Left Ventricular Oxygen Research Articles

Myocardial External Efficiency in Asymptomatic Severe Primary Mitral Regurgitation Using 11C-Acetate PET.

Subjects with asymptomatic moderate-to-severe or severe primary mitral regurgitation are closely observed for signs of progression or symptoms requiring surgical intervention. The role of myocardial metabolic function in progression of mitral regurgitation is poorly understood. We used 11C-acetate PET to noninvasively measure myocardial mechanical external efficiency (MEE), which is the energetic ratio of external cardiac work and left ventricular (LV) oxygen consumption. Methods: Forty-seven patients in surveillance with mitral regurgitation and no or minimal symptoms prospectively underwent PET, echocardiography, and cardiac MRI on the same day. PET was used to simultaneously measure cardiac output, LV mass, and oxygen consumption to establish MEE. PET findings were compared between patients and healthy volunteers (n = 9). MEE and standard imaging indicators of regurgitation severity, LV volumes, and function were studied as predictors of time to surgical intervention. Patients were followed a median of 3.0 y (interquartile range, 2.0-3.8 y), and the endpoint was reached in 22 subjects (47%). Results: MEE in patients reaching the endpoint (23.8% ± 5.0%) was lower than in censored patients (28.5% ± 4.5%, P = 0.002) or healthy volunteers (30.1% ± 4.9%, P = 0.001). MEE with a cutoff lower than 25.7% was significantly associated with the outcome (hazard ratio, 7.5; 95% CI, 2.7-20.6; P < 0.0001) and retained independent significance when compared with standard imaging parameters. Conclusion: MEE independently predicted time to progression requiring valve surgery in patients with asymptomatic moderate-to-severe or severe primary mitral regurgitation. The study suggests that inefficient myocardial oxidative metabolism precedes clinically observed progression in mitral regurgitation.

Myocardial efficiency in severe asymptomatic primary mitral regurgitation: relation to quantitative measures of regurgitation

Abstract Objectives To study the association of myocardial external efficiency (MEE) in mitral regurgitation (MR) towards routinely used quantitative indicators of disease severity and progression. Background Quantitative assessment of LV function and regurgitation in asymptomatic severe primary MR is crucial for management. MEE is a load-independent indicator of mechano-energetic coupling and can be measured non-invasively using 11C-acetate positron emission tomography (PET). The role of MEE in this setting has not been studied. Methods 48 asymptomatic patients with severe primary mitral regurgitation underwent PET, echo, and CMR on the same day. MEE was automatically derived from PET as the ratio of cardiac work (cardiac output * mean arterial pressure) and total left ventricular (LV) oxygen consumption (mean MVO2 * LV mass). LV function and mitral regurgitant volumes (RegVol) were measured by echo and CMR. MEE in MR was compared to healthy volunteers (n=9). MEE and parameters of regurgitation severity and of LV volumes and function were studied as predictors of outcome (valve surgery or death). Results MEE was reduced in MR (21.5±4.2%) vs healthy volunteers (32.0±5.6%, p&amp;lt;0.001) and showed weak but significant correlations (r2&amp;lt;0.25) with regurgitation severity and LV volumes. There were 23 cardiac events (valve surgery: 22; cardiovascular death: 1) during follow-up (median 2.7 years, IQR 1.9–3.2). Univariate Cox models showed that MEE, echocardiographic left atrial volume as well as RegVol and LV ventricular volumes from both echo and CMR were significant outcome predictors (all p&amp;lt;0.05), while LVEF and NT-pro-BNP were not (p&amp;gt;0.05). Prediction by MEE was not affected by age, sex or BMI. When categorically divided by the median MEE was a strong predictor in Kaplan-Meier analysis (log-rank p=0.0004, figure 1) and remained independently significant, compared to all other univariate predictors in bivariate Cox models. Conclusions This study suggests an important role of energetic insufficiency in progression of asymptomatic severe primary MR. Reduced MEE was linked to outcome independently of standard functional measures of regurgitation severity or left ventricular size and function. Strategies for improvement of myocardial energetics in MR are warranted. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swedish Heart-Lung Foundation Figure 1

Abstract P100: Enhanced External Counterpulsation Reduces Central Blood Pressure In Stable Angina Patients: A Meta Analysis

Introduction: Emerging evidence suggests central systolic blood pressure (cSBP) and augmentation index are superior predictors of adverse cardiovascular outcomes as compared to peripheral systolic blood pressure (pSBP). Enhanced external counterpulsation (EECP) is a non-invasive treatment modality approved for the management of refractory angina. The degree of benefit from EECP on central hemodynamics and arterial stiffness remains unknown. This meta-analysis evaluated the effect of EECP on peripheral (office) blood pressure and central hemodynamic parameters. Methods: A comprehensive literature search was conducted in Pubmed, CINAHL, and Cochrane Library databases. All prospective clinical trials assessing the impact of EECP in patients with stable angina and CAD were included. Studies were excluded for not completing a full course of EECP, having a baseline peripheral systolic blood pressure &amp;lt100 mmHg, or not reporting adequate data for analysis. The primary endpoint was the change in cSBP before and after EECP. The change in pSBP, pDBP, cDBP, and augmentation index before and after EECP were also assessed. The weighted mean difference using the DerSimonian and Laird random-effect model was utilized for determining the change in each parameter before and after EECP. Statistical heterogeneity was evaluated using the Egger’s bias statistic. Results: Five studies containing 137 unique patients were included for the cSBP analysis. cSBP was reduced significantly by -7.56 mmHg (95% CI -11.83 to -3.28; Cochrane Q=1.81) post-EECP. In the same set of studies, pSBP was reduced significantly by -9.65 mmHg (95% CI -14.32 to -4.98) post-EECP. pDBP [-4.67 mmHg (95% CI -8.56 to -0.77)] was reduced post-EECP, while no changes were evident in cDBP. Augmentation index was reduced by -3.74% (95% CI -7.05 to -0.43) post-EECP. Two studies included a sham-EECP intervention arm and demonstrated no significant changes in cSBP [0.67 mmHg (95% CI -5.66 to 7.01)] or other parameters. Conclusion: EECP significantly reduced cSBP and pSBP by approximately 8 mmHg and 10 mmHg respectively. EECP also demonstrated a mild improvement in arterial stiffness, which translates to reduced wasted left ventricular energy and myocardial oxygen demand. In patients with stable angina and CAD, EECP exerts beneficial effects in both peripheral and central hemodynamics but whether these benefits are sustained over a longer duration need further exploration.

Effects of 6 weeks of treatment with dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, on myocardial function and metabolism in patients with type 2 diabetes: A randomized, placebo-controlled, exploratory study.

To explore the early effects of dapagliflozin on myocardial function and metabolism in patients with type 2 diabetes without heart failure. Patients with type 2 diabetes on metformin treatment were randomized to double-blind, 6-week placebo or dapagliflozin 10 mg daily treatment. Investigations included cardiac function and structure with myocardial resonance imaging; cardiac oxygen consumption, perfusion and efficiency with [11 C]-acetate positron emission tomography (PET); and cardiac and hepatic fatty acid uptake with [18 F]-6-thia-heptadecanoic acid PET, analysed by ANCOVA as least square means with 95% confidence intervals. Evaluable patients (placebo: n = 24, dapagliflozin: n = 25; 53% males) had a mean age of 64.4 years, a body mass index of 30.2 kg/m2 and an HbA1c of 6.7%. Body weight and HbA1c were significantly decreased by dapagliflozin versus placebo. Dapagliflozin had no effect on myocardial efficiency, but external left ventricular (LV) work (-0.095 [-0.145, -0.043] J/g/min) and LV oxygen consumption were significantly reduced (-0.30 [-0.49, -0.12] J/g/min) by dapagliflozin, although the changes were not statistically significant versus changes in the placebo group. Change in left atrial maximal volume with dapagliflozin versus placebo was -3.19 (-6.32, -0.07) mL/m2 (p = .056). Peak global radial strain decreased with dapagliflozin versus placebo (-3.92% [-7.57%, -0.28%]; p = .035), while peak global longitudinal and circumferential strains were unchanged. Hepatic fatty acid uptake was increased by dapagliflozin versus placebo (0.024 [0.004, 0.044] μmol/g/min; p = .018), while cardiac uptake was unchanged. This exploratory study indicates reduced heart work but limited effects on myocardial function, efficiency and cardiac fatty acid uptake, while hepatic fatty acid uptake increased, after 6 weeks of treatment with dapagliflozin.

Hybrid and parallel extracorporeal membrane oxygenation circuits

Hybrid and parallel extracorporeal membrane oxygenation circuits

Abstract 13306: Impella Combined With Extracorporeal Membrane Oxygenation Synergistically Unloads the Left Ventricle and Reduces Infarct Size in a Model of Myocardial Infarction With Cardiogenic Shock

Introduction: Extracorporeal membrane oxygenation (ECMO) supports hemodynamics in cardiogenic shock (CS) at the expense of left ventricular (LV) overload. LV assist device (LVAD) also supports hemodynamics, whereas LVAD unloads LV. Therefore, the combination of ECMO and LVAD would augment hemodynamic support and unload LV. We hypothesized that the combination therapy in acute myocardial infarct (AMI) in CS could synergistically improve hemodynamics and unload LV, which, in turn, reduces infarct size. Methods: In protocol 1, we ligated coronary arteries and created AMI with CS in 5 mongrel dogs (15.1±0.3 kg). We transvascularly introduced Impella CP into LV. We kept the ECMO flow constant at 1.8L/min. We compared hemodynamics and the LV pressure-volume area (PVA, an index of LV oxygen consumption) under 3 conditions; Control, ECMO, and ECMO+Impella (ECPELLA) in each dog. In protocol 2 (n=15), we ligated coronary arteries for 180 min and then reperfused. We activated Impella CP and/or ECMO from 60 min after the coronary ligation to the end of the experiment. We allocated dogs into 3 groups, no support (Control), ECMO, and ECPELLA and compared infarct size at 180 min after reperfusion among 3 groups. Results: In protocol 1, both ECMO and ECPELLA increased arterial pressure compared to Control (Control: 63±9, ECMO: 88±10 and ECPELLA: 97±18 mmHg, p &lt; 0.05), and resolved the CS status. ECPELLA strikingly reduced PVA by 83% relative to Control (1500±326, 2038±357 and 258±182 mmHg*ml, p&lt;0.001). In protocol 2, ECPELLA markedly reduced the infarct size (15±8%) compared to Control (53±7%, p&lt;0.05) and ECMO (39±10%, p&lt;0.05). Conclusions: ECPELLA before reperfusion markedly improved hemodynamics, reduced PVA, and limited infarct size in a dog model of MI with CS. ECPELLA could prevent ECMO-induced LV overload and synergistically exert powerful anti-infarct effects in AMI with CS.

Thigh intramuscular fat predicts the prognosis in patients in non-ischemic cardiomyopathy with reduced ejection fraction

Abstract Background Skeletal muscle atrophy is an independent prognostic predictor for patients with chronic heart failure, and the concept of sarcopenia is drawing attention. Furthermore, the importance of not only muscle mass but also intramuscular fat (IMF) has been pointed out. However, there is a lack of consensus on the implications of ectopic fat for the prognosis in patients with non-ischemic cardiomyopathy. Purpose We investigated whether ectopic fat in the thigh affects the prognosis with non-ischemic cardiomyopathy. Methods We recruited 105 patients who were diagnosed with non-ischemic cardiomyopathy by cardiac catheterization and echocardiographic date between September 2017 and November 2019. Finally 73 patients with reduced EF (EF 40% or less) enrolled in this prospective study. Functional status was evaluated by using cardiopulmonary exercise test at baseline. All patients were measured quantity of epicardial fat and thigh IMF percentage (%IMF) using computed tomography scan. Demographic, laboratory and echocardiographic date were collected from the patients' medical records. Clinical endpoints were unexpected readmission. Results During the follow-up period 18 patients had adverse events. The %IMF was significantly higher in the group with adverse events than without (5.57±5.70 and 3.02±2.44%, respectively; p&amp;lt;0.01). Spearman correlation coefficient analysis showed a modest correlation between %IMF and lower limb extension strength (Spearman r=−0.280; p=0.0315), but there was no significant correlation between %IMF and exercise tolerance such as anaerobic threshold and peak oxygen uptake. Patients were divided into 2 groups according to the median values of %IMF. Kaplan-Meier analysis demonstrated that events were significantly higher in the high %IMF group (log-rank p=0.033). Multivariate Cox regression analysis adjusted for left ventricular end-diastolic diameter and peak ventricular oxygen consumption found %IMF as an independent factor of adverse events (hazard ratio 1.545; 95% confidential interval 1.151–2.087; p=0.004). Conclusions In non-ischemic cardiomyopathy patients with reduced EF, %IMF may have important adverse consequences such as increased cardiac-related events. Kaplan-Meier curves Funding Acknowledgement Type of funding source: None

P5735Feasibility and safety of Impella mechanical circulatory support in different clinical scenarios: a single-centre experience

Abstract Background The Impella (Abiomed, Danvers, MA) mechanical circulatory support is a catheter-based axial-flow pump. It reduces left ventricular (LV) stroke work and myocardial oxygen demand while increasing systemic and coronary perfusion in the setting of cardiogenic shock (CS), and it provides hemodynamic support during high-risk percutaneous coronary intervention (PCI). Purpose To evaluate the outcomes of Impella-supported patients in the context of CS and protected-PCI. Methods This single-center registry includes all patients implanted with Impella device at our institution between February 2013 and June 2018. Indications for Impella support were CS (hypotension despite adequate filling status with signs of hypoperfusion) and protected-PCI (prophylactic hemodynamic support during non-emergent high-risk PCI). Results A total of 145 patients were implanted with Impella: 130 (89.7%) for CS and 15 (10.3%) for protected-PCI. Among CS patients, mean age was 61.6±12.9, 79.2% males. The prevalence of chronic heart failure (HF) was 26.1%, prior myocardial infarction (MI) 29% and myocardial revascularization 36.6%, chronic kidney disease (CKD) 18.3%. Among protected PCI patients, mean age was 73.4±8.7 years, 86.7% males. The prevalence of HF was 85.7%, prior MI 42.9%, myocardial revascularization 35.7%, CKD 57.1%. In CS group, the indications for Impella implantation were myocarditis in 8 (6.2%) patients, acute coronary syndromes in 77 (59.2%), periprocedural ventricular tachycardia ablation CS in 10 (7.7%), decompensated heart failure in 26.9%. Out of hospital cardiac arrest occurred in 35 (30.4%) patients, INTERMACS I class in 70 (59.3%), mean arterial pressure was 65.4±18.4 mmHg, serum lactate 6.7±5.5 mmol/l, at least 1 inotropic agent use in 73 (66.4%), mean LV EF 21.4±11,7%, right ventricular dysfunction in 53 (48.6%). The rate of device-related complications was not negligible in CS group: 18 (14.5%) patients had limb ischemia and vascular surgery was required in 14, 17 (14.3%) had access-site bleeding. A total of 42 (33.3%) had haemolysis, and 67 (56.8%) acute kidney injury (AKI), half of whom requiring renal replacement therapy. Escalation to other therapies was necessary in 43 cases. Conversely, in the protected-PCI group a low rate of AKI (n=4, 28.6%) and acute limb ischemia (n=1, 7.1%) was observed, whereas no cases of haemolysis nor need of escalation therapy were recorded. Mean Impella support was 135.5±167.21 days for CS group, 60.6±80 for protected-PCI group. Survival at 30 days was 60.33% for CS group and 92.9% for protected-PCI group. One-year all-cause death was 50% for CS group and 13.3% for protected-PCI group. Conclusion Mechanical circulatory support with Impella is associated with good outcomes and reasonable rates of complications in the protected-PCI group, whereas less favorable results were observed in CS population probably due to the greater severity of clinical presentation.

P1712The Impella percutaneous mechanical circulatory support device in cardiogenic shock: a single-center, real-world, observational experience

Abstract Background The Impella () percutaneous mechanical circulatory support device is a catheter-based, impeller-driven, axial-flow pump. It reduces left ventricular (LV) stroke work and myocardial oxygen demand while increasing systemic and coronary perfusion in the setting of cardiogenic shock (CS). Purpose The aim of the study was to evaluate clinical characteristics and outcomes of patients with CS treated with Impella at our center. Methods Our single-center, real-world, observational registry included all consecutive patients with CS treated with Impella 2.5, CP, 5.0, or RP at our center from February 2013 to June 2018. Indication for Impella implantation was CS, defined as hypotension (systolic blood pressure &lt;90 mmHg) despite adequate filling status with signs of hypoperfusion. Results A total of 130 patients were included in the registry, mean age was 61±12 years, and 79.2% were males. A history of prior MI, chronic heart failure, and chronic kidney disease was present in 28.9%, 26.1%, and 18.3%, respectively. The etiologies of CS were the following: fulminant myocarditis in 6.1% of the patients, acute coronary syndromes in 59.2%, peri-procedural CS during ventricular tachycardia ablation in 7.7% and acute heart failure in 27%. Out-of-hospital cardiac arrest was present in 30.4% of the patients; 60.2% were in INTERMACS I class at presentation. At admission, mean arterial pressure (MAP) was 65±18 mmHg, serum lactate was 6.7±5.5 mmol/L, mean left ventricular ejection fraction 21.4±11.7%, right ventricular dysfunction was indeed present in 48.6% of the patients. Inotropic drugs support was used in 66.4% of the patients. Impella 2.5, CP, and 5.0 were implanted in 76.1%, 15.4%, and 1.5% of the patients, respectively. Impella RP was also used in 11.5% of patients.The mean duration of support was 135±167 hours. Of note, extra-corporeal membrane oxygenation (ECMO) and intra-aortic balloon pump (IABP) were implanted before Impella insertion in 42.8% and 46.7% of the patients, respectively. Escalation to ECMO, ventricular assist device, or heart transplantation was needed in 35.8% of the patients. During hospital stay, acute kidney injury occurred in 56.7% of the patients; need of renal replacement therapy (RRT) 31.7%; access site-related bleeding 14.3%; life-threatening bleeding 31.5%; acute limb ischemia 14.5%; hemolysis 33.3%. The rate of all-cause mortality at 30 day was 39.7%. Need of RRT was the only independent predictor of 30-day mortality (OR 6.56; CI 1.71–25.15; p=0.006). Conclusion Our single-center, real-world, observational experience reports acceptable clinical outcomes after Impella implantation in a particularly complex population of patients with CS (INTERMACS class I in 60.2% of patients, prior use of ECMO in 42.8% of patients). All-cause mortality at 30 days was 39.7%, and need of RRT was the only independent predictor for 30-day mortality.

Evaluation of ECG-gated [11C]acetate PET for measuring left ventricular volumes, mass, and myocardial external efficiency

BackgroundNoninvasive estimation of myocardial external efficiency (MEE) requires measurements of left ventricular (LV) oxygen consumption with [11C]acetate PET in addition to LV stroke volume and mass with cardiovascular magnetic resonance (CMR). Measuring LV geometry directly from ECG-gated [11C]acetate PET might enable MEE evaluation from a single PET scan. Therefore, we sought to establish the accuracy of measuring LV volumes, mass, and MEE directly from ECG-gated [11C]acetate PET. MethodsThirty-five subjects with aortic valve stenosis underwent ECG-gated [11C]acetate PET and CMR. List mode PET data were rebinned into 16-bin ECG-gated uptake images before measuring LV volumes and mass using commercial software and compared to CMR. Dynamic datasets were used for calculation of mean LV oxygen consumption and MEE. ResultsLV mass, volumes, and ejection fraction measured by CMR and PET correlated strongly (r = 0.86-0.92, P < .001 for all), but were underestimated by PET (P < .001 for all except ESV P = .79). PET-based MEE, corrected for bias, correlated fairly with PET/CMR-based MEE (r = 0.60, P < .001, bias −3 ± 21%, P = .56). PET-based MEE bias was strongly associated with LV wall thickness. ConclusionsAlthough analysis-related improvements in accuracy are recommended, LV geometry estimated from ECG-gated [11C]acetate PET correlate excellently with CMR and can indeed be used to evaluate MEE.

PM120 Electrical Myostimulation Improves Quality of Life, Left Ventricular Function and Peak Oxygen Consumption in Patients With Chronic Heart Failure - Results From the EMS Study Comparing Different Stimulation Strategies

PM120 Electrical Myostimulation Improves Quality of Life, Left Ventricular Function and Peak Oxygen Consumption in Patients With Chronic Heart Failure - Results From the EMS Study Comparing Different Stimulation Strategies

Gender Differences in Ventricular-vascular Coupling Following Exercise.

To study the differences of cardiovascular system between men and women in response to exercise stress. Forty healthy youth were tested according to Bruce protocol of exercise stress. They were detected by ultrasonography during the rest, peak exercise, and recovery stages, respectively. The left ventricular diastolic elastance (Ed), effective arterial elastance (Ea), left ventricular end-systolic elatance (Ees), ventricular-vascular coupling index (VVI), and total stiffness index (TSI) were measured and calculated according to the formulas. The results of all stages were compared according to genders. All stages, the Ed, TSI, and VVI of women were higher than those of men, but the Ees was lower than that of men (all P<0.05); there was no significant difference in Ea between men and women. The Ed, Ees, Ea, and TSI were closely related with left ventricular oxygen consumption and heart function, and women showed more closely. Before and after exercise, the changes were different in Ed, Ees, Ea, TSI, and VVI (all P<0.05), and VVI changed least. Before and after exercise, the ventricular stiffness matched well with arterial stiffness and maintained within a narrow range. For women, the tolerance of exercise was lower than that of men.

ROLES OF SO2 INDEX FOR PREDICTING OF FLUID RESPONSIVENESS IN HIGH RISK CARDIAC SURGICAL PATIENTS

Purpose: (1) Study the change in SO2 value in fluid therapy in patients after cardiac surgery; (2) Evaluate the role of SO2 monitoring in serving as an indicator of fluid responsiveness in patients after cardiac surgery. Methods: This was a prospective study reported earlier on critically ill patients with clinical hypovolemia after cardiac surgery. Fluid therapy was guided by changes in pulmonary artery wedge pressure or central venous pressure. Fluid responsiveness was defined as ≥15% increase in cardiac index. Hemodynamics, including left ventricular ejection fraction, cardiac index, and oxygen delivery were measured when SO2 blood samples taken. Results: There was 110 patients receiving fluid therapy in postoperative period. The SO2 increased in 104 patients responding to fluid loading (≥15% in cardiac index in n=107) versus those not responding (n=6). The increase in ejection fraction, cardiac index and oxygen delivery was also greater in responders (p=0.005). The area under the receiver operating characteristic curve for fluid responsiveness of changes in SO2 was 0.78 (p=0.05), with an optimal cutoff of 2%. The value of SO2 increased to reflect cardiac index increases with fluid loading was in 66.7% of patients. Conclusions: An increase in SO2 ≥ 2% can thus be used as an indicator of fluid responsiveness in clinically hypovolemic patients after cardiac surgery, particularly in those with systolic cardiac dysfunction. Fluid responsiveness concurs with increased tissue oxygen delivery. Key words: mixed venous oxygen saturation (SO2); oxygen delivery (DO2); oxygen consumption (VO2); central venous pressure (CVP), pulmonary artery wedge pressure (PAWP); cardiac index (CI); hypovolemia; fluid therapy.

Effects of Shenfu injection on the expression of transcription factors T-bet / GATA-3 in pigs with post-resuscitation myocardial dysfunction

To examine whether Shenfu injection (SFI) reduces post-resuscitation myocardial dysfunction in a pig model by modulating expression imbalance of transcription factors of regulatory T cell, namely GATA-3 and T-bet. Thirty pigs were randomly divided into sham group (n = 6) and cardiopulmonary resuscitation (CPR) group (n = 24) according to the random number table method, and the pigs in the CPR group were randomly subdivided into normal saline (NS) group, epinephrine (EP) group, and SFI group (n = 8 per group). After 8 minutes of untreated ventricular fibrillation (VF) followed by 2 minutes of CPR, animals in three groups respectively received central venous injection of either 20 mL SFI (1.0 mL/kg, SFI group), EP (0.02 mg/kg, EP group) or NS (NS group). Blood samples were obtained before VF and 0.5, 2, 6 hours after restoration of spontaneous circulation (ROSC), and the parameters of hemodynamics and oxygen metabolism were determined. Surviving pigs were sacrificed at 24 hours after ROSC, the pathological changes in myocardium were observed, the levels of interleukin-4 (IL-4), tumor necrosis factor-α (TNF-α) and γ-interferon (IFN-γ) were measured by enzyme linked immunosorbent assay (ELISA), and expressions of protein and mRNA of GATA-3 and T-bet were determined by Western Blot and quantitative real-time polymerase chain reaction (RT-qPCR), respectively. Six pigs of three resuscitation groups were successfully resuscitated. The CPR time, number of defibrillation, defibrillation energy, and ROSC time were significantly decreased in the EP and SFI groups compared with those in the NS group. Compared with the sham group, the parameters of left ventricular systolic function and oxygen metabolism were significantly decreased, myofibril organelles were extensively damaged, and progressive and severe deterioration of the myocardium was found, and mitochondrial structure was not recognizable in the NS group; the level of IL-4 in myocardium were markedly decreased, while that of TNF-α, IFN-γ and IFN-γ/ IL-4 [reflecting helper T cell 1/2 (Th1/Th2)] were significantly increased. Protein and mRNA expressions of GATA-3 were markedly reduced in the myocardium of pigs in the NS group compared with that of the sham group at 24 hours after ROSC, while T-bet was significantly increased. Compared with the NS group, animals treated with SFI had minimal myocardial intracellular damage, with decreased heart rate (HR, bpm: 90.33 ± 3.79 vs. 106.83 ± 5.36) and increased mean arterial pressure (MAP), cardiac output (CO), oxygen delivery (DO₂), and oxygen consumption (VO₂) at 6 hours after ROSC [MAP (mmHg, 1 mmHg = 0.133 kPa): 107.67 ± 1.96 vs. 86.83 ± 1.85, CO (L/min): 2.47 ± 0.08 vs. 2.09 ± 0.04, DO₂ (mL/min): 364.31 ± 4.21 vs. 272.33 ± 3.29, VO₂(mL/min): 95.00±2.22 vs. 82.50 ±2 .28, all P < 0.05]. Compared with the NS groups at 24 hours after ROSC, level of IL-4 was markedly increased in myocardial cells (ng/L: 33.80 ± 3.06 vs. 16.15 ± 1.34, P < 0.05), while the levels of TNF-α, IFN-γ and IFN-γ/IL-4 were lowered significantly [TNF-α (ng/L): 18.16 ± 0.71 vs. 29.64 ± 1.89, IFN-γ (ng/L): 373.75 ± 18.36 vs. 512.86 ± 27.86, IFN-γ/IL-4: 16.15 ± 1.34 vs. 33.80 ± 3.06, all P < 0.05], and myocardial T-bet protein and mRNA expressions were reduced [T-bet protein (gray value): 0.41 ± 0.07 vs. 0.59 ± 0.11, T-bet mRNA (2(-ΔΔCt)): 4.37 ± 0.21 vs. 7.57 ± 0.55, both P < 0.05], furthermore, myocardial GATA-3 protein and mRNA expressions were significantly up-regulated in SFI group [GATA-3 protein (gray value): 0.25 ± 0.07 vs. 0.16 ± 0.07, GATA-3 mRNA (2(-ΔΔCt)): 0.63 ± 0.07 vs. 0.34 ± 0.05, both P < 0.05]. The parameters in SFI group were significantly improved compared with those of the EP group. Myocardial immune dysfunction is induced by Th1/Th2 imbalance following myocardial injury subsequent to CPR in pigs. SFI can attenuate myocardial injury and regulate myocardial immune disorders, protect post-resuscitation myocardial injury by modulating expression imbalance of transcription factors GATA-3 and T-bet.

Mechanisms of increased right and left ventricular oxygen uptake during inotropic stimulation

AimsFew studies have investigated oxygen supply/demand relations in right ventricle (RV). The current study compared changes in myocardial oxygen uptake (MVO2) and its determinants, myocardial blood flow (MBF) and oxygen extraction (EO2), in RV and left ventricle (LV) during stimulation with inotropic drugs. Main methodsTwenty-one anesthetized dogs were studied. MBF was measured with radioactive microspheres. A-VO2 difference was determined separately for RV and LV, and used to calculate MVO2 (Fick equation) and EO2. Responses to iv. infusions of isoproterenol (0.1μg/kg/min), dobutamine (5μg/kg/min), and amrinone (1mg/kg+10μg/kg/min) were assessed. Key findingsBaseline MVO2 in RV was 50–60% of that in LV. The inotropes increased MVO2 in both RV and LV (range 32–63%; P<0.05). With isoproterenol, the increased MVO2 in the RV was due to increases in both MBF and EO2, whereas in LV it was due only to increases in MBF. With dobutamine and amrinone, the increased MVO2 in RV was due to increased MBF while EO2 was constant (dobutamine) or decreased (amrinone), and that in the LV was due to increased MBF while EO2 decreased. SignificanceRV possesses EO2 reserve that contributed to increased MVO2 during isoproterenol infusion, whereas LV depended on increased MBF alone. Because dobutamine and amrinone caused direct coronary vasodilation, i.e., “luxuriant perfusion,” it was not necessary to recruit the EO2 reserve. Thus, it remained available to meet further increases in MVO2 or to maintain MVO2 in the face of reductions in MBF.

Optimal Timing Algorithms of Para-Aortic Counterpulsation Device

Para-aortic counterpulsation device (PACD) is a promising therapy for severe heart failure (HF). However, the lack of knowledge about mechanisms has limited its clinical application. The aim of this study was to investigate the optimal timing algorithms. At the following four triggering algorithms, pre-R-wave-deflation and dicrotic notch-inflation (PD), pre-R-wave-deflation and postdicrotic notch-inflation (PP), R-wave-deflation and dicrotic notch-inflation (RD), and R-wave-deflation and postdicrotic notch-inflation (RP), hemodynamic effects of PACD were assessed in vivo. There was more significant promotion of left mean coronary artery flow (Q(LM)), carotid artery flow (Q(CA)), cardiac output (CO), pulmonary artery flow/LA pressure ratio (Q(PA)/LAP), left ventricular myocardial oxygen consumption (LVVO(2)), external LV work (ELVW), and cardiac mechanical efficiency (CME) at RD and RP models than PD and PP models. R-wave-deflation and postdicrotic notch-inflation model provided further benefits. There was significant correlation between LV functional parameters and carotid arterial reflux, but aortic pressure-related parameters. Filling at beginning of LV systolic phase and ejection at the end of isovolumic relaxation phase were the optimal triggering algorithms of PACD. It is suggested that carotid artery reflows and ventricular pressure-related parameters should be used as reference standard to adjust the timing of balloon inflation or deflation.

Heart Rate Reduction Induced by the If Current Inhibitor Ivabradine Improves Diastolic Function and Attenuates Cardiac Tissue Hypoxia

Enhanced heart rate (HR) is a compensatory mechanism in chronic heart failure (CHF), preserving cardiac output, but at the cost of increased left ventricular (LV) oxygen consumption and impaired diastolic function. The HR reduction (HRR) induced by the If current inhibitor ivabradine prevents LV systolic dysfunction in CHF, but whether HRR improves LV diastolic function is unknown. LV diastolic function and remodeling were assessed in rats with CHF after coronary ligation after long-term (90 days, starting 7 days after ligation) and delayed short-term (4 days, starting 93 days after ligation) ivabradine treatment (10 mg·kg·d). Long- and short-term HRR reduced LV end-diastolic pressure, LV relaxation, and LV end-diastolic pressure-volume relation. Simultaneously, LV hypoxia-inducible factor-1α expression was reduced. Long-term and, to a more marked extent, short-term HRR increased endothelial cell proliferation, associated after long-term HRR with the prevention of CHF-related LV capillary rarefaction. Long-term and, to a lesser extent, short-term HRR increased endothelial nitric oxide synthase expression, associated after long-term HRR with improved nitric oxide-dependent coronary vasodilatation. Long-term HRR induced by ivabradine improves diastolic LV function probably involving attenuated hypoxia, reduced remodeling, and/or preserved nitric oxide bioavailability, resulting from processes triggered early after HRR initiation: angiogenesis and/or preservation of endothelial nitric oxide synthase expression.

A dose–response study of levosimendan in a porcine model of acute ischaemic heart failure

Levosimendan is a novel inotropic agent claimed to improve myocardial contractility by a calcium-sensitizing effect. Our aim was to evaluate dose-dependent effects of levosimendan on left ventricular (LV) contractility and energetic properties in an acute, ischaemic heart failure porcine model. Six pigs were used in an anaesthetized in vivo open-chest model. The time points of measurements were: baseline, after heart failure induction and after dose 1-4 (D1-D4). Heart failure was induced by microembolization of the left coronary artery before infusion of four different doses (D1: 2.5 µg/kg, D2: 10 µg/kg, D3: 40 µg/kg, D4: 80 µg/kg) of levosimendan. Haemodynamics were assessed by the pressure-conductance catheter technique. LV oxygen consumption was calculated from coronary flow measurements and coronary sinus blood gases. Mitochondrial respiration was studied in biopsies of the LV. Levosimendan had no significant, load-independent effect on contractile force (slope of preload recruitable stroke work was 34 mmHg immediately following failure and 39 (P = 0.406), 42 (P = 0.219), 46 (P = 0.067) and 41 (P = 0.267) at D1-D4), although the more load-dependent contractility indicator of dP/dt(max) was slightly increased at dose 4 (P < 0.05). LV energy conversion efficiency (PVA-MVO2 relationship) remained unaltered at all doses. Maximal mitochondrial respiration decreased after induction of failure and remained at an unaltered low level during levosimendan infusion. Surprisingly, levosimendan had no significant effect on contractility, energy efficiency and mitochondrial respiration of the LV, in a porcine model of acute heart failure. At high doses, levosimendan induced vasodilatation and increased heart rate and cardiac output.

Prognostic Value of NT-proBNP at Rest and Peak Exercise in Patients With Impaired Left Ventricular Function

We aimed to identify whether N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) at peak exercise can provide incremental clinical information over resting levels. A total of 90 patients with systolic heart failure were prospectively studied. Levels of plasma NT-proBNP were assessed at rest and at peak exercise during a cardiopulmonary exercise test. Patients were followed-up for 30 ± 10 months. Levels of NT-proBNP at baseline and peak exercise were significantly correlated with left ventricular ejection fraction ([LVEF] r = -.629, P < .001 and r = -.630, P < .001, respectively) and peak oxygen uptake ([Vo (2)] r = -.752, P < .001 and r = -.740, P < .001, respectively). Levels of plasma NT-proBNP at peak exercise demonstrated similar predictive ability for the detection of patients with low peak Vo (2) and LVEF <28%. Levels of plasma NT-proBNP can detect low-functional class patients and patients who may be the candidates for heart transplantation with high sensitivity and specificity. At baseline and peak exercise, NT-proBNP demonstrates similar prognostic and predictive ability.

O-24 Desflurane anaesthesia results in more stable left ventricular function and lower oxygen extraction ratio compared to propofol during off-pump coronary surgery

O-24 Desflurane anaesthesia results in more stable left ventricular function and lower oxygen extraction ratio compared to propofol during off-pump coronary surgery