Left Ventricular Pressure Recordings Research Articles

Эффекты кардиотоксинов кобры на папиллярной мышце и сердце крысы, перфузируемом по Лангендорфу, не связаны с выбросом адреналина

In a study of the effects of cobra cardiotoxins on myocardial tissue, both right ventricular (papillary muscle) and left ventricular contractility (isovolumic recording of left ventricular pulse pressure during Langendorff perfusion of the heart) were assessed. In papillary muscle, both toxins, at a concentration of 5 μg/mL, caused short-term increases in contractility to 200±25% and 171±15% for CTX-1 and CTX-2, respectively, at the point of maximum effect. At the same time, for CTX-1 and CTX-2, the time to peak tension (TPT) increased from 104±2 to 111±2 and from 96±2 to 104±5 ms, the relaxation time to 50%(TR50%) from 64±4 to 70±6 and from 64±6 to 69±7 ms, and the relaxation time to 95%(TR95%) from 163±10 to 190±22 and from 148±16 to 155±20 ms, respectively. This significantly differs from the positive inotropic effect of the β-adrenomimetic isoproterenol (170±31%), which causes acceleration of TPT from 106±5 to 89±4 ms, TR50% from 58±6 to 43±4 ms, and TR95% from 145±15 to 90±14 ms. When the whole heart was exposed to cardiotoxins, an increase in contractility was also observed, followed by its suppression and contracture, in contrast to isoproterenol, which caused a steady increase in contractility coupled with an increase in heart rate. Pretreatment of papillary muscles with the β-blocker propranolol 
 (10 μM) did not prevent the development of cardiotoxin effects, but completely blocked the effects of isoproterenol. Our data indicate that the temporary increase in contractility under the action of cardiotoxins is not associated with the release of endogenous adrenaline, but rather is caused by changes in calcium homeostasis in cardiomyocytes.

Invasive validation of pressure-volume loops derived from cardiovascular magnetic resonance imaging and brachial blood pressure in heart failure patients

Abstract Introduction Left ventricular (LV) pressure-volume (PV) loops provide gold-standard physiological information but require invasive measurements of ventricular intracavity pressure, limiting clinical and research applications. Recent development has seen the introduction of non-invasively computed PV loops from cardiovascular magnetic resonance (CMR) volumetry and a brachial blood pressure measurement. The approach combines LV volumes with a time-varying elastance function to compute time-resolved LV pressures and was validated on invasive pressure data from a porcine model. The method is readily implemented using standard CMR sequences and provides measures of hemodynamic parameters including stroke work, myocardial efficiency, and contractile state. However, the method remains to be validated in patients using invasive left ventricular pressure recordings. Purpose To validate for the first time in human patients the performance of non-invasively computed PV loops against invasive measures. Methods Four heart failure patients underwent two subsequent sessions of CMR cine imaging and simultaneous brachial blood pressure measurement, with intravenous administration of two different vasoactive drugs, resulting in two different haemodynamic states for each patient. LV catheterization was then conducted with repeat administration of the same infusions. Pressure-volume loops were computed from CMR volumes combined with 1) a time-varying elastance function scaled to brachial blood pressure and temporally stretched to match volume data, and 2) invasive pressures averaged from multiple sampled beats. Method comparison was conducted using linear regression and Bland-Altman analysis. Results Figure 1 shows non-invasively derived PV loop parameters compared to invasive data. The non-invasive method demonstrated strong correlations and low bias for stroke work (R2=0.97, bias 4.6%, p<0.0001), potential energy (R2=0.83, bias 1.5%, p=0.001), end-systolic pressure-volume relationship (R2=0.90, bias 5.4%, p=0.0003), energy per ejected volume (R2=0.93, bias 3.5%, p=0.0001), ventricular efficiency (R2=0.99, bias 1.1%, p<0.0001), arterial elastance (R2=0.87, bias −7.8%, p=0.0006), and mean external power (R2=0.89, bias 4.6%, p=0.0005). Conclusions Pressure-volume loops can be precisely and accurately computed from cardiovascular magnetic resonance imaging and brachial cuff blood pressure in humans, and is ready for use in research applications. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Swedish Heart Lung Foundation

Effect and mechanism of leonurine on pressure overload-induced cardiac hypertrophy in rats

To investigate the effects of leonurine(Leo) on abdominal aortic constriction(AAC)-induced cardiac hypertrophy in rats and its mechanism. A rat model of pressure overload-induced cardiac hypertrophy was established by AAC method. After 27-d intervention with high-dose(30 mg·kg~(-1)) and low-dose(15 mg·kg~(-1)) Leo or positive control drug losartan(5 mg·kg~(-1)), the cardiac function was evaluated by hemodynamic method, followed by the recording of left ventricular systolic pressure(LVSP), left ventricular end-diastolic pressure(LVESP), as well as the maximum rate of increase and decrease in left ventricular pressure(±dp/dt_(max)). The degree of left ventricular hypertrophy was assessed based on heart weight index(HWI) and left ventricular mass index(LVWI). Myocardial tissue changes and the myocardial cell diameter(MD) were measured after hematoxylin-eosin(HE) staining. The contents of angiotensin Ⅱ(AngⅡ) and angiotensin Ⅱ type 1 receptor(AT1 R) in myocardial tissue were detected by ELISA. The level of Ca~(2+) in myocardial tissue was determined by colorimetry. The protein expression levels of phospholipase C(PLC), inositol triphosphate(IP3), AngⅡ, and AT1 R were assayed by Western blot. Real-time quantitative PCR(qRT-PCR) was employed to determine the mRNA expression levels of β-myosin heavy chain(β-MHC), atrial natriuretic factor(ANF), AngⅡ, and AT1 R. Compared with the model group, Leo decreased the LVSP, LVEDP, HWI, LVWI and MD values, but increased ±dp/dt_(max) of the left ventricle. Meanwhile, it improved the pathological morphology of myocardial tissue, reduced cardiac hypertrophy, edema, and inflammatory cell infiltration, decreased the protein expression levels of PLC, IP3, AngⅡ, AT1 R, as well as the mRNA expression levels of β-MHC, ANF, AngⅡ, AT1 R, c-fos, and c-Myc in myocardial tissue. Leo inhibited AAC-induced cardiac hypertrophy possibly by influencing the RAS system.

Novel insights into the athlete's heart: is myocardial work the new champion of systolic function?

AimsWe sought to investigate the correlation between speckle-tracking echocardiography (STE)-derived myocardial work (MW) and invasively measured contractility in a rat model of athlete's heart. We also assessed MW in elite athletes and explored its association with cardiopulmonary exercise test (CPET)-derived aerobic capacity.Methods and resultsSixteen rats underwent a 12-week swim training program and were compared to controls (n = 16). STE was performed to assess global longitudinal strain (GLS), which was followed by invasive pressure-volume analysis to measure contractility [slope of end-systolic pressure–volume relationship (ESPVR)]. Global MW index (GMWI) was calculated from GLS curves and left ventricular (LV) pressure recordings. In the human investigations, 20 elite swimmers and 20 healthy sedentary controls were enrolled. GMWI was calculated through the simultaneous evaluation of GLS and non-invasively approximated LV pressure curves at rest. All subjects underwent CPET to determine peak oxygen uptake (VO2/kg). Exercised rats exhibited higher values of GLS, GMWI, and ESPVR than controls (−20.9 ± 1.7 vs. −17.6 ± 1.9%, 2745 ± 280 vs. 2119 ± 272 mmHg·%, 3.72 ± 0.72 vs. 2.61 ± 0.40 mmHg/μL, all PExercise < 0.001). GMWI correlated robustly with ESPVR (r = 0.764, P < 0.001). In humans, regular exercise training was associated with decreased GLS (−17.6 ± 1.5 vs. −18.8 ± 0.9%, PExercise = 0.002) but increased values of GMWI at rest (1899 ± 136 vs. 1755 ± 234 mmHg·%, PExercise = 0.025). GMWI exhibited a positive correlation with VO2/kg (r = 0.527, P < 0.001).ConclusionsGMWI precisely reflected LV contractility in a rat model of exercise-induced LV hypertrophy and captured the supernormal systolic performance in human athletes even at rest. Our findings endorse the utilization of MW analysis in the evaluation of the athlete’s heart.

To Vent or Not to Vent: A Loaded Question During Venoarterial Extracorporeal Membrane Oxygenation Support for Cardiogenic Shock

To Vent or Not to Vent: A Loaded Question During Venoarterial Extracorporeal Membrane Oxygenation Support for Cardiogenic Shock

Natural shear wave propagation speed is influenced by both changes in myocardial structural properties as well as loading conditions

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research Foundation - Flanders (FWO) Background Shear wave elastography (SWE) is a promising tool for the non-invasive assessment of myocardial stiffness. It is based on the evaluation of the propagation speed of shear waves by high frame rate echocardiography. These waves can be induced by for instance mitral valve closure (MVC) and the speed at which they travel is related to the instantaneous stiffness of the myocardium. Myocardial stiffness is defined by the local slope of the stress-strain relation and can therefore be altered by both changes in structural properties of the myocardium as well as loading conditions. Purpose The aim of this study was to investigate how changes in myocardial structural properties as well as loading conditions affect shear wave speed after MVC. Methods Until now, 8 pigs (weight: 33.6 ± 5.4 kg) were included. The following interventions were performed: 1) preload was reduced by balloon occlusion of the vena cava inferior, 2) afterload was increased by balloon occlusion of descending aorta, 3) preload was increased by intravenous administration of 500 ml of saline and 4) ischemia/reperfusion injury (I/R injury) was induced in the septal wall by balloon occlusion of the LAD for 90 min. with subsequent reperfusion for 40 min. Echocardiographic and left ventricular pressure recordings were simultaneously obtained during each intervention. Left ventricular parasternal long-axis views were acquired with an experimental high frame rate ultrasound scanner (average frame rate: 1279 ± 148 Hz). Shear waves were visualized on tissue acceleration maps by drawing an M-mode line along the interventricular septum. Shear wave propagation speed after MVC was calculated by assessing the slope of the wave pattern on the tissue acceleration map (Figure A). Results The change in left ventricular end-diastolic pressure (LVEDP) and shear wave speed after MVC between baseline and each intervention are shown in Figure B and C, respectively. Preload reduction resulted in significant lower LVEDP compared to baseline (p &amp;lt; 0.01), while the other loading changes did not have a significant effect. Shear wave speed after MVC significantly increased by afterload and preload increase (p &amp;lt; 0.01). I/R injury resulted in increased shear wave speed (p &amp;lt; 0.01) without significantly altering LVEDP. There was a good positive correlation between the change in LVEDP and the change in shear wave speed induced by loading changes (r = 0.76; p &amp;lt; 0.001) (Figure D). However, the correlation became less strong if data of I/R injury was taken into account as well (r = 0.63; p &amp;lt; 0.001). Conclusion Our results suggest that SWE is capable to characterize myocardial tissue properties and besides has the potential as a novel method for the estimation of left ventricular filling pressures. However, in the presence of structural changes of the myocardium, care should be taken when estimating filling pressures based on shear wave propagation speed. Abstract Figure.

The behaviour of natural shear waves under different loading conditions

Abstract Background Shear wave imaging (SWI) is a novel ultrasound technique based on the detection of transverse waves traveling through the myocardium using high frame rate echocardiography. These waves can be naturally induced e.g. by mitral valve closure (MVC). Their propagation velocity is dependent on the stiffness of the myocardium. Previous studies have shown the potential of SWI for the non-invasive assessment of myocardial stiffness. So far, the influence of loading on shear wave propagation velocities has not been extensively investigated. Purpose The aim of this study was to explore how loading changes affect shear wave propagation velocities after MVC. Methods Until now, 5 pigs (weight: 33.5±6.9 kg) were included. Echocardiographic images and left ventricular pressure recordings were simultaneously acquired during acute loading alterations: 1) preload was reduced by balloon occlusion of the vena cava inferior, 2) afterload was increased by balloon occlusion of the descending aorta and 3) preload was increased by intra-venous administration of 500 ml of saline. Left ventricular parasternal long-axis views were acquired with an experimental high frame rate ultrasound scanner (average frame rate: 1247±179 Hz). Shear waves were visualized on tissue acceleration maps by drawing an M-mode line along the interventricular septum. Shear wave propagation velocities after MVC were calculated by measuring the slope of the wave front on the acceleration maps (Figure A). Results The changes in left ventricular end-diastolic pressures (LV EDP) between baseline and each intervention are shown in Figure B. Preload reduction resulted in significantly reduced LV EDP (p&amp;lt;0.01). The shear wave propagation velocities after MVC dropped with preload reduction and increased significantly by increasing afterload as well as preload (both p&amp;lt;0.05) (Figure C). There was a good positive correlation between the change in LV EDP and the change in shear wave velocities (r=0.83; p&amp;lt;0.001) (Figure D). Conclusion The shear wave propagation velocity after MVC was significantly influenced by alterations in left ventricular loading conditions and changes in these velocities were related to changes in LV EDP. These results indicate that shear wave measurements at MVC might be a potential novel parameter for the estimation of left ventricular filling pressures. More pigs will be included in the future to further confirm these findings. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Fonds Wetenschappelijk Onderzoek - Vlaanderen

Echocardiographic assessment of simultaneously measured left ventricular filling pressures in patients with normal left ventricular ejection fraction

Assessment of left ventricular (LV) diastolic function is part of routine echocardiographic examinations. Accuracy of the 2016 ASE/EACVI algorithm to detect LV diastolic dysfunction in patients with a normal LV ejection fraction (LVEF) has been examined but simultaneous measurements of LV pressures and echocardiographic parameters of diastolic function are sparse. The accuracy of multiple echo parameters of diastolic dynamics and the 2016 guidelines were assessed by simultaneous transthoracic echocardiography and LV pressure recordings in 120 patients (derivation cohort) and 60 patients (validation cohort) with suspected coronary artery disease and normal LVEF. Receiver-operating characteristic (ROC) curves defined optimal cut points for each echocardiographic parameter. A new algorithm was proposed to estimate LV diastolic pressures using 5 parameters based on ROC data: tricuspid regurgitation velocity >280cm/s, average e' <9cm/s, average E/e' ratio >13, velocity of pulmonary vein A-wave reversal >32cm/s, and left atrial volume index >32mL/m2 . Performances of the 2016 guidelines and a proposed algorithm were examined for detecting a LV pre-A >12 and LV end-diastolic pressure (LVEDP) >15mmHg. In the derivation cohort, the 2016 algorithm identified an elevated LVEDP >15mmHg with an accuracy of 74.2% (63.8-82.9); the modified algorithm improved accuracy to 86.0% (77.6-92.1), P<.05. In the validation cohort, the proposed algorithm improved sensitivities with accuracies remaining like the 2016 algorithm. LV diastolic pressures in patients with normal LVEF were reliably assessed by the 2016 guidelines. The proposed algorithm improved sensitivities and may improve the accuracies for detecting abnormal LV filling pressures.

Left Ventricular End-Systolic Volume Is a Reliable Predictor of New-Onset Heart Failure with Preserved Left Ventricular Ejection Fraction.

Background Left ventricular (LV) ejection fraction (EF) and LV volumes were reported to have prognostic efficacy in cardiac diseases. In particular, the end-systolic volume index (LVESVI) has been featured as the most reliable prognostic indicator. However, such efficacy in patients with LVEF ≥ 50% has not been elucidated. Methods We screened the patients who received cardiac catheterization to evaluate coronary artery disease concomitantly with both left ventriculography and LV pressure recording using a catheter-tipped micromanometer and finally enrolled 355 patients with LVEF ≥ 50% and no history of heart failure (HF) after exclusion of the patients with severe coronary artery stenosis requiring early revascularization. Cardiovascular death or hospitalization for HF was defined as adverse events. The prognostic value of LVESVI was investigated using a Cox proportional hazards model. Results A univariable analysis demonstrated that age, log BNP level, tau, peak − dP/dt, LVEF, LV end-diastolic volume index (LVEDVI), and LVESVI were associated with adverse events. A correlation analysis revealed that LVESVI was significantly associated with log BNP level (r = 0.356, p < 0.001), +dP/dt (r = −0.324, p < 0.001), −dP/dt (r = 0.391, p < 0.001), and tau (r = 0.337, p < 0.001). Multivariable analysis with a stepwise procedure using the variables with statistical significance in the univariable analysis revealed that aging, an increase in BNP level, and enlargement of LVESVI were significant prognostic indicators (age: HR: 1.071, 95% CI: 1.009–1.137, p=0.024; log BNP : HR : 1.533, 95% CI: 1.090–2.156, p=0.014; LVESVI : HR : 1.051, 95% CI: 1.011–1.093, p=0.013, respectively). According to the receiver-operating characteristic curve analysis for adverse events, log BNP level of 3.23 pg/ml (BNP level: 25.3 pg/ml) and an LVESVI of 24.1 ml/m2 were optimal cutoff values (BNP : AUC : 0.753, p < 0.001, LVESVI : AUC : 0.729, p < 0.001, respectively). Conclusion In patients with LVEF ≥ 50%, an increased LVESVI is related to the adverse events. LV contractile performance even in the range of preserved LVEF should be considered as a role of a prognostic indicator.

P6341Impact of left-ventricular hemodynamics on treadmill exercise intolerance in conscious rats: pilot evaluation in animals with diastolic dysfunction

Abstract Introduction Exercise intolerance is a clinical hallmark of patients with hypertrophic cardiomyopathy and/or impaired diastolic function. Elevated LV filling pressures, particularly in response to acute exercise bouts, are thought to play a role limiting exercise capacity in ventricles with abnormal relaxation/compliance. However, it is experimentally difficult to obtain in vivo hemodynamic measures necessary for the evaluation of centrally mediated dysfunction. Leveraging radio-telemetry, we evaluated central hemodynamic parameters as mediators of exercise intolerance in obese ZSF1 rats with diabetes, hypertension, and diastolic dysfunction. Methods Both ZSF1 (637+12g, n=8) and age-matched (28 weeks) healthy control (CTRL, 543+14g, n=4, P&lt;0.05) rats were instrumented for telemetric left-ventricular pressure (LVP) recordings. Following surgical recovery rats were familiarized to treadmill running and subsequently challenged with an exercise protocol aimed at increasing heart rate by 200 beats/min (5° incline, 15 m/min, increased by 3 m/min every 2-min) until volitional exhaustion. LV pressures were collected continuously during cage resting, treadmill resting, and post-exercise until heart rate returned to baseline. Additionally, resting echocardiographic and blood glucose measures were collected. Results At rest, ZSF1 rats had preserved ejection fraction (73+6 vs 79+9%), elevated (P&lt;0.05) blood glucose (237+83 vs 94+23 mg/dL), end-systolic (147+18 vs 103+13 mmHg), and end-diastolic pressures (16+3 vs 9+3 mmHg), with preserved indexed end-diastolic volumes (670+95 vs 741+89 μL/kg), suggesting impaired diastolic compliance. ZSF1 rats terminated exercise prematurely (8:26+1:20 vs 10:27+1:18 min, P&lt;0.05), indicating a limitation in exercise capacity. This early volitional exhaustion was noted while end-diastolic pressures were not further increased (17+7 mmHg), suggesting that other pathological derangement may play a role modulating exercise capacity. For instance, ZSF1 rats tended to have a blunted increase in the systolic index dP/dt40 (+2589+1450 vs +3938+749 mmHg/s, P&lt;0.1) despite achieving comparable increases in HR (193+34 vs 196+38 bpm) with exercise. Conclusion This pilot study demonstrates the feasibility for evaluation of left-ventricular hemodynamics during exercise in rodents with diastolic dysfunction, establishing a platform to evaluate both the mechanisms of exercise intolerance as well as potential therapeutic approaches to rescue exercise capacity. Acknowledgement/Funding MyoKardia

Usefulness of Cibenzoline Stress Echocardiography to Determine Severity of Aortic Stenosis in a Patient with Combined Left Ventricular Outflow Tract Obstruction and Aortic Stenosis

Left ventricular outflow tract obstruction (LVOTO) is sometimes accompanied by aortic stenosis (AS). Reliable estimation of the true severity of AS is often difficult because it cannot be discriminated from dual stenosis. A 75-year-old woman was referred to our hospital due to traumatic hemopneumothorax with exertional dyspnea. Echocardiography revealed AS and LVOTO by chance. A continuous Doppler echocardiography revealed a late-systolic peaking dagger-shaped profile with a 6.0 m/s of peak jet velocity across the LVOT and aortic valve, but it was difficult to discriminate between the coexisting peak flows. For an accurate evaluation of AS, we performed landiolol (short acting beta-blocker) and cibenzoline (Na+ channel-blocking agent) stress echocardiography with simultaneous recordings of both left ventricular and aortic pressure by catheter examination. Cibenzoline successfully eliminated the LVOTO, but landiolol did not. Cibenzoline stress echocardiography enabled us to evaluate the AS severity as less than moderate, resulting in proper decision-making. The findings in this case clearly showed that cibenzoline stress echocardiography has a potential utility for determining AS severity in a patient with coexistent dynamic LVOTO.

Assessment of Intra-Aortic Counterpulsation in an Animal Model of Heart Failure and Myocardial Ischemia.

The effectiveness of intra-aortic balloon pumping (IABP) is currently evaluated using indirect indexes. The diastolic pressure augmentation is quantified using the subendocardial viability ratio (SEVR) and the DABAC/SABAC index (areas beneath the aortic pressure-time signals during the diastolic and systolic periods, respectively). The SEVR requires invasive recordings of left ventricular pressure; the DABAC/SABAC index may represent an alternative, since it only requires an aortic pressure signal. Nonetheless, it has never been used in an animal model of counterpulsated heart failure and ischemia-reperfusion episode. The aims of this work were: (i) to develop an animal model of heart failure, with a myocardial ischemia-reperfusion episode, treated with IABP during the reperfusion period; (ii) to evaluate the effects of the IABP using the SEVR and DABAC/SABAC indices; and (iii) to assess the relationship between both ratios. Cardiovascular parameters were obtained in anesthetized sheep, in which induced heart failure and ischemia-reperfusion episodes were monitored with and without IABP 1:2. Systolic and diastolic blood pressure signals were assessed in the aorta and in the left ventricle. Values of cardiac output and left ventricular wall thickness signals were obtained. Induction of ischemia and heart failure determined decreases in SEVR and DABAC/SABAC indices with respect to their basal stage (0.807±0.118 vs. 0.601±0.107, P<0.05 and 1.062±0.136 vs. 0.902±0.161, P<0.05, respectively). Counterpulsated animals whose myocardial reperfusion was accompanied by heart failure showed a significant improvement of wall thickening fraction along time (R2 =0.7627, P<0.001). During counterpulsated heart failure accompanied by myocardial reperfusion, the SEVR was positively correlated with DABAC/SABAC index.

O14-5 - Constrictive Pericarditis after Repeated Accumulation of Pericardial Effusion due to Long-term Chylopericardium

Primary chylopericardium is a rare disease characterized by the accumulation of chylous fluid containing high triglyceride in the pericardial cavity without a specific cause. We report a case of severe constrictive pericarditis due to 9-year history of primary chylopericardium and surgical ligation of the thoracic duct and pericardial window creation. A 24-year old woman diagnosed as primary chyropericardium, was admitted to our hospital for further treatment of heart failure. She had undergone ligation of the thoracic duct and the creation of a pericardial window. She complained of exertional dyspnea and physical examination revealed elevated jugular venous pressure. Chest X-ray showed a normal cardiac silhouette with extensive transudative pleural effusion. Echocardiogram showed severe mitral regurgitation which was slightly observed before surgery, a few pericardial effusion. Left and right ventricular simultaneous pressure recordings revealed equilibration of both ventricular diastolic pressures and a dip-and-plateau configuration. A CT scan demonstrated the thickened pericardium. Based on these findings, she was diagnosed as constrictive pericarditis and severe mitral regurgitation probably due to worsening mitral annular disjunction caused by the tight pericardium adhesion to the myocardium. During surgery, extensive tissue adhesions were observed from pericardium to epicardium. Histological examination revealed fibro-adipose pericardium with chronic inflammation and myxoid degeneration. She successfully underwent pericardiectomy and mitral valve plasty, and discharged home with greatly improved symptoms.

256 NEW EVIDENCE FOR VAGAL CONTROL OF THE LEFT HEART

The role of the parasympathetic innervation of the left ventricle remains controversial, although there is some evidence that vagus nerve stimulation decreases left ventricular contractility in vivo in the human and pig heart. The aim of this study was to identify the anatomical location of vagal preganglionic neurones that control ventricular contractility using an anaesthetised rat model. Male Sprague-Dawley rats (350–400 g, n=6) were anaesthetised with pentobarbitone sodium (induction 60 mg/kg i.p.; maintenance 15–20 mg/kg/hr i.v.) and artificially ventilated. The left femoral artery and both femoral veins were cannulated for the measurement of arterial pressure and administration of fluids and drugs. The right carotid artery was cannulated for left ventricular pressure recording using a Millar pressure probe. Lead II ECG was also monitored. The animal was placed in a stereotaxic frame and the dorsal surface of the brainstem was exposed. To activate vagal preganglionic neurones, an excitatory neurotransmitter glutamate (10 mM, 40 nl, pH 7.4) was microinjected into three discrete locations (separated by 0.5 mm) along the rostro-caudal extent of the left and right dorsal motor nuclei of the vagus nerve (DVMN). Responses were measured in a second group (n=3) with transoesophageal atrial pacing (TAP) to abolish chronotropic changes. A third group (n=2) underwent a spinal transection at C1 to remove sympathetic influences followed by gelofusine and vasopressin infusion to maintain mean arterial blood pressure at ∼100mmHg. Values are means±S.E.M., compared by paired student’s t-test. Glutamate microinjections into the most caudal part of the left DVMN caused a significant (p

Dual recordings of left ventricular and arterial pressure in conscious rats via telemetry

Dual recordings of left ventricular and arterial pressure in conscious rats via telemetry

Strain, Strain Rate, and the Force Frequency Relationship in Patients with and without Heart Failure

The aim of this study was to examine the effect of heart rate (HR) on indices of deformation in adults with and without heart failure (HF) who underwent simultaneous high-fidelity catheterization of the left ventricle to describe the force-frequency relationship. Right atrial pacing to control HR and high-fidelity recordings of left ventricular (LV) pressure were used to inscribe the force-frequency relationship. Simultaneous two-dimensional echocardiographic imaging was acquired for speckle-tracking analysis. Thirteen patients with normal LV function and 12 with systolic HF (LV ejection fraction, 31 ± 13%) were studied. Patients with HF had depressed isovolumic contractility and impaired longitudinal strain and strain rate. HR-dependent increases in LV+dP/dt(max), the force-frequency relationship, was demonstrated in both groups (normal LV function, baseline to 100 beats/min: 1,335 ± 296 to 1,564 ± 320 mm Hg/sec, P < .0001; HF, baseline to 100 beats/min: 970 ± 207 to 1,083 ± 233 mm Hg/sec, P < .01). Longitudinal strain decreased significantly (normal LV function, baseline to 100 beats/min: 18.0 ± 3.5% to 10.8 ± 6.0%, P < .001; HF: 9.4 ± 4.1% to 7.5 ± 3.4%, P < .01). The decrease in longitudinal strain was related to a decrease in LV end-diastolic dimensions. Strain rate did not change with right atrial pacing. Despite the inotropic effect of increasing HR, longitudinal strain decreases in parallel with stroke volume as load-dependent indices of ejection. Strain rate did not reflect the modest HR-related changes in contractility; on the other hand, the use of strain rate for quantitative stress imaging is also less likely to be confounded by chronotropic responses.

Short-term ventricular restraint attenuates post-infarction remodeling in rats

Background/objectivesLeft ventricular restraint attenuates post-infarction remodeling, but may be associated with unfavorable long-term histological response. We hypothesized that beneficial effects can be obtained with short-term restraint during the early post-infarction period; for this purpose, we evaluated a biodegradable scaffold in the in vivo rat model and compared it with epicardial hydrogel application. MethodsA total of 230 Wistar rats (358±7g) were studied. Implantation was performed with and without prior myocardial infarction, induced by permanent coronary artery ligation. Diastolic filling was evaluated by left ventricular pressure recordings after scaffold implantation. Degradation rates and inflammatory/foreign body response were studied at 3, 7 and 15days post-ligation. Remodeling indices were evaluated by echocardiography 15days post-ligation. ResultsNo differences were found in diastolic pressure. Biodegradability was ~50% by 7days and 100% by 15days for both materials. Likewise, inflammatory/foreign body response peaked at 3days post-implant, with subsequent remission, but fibroblastic reaction was more pronounced after scaffold than after hydrogel implantation. Post-ligation, ejection fraction was higher in the scaffold (40.0±1.5%) or hydrogel groups (37.0±1.3%), compared to controls (30.6±1.9%). Wall tension index was lower with either biomaterial, but left ventricular end-diastolic diameter was shorter (p=0.044) and sphericity was attenuated (p=0.029) after scaffold, compared to hydrogel implantation. ConclusionsBoth biomaterials showed a favorable histological response and attenuated remodeling, but epicardial restraint produced better results compared to hydrogel alone. The latter approach merits further investigation due to the ease of implantation.

Early ion-channel remodeling and arrhythmias precede hypertrophy in a mouse model of complete atrioventricular block

Complete atrioventricular block (CAVB) and related ventricular bradycardia are known to induce ventricular hypertrophy and arrhythmias. Different animal models of CAVB have been established with the most common being the dog model. Related studies were mainly focused on the consequences on the main repolarizing currents in these species, i.e. IKr and IKs, with a limited time point kinetics post-AVB. In order to explore at a genomic scale the electrical remodeling induced by AVB and its chronology, we have developed a novel model of CAVB in the mouse using a radiofrequency-mediated ablation procedure. We investigated transcriptional changes in ion channels and contractile proteins in the left ventricles as a function of time (12 h, 1, 2 and 5 days after CAVB), using high-throughput real-time RT-PCR. ECG in conscious and anesthetized mice, left ventricular pressure recordings and patch-clamp were used for characterization of this new mouse model. As expected, CAVB was associated with a lengthening of the QT interval. Moreover, polymorphic ventricular tachycardia was recorded in 6/9 freely-moving mice during the first 24 h post-ablation. Remarkably, myocardial hypertrophy was only evident 48 h post-ablation and was associated with increased heart weight and altered expression of contractile proteins. During the first 24 hours post-CAVB, genes encoding ion channel subunits were either up-regulated (such as Nav1.5, + 74%) or down-regulated (Kv4.2, −43%; KChIP2, −47%; Navβ1, −31%; Cx43, −29%). Consistent with the transient alteration of Kv4.2 expression, I to was reduced at day 1, but restored at day 5. In conclusion, CAVB induces two waves of molecular remodeling: an early one (≤ 24 h) leading to arrhythmias, a later one related to hypertrophy. These results provide new molecular basis for ventricular tachycardia induced by AV block.

Echocardiographic Evaluation of Left Ventricular Filling Pressures Validated Against an Implantable Left Ventricular Pressure Monitoring System

Aim of this study was to assess the ability of different echocardiographic indices to evaluate left ventricular (LV) filling pressures in patients with reduced LV function. In 5 patients scheduled for aortocoronary bypass surgery, a telemetric intraventricular pressure sensor was implanted. Over 6 months, these patients underwent a total of 21 echocardiographic examinations with a simultaneous recording of left ventricular mean (LVMDP) and end-diastolic pressure (LVEDP). The following echocardiographic parameters were extracted from the transmitral flow profile: early (E) and late (A) diastolic flow velocity, deceleration time of the E-wave (DT) and the isovolumic relaxation time (IVRT). Early diastolic velocity of the mitral ring (E') was recorded using pulsed-wave tissue Doppler echocardiography. All patients were in NYHA class III and mean ejection fraction was 30%. E correlated only moderately with LVMDP (r =-0.60, P = 0.003), but revealed the highest area under the receiver operating characteristic curve for the prediction of an elevated LVMDP > 12 mmHg (AUC = 0.94, sensitivity of 92% and specificity of 86%, cut-off value 7.5 cm/s). E/A > 1 predicted LVEDP > 15 mmHg with a sensitivity of 87% and a specificity of 80%. E/E' was not correlated with LVMDP or LVEDP. Although linear correlation between echocardiographic parameters and diastolic LV pressures reached statistical significance, the correlation coefficients were low. However, in these patients with severely reduced LV function due to ischemic heart disease conventional echocardiographic parameters of transmitral flow showed higher predictive values for elevated LV filling pressures than E/E'.

Left ventricular pressure measurement in the telemetered dog

Cardiac contractility is defi ned as the intrinsic ability of cardiac muscle fi bers to contract at a given fi ber length. Changes in the ability to produce strong contractions result from different degrees of binding between myosin and actin fi laments that depend in turn on the concentration of calcium ions in the cytosol of cardiac muscle cells. This is controlled by the action of noradrenaline and acetylcholine, neurotransmitters of the autonomic nervous system. The inotropic state of the heart is evaluated using the Left Ventricular Pressure (LVP) signal as an indirect measure of the force of ventricular myofi ber contraction. From the LVP, we can also derive useful parameters such as the maximum rate of ventricular pressure increase (dP/dt Max), the maximum rate of ventricular pressure decrease (dP/dt Min), and the Ejection Time (the duration of blood ejection from the left ventricle, beginning with opening of the aortic valve and ending with closing of the aortic valve). The aim of this study was to validate a chronic model of telemetered dog, thus allowing the evaluation of cardiac contractility by the recording of LVP in conjunction with ABP and ECG (Fig. 1) after oral administration of three known inotropic compounds.