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Biomedical subjects

Frits W Prinzen

Publications and source records attributed to Frits W Prinzen.

26 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗