Laboratory performance testing of venous cannulae during inlet obstruction.

Venous cannulae undergo continuous improvements to achieve better and safer venous drainage. Several cannula tests have been reported, though cannula performance during inlet obstruction has never been a test criterion. In this study, five different cannulae for proximal venous drainage were tested in a mock circulation that enabled measurement of hydraulic conductance after inlet obstruction by vessel collapse. Values for hydraulic conductance ranged from 1.11 x 10(-2) L/min/mm Hg for a Thin-Flex Single Stage Venous Cannula with an open-end lighthouse tip to 1.55 x 10(-2) L/min/mm Hg for a DLP VAD Venous Cannula featuring a swirled tip profile, showing a difference that amounts to nearly 40% of the lowest conductance value. Excessive venous drainage results in potentially dangerous high-negative venous line pressures independent of cannula design. Cannulatip design featuring swirled and grooved tip structures increases drainage capacity and enhances cannula performance during inlet obstruction.

Combined Impella and intra-aortic balloon pump support to improve both ventricular unloading and coronary blood flow for myocardial recovery: an experimental study.

Some patients in need of hemodynamic support do not respond to intra-aortic balloon pump (IABP) therapy. Hemodynamic stability can then be obtained by a more potent cardiac assist device, like the Impella catheter pump. Whether additional IABP support additional to Impella support can provide more optimal hemodynamic myocardial conditions is examined in this study. Seven sheep were implemented with IABP and Impella. An acute myocardial infarction was induced. Hemodynamic performance was assessed during baseline, during Impella support and IABP support individually, and during the combined Impella plus IABP support. The Impella support provided a reduction of afterload with 30% and an increase of coronary artery flow with 47%. The IABP increased coronary artery flow (13%), carotid artery flow (16%), and aortic ascending blood pressure (6%); a similar (but stronger) effect was provided when using the IABP support additional to Impella support and, respectively, increases of 33, 21, and 19% were established. The oxygen demand-supply ratio decreased by 25% due to the extra use of the IABP. A combination of IABP and Impella provides the most optimal hemodynamic myocardial conditions compared to either stand-alone support.

Suction due to left ventricular assist: implications for device control and management.

Left ventricular assist device (LVAD) overpumping is associated with hemolysis, thrombus release, and tissue damage at the pump inlet. However, the impact of LVAD suction on pulmonary circulatory function remains unknown. We investigated LVAD suction as induced by pulmonary artery banding and overpumping in experimental animals and in a computer model. In six sheep, a rotary LVAD was implanted. Before inducing suction, partial support (40-60% of cardiac output) was established and characterized by measuring pressures and flows. In the animals, pulmonary artery occlusion (PAOC) elicited LVAD suction (left ventricular pressure was from -10 to -20 mm Hg) within 5-10 heartbeats. During suction, aortic pressure dropped to 50% and LVAD flow decreased significantly. After releasing the occlusion (20 s), the collapsed state persisted for another 20 s. A similar trend was obtained by simulating PAOC in the computer model. Additional simulations showed that pulmonary vascular resistance (PVR), volume status, and right ventricular (RV) contractility are exponentially related to the persistence of collapse after a suction event. Even modest increases in predisposing factors (elevated PVR, RV dysfunction, hypovolemia) caused sustained hemodynamic collapse lasting in excess of 15 min. Both in selected animals and the computer model, comparable suction-induced collapse was obtained by increasing LVAD speed by about 33%. Attempted compensation by simply decreasing speed was not effective, but temporarily shutting down the LVAD caused rapid reversal of collapse. In conclusion, rotary LVAD suction causes unfavorable conditions for effective unloading. The use of pump interventions appears a promising tool to detect suction and to avoid the associated hemodynamic depression.

Serial left-ventricular biopsy sampling using a minimally invasive trans-thoracic approach in adult dogs.

Myocardial biopsies are an increasingly important tool to unravel the molecular mechanisms of cardiac disease. We evaluate a novel minimally invasive trans-thoracic approach for left-ventricular (LV) intra-mural biopsies, which enables repetitive individual sampling in adult dogs. Forty three generally anaesthesised dogs were studied during sinus rhythm (SR, control) and multiple times after the induction of volume overload hypertrophy (complete atrioventricular block [AVB]). Through a small cutaneous incision, an automatic biopsy needle was advanced into the apicolateral LV, guided by fluoroscopy. Electrocardiography (ECG), LV pressure and echocardiography served to monitor the procedure. One hundred eighty-eight intra-mural LV biopsies were obtained in 82 serial experiments (usually SR, 1, 2 and 6 weeks AVB) with a maximum of 8 repeated biopsies. All biopsies ( approximately 10 mm(3)) were suitable for simultaneous application of different cell-biological (light and electron microscopy, immunohistochemistry) and molecular techniques (PCR, Western blotting). In chronic experiments, repeated biopsy sampling did not influence haemodynamics, mechanics, electrocardiographic parameters or myocardial remodelling during SR or AVB. The rate of significant complications was as low as 4% of experiments. Minimally invasive sampling of LV needle biopsies enables serial assessment of myocardial remodelling using different molecular techniques in individual animals. The technique is safe and has no long-term effects on cardiac function or structure.

An in vitro and in vivo study of the detection and reversal of venous collapse during extracorporeal life support.

The objective of this study was to investigate venous collapse (VC) related to venous drainage during the use of an extracorporeal life support circuit. A mock circulation was built containing a centrifugal pump and a collapsible vena cava model to simulate VC under controlled conditions. Animal experiments were performed for in vivo verification. Changing pump speed had a different impact on flow during a collapsed and a distended caval vein in both models. Flow measurement in combination with pump speed interventions allows for the detection and quantitative assessment of the degree of VC. Additionally, it was verified that a quick reversal of a VC situation could be achieved by a two-step pump speed intervention, which also proved to be more effective than a straightforward decrease in pump speed.

Atrial-specific drug AVE0118 is free of torsades de pointes in anesthetized dogs with chronic complete atrioventricular block.

BACKGROUND: The novel compound AVE0118 has been shown to prevent and terminate persistent atrial fibrillation. AVE0118 blocks I(Kur), I(KAch), and I(to), leading to prolongation of atrial repolarization with no change in ventricular repolarization. This finding suggests that AVE0118 may be devoid of proarrhythmic side effects. Experimentally, AVE0118 has been antiarrhythmic against some specific ventricular arrhythmias. OBJECTIVES: The purpose of this study was to investigate the proarrhythmic and antiarrhythmic effects of AVE0118 in anesthetized dogs with chronic complete AV block, known for a high proclivity for torsades de pointes (TdP). METHODS: AVE0118 was administered intravenously as a fast infusion (0.5 mg/kg/5 min) and a slow infusion (3 or 10 mg/kg/60 min). Dofetilide was given to induce TdP. ECG and monophasic action potentials were recorded. Short-term beat-to-beat variability (STV) of the left ventricular monophasic action potential duration (MAPD) was calculated. We examined whether AVE0118 (1) caused ventricular proarrhythmia (both infusions), (2) prevented dofetilide-induced TdP (slow infusion + dofetilide after 30 minutes), and (3) abolished TdP (fast infusion). RESULTS: At 0.55 +/- 0.10 microg/mL (fast infusion at 10 minutes), AVE0118 did not increase ventricular repolarization or induce TdP; however, right atrial MAPD(50) and MAPD(90) were significantly increased by 26% +/- 9% and 10% +/- 5%, respectively (P <.05 vs baseline). At 1.9 +/- 0.5 microg/mL and 6.1 +/- 1.2 microg/mL (30 minutes of 3 or 10 mg/kg/h), AVE0118 did not induce TdP (0/6 and 0/4) nor prevent dofetilide-induced TdP (6/6 and 2/2). Dofetilide significantly increased all repolarization parameters, including STV from 2.1 +/- 0.4 ms to 4.6 +/- 1.8 ms (P <.05 vs baseline), which were not changed by AVE0118 (to 2.1 +/- 0.3 ms after 30 minutes). Rapid infusion of AVE0118 did not suppress dofetilide-induced TdP. CONCLUSION: In the anesthetized chronic complete AV block dog, the atrial-specific drug AVE0118 is free of TdP and has no antiarrhythmic properties against dofetilide-induced torsades de pointes.

Temporal patterns of electrical remodeling in canine ventricular hypertrophy: focus on IKs downregulation and blunted beta-adrenergic activation.

OBJECTIVES: Electrical remodeling in cardiac hypertrophy often involves the downregulation of K+ currents, including beta-adrenergic (beta-A)-sensitive IKs. Temporal patterns of ion-channel downregulation are poorly resolved. In dogs with complete atrioventricular block (AVB), we examined (1) the time course of molecular alterations underlying IKs downregulation from acute to chronic hypertrophy; and (2) concomitant changing responses of repolarization to beta-adrenergic receptor (beta-AR) stimulation. METHODS AND RESULTS: Serial left-ventricular (LV) biopsies were collected from anesthetized dogs during sinus rhythm (SR; control) and at 3, 7 and 30 days of AVB. KCNQ1 mRNA and protein decreased within 3 days (protein expression 58 +/- 10% of control), remaining low thereafter. beta1-AR mRNA and protein decreased more gradually to 53 +/- 8% at 7 days. In chronic-AVB LV myocytes, IKs -tail density was reduced: 1.4 +/- 0.3 pA/pF versus 2.6 +/- 0.4 pA/pF in controls. beta-A enhancement of IKs was reduced. Isoproterenol shortened action-potential duration in control cells, while causing heterogeneous repolarization responses in chronic AVB. beta-A early afterdepolarizations were induced in 4 of 13 chronic-AVB cells, but not in controls. In intact conscious dogs, isoproterenol shortened QTc at SR (by -8 +/- 3% from 295 ms), left it unaltered at 3 days AVB (+1 +/- 3% from 325 ms) and prolonged QTc at 30 days (+6 +/- 3% from 365 ms). CONCLUSIONS: Profound decrease of KCNQ1 occurs within days after AVB induction and is followed by a more gradual decrease of beta1-AR expression. Downregulation and blunted beta-A activation of IKs contribute to the loss of beta-A-induced shortening of ventricular repolarization, favoring proarrhythmia. Provocation testing with isoproterenol identifies repolarization instability based on acquired channelopathy.

Synchronously counterpulsating extracorporeal life support enhances myocardial working conditions regardless of systemic perfusion pressure.

OBJECTIVE: A new pulsatile extracorporeal life support (pECLS) system has entered the market. We wanted to investigate what potential advantages pECLS may have over current non-pulsatile systems (NPS). Our research was focused on the pump's functional interaction with the left ventricle and the coronary circulation. METHODS: Extensive hemodynamic measurements were performed during asynchronous and synchronous pECLS in 10 calves. The two extremes regarding LV afterload, namely systolic arrival (SA) and diastolic arrival (DA) of the pump pulse were studied. RESULTS: SA was associated with increased oxygen consumption (+57%) and decreased diastolic coronary perfusion (-43%). DA increased left ventricular output (DA: 4.5+/-2.4 l/min vs SA: 3.5+/-2.2 l/min), LV ejection fraction (+10%), and ventricular efficiency (+17%). Mean aortic pressure and mean coronary flow were only marginally affected by pulse incidence. Systolic impairment was more pronounced with higher bypass flows. These results indicate that myocardial working conditions can be optimized by phasing pECLS ejection into cardiac diastole. CONCLUSION: We conclude that during pECLS, myocardial working conditions can be improved by avoidance of systolic impairment. Synchronously counterpulsating pECLS could be a more economic and versatile alternative to NPS or NPS combined with intra-aortic balloon pumping. The potential benefits of synchronously counterpulsating pECLS over the current alternatives remain to be investigated.

Physiologic-insensitive left ventricular assist predisposes right-sided circulatory failure: a pilot simulation and validation study.

Right-sided circulatory failure (RSCF) is a serious complication in 15-30% of patients receiving a left ventricular assist device (LVAD). It is hypothesized that left ventricular support which lacks physiologic properties predisposes to RSCF. An integral computer simulation and experimental validation protocol was performed. The results suggest that with conventional insensitive left ventricular support right-sided circulatory function is compromised, which may form a substrate for the onset or progress of RSCF. Feedback control of the LVAD could provide a means to counter this problem. A control concept for the LVAD which aims to preserve right-sided circulatory function, while supporting peripheral perfusion, is proposed

Left ventricular pressure-volume measurements in mice: comparison of closed-chest versus open-chest approach.

OBJECTIVE: We investigated whether in vivo closed-chest left ventricular pressure-volume measurements would yield similar values for LV hemodynamics compared with open-chest PV measurements under several anesthetics. METHODS: The right common carotid of C57Bl/6 mice was cannulated with a combined pressure-conductance catheter and inserted retrogradely into the left ventricle in the closed-chest model. The open-chest model consisted of an abdominal approach involving the opening of the thoracic cavity by transverse opening of the diaphragm and ventricular catheterization by apical stab. Measurements were performed under urethane or pentobarbital intraperitoneal injection anesthesia. RESULTS: Cardiac function in the open-chest model was characterized by larger ejection fraction and stroke volume with a leftward shift in ventricular volume compared to the closed-chest model. Further observed characteristics include low end-systolic pressure and arterial-ventricular coupling mismatch in the open-chest model. Arrhythmias were not detected in either model. CONCLUSION: Murine cardiac function determination via open-chest or closed-chest protocols is sensitive, reproducible and comparable. The choice for open- or closed-chest pressure-volume measurements in mice depends on the aims of the study.

Feasibility study of a fiber-optic system for invasive blood pressure measurements.

A comparative study was conducted to evaluate the feasibility of a fiber-optic sensor in invasive blood pressure measurements. Static and wide-bandwidth stimuli were offered to the fiber-optic, Millar, Baxter, and Sentron devices to measure static transfer function and transient response. Animal experiments focused on offset drift, dynamic accuracy, and electromagnetic sensitivity. Compared to the Millar, Sentron, and Baxter devices, the fiber-optic sensor had a near-identical static transfer function. Gain and offset errors were < 3.4% and < 0.25%, respectively. Hysteresis nonlinearity was < 0.1%. The dynamic accuracy of the fiber-optic system matched that of the Millar and Sentron systems. Time delay was < 1 msec. Maximum rate of change was > 30,000 mm Hg/sec and bandwidth was 0-150 Hz minimum. Offset drift was 0.6 +/- 0.03 mm Hg. Application of diathermy highlighted the fiber-optic sensor's excellent electromagnetic disturbance rejection. The fiber-optic system appears to be a reliable, high-fidelity pressure monitor in demanding clinical environments.

Quantification of interventricular asynchrony during LBBB and ventricular pacing.

The quantification of mechanical interventricular asynchrony (IVA) was investigated. In 12 dogs left bundle branch block (LBBB) was induced by radio frequency ablation. Left ventricular (LV) and right ventricular (RV) pressures were recorded before and after induction of LBBB and during LBBB + LV apex pacing at different atrioventricular (AV) delays. Four IVA measures were validated using computer simulations on experimentally obtained pressure signals. The most robust measure for IVA was the time delay between the upslope of the LV and RV pressure signals (DeltaT(up)), estimated by cross correlation. The induction of experimental LBBB decreased DeltaT(up) from -6.9 +/- 7.0 ms (RV before LV) to -33.9 +/- 7.6 ms (P < 0.05) in combination with a significant decrease of LV maximal first derivative of pressure development over time (dP/dt(max)). During LV apex pacing, DeltaT(up) increased with decreasing AV delay up to +20.9 +/- 14.6 ms (P < 0.05). Interventricular resynchronization (DeltaT(up) = 0 ms) significantly improved LV dP/dt(max) by 15.1 +/- 5.9%. QRS duration increased significantly after induction of LBBB but did not change during LV apex pacing. In conclusion, DeltaT(up) is a reliable measure of mechanical IVA, which adds valuable information concerning the nature of asynchronous activation of the ventricles.