Intrinsic Cardiac Function Research Articles

Subcutaneous B16 melanoma impairs intrinsic pressure generation and relaxation of the heart, which are not restored by short-term voluntary exercise in mice.

The aim of this study was to investigate whether subcutaneous melanoma impairs intrinsic cardiac function and hypoxia tolerance in mice. In addition, it was investigated whether these changes could be prevented by voluntary wheel-running exercise. The roles of different molecular pathways were also analyzed. Male mice (C57Bl/6NCrl) were divided into unexercised tumor-free group, unexercised melanoma group, and exercised melanoma group. The experiment lasted 2.7 ± 0.1 wk (determined by the tumor size) after which the heart function was measured in different oxygen levels ex vivo using Langendorff method. All the melanoma mice had lower pressure amplitude (50.3%), rate of pressure production (54.1%), and decline (52.5%) in hearts ex vivo when compared with tumor-free group. There were no functional differences between the two melanoma groups. All the groups had similar weight changes, heart weights, cardiomyocyte sizes, levels of Ca2+ channels, energy metabolism enzyme activities, lipid peroxidation, and reactive oxygen species in their cardiac tissue homogenates. However, all the melanoma mice had 7.4% lower superoxidase dismutase activity compared with the control animals, which might reduce the ability of the heart to react to changes in oxidative stress. The exercising melanoma group had a 28.6% higher average heart capillary density compared with the unexercised melanoma group. Short-term wheel running did not affect the tumor growth. In conclusion, subcutaneous melanoma seems to impair intrinsic heart function even before cachexia, and these functional alterations were not caused by any of the measured molecular markers. Short-term voluntary wheel-running exercise was insufficient to alleviate the intrinsic cardiac impairments caused by melanoma.NEW & NOTEWORTHY Melanoma has been shown to induce cardiac atrophy and impair cardiac function in vivo, however, it has not been investigated how melanoma affects the intrinsic heart function. Here, we showed that subcutaneous melanoma can impair intrinsic heart function in noncachectic mice, decreasing the heart's pressure production and relaxation. In addition, we investigated whether short-term voluntary wheel-running exercise could attenuate the impairment of intrinsic cardiac function. However, our results do not seem to support this hypothesis.

Microelectrode Array Recording of Sinoatrial Node Firing Rate to Identify Intrinsic Cardiac Pacemaking Defects in Mice.

The sinoatrial node (SAN), located in the right atrium, contains the pacemaker cells of the heart, and dysfunction of this region can cause tachycardia or bradycardia. Reliable identification of cardiac pacemaking defects requires the measurement of intrinsic heart rates by largely preventing the influence of the autonomic nervous system, which can mask rate deficits. Traditional methods to analyze intrinsic cardiac pacemaker function include drug-induced autonomic blockade to measure in vivo heart rates, isolated heart recordings to measure intrinsic heart rates, and sinoatrial strip or single-cell patch-clamp recordings of sinoatrial pacemaker cells to measure spontaneous action potential firing rates. However, these more traditional techniques can be technically challenging and difficult to perform. Here, we present a new methodology to measure intrinsic cardiac firing rate by performing microelectrode array (MEA) recordings of whole-mount sinoatrial node preparations from mice. MEAs are composed of multiple microelectrodes arranged in a grid-like pattern for recording in vitro extracellular field potentials. The method described herein has the combined advantage of being relatively faster, simpler, and more precise than previous approaches for recording intrinsic heart rates, while also allowing easy pharmacological interrogation.

Cardiac Response to β-Adrenergic Stimulation Determined by Pressure-Volume Loop Analysis

Here we describe a cardiac pressure-volume loop analysis under increasing doses of intravenously infused isoproterenol to determine the intrinsic cardiac function and the β-adrenergic reserve in mice. We use a modified open-chest approach for the pressure-volume loop measurements, in which we include ventilation with positive end-expiratory pressure.

Exercise heat acclimation has minimal effects on left ventricular volumes, function and systemic hemodynamics in euhydrated and dehydrated trained humans.

Heat acclimation (HA) may improve the regulation of cardiac output (Q̇) through increased blood volume (BV) and left ventricular (LV) diastolic filling and attenuate reductions in Q̇ during exercise-induced dehydration; however, these hypotheses have never been directly tested. Before and following 10-days exercise HA, eight males completed two trials of submaximal exercise in 33°C and 50% relative humidity while maintaining preexercise euhydrated body mass (EUH; -0.6 ± 0.4%) or becoming progressively dehydrated (DEH; -3.6 ± 0.7%). Rectal (Tre) and skin (Tsk) temperatures, heart rate (HR), LV volumes and function, systemic hemodynamics and BV were measured at rest and during bouts of semirecumbent cycling (55% V̇o2max) at 20, 100 and 180 min, interspersed by periods of upright exercise. Tre, BV, HR, LV volumes, LV systolic and diastolic function, and systemic hemodynamics were similar between trials at rest and during the first 20 min of exercise (all P > 0.05). These responses were largely unaffected by HA at 180 min in either hydration state. However, DEH induced higher Tre (0.6 ± 0.3°C) and HR (16 ± 7 beats/min) and lower end-diastolic volume (29 ± 16 mL), stroke volume (26 ± 16 mL), and Q̇ (2.1 ± 0.8 L/min) compared with EUH at 180 min (all P < 0.05), yet LV twist and untwisting rate were increased or maintained (P = 0.028 and 0.52, respectively). Findings indicate HA has minimal effects on LV volumes, LV mechanical function, and systemic hemodynamics during submaximal exercise in moderate heat, where HR and BV are similar. In contrast, DEH evokes greater hyperthermia and tachycardia, reduces BV, and impairs diastolic LV filling, lowering Q̇, regardless of HA state.NEW & NOTEWORTHY This study demonstrates that 10 days of exercise heat acclimation has minimal effects on left ventricular volumes, intrinsic cardiac function, and systemic hemodynamics during prolonged, repeated semirecumbent exercise in moderate heat, where heart rate and blood volume are similar to preacclimation levels. However, progressive dehydration is consistently associated with similar degrees of hyperthermia and tachycardia and reductions in blood volume, diastolic filling of the left ventricle, stroke volume, and cardiac output, regardless of acclimation state.

Load-independent effects of empagliflozin contribute to improved cardiac function in experimental heart failure with reduced ejection fraction

Background and aimsSodium–glucose linked cotransporter-2 (SGLT2) inhibitors reduce the likelihood of hospitalization for heart failure and cardiovascular death in both diabetic and non-diabetic individuals with reduced ejection fraction heart failure. Because SGLT2 inhibitors lead to volume contraction with reductions in both preload and afterload, these load-dependent factors are thought to be major contributors to the cardioprotective effects of the drug class. Beyond these effects, we hypothesized that SGLT2 inhibitors may also improve intrinsic cardiac function, independent of loading conditions.MethodsPressure–volume (P–V) relationship analysis was used to elucidate changes in intrinsic cardiac function, independent of alterations in loading conditions in animals with experimental myocardial infarction, a well-established model of HFrEF. Ten-week old, non-diabetic Fischer F344 rats underwent ligation of the left anterior descending (LAD) coronary artery to induce myocardial infarction (MI) of the left ventricle (LV). Following confirmation of infarct size with echocardiography 1-week post MI, animals were randomized to receive vehicle, or the SGLT2 inhibitor, empagliflozin. Cardiac function was assessed by conductance catheterization just prior to termination 6 weeks later.ResultsThe circumferential extent of MI in animals that were subsequently randomized to vehicle or empagliflozin groups was similar. Empagliflozin did not affect fractional shortening (FS) as assessed by echocardiography. In contrast, load-insensitive measures of cardiac function were substantially improved with empagliflozin. Load-independent measures of cardiac contractility, preload recruitable stroke work (PRSW) and end-systolic pressure volume relationship (ESPVR) were higher in rats that had received empagliflozin. Consistent with enhanced cardiac performance in the heart failure setting, systolic blood pressure (SBP) was higher in rats that had received empagliflozin despite its diuretic effects. A trend to improved diastolic function, as evidenced by reduction in left ventricular end-diastolic pressure (LVEDP) was also seen with empagliflozin. MI animals treated with vehicle demonstrated myocyte hypertrophy, interstitial fibrosis and evidence for changes in key calcium handling proteins (all p < 0.05) that were not affected by empagliflozin therapy.ConclusionEmpagliflozin therapy improves cardiac function independent of loading conditions. These findings suggest that its salutary effects are, at least in part, due to actions beyond a direct effect of reduced preload and afterload.

Assessment of PEEP-Ventilation and the Time Point of Parallel-Conductance Determination for Pressure-Volume Analysis Under β-Adrenergic Stimulation in Mice.

Aim: Cardiac pressure-volume (PV loop) analysis under β-adrenergic stimulation is a powerful method to simultaneously determine intrinsic cardiac function and β-adrenergic reserve in mouse models. Despite its wide use, several key approaches of this method, which can affect murine cardiac function tremendously, have not been experimentally investigated until now. In this study, we investigate the impact of three lines of action during the complex procedure of PV loop analysis: (i) the ventilation with positive end-expiratory pressure, (ii) the time point of injecting hypertonic saline to estimate parallel-conductance, and (iii) the implications of end-systolic pressure-spikes that may arise under β-adrenergic stimulation.Methods and Results: We performed pressure-volume analysis during β-adrenergic stimulation in an open-chest protocol under Isoflurane/Buprenorphine anesthesia. Our analysis showed that (i) ventilation with 2 cmH2O positive end-expiratory pressure prevented exacerbation of peak inspiratory pressures subsequently protecting mice from macroscopic pulmonary bleedings. (ii) Estimations of parallel-conductance by injecting hypertonic saline prior to pressure-volume recordings induced dilated chamber dimensions as depicted by elevation of end-systolic volume (+113%), end-diastolic volume (+40%), and end-diastolic pressure (+46%). Further, using this experimental approach, the preload-independent contractility (PRSW) was significantly impaired under basal conditions (−17%) and under catecholaminergic stimulation (−14% at 8.25 ng/min Isoprenaline), the β-adrenergic reserve was alleviated, and the incidence of ectopic beats was increased >5-fold. (iii) End-systolic pressure-spikes were observed in 26% of pressure-volume recordings under stimulation with 2.475 and 8.25 ng/min Isoprenaline, which affected the analysis of maximum pressure (+11.5%), end-diastolic volume (−8%), stroke volume (−10%), and cardiac output (−11%).Conclusions: Our results (i) demonstrate the advantages of positive end-expiratory pressure ventilation in open-chest instrumented mice, (ii) underline the perils of injecting hypertonic saline prior to pressure-volume recordings to calibrate for parallel-conductance and (iii) emphasize the necessity to be aware of the consequences of end-systolic pressure-spikes during β-adrenergic stimulation.

Comparative study of perfusion medium impact on hemodynamics of ex vivo swine hearts perfused in the biventricular working model

Large animal ex vivo biventricular working hearts are a recent breakthrough in the scientific experimental community. This model allows a greater insight into intrinsic cardiac electrophysiology and hemodynamic function without interference from autonomous nervous system. Perform a comparative study between different perfusion mediums and their impact on intrinsic hearts hemodynamics. Pig hearts were excised with the pericardium. Cardiac arrest was induced in vivo by infusion of cold cardioplegic solution into the aortic root, followed by a rapid excision and immersion in a cold 0.9% saline solution. Some hearts were perfused with autologous blood (1.5 diluted in 10L Tyrode's solution). The aorta, pulmonary artery, pulmonary veins and vena cava were cannulated and remaining vessels were sutured. Hearts were placed on the setup and perfused at fixed pre- and afterloads. All hearts were perfused with Tyrode's solution with BSA and fatty acids (FA) (group 1), or BSA/FA and blood (group 2) or blood (group 3). An increased aortic flow was observed in hearts perfused with blood without (+110%, P < 0.05) and with BSA/FA (+50%, non-significant) compared to BSA/FA group. A drop was noted in LV and RV minimum pressure (−75 to 100%), end diastolic pressure (−40 to 80%) and dP/dtmin (−50%) in hearts perfused with blood ± BSA/FA compared to BSA/FA only. dP/dtmax did not change in LV, but increased in the RV (+120–60% in blood ± BSA/FA groups). All hearts perfused with BSA/FA ± blood displayed a lower heart rate than hearts perfused with blood without BSA/FA ( P < 0.05). This study shows significant advantages the addition of blood has on the ex vivo heart hemodynamics, especially for diastolic parameters, leading to a better maintenance of function during perfusion. Limitation of edema and a better oxygen carrying capacity of blood help reduce localised ischemia by improving the overall perfusion of the myocardium.

Moderate Hypothermia Improves Cardiac and Vascular Function in a Pig Model of Ischemic Cardiogenic Shock Treated With Veno-Arterial ECMO.

Cardiogenic shock (CS) patients treated with extracorporeal membrane oxygenation (ECMO) have severe cardiac failure, associated with ischemia-reperfusion. The use of moderate hypothermia during ischemia-reperfusion syndrome is supported by experimental data. We therefore studied the effects of moderate hypothermia on cardiac and vascular function in pig ischemic CS treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). CS was induced in 12 anesthetized pigs by coronary ligation. After 1 h of CS, VA-ECMO was initiated and pigs were randomized to normothermia (38°C) or moderate hypothermia (34°C) during 8 h. Intrinsic cardiac function was measured using a left ventricular conductance catheter. At the end of the experiment, tissues were harvested for Western blotting. ECMO associated with norepinephrine infusion and volume resuscitation increased mean arterial pressure, mixed venous oxygen saturation as well as carotid, renal, and coronary blood flow without any differences between normothermia and hypothermia. Hypothermia was associated with less fluid and less norepinephrine infusion, lower lactate level, and higher urinary output. Vascular reactivity was superior in hypothermia comparatively to normothermia as expressed using norepinephrine dose-response curves. Pressure development during isovolumic contraction, left ventricular ejection fraction, and prerecruitable stroke work index were higher in the hypothermia group. There were no differences between normothermia and hypothermia with regard to carotid and mesenteric protein expression for iNOs, eNOS, and phospho AKt/AKt measured at the end of the experimentation. The incidence of surgical bleeding and coagulation disorders was the same in both groups. In conclusion, moderate and rapid hypothermia improves hemodynamics and cardiac and vascular function in a pig model of ischemic CS treated with ECMO.

Beneficial Effects of Norepinephrine Alone on Cardiovascular Function and Tissue Oxygenation in a Pig Model of Cardiogenic Shock.

The present study was developed to investigate the effects of norepinephrine alone on hemodynamics and intrinsic cardiac function in a pig model of cardiogenic shock mimicking the clinical setting. Cardiogenic shock was induced by 1-h ligation of the left anterior descending (LAD) artery followed by reperfusion. Pigs were monitored with a Swan-Ganz catheter, a transpulmonary thermodilution catheter, and a conductance catheter placed in the left ventricle for pressure-loop measurements. Measurements were performed before LAD occlusion, 1 h after LAD occlusion, and 4 h after myocardial reperfusion. Myocardial infarction and reperfusion was followed by cardiogenic shock characterized by a significant increase in heart rate and significant decreases in mean arterial pressure (MAP), mixed venous oxygen saturation (SVO2), left ventricular end-diastolic pressure (LVEDP), prerecruitable stroke work (PRSW), and cardiac power index (CPI). Lactate levels were significantly increased. The systemic vascular resistance index (SVRI) and global end-diastolic volume index (GEDVI) remained unchanged. When compared with the control group (n = 6), norepinephrine infusion (n = 6) was associated with no changes in heart rate, a significant increase in MAP, SVO2, left ventricular ejection fraction, pressure development during isovolumic contraction, SVRI, and CPI and a decrease in lactate level. Cardiac index tended to increase (P = 0.059), whereas PRSW did not change in the norepinephrine group. LVEDP and GEDVI remained unchanged. Norepinephrine alone is able to improve hemodynamics, cardiac function, and tissue oxygenation in a pig model of ischemic cardiogenic shock.

Magnetic resonance-compatible model of isolated working heart from large animal for multimodal assessment of cardiac function, electrophysiology, and metabolism.

To provide a model close to the human heart, and to study intrinsic cardiac function at the same time as electromechanical coupling, we developed a magnetic resonance (MR)-compatible setup of isolated working perfused pig hearts. Hearts from pigs (40 kg, n = 20) and sheep (n = 1) were blood perfused ex vivo in the working mode with and without loaded right ventricle (RV), for 80 min. Cardiac function was assessed by measuring left intraventricular pressure and left ventricular (LV) ejection fraction (LVEF), aortic and mitral valve dynamics, and native T1 mapping with MR imaging (1.5 Tesla). Potential myocardial alterations were assessed at the end of ex vivo perfusion from late-Gadolinium enhancement T1 mapping. The ex vivo cardiac function was stable across the 80 min of perfusion. Aortic flow and LV-dP/dtmin were significantly higher (P < 0.05) in hearts perfused with loaded RV, without differences for heart rate, maximal and minimal LV pressure, LV-dP/dtmax, LVEF, and kinetics of aortic and mitral valves. T1 mapping analysis showed a spatially homogeneous distribution over the LV. Simultaneous recording of hemodynamics, LVEF, and local cardiac electrophysiological signals were then successfully performed at baseline and during electrical pacing protocols without inducing alteration of MR images. Finally, (31)P nuclear MR spectroscopy (9.4 T) was also performed in two pig hearts, showing phosphocreatine-to-ATP ratio in accordance with data previously reported in vivo. We demonstrate the feasibility to perfuse isolated pig hearts in the working mode, inside an MR environment, allowing simultaneous assessment of cardiac structure, mechanics, and electrophysiology, illustrating examples of potential applications.

Expression and function of Kv1.1 potassium channels in human atria from patients with atrial fibrillation.

Voltage-gated Kv1.1 channels encoded by the Kcna1 gene are traditionally regarded as being neural-specific with no known expression or intrinsic functional role in the heart. However, recent studies in mice reveal low-level Kv1.1 expression in heart and cardiac abnormalities associated with Kv1.1-deficiency suggesting that the channel may have a previously unrecognized cardiac role. Therefore, this study tests the hypothesis that Kv1.1 channels are associated with arrhythmogenesis and contribute to intrinsic cardiac function. In intra-atrial burst pacing experiments, Kcna1-null mice exhibited increased susceptibility to atrial fibrillation (AF). The atria of Kcna1-null mice showed minimal Kv1 family ion channel remodeling and fibrosis as measured by qRT-PCR and Masson's trichrome histology, respectively. Using RT-PCR, immunocytochemistry, and immunoblotting, KCNA1 mRNA and protein were detected in isolated mouse cardiomyocytes and human atria for the first time. Patients with chronic AF (cAF) showed no changes in KCNA1 mRNA levels relative to controls; however, they exhibited increases in atrial Kv1.1 protein levels, not seen in paroxysmal AF patients. Patch-clamp recordings of isolated human atrial myocytes revealed significant dendrotoxin-K (DTX-K)-sensitive outward current components that were significantly increased in cAF patients, reflecting a contribution by Kv1.1 channels. The concomitant increases in Kv1.1 protein and DTX-K-sensitive currents in atria of cAF patients suggest that the channel contributes to the pathological mechanisms of persistent AF. These findings provide evidence of an intrinsic cardiac role of Kv1.1 channels and indicate that they may contribute to atrial repolarization and AF susceptibility.

The contribution of cardiac mechanics to isolated increases in peripheral blood flow (1073.4)

The human heart responds to whole‐body increases in cardiovascular demand by enhancing heart rate (HR) and intrinsic cardiac muscle function. However, it is not known if enhanced left ventricular (LV) muscle function ('LV mechanics') also contributes to localized increases in peripheral blood flow and, if so, whether enhanced peripheral blood flow per se or other arterial hemodynamic signals are the mechanism for acutely adjusting LV mechanics. We performed cardiac and vascular ultrasonography in eight healthy individuals (4 women) during 1) Baseline, 2) Bilateral arm heating (BAH), and 3) BAH with partial brachial artery occlusion (BAH+OCC) at mean arterial pressure (MAP, 85±15 mmHg). BAH markedly increased skin temperatures (32.71±0.69 to 39.21±0.60 deg. C, p&lt;0.0001) while rectal core temperature was unaltered (p=0.54). Brachial artery blood flow measured in the left arm increased almost threefold with BAH (98±46 to 266±96 mL/min, P&lt;0.0001) and returned to baseline levels with BAH+OCC. Arterial wave reflection, as assessed by applanation tonometry, had a tendency to increase with BAH and remained elevated with BAH+OCC (p=0.07). Increased cardiac output (p=0.02) was entirely explained by increased HR of 3‐4 bpm (P=0.002). In contrast, LV mechanics ‐ evaluated by systolic longitudinal strain and diastolic untwisting velocity ‐ did not change with BAH but they declined significantly with BAH+OCC (both p&lt;0.05), which was accompanied by a rise in MAP (P&lt;0.0001).In conclusion, the heart contributes to isolated increases in peripheral blood flow by enhancing HR but not its intrinsic LV muscle mechanics. Because LV output was maintained during the period of enhanced blood flow demand and increased afterload (=BAH+OCC), reduced systolic and diastolic LV mechanics during this condition may reflect an intrinsic protection of LV myofibers from pressure stress rather than a decline in LV function.

Assessment of myocardial viability and left ventricular function in patients supported by a left ventricular assist device

Chronically supported left ventricular assist device (LVAD) patients may be candidates for novel therapies aimed at promoting reverse remodeling and myocardial recovery. However, the effect of hemodynamic unloading with a LVAD on myocardial viability and LV function in chronically supported LVAD patients has not been fully characterized. We aimed to develop a non-invasive imaging protocol to serially quantify native cardiac structure, function, and myocardial viability while at reduced LVAD support. Clinically stable (n = 18) ambulatory patients (83% men, median age, 61 years) supported by a HeartMate II (Thoratec, Pleasanton, CA) LVAD (median durations of heart failure 4.6 years and LVAD support 7 months) were evaluated by echocardiography and technetium-99m ((99m)Tc)-sestamibi single photon emission computed tomography (SPECT) imaging at baseline and after an interval of 2 to 3 months. Echocardiographic measures of LV size and function, including speckle tracking-derived circumferential strain, were compared between ambulatory and reduced LVAD support at baseline and between baseline and follow-up at reduced LVAD support. The extent of myocardial viability by SPECT was compared between baseline and follow-up at reduced LVAD support. With reduction in LVAD speeds (6,600 rpm; interquartile range: 6,200, 7,400 rpm), LV size increased, LV systolic function remained stable, and filling pressures nominally worsened. After a median 2.1 months, cardiac structure, function, and the extent of viable myocardium, globally and regionally, was unchanged on repeat imaging while at reduced LVAD speed. In clinically stable chronically supported LVAD patients, intrinsic cardiac structure, function, and myocardial viability did not significantly change over the pre-specified time frame. Echocardiographic circumferential strain and (99m)Tc-sestamibi SPECT myocardial viability imaging may provide useful non-invasive end points for the assessment of cardiac structure and function, particularly for phase II studies of novel therapies aimed at promoting reverse remodeling and myocardial recovery in LVAD patients.

Myocardial Innervation and Perfusion Imaging During LVAD Implantation

In recent years, heart failure has been recognized as a major and increasing public health issue. In the context of the shortage of heart donors and increasing waiting time on the transplantation list, nonpulsatile left ventricular assist devices (LVAD) have shown their efficiency in reducing mortality and improving quality of life in patients with end-stage heart failure. Among LVAD recipients, a minority of patients will recover a normal cardiac function, allowing pump weaning. However, the evaluation of intrinsic cardiac function is particularly challenging and still a matter of debate in LVAD recipients.

Successful rescue of a "suicide ventricle" during transfemoral transcatheter aortic valve implantation (TF-TAVI)

Introduction: Circulatory collapse during transfemoral transcatheter aortic valve implantation (TF-TAVI) procedure is a life-threatening complication. We present an important and poorly described cause. Case report description: An 82 year old male was accepted by the TAVI multi-disciplinary team for TF-TAVI. He had severely impaired left ventricular (LV) function (LVEF 25%), normal LV wall thickness and severe aortic stenosis (PG 63 mmHg, AVA 0.9cm2). Coronary angiography revealed significant disease in the proximal-mid LAD, mid-OM1 and an occluded RCA. His logistic EuroScore was 17.45%. It was felt that since his primary complaint was dyspnoea and he reported no anginal symptoms, in the absence of prognostic coronary disease, he did not require pre-TAVI revascularisation. The procedure was performed under a general anaesthetic with peri-operative tranoesophageal echocardiography (TOE) using a 29 mm Edwards SAPIEN XT with a good final position, no AR and good antegrade haemodynamics. He suffered a rapid loss of blood pressure and ventricular tachycardia, which reverted to asystole after defibrillation. CPR was performed according to guidelines. TOE was used to exclude annular or root injury, iatrogenic disruption of the mitral valve apparatus and prosthesis structural failure or malposition. Angiography confirmed patency of the coronary arteries and ilio-femoral integrity. A suicide ventricle was diagnosed and the decision was made to initiate femoral-femoral cardiopulmonary bypass to stabilise the patient. This was gradually weaned over 30 minutes with successful return of intrinsic cardiac function. Initial post-procedural transthoracic echocardiography demonstrated improvement of LV function (LVEF 45%) with normal prosthetic forward flow and only trivial regurgitation. This echocardiographic improvement was maintained at 60 day follow up with marked symptomatic improvement. Discussion and conclusion: A suicide ventricle is important cause of peri-procedural hypotension and circulatory collapse in TAVI patients. Immediately available fluoroscopic and TOE imaging can help to exclude the other major causes. A perfusionist and a primed CPB machine in the room can allow a desperate situation to be recovered and provide effective bridging for return of myocardial function. The mechanism and aetiology of this difficult complication is not yet known; revascularisation of large areas of at-risk myocardium may be protective. The effects of treatment of coronary artery disease prior to TAVI will be addressed in ongoing the ACTIVATION trial ([ISRCTN75836930][1]). [1]: /external-ref?link_type=ISRCTN&access_num=ISRCTN75836930

A non-cardiomyocyte autonomous mechanism of cardioprotection involving the SLO1 BK channel

Opening of BK-type Ca2+ activated K+ channels protects the heart against ischemia-reperfusion (IR) injury. However, the location of BK channels responsible for cardioprotection is debated. Herein we confirmed that openers of the SLO1 BK channel, NS1619 and NS11021, were protective in a mouse perfused heart model of IR injury. As anticipated, deletion of the Slo1 gene blocked this protection. However, in an isolated cardiomyocyte model of IR injury, protection by NS1619 and NS11021 was insensitive to Slo1 deletion. These data suggest that protection in intact hearts occurs by a non-cardiomyocyte autonomous, SLO1-dependent, mechanism. In this regard, an in-situ assay of intrinsic cardiac neuronal function (tachycardic response to nicotine) revealed that NS1619 preserved cardiac neurons following IR injury. Furthermore, blockade of synaptic transmission by hexamethonium suppressed cardioprotection by NS1619 in intact hearts. These results suggest that opening SLO1 protects the heart during IR injury, via a mechanism that involves intrinsic cardiac neurons. Cardiac neuronal ion channels may be useful therapeutic targets for eliciting cardioprotection.

Assessment of Intrinsic Cardiac Function, Myocardial Blood Flow and Metabolism in Patients Supported on Mechanical Circulatory Assist Devices

While novel therapies may assist in myocardial recovery in patients maintained on LV assist devices (LVADs), it is not clear how best to measure intrinsic cardiac contractile function in the unloaded state. We sought to determine if global and regional cardiac strain measured by echocardiographic deformation imaging could be accurately and reproducibly measured in LVAD patients, and to determine the relationship between these measures and estimates of myocardial metabolism and blood flow by positron emission tomography (PET).

Aortic Valve Opening at Hospital Discharge After HeartMate II Left Ventricular Assist Device Implantation Is Associated With Improved Renal Function at 3 Months

Background: While novel therapies may assist in myocardial recovery in patients maintained on LVassist devices (LVADs), it is not clear how best to measure intrinsic cardiac contractile function in the unloaded state. We sought to determine if global and regional cardiac strain measured by echocardiographic deformation imaging could be accurately and reproducibly measured in LVAD patients, and to determine the relationship between these measures and estimates of myocardial metabolism and blood flow by positron emission tomography (PET). Objective: To describe the interrelation between measures of cardiac function and structure, myocardial blood flow and metabolism in patients with advanced heart disease living on left ventricular assist devices. Methods: 7 Patients with end-stage heart failure (4 ischemic, 3 nonischemic) on LVAD support were prospectively evaluated using both PET and ECHO, imaged on the same day, at the same VAD settings. Regional circumferential strain, myocardial blood flow, and glucose metabolism were assessed in mid-short axis slices at the level of the papillary muscles and related. Results: Mid-ventricular global strain was low in all patients, but it was lower in patients with CAD versus non-ischemic patients (-4.6% 6 0.4 vs. -7.3% 6 2.9, p50.054; normal 5 O -23%). Despite 4 patients labelled with ischemic cardiomyopathy, only 1 had a definite region of infarction on PET. Regional strain correlated well with myocardial perfusion (r5 -0.89, p50.01) and metabolism (r5 -0.843, p50.03) in the CAD patient with an infarcted region (Figure 1), but not in CAD patients without MI or in non-ischemic patients.

Carbamazepine does not alter the intrinsic cardiac function in rats with epilepsy

Among the causes for sudden unexpected death (SUDEP) in epilepsy, the effects of antiepileptic drugs on the heart have been poorly explored. Based on this, the aim of our study was to evaluate the heart rate (in vivo and isolated ex vivo) and ventricular pressure (isolated ex vivo) of rats with and without epilepsy treated with carbamazepine. Four groups of adult, male Wistar rats (200-250 g) were studied: [A] control rats (n=8), received neither pilocarpine nor carbamazepine [B] carbamazepine-treated rats (n=8), received a daily dose of 120 mg/Kg, i.p. of carbamazepine for two weeks; [C] rats with epilepsy that received just saline solution (n=8); [D] rats with epilepsy that received a daily dose of 120 mg/Kg, i.p. of carbamazepine for two weeks (n=8). Our results showed significant increase in heart rate in animals with epilepsy (with and without the use of carbamazepine) when compared to the control groups in vivo. In contrast, we did not find differences during isolated ex vivo experiments comparing animals with and without epilepsy and despite the use of carbamazepine. Our results suggest that, in isolation, carbamazepine may not be a potential risk factor for sudden unexpected death in epilepsy.

Optimal screening of heart failure patients: tissue Doppler imaging or plasma NTpro BNP measurement?

Early detection and treatment of left ventricular dysfunction is of major importance. Ideally, therapy will be performed before irreversible cardiac damage has occurred. To do this, a sensitive evaluation of cardiac function and cardiac mechanics is required. However, cardiac function is difficult to define and the assessment of function in a clinical context often uses a surrogate for function. One can divide cardiac function in intrinsic myocyte function or contractility and ventricular pump function [1]. Force development results in the generation of sufficient pressure to open the cardiac valves. On the other hand results deformation of the ventricles in the ejection of blood. The interaction between force development and deformation are determined by ventricular wall properties such as tissue composition, fibre structure and global geometry on one hand and the interaction between the heart and the loading conditions on the other hand. The most reliable parameter to measure intrinsic myocardial contractility is by calculation of the end-systolic pressure-volume relationship (E-max) [2]. This is an invasive technique and not always applicable in clinical practice. Therefore in clinical practice, surrogate measurements of force development and volume ejection are used with non-invasive techniques, like echocardiography, magnetic resonance imaging or computed tomography. The evaluation of ejection fraction with these techniques, however has severe shortcomings because the assessment of intrinsic cardiac function using ejection fraction depends on geometric assumptions. Volume based indices are load dependent and these parameters only assess global function. To overcome these problems, new echocardiographic techniques, like tissue Doppler imaging have been developed, which measure myocardial motion and deformation. Tissue Doppler imaging uses the shifts of ultrasound waves to calculate myocardial velocity. It can be done with the pulsed Doppler technique and the color-coded tissue Doppler technique. Measurement of the ratio of transmitral peak inflow velocity of early rapid diastolic filling (E), and measurement of Ea, obtained by pulsed-TDE sample volume placed in the lateral annulus imaged from the four chamber view can be used as an indicator of left ventricular filling pressures [3]. Brain natriuretic peptide is a natriuretic hormone, that is present in the heart, particularly in the ventricles. Brain natriuretic peptide has diuretic, natriuretic and hypotensive effects. It inhibits the rennin-angiotensin system, endothelin secretion and sympathetic activity [4]. The release of BNP is increased in heart failure, as ventricular cells secrete BNP in response to high ventricular filling pressures [5]. In normal subjects, the plasma concentrations of BNP and NT-proBNP are similar. However, in patients with left ventricular dysfunction, plasma NT-proBNP rises more than BNP [6]. It can be used to diagnose but more to rule out heart failure. BNP can be used as a bedside test to rule out heart failure at the first aid department in patients with dyspnea [7]. Although the sensitivity, specificity and predictive value are high in patients with sinusrythm, BNP loses its sensitivity and specificity in patients with atrial fibrillation [8]. False positive NT pro-BNP results can be diminished by adding the age of and clinical characteristics of the individual for stratification of patients with dyspnea [9, 10]. The current study of Mornos et al. [11] showed a close correlation of NT-proBNP with a combination of conventional Doppler echocardiography of the E velocity of transmitral flow and two TDI parameters: Ea and Sa. The last parameters explore both diastolic and systolic left ventricular performance. The study shows, that after initial screening of heart failure patients with BNP or NT-proBNP additional echocardiographic imaging with TDI can give the information about ventricular geometry, morphology and the presence of systolic or diastolic function. The study also shows, that tissue Doppler imaging has to become a standard tool for the evaluation of heart failure patients. We have to keep in mind however, that measurement of plasma BNP or NT-proBNP can help in discrimination of dyspnea of cardiac or non-cardiac causes, but gives no information about the etiology of cardiac dyspnea. Cardiac imaging with echo, Doppler echo, tissue Doppler echo, Stress Echo, Magnetic Resonance Imaging, Stress MRI, Nuclear (Stress Imaging) and Conventional Coronary angiography or CT coronary angiography is still needed to explore the underlying cardiac pathology.