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Biomedical subjects

Frits W Prinzen

Publications and source records attributed to Frits W Prinzen.

16 recordsLinked to original sources
PubMed2004

Left bundle branch block induces ventricular remodelling and functional septal hypoperfusion.

AIMS: Left ventricular (LV) dilatation, hypertrophy, and septal perfusion defects are frequently observed in patients with left bundle branch block (LBBB). We investigated whether isolated LBBB causes these abnormalities. METHODS AND RESULTS: In eight dogs, LBBB was induced by radio frequency ablation. Two-dimensional echocardiography showed that 16 weeks of LBBB decreased LV ejection fraction (by 23+/-14%) and increased LV cavity volume (by 25+/-19%) and wall mass (by 17+/-16%). The LV septal-to-lateral wall mass ratio decreased by 6+/-9%, indicating asymmetric hypertrophy. After onset of LBBB, myocardial blood flow (MBF, fluorescent microspheres) and systolic circumferential shortening [CS(sys), magnetic resonance (MR) tagging] decreased in the septum to 83+/-16% and -11+/-20% of baseline, respectively, and increased in LV lateral wall to 118+/-12% and 180+/-90% of baseline, respectively. MBF and CS(sys) values did not change over 16 weeks of LBBB. Changes in external mechanical work paralleled those in CS(sys). Glycogen content was not significantly different between septum and LV lateral wall of LBBB hearts (16 weeks) and control samples, indicating absence of hibernation. CONCLUSIONS: The asynchronous ventricular activation during LBBB leads to redistribution of circumferential shortening and myocardial blood flow and, in the long run, LV remodelling. Septal hypoperfusion during LBBB appears to be primarily determined by reduced septal workload.

Animals↗
PubMed2004

Adaptation to mechanical load determines shape and properties of heart and circulation: the CircAdapt model.

With circulatory pathology, patient-specific simulation of hemodynamics is required to minimize invasiveness for diagnosis, treatment planning, and followup. We investigated the advantages of a smart combination of often already known hemodynamic principles. The CircAdapt model was designed to simulate beat-to-beat dynamics of the four-chamber heart with systemic and pulmonary circulation while incorporating a realistic relation between pressure-volume load and tissue mechanics and adaptation of tissues to mechanical load. Adaptation was modeled by rules, where a locally sensed signal results in a local action of the tissue. The applied rules were as follows: For blood vessel walls, 1) flow shear stress dilates the wall and 2) tensile stress thickens the wall; for myocardial tissue, 3) strain dilates the wall material, 4) larger maximum sarcomere length increases contractility, and 5) contractility increases wall mass. The circulation was composed of active and passive compliances and inertias. A realistic circulation developed by self-structuring through adaptation provided mean levels of systemic pressure and flow. Ability to simulate a wide variety of patient-specific circumstances was demonstrated by application of the same adaptation rules to the conditions of fetal circulation followed by a switch to the newborn circulation around birth. It was concluded that a few adaptation rules, directed to normalize mechanical load of the tissue, were sufficient to develop and maintain a realistic circulation automatically. Adaptation rules appear to be the key to reduce dramatically the number of input parameters for simulating circulation dynamics. The model may be used to simulate circulation pathology and to predict effects of treatment.

Adaptation, Physiological↗
PubMed2004

Increase in left ventricular torsion-to-shortening ratio in children with valvular aortic stenosis.

Perfusion of left ventricular (LV) subendocardium in valvular aortic stenosis (AS) patients is impaired. It was expected that this may lead to a reduction of subendocardial fiber contraction and, consequently, to an increase of LV torsion per amount of ejection. Using MR tagging (MRT), it was investigated whether the torsion-to-shortening ratio (TSR) is elevated in valvular AS patients. Six asymptomatic children with valvular AS were investigated using echo Doppler, ECG, exercise test, and MRT. LV torsion and natural strain of the inner diameter were determined from measured tag displacements in two short-axis slices of the LV. In all AS patients TSR was approximately 40% increased (0.62 +/- 0.04 rad; mean +/- SD) as compared to pediatric (0.44 +/- 0.08 rad; n=5) and adult controls (0.46 +/- 0.08 rad; n=9), indicating subendocardial contractile dysfunction. With other techniques hitherto used this type of dysfunction could not be detected.

Adolescent↗
PubMed2004

The left ventricular apex is the optimal site for pediatric pacing: correlation with animal experience.

Pacing at the commonly used right ventricular (RV) apex results in impaired ventricular performance. Previous animal studies indicated that the left ventricular (LV) apex is a superior pacing site. The purpose of this study was to investigate in dogs whether this good performance is associated with a more synchronous electrical activation pattern of the LV and whether the LV apex is also a good pacing site in children. In 11 healthy dogs and 8 children undergoing cardiac surgery, dual chamber pacing was performed at the RV apex, LV apex and LV lateral free wall (LVFW). In dogs, a basket electrode was inserted into the LV to assess pattern and timing of LV endocardial activation. In the children, hemodynamic measurements were performed immediately after recovery from cardiopulmonary bypass. In dogs, LV apex pacing resulted in synchronous activation around the LV circumference whereas RV apex and LVFW pacing resulted in asynchrony of activation between the septum and LVFW. In both canine and children's hearts most hemodynamic variables remained at sinus rhythm level during LV apex pacing, but LVdPdtmax, stroke work (dogs), and pulse pressure (children) were reduced as compared with sinus rhythm during RV apex and LVFW pacing. LV apex pacing results in synchronous activation of the LV and is, in adult dogs and in children, associated with superior hemodynamic performance.

Adolescent↗
PubMed2003

Intra-ventricular resynchronization for optimal left ventricular function during pacing in experimental left bundle branch block.

OBJECTIVES: We sought to investigate to what extent intra-ventricular asynchrony (intraVA) and inter-ventricular asynchrony (interVA) determine left ventricular (LV) function in canine hearts with left bundle branch block (LBBB) during ventricular pacing. BACKGROUND: Pacing therapy improves LV pump function in patients with heart failure and abnormal ventricular conduction supposedly due to resynchronization. However, the relationship between LV pump function and measures of asynchrony is not well established. METHODS: In 15 experiments, LV (various sites) and biventricular (BiV) pacing was performed at atrioventricular (AV) delays of 20 to 140 ms. Measured were the maximum rate of increase (dP/dt(max)) of LV pressure and LV stroke work (SW) (conductance catheter), interVA (time delay between the upslope of LV and RV pressures), and intraVA (from endocardial electrical activation maps). RESULTS: Induction of LBBB increased interVA (-6.4 +/- 8.6 to -28.4 +/- 8.5 ms [RV earlier]) and intraVA (4.9 +/- 2.4 to 18.0 +/- 3.3 ms), whereas LV dP/dt(max) and SW decreased (-13 +/- 18% and -39 +/- 24%, respectively). During LBBB, LV and BiV pacing increased LV dP/dt(max) and SW (mean increases 14% to 21% and 11% to 15%, respectively) without changing diastolic function or preload. Optimal improvement in LV function was obtained consistently when intraVA returned to pre-LBBB values, while interVA remained elevated. Normalization of intraVA required AV delays shorter than the baseline PQ time during LV apex and BiV pacing, thus excluding endogenous LV activation, but AV delays virtually equal to the baseline PQ time (difference 4 +/- 9 ms, p = NS) during pacing at (mid)lateral LV sites to obtain fusion between pacing-induced and endogenous activation. CONCLUSIONS: In LBBB hearts, optimal restoration of LV systolic function by pacing requires intra-ventricular resynchronization. The optimal AV delay to achieve this depends on both the site of pacing and baseline PQ time.

Animals↗
PubMed2003

Absence of reverse electrical remodeling during regression of volume overload hypertrophy in canine ventricles.

OBJECTIVE: Ventricular hypertrophy predisposes for cardiac arrhythmias, presumably due to prolongation of repolarization (electrical remodeling). The temporal relation between the development of hypertrophy and electrical remodeling, as well as their reversibility upon restoration of normal load, however, are poorly understood. This was investigated in the present study using volume overload hypertrophy induced by atrio-ventricular (AV) block and normalization of load by pacing. METHODS: Dogs were subjected to either 16 weeks of AV-block (CAVB group, n=9) or 8 weeks of AV-block followed by 8 weeks of right ventricular (RV) pacing at physiological heart rate (CAVB+PACE group, n=9). RESULTS: Left ventricular (LV) mass (2D-echocardiography) increased after 8 weeks of AV-block to approximately 30% above baseline and returned to 10+/-14% after 8 weeks of pacing. QT-time (surface ECG) also increased after AV-block. However, 8 weeks of pacing did not decrease QT and QTc-time (c=corrected for heart rate), neither during physiological pacing nor during temporary pacing at 100 beats/min. Lack of reverse electrical remodeling was confirmed by the absence of changes in LV and RV action potential duration (monophasic action potentials) at week 8 and 16. CONCLUSIONS: In volume overload hypertrophy due to AV-block, structural and electrical remodeling develop in parallel but restoration of physiological heart rate causes dissociation between reverse structural remodeling and reverse electrical remodeling.

Action Potentials↗
PubMed2003

Left ventricular septal and apex pacing for optimal pump function in canine hearts.

OBJECTIVES: The goal of this study was to test the hypothesis that left ventricular (LV) pump function is optimal when pacing is performed at the LV near the sites where the impulses exit the Purkinje system. BACKGROUND: Pacing at the conventional site, the right ventricular (RV) apex, adversely affects hemodynamics. During normal sinus rhythm (SR), electrical activation of the working myocardium starts at the LV septal endocardium and spreads from apex to base. METHODS: Experiments were conducted in anesthetized open-chest dogs with normal ventricular conduction to investigate hemodynamic effects of pacing at various epicardial LV sites, the RV apex, and combinations of these sites (n = 11) and of RV and LV septal pacing (n = 8). The LV septal endocardium was reached via the RV by puncturing through the septum with a barbed electrode. Left ventricular systolic (LVdP/dtpos and stroke work) and diastolic (LVdP/dtneg and Tau) function were assessed using pressure-volume relations (conductance catheter technique). RESULTS: Left ventricular systolic and diastolic function were highly dependent on the site of pacing, but not on QRS duration. Left ventricular function was maintained at SR level during LV septal, LV apex, and multisite pacing, was moderately depressed during pacing at epicardial LV free wall sites, and was most severely depressed during RV apex pacing. On average, RV septal pacing did not improve LV function, compared with RV apex pacing, but in each experiment one (variable) RV pacing site was found, which only moderately reduced LV function. CONCLUSIONS: During ventricular pacing, LV pump function is maintained best (i.e., at SR level) when pacing at the LV septum or LV apex, potentially because pacing from these sites creates a physiological propagation of electrical conduction.

Analysis of Variance↗
PubMed2003

Proteins involved in salvage of the myocardium.

In the Western world, cardiac ischemic disease is still the most common cause of death despite significant improvements of therapeutic drugs and interventions. The fact that the heart possesses an intrinsic protection mechanism has been systematically overlooked before the 1980s. It has been clearly shown that the activation of this mechanism can reduce the infarct size after an ischemic insult. Prerequisite is the induction of the synthesis of such cardio-protective proteins as heat shock proteins (HSPs) and anti-oxidative enzymes. HSPs are involved in the maintenance of cell homeostasis by guiding the synthesis, folding and degradation of proteins. Besides, the various family members cover a broad spectrum of anti-oxidative, anti-apoptotic and anti-inflammatory activities. Although the major inducible HSP72 has received most attention, other HSPs are able to confer cardioprotection as well. In addition, it seems that there is a concerted action between the various cardio-protective proteins. One drawback is that the beneficial effects of HSPs seem to be less effective in the compromised than in the normal heart. Although clinical studies have shown that there is a therapeutic potential for HSPs in the compromised heart, major efforts are needed to fully understand the role of HSPs in these hearts and to find a safe and convenient way to activate these protective proteins.

Animals↗
PubMed2003

Relation between abnormal ventricular impulse conduction and heart failure.

Ventricular pacing and left bundle branch block (LBBB) are two of the most common causes of asynchronous electrical activation of the ventricles. The sequence of activation is an important determinant of cardiac pump function. The sequence of activation during LBBB and during pacing at the conventional pacing site, the RV apex, is similar. In this article the literature on the effect of RV pacing and LBBB on regional and global LV pump function, on long-term adaptations (remodeling) and on their possible contribution to the development of heart failure is discussed. Evidence is increasing that asynchronous electrical activation contributes significantly to the development of heart failure.

Animals↗
PubMed2003

Timing of depolarization and contraction in the paced canine left ventricle: model and experiment.

INTRODUCTION: For efficient pump function, contraction of the heart should be as synchronous as possible. Ventricular pacing induces asynchrony of depolarization and contraction. The degree of asynchrony depends on the position of the pacing electrode. The aim of this study was to extend an existing numerical model of electromechanics in the left ventricle (LV) to the application of ventricular pacing. With the model, the relation between pacing site and patterns of depolarization and contraction was investigated. METHODS AND RESULTS: The LV was approximated by a thick-walled ellipsoid with a realistic myofiber orientation. Propagation of the depolarization wave was described by the eikonal-diffusion equation, in which five parameters play a role: myocardial and subendocardial velocity of wave propagation along the myofiber cm and ce; myocardial and subendocardial anisotropy am and ae; and parameter k, describing the influence of wave curvature on wave velocity. Parameters cm, ae, and k were taken from literature. Parameters am and ce were estimated by fitting the model to experimental data, obtained by pacing the canine left ventricular free wall (LVFW). The best fit was found with cm = 0.75 m/s, ce = 1.3 m/s, am = 2.5, ae = 1.5, and k = 2.1 x 10(-4) m2/s. With these parameter settings, for right ventricular apex (RVA) pacing, the depolarization times were realistically simulated as also shown by the wavefronts and the time needed to activate the LVFW. The moment of depolarization was used to initiate myofiber contraction in a model of LV mechanics. For both pacing situations, mid-wall circumferential strains and onset of myofiber shortening were obtained. CONCLUSION: With a relatively simple model setup, simulated depolarization timing patterns agreed with measurements for pacing at the LVFW and RVA in an LV. Myocardial cross-fiber wave velocity is estimated to be 0.40 times the velocity along the myofiber direction (0.75 m/s). Subendocardial wave velocity is about 1.7 times faster than in the rest of the myocardium, but about 3 times slower than as found in Purkinje fibers. Furthermore, model and experiment agreed in the following respects. (1) Ventricular pacing decreased both systolic pressure and ejection fraction relative to natural sinus rhythm. (2) In early depolarized regions, early shortening was observed in the isovolumic contraction phase; in late depolarized regions, myofibers were stretched in this phase. Maps showing timing of onset of shortening were similar to previously measured maps in which wave velocity of contraction appeared similar to that of depolarization.

Algorithms↗
PubMed2003

Dexmedetomidine decreases perioperative myocardial lactate release in dogs.

UNLABELLED: The sympatholytic effect of the alpha(2)-adrenergic agonist dexmedetomidine may decrease emergence-related myocardial ischemic load in patients. However, a direct measure of myocardial ischemia, such as myocardial lactate release, is difficult to obtain in patients. Therefore, we studied mongrel dogs and measured myocardial lactate release, myocardial oxygen supply, hemodynamic variables, and neurohumoral indices of the stress response. After the induction of a standardized degree of borderline myocardial ischemia, either dexmedetomidine (dexmed group, n = 9) or normal saline (control group, n = 9) was infused. Measurements were repeated at the end of the anesthetic period and every 10 min during the 90-min emergence period. In the dexmed group, the cumulative emergence-related lactate release was 46% less than in the control group (95% confidence interval, 20%-80%; P = 0.02). Simultaneously, dexmedetomidine increased the endo-/epicardial blood flow ratio by 35% (control group, 0.4 +/- 0.1; dexmed group, 0.6 +/- 0.1; P = 0.03). These antiischemic effects of dexmedetomidine were accompanied by reduced plasma concentrations of norepinephrine (126 versus 577 pg/mL) and epinephrine (158 versus 1909 pg/mL) and a slower heart rate (123 +/- 6 versus 160 +/- 10 bpm, dexmed versus control). The antiischemic effect of dexmedetomidine started before emergence, as evidenced by a decreased prevalence of myocardial lactate release at that time (zero of eight dogs in the dexmed group and four of seven dogs in the control group had lactate release before emergence; P = 0.03). IMPLICATIONS: Dexmedetomidine decreases plasma catecholamines and heart rate during emergence from anesthesia. In dogs with a coronary stenosis, these sympatholytic effects decrease myocardial lactate release and, therefore, minimize emergence-related myocardial ischemia.

Adrenergic alpha-Agonists↗
PubMed2002

Relation between local myocardial growth and blood flow during chronic ventricular pacing.

UNLABELLED: Several studies have shown that, per unit mass, myocardial blood flow (MBF) and oxygen consumption are similar in hypertrophic and non-hypertrophic ventricles. This observation may be explained by the degree of myocardial growth matching the increase in oxygen demand. Such matching may, however, not be perfect at the local level, because substantial heterogeneity of MBF exists within the ventricular wall. We investigated to what extent local growth and MBF are matched after redistribution of workload within the left ventricular (LV) wall. Redistribution of workload was established by ventricular pacing at physiological heart rate, which induces asynchronous activation and contraction. Local wall mass (2D-echocardiography) and MBF (fluorescent microspheres) were determined in the canine LV wall before (t=0) and after 6 months of normal sinus rhythm (SHAM group, n=5) or 6 months of pacing at the LV free wall (PACE group, n=8). During acute pacing MBF (ml/min/g) increased with increasing distance to the pacing site. Local relative MBF (rMBF, local MBF normalized to mean MBF in the LV wall) varied from 0.8 adjacent to the pacing site to 1.2 in remote regions. After 6 months of pacing these regional differences had disappeared, probably due to changes in wall mass, which increased with increasing distance to the pacing site (by up to 39+/-13%). In SHAM animals rMBF at t=0 correlated well with rMBF 6 months later (r=0.71). In PACE animals, however, this correlation was poor (r=0.33), because rMBF increased in regions close to the pacing site with initial rMBF<1 and rMBF decreased in regions remote from the pacing site with initial rMBF>1. CONCLUSIONS: After redistribution of workload within the LV wall as induced by ventricular pacing, local load-regulated growth tends to equalize MBF distribution, but local adaptation of MBF also depends on initial MBF.

Animals↗
PubMed2002

Relation between the pacing induced sequence of activation and left ventricular pump function in animals.

The main goal of this article was to review animal experimental work on the effect of asynchronous activation on ventricular pump function. During normal sinus rhythm and atrial pacing, the Purkinje system contributes significantly to the rapid electrical activation of the ventricles. In contrast, during ventricular pacing the impulse is almost exclusively conducted through the normal myocardium. As a consequence, electrical activation of the ventricles becomes asynchronous and has an abnormal sequence. The abnormal impulse conduction causes considerable disturbances to occur in regional systolic fiber shortening, mechanical work, blood flow, and oxygen consumption; low values occurring in early activated regions and values above normal being present in late activated regions. Many animal studies have now shown that the abnormal electrical activation, induced by ventricular pacing, leads to a depression of systolic and diastolic LV function. Pacing at the right ventricular apex (the conventional pacing site) reduces LV function more than pacing at the high ventricular septum or at LV sites. In canine hearts with experimental LBBB, LV pacing significantly improves LV pump function. Differences in LV pump function between (combinations of) pacing sites are poorly correlated with QRS duration. Therefore, the cause of the depression of LV function during abnormal electrical activation appears to be a combination of the asynchrony and the sequence of activation. These experimental findings justify continuing attention for optimizing the site(s) of ventricular pacing in patients with normal and abnormal ventricular impulse conduction.

Animals↗
PubMed2002

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.

Animals↗
PubMed2002

Effects of single- and biventricular pacing on temporal and spatial dynamics of ventricular contraction.

Resynchronization is frequently used for the treatment of heart failure, but the mechanism for improvement is not entirely clear. In the present study, the temporal synchrony and spatiotemporal distribution of left ventricular (LV) contraction was investigated in eight dogs during right atrial (RA), right ventricular apex (RVa), and biventricular (BiV) pacing using tagged magnetic resonance imaging. Mechanical activation (MA; the onset of circumferential shortening) was calculated from the images throughout the left ventricle for each pacing protocol. MA width (time for 20-90% of the left ventricle to contract) was significantly shorter during RA (43.6 +/- 17.1 ms) than BiV and RVa pacing (67.4 +/- 15.2 and 77.6 +/- 16.4 ms, respectively). The activation delay vector (net delay in MA from one side of the left ventricle to the other) was significantly shorter during RA (18.9 +/- 8.1 ms) and BiV (34.2 +/- 18.3 ms) than during RVa (73.8 +/- 16.3 ms) pacing. Rate of LV pressure increase was significantly lower during RVa than RA pacing (1,070 +/- 370 vs. 1,560 +/- 300 mmHg/s) with intermediate values for BiV pacing (1,310 +/- 220 mmHg/s). BiV pacing has a greater impact on correcting the spatial distribution of LV contraction than on improving the temporal synchronization of contraction. Spatiotemporal distribution of contraction may be an important determinant of ventricular function.

Animals↗