk: CONTROL; 41.8 ± 6.4, p-LVAD; 29.1 ± 5.6 and t-LVAD; 5.0 ± 3.1%, p<0.01). Changes in creatine kinase-MB paralleled those in infarct size. CONCLUSIONS: Total LVAD support that minimizes metabolic demand maximizes the benefit of LVAD in the treatment of acute myocardial infarction.

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.

Prediction of the impact of venoarterial extracorporeal membrane oxygenation on hemodynamics.

Although venoarterial extracorporeal membrane oxygenation (ECMO) was developed to rescue patients with cardiogenic shock, the impact of ECMO on hemodynamics is often unpredictable and can lead to hemodynamic collapse. In this study, we developed a framework in which we incorporated ECMO into the extended Guyton's model of circulatory equilibrium and predicted hemodynamic changes in response to ECMO. We first determined the cardiac output (CO) curves of left and right heart (to generate the integrated CO curve) without ECMO in eight normal and seven dogs with left ventricular dysfunction. Using the CO curves obtained and standard parameters for the venous return surface, we predicted the circulatory equilibrium under various levels of ECMO support. The predicted total flow (native left heart flow plus ECMO flow), right atrial pressure (PRA), and left atrial pressure (PLA) matched well with those measured [total flow: coefficient of determination (r(2)) = 0.99, standard error of estimate (SEE) = 5.8 ml·min(-1)·kg(-1), PRA: r(2) = 0.95, SEE = 0.23 mmHg, PLA: r(2) = 0.99, SEE = 0.59 mmHg]. Lastly, we estimated the CO curves under ECMO support from minute changes in hemodynamics induced by change in ECMO. From the CO curves estimated, we predicted the circulatory equilibrium. The predicted total flow (r(2) = 0.93, SEE = 0.5 ml·min(-1)·kg(-1)), PRA (r(2) = 0.99, SEE = 0.54 mmHg), and PLA (r(2) = 0.95, SEE = 0.89 mmHg) matched reasonably well with those measured. A numerical simulation indicated that ECMO support may cause pulmonary edema, if right ventricular function is compromised. We conclude that the proposed framework may enhance the benefit and reduce the risk of ECMO support in patients with critical hemodynamic conditions.

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.