Effect of ectopic excitation on the ventricular pump function in chicken

The pump function of the heart ventricles was studied in chest-open anaesthetized adult female chickens under sinus rhythm and ectopic excitation of different localization. The intraventricular pressure in the right and left heart ventricles was measured by insertion of catheters through the ventricular free walls. Maximum systolic pressure, end-diastolic pressure, contractility (dP/dtmax) and relaxation (dP/dtmin) of both heart ventricles, and duration of the asynchronous contraction time of the left ventricle were analyzed. It was revealed that reduction of the pump function of the left ventricle tends to be greater under right ventricular ectopic excitation compared with left ventricular one. In comparison with the sinus rhythm, the pump function of the right ventricle was preserved to a greater extent under stimulation of the left ventricular apex and was significantly impaired under right ventricular ectopic excitation. Relaxation of both heart ventricles was more susceptible to ventricular ectopic excitation than contractility, and was more vulnerable in the right ventricle than in the left one. The direction of changes of the pump function of the heart ventricles in chickens under ventricular ectopic excitation was similar to changes of the pump function of mammalian hearts.     

Ventricular pump function under ectopic excitation of the frog heart

The ventricular pump function under ectopic excitation of the heart was studied in decapitated and pithed adult frogs Rana temporaria (n = 21) at 18-19 degrees C. The intraventricular pressure was recorded with a catheter via ventricular wall. During pacing of the ventricular base and apex, the systolic pressure decreased (6.1 +/- 4.5 mm Hg and 8.9 +/- 5.0 mm Hg, respectively) as compared to the supraventricular rhythm (8.9 +/- 5.0 mm Hg, p < 0.05). The end-diastolic pressure decreased insignificantly both under basal and apical pacing. The systolic rate of pressure rise during dP/dtmax decreased under ventricular pacing, especially during pacing of the ventricular apex, as compared to the supraventricular rhythm (14.4 +/- 6/9 mm Hg/s and 22.1 +/- 11.2 mm Hg/s, respectively, p < 0.003). The isovolumetric relaxation (dP/dtmin) slowed during apical pacing as compared to the supraventricular rhythm (-25.1 +/- 13.6 and -35.6 +/- 18.3 mm Hg/s, respectively, p < 0.03). Ectopic excitation of the ventricular base and apex resulted in increase of the QRS duration (93 +/- 33 ms and 81 +/- 30 ms, respectively) as compared to the supraventricular rhythm (63 +/- 13 ms, p < 0.05). Thus, pacing of different ventricular areas ventricular myocardium with the ventricular pump function being reduced more obviously during the apical pacing compared to the pacing of ventricular base.     

Ectopic atrial arrhythmias arising from canine thoracic veins during in vivo stellate ganglia stimulation

The purpose of the present study was to determine whether thoracic veins may act as ectopic pacemakers and whether nodelike cells and rich sympathetic innervation are present at the ectopic sites. We used a 1,792-electrode mapping system with 1-mm resolution to map ectopic atrial arrhythmias in eight normal dogs during in vivo right and left stellate ganglia (SG) stimulation before and after sinus node crushing. SG stimulation triggered significant elevations of transcardiac norepinephrine levels, sinus tachycardia in all dogs, and atrial tachycardia in two of eight dogs. Sinus node crushing resulted in a slow junctional rhythm (51 +/- 6 beats/min). Subsequent SG stimulation induced 20 episodes of ectopic beats in seven dogs and seven episodes of pulmonary vein tachycardia in three dogs (cycle length 273 +/- 35 ms, duration 16 +/- 4 s). The ectopic beats arose from the pulmonary vein (n = 11), right atrium (n = 5), left atrium (n = 2), and the vein of Marshall (n = 2). There was no difference in arrhythmogenic effects of left vs. right SG stimulation (13/29 vs. 16/29 episodes, P = nonsignificant). There was a greater density of periodic acid Schiff-positive cells (P < 0.05) and sympathetic nerves (P < 0.05) at the ectopic sites compared with other nonectopic atrial sites. We conclude that, in the absence of a sinus node, thoracic veins may function as subsidiary pacemakers under heightened sympathetic tone, becoming the dominant sites of initiation of focal atrial arrhythmias that arise from sites with abundant sympathetic nerves and periodic acid Schiff-positive cells.     

Significance of the site of premature excitation for the left and right ventricular performance in open chest dogs

The haemodynamic response to premature excitation was studied in open-chest dog hearts. Intraventricular pressure, dP/dt and outflow rate of the left and right heart (5 experiments each) were compared at variable preextrasystolic intervals and with the stimulation at three different sites (left ventricle--LV apex and base, right ventricle--RV free wall). In both ventricles and at any driving interval the reduction of all extrasystolic parameters is significantly more pronounced on ipsilateral stimulation. This reduction is apparent even at the fusion interval, demonstrating the importance of normal spread of excitation. The differences between apex and base stimulation are, however, only insignificant. The outflow valves opening interval greatly differs in aorta and pulmonary artery, namely if LV is stimulated, which results in a considerable disproportion between LV and RV extrasystolic stroke volumes. The extrasystolic augmentation is revealed by all parameters in the right heart but is surprisingly absent in the peak pressure and relaxation rate (dP/dt) in the LV.     

Effect of localization of the ectopic excitation site on the sequence and duration of depolarization in the ventricular epicardium in dogs

The depth of the myocardial wall ectopic focus was found to affect spatial and temporal characteristics of the depolarization process in the heart ventricular surface. Duration of the ventricular epicardial depolarization under the ectopic foci located in subendocardial and intramural layers of the myocardium was shorter than in epicardial stimulation of the ventricles. A dependence of the ectopic excitation duration on the pacing site localization in the epicardium, was revealed. The shortest duration of the depolarization occurred under electrical stimulation of the apex and ventral part of the interventricular septum, whereas the longer one--under pacing the left ventricular base.     

Left ventricular resynchronization therapy in a canine model of left bundle branch block

Positive responses to left (LV) and biventricular (BV) stimulation observed in heart failure patients with left bundle branch block (LBBB) suggest a possible mechanism of LV resynchronization. An anesthetized canine LBBB model was developed using radio frequency ablation. Before and after ablation, LV pressure derivative over time (dP/dt) and aortic pulse pressure (PP) were assessed during normal sinus rhythm with right ventricle (RV), LV, or BV stimulation combined with four atrioventricular delays in six dogs. In three more dogs, M-mode echocardiograms of septal and LV posterior wall motion were obtained before and after LBBB and during LV stimulation. LBBB caused QRS widening and hemodynamics deterioration. Before ablation, stimulation alone worsened LV dP/dt and PP. After ablation, LV and BV stimulation maximally increased LV dP/dt by 16% and PP by 7% (P < 0.001), whereas little improvement was observed during RV stimulation. M-mode echocardiogram showed that LBBB resulted in a paradoxical septal wall motion that was corrected by LV stimulation. In conclusion, LV and BV stimulation improved cardiac function in a canine LBBB model via resynchronization of LV excitation and contraction.     

Left ventricular myocardal activation under ventricular paced beats in chickens Gallus gallus domesticus

The aim of the study was to advance our knowledge regarding the activation process of the ventricular myocardium in birds in which Purkinje fibres penetrate into the ventricular wall to reach the epicardium. A depolarization pattern of the left ventricular free wall was studied in chickens (Gallus gallus) during ventricular paced beats. Duration of the activation process of the left ventricular free wall is significantly increased during ventricular ectopic excitation as compared with sinus rhythm. Its lowest increase occurs during subendocardial pacing of the middle part of the left ventricle, but its greatest increase is observed during subepicardial pacing of the left ventricular base. Multifocality and mosaicity of depolarization of the left ventricular free wall myocardium in chicken are expressed in a considerably less degree during ventricular paced beats in comparison with sinus rhythm. During ventricular paced beats, excitation of the left ventricular free wall is mostly due to the successive spreading of the depolarization wave from pacing sites.     

Reflection of distribution of the epicardial ventricular potential on the dog body surface during electrical stimulation of the myocardium]

Electrical pacing of the apex, base, and free wall of the heart right and left ventricles, as well as the left ventricle's interventricular septum revealed that localisation of the ectopic focus determined the sequence of ventricular depolarisation, the site formation, and the pathway of displacement of the areas' positive and negative potentials and their extrema on the thoracic surface. Time of the mutual movement (inversion) of positive and negative zones on the body surface was found to depend on the pacing site in the wall of ventricles.     

Effect of hypothermia on sequence of the ventricle epicardium repolarization in rabbits]

In anaesthetised rabbits at normal body temperature, the earliest ventricles' epicardial recovery occurs at the heart apex and adjacent left ventricle's surface whereas the latest one occurs at the epicardium of the right ventricle's base. A decrease in the mediastinum temperature to 32 degrees C reversed the recovery sequence. Following the cooling of the heart, the longest prolongation of the activation-recovery interval occurred at the heart apex area and the lowest one--at the right ventricle base.     

Effect of increased left atrial pressure on breathing frequency in anesthetized dog

Distension or loading of the isolated canine left heart caused reflex tachypnea in prior studies. The object of the present effort was to explore the possibility that this depended primarily on atrial distension. Cardiopulmonary bypass perfusion and ligation of pulmonary veins were used to isolate the left-heart chambers of anesthetized dogs. Simultaneous distension of the beating left atrium and fibrillating ventricle stimulated breathing frequency (f), whereas isolated ventricular distension did not. At other times, intervals of atrial fibrillation were imposed under two different conditions: 1) while the right heart and lungs were bypassed and systemic perfusion was provided by the left ventricle using blood returned to the left atrium by pump and 2) while the ventricles fibrillated and systemic perfusion was supplied directly by the pump. Atrial fibrillation increased left atrial pressure and stimulated f in condition 1. In condition 2, f increased only if fibrillation was associated with a rise in left atrial pressure. Vagal cooling blocked the effect of fibrillation. I conclude that left atrial distension may initiate reflex tachypnea.     

Dynamics of contraction of the left and right ventricles of the heart (according to kinetocardiography data) in the development of renovascular hypertension in dogs of various ages]

Kinetocardiograms of the left and the right ventricles of the heart were recorded in puppies and adult dogs during development in them of experimental renovascular hypertension. Development of hypertension in adult dogs led to the shortening of ejection period, and in puppies--to its prolongation. The vector analysis of kinetocardiograms demonstrated in adult dogs the appearance of the syndrome of hypodynamics of the left ventricle replaced later by the syndrome of high diastolic pressure. In the puppies' left ventricle there appeared the phasic syndrome of high diastolic pressure replaced by the syndrome of stenosis of the exit tract. The phasic structure of the cycle of the right ventricle is characterized by the appearance of the syndrome of hyperdynamia detectable earlier in adult dogs.     

Inhomogeneity in the response to mechanical stimulation: cardiac muscle function and gene expression

Mechanical stimulation has important consequences for myocardial function. However, this stimulation and the response to it, is not uniform. The right ventricle is thinner walled and operates at lower pressure than the left ventricle. Within the ventricles, differences in the orientation of myocardial fibres exist. These differences produce inhomogeneity in the stress and strain between and across the ventricles. Possibly as a result of these variations in mechanical stimulation, there are well characterised inhomogeneities in gene expression and protein function within the ventricular myocardium, for example in the transient outward K+ current and its associated Kv channels. Perhaps not surprisingly, it is becoming apparent that gradients of expression and function exist for proteins that are intimately involved in the response to mechanical stimulation in the heart, for example in the left ventricle of the rat there is a transmural gradient in mRNA and current density of the mechanosensitive two-pore domain K+ channel TREK-1 (ENDO>EPI). In healthy hearts it is assumed that these gradients are important for normal function and therefore that their disruption in diseased myocardium is involved in the dysfunction that occurs.     

Intramural chronotopography of myocardial depolarization in the heart ventricles of the pig (Sus scrofa domesticus)

Multichannel synchronous cardioelectrotopography is used to analyze the sequence of myocardial depolarization in the ventricles of the pig heart. Formation of early depolarization areas has been established in subendocardium of interventricular septum and in the base of papillary muscles of the left ventricle; of multiple foci-in the thickness of myocardial walls; of areas of late depolarization-in subepicardium of the dorsolateral side of the left ventricle. In pig heart ventricles, as compared with other ungulates (reindeer and sheep) there are revealed differences in location of areas of the early and late depolarization areas and the breakthrough of excitation wave onto subepicardium.     

O2 extraction of right and left ventricles.

O2 extraction was measured simultaneously in right and left ventricles of dogs. Extraction was about 2.5 vol% higher in left ventricle. This figure, together with flow measurements of others (1-3), indicates that VO2/100g is at least twice as great in left ventricle as in right.     

Heart rate as a determinant of the decay rate of the cardiac inotropic response to sympathetic nervous activity

The cardiac responses to sympathetic nerve stimulation were measured in a series of open-chest, anesthetized dogs. In half the animals, the hearts were in a sinus rhythm; in the remaining animals, the hearts were in an atrioventricular (AV) junctional rhythm. Cocaine markedly prolonged the decay times of the chronotropic responses after cessation of sympathetic stimulation, regardless of the type of rhythm. The decay times of the inotropic responses were only slightly prolonged by cocaine in animals with a sinus rhythm, but the prolongations were pronounced in animals with an AV junctional rhythm. The lower basal heart rate appeared to be more responsible for the greater decay times of the inotropic responses in the animals with an AV junctional rhythm than in those with a sinus rhythm. In a second series of dogs, complete heart block was produced, cocaine was given, AND the hearts were paced at four different frequencies. The mean decay time of the inotropic response to sympathetic stimulation varied inversely AND substantially with the pacing frequency. The change in contraction frequency probably affects the rate of neurotransmitter dissipation from the ventricular myocardium, by altering either the coronary blood flow or the massaging action of the cardiac contractions.     

Ratiometric intracellular calcium imaging in the isolated beating rat heart using indo-1 fluorescence.

Abnormalities in intracellular calcium (Ca(i)(2+)) handling have been implicated as the underlying mechanism in a large number of pathologies in the heart. Study into the relation between Ca(i)(2+) behavior and performance of the whole heart function could provide detailed information into the cellular basis of heart function. In this study we describe an optical ratio imaging setup and an analysis method for the beat-to-beat Ca(i)(2+) videofluorescence images of an indo-1 loaded, isolated Tyrode-perfused beating rat heart. The signal-to-noise ratio and the spatiotemporal resolution (with an optimum of 1 ms and 0.6 mm, respectively) made it possible to register different temporal Ca(i)(2+) transients together with left ventricle pressure changes. The Ca(i)(2+) transients showed that Ca(i)(2+) activation propagates horizontally from left to right during sinus rhythm or from the stimulus site during direct left ventricle stimulation. The indo-1 ratiometric video technique developed allows the imaging of ratio changes of Ca(i)(2+) with a high temporal (1 ms) and spatial (0.6 mm) resolution in the isolated Tyrode-perfused beating rat heart.     

The quantitative relationship between longitudinal and radial function in left, right, and total heart pumping in humans

The total heart volume variation (THVV) during systole has been proposed to be caused by radial function of the ventricles, but definitive data for both ventricles have not been presented. Furthermore, the right ventricle (RV) has been suggested to have a greater longitudinal pumping component than the left ventricle (LV). Therefore, we aimed to compare the stroke volume (SV) generated by radial function to the volume variation of the left, right, and total heart. To do this, we also needed to develop a new method for measuring the contribution of the longitudinal atrioventricular plane displacement (AVPD) to the RVSV (RVSV(AVPD)). For our study, 11 volunteers underwent cine MRI in the short- and long-axis planes and MRI flow measurement in all vessels leading to and from the heart. The left, right, and total heart showed correlations between volume variation from flow measurements and radial function calculated as SV minus the longitudinal function (r = 0.81, P < 0.01; r = 0.80, P < 0.01; and r = 0.92, P < 0.001, respectively). Compared with the LV, the RV had a greater AVPD (23.4 +/- 0.8 vs. 16.4 +/- 0.5 mm), center of volume movement (13.0 +/- 0.7 vs. 7.8 +/- 0.4 mm), and, RVSV(AVPD) (82 +/- 2% vs. 60 +/- 2%) (P < 0.001 for all). We found that THVV is predominantly caused by radial function of the ventricles. Longitudinal AVPD accounts for approximately 80% of the RVSV, compared with approximately 60% for the LVSV. This difference explains the larger portion of THVV found on the left side of the heart.     

Protein synthesis during right-ventricular hypertrophy after pulmonary-artery stenosis in the dog.

The rate of protein synthesis in the heart of normal dogs and those with pulmonary-artery stenosis was measured by a continuous intravenous infusion of [14C]tyrosine. The protein-synthesis rate of both ventricles was the same in normal dogs and averaged 7.5% per day. The right ventricle hypertrophied rapidly after the acute imposition of pulmonary-artery stenosis, the wet weight increasing by 84% after 24 days, with the rate of increase being most rapid over the first 5 days. The left ventricle remained largely unaffected and served as an internal control. During hypertrophy there was an increased incorporation of [14C]tyrosine into protein without a significant change in the specific radioactivity of free tyrosine in the ventricles. After 5 days of stenosis the synthesis rate of the total mixed proteins of the right ventricle had increased to 13.6% per day, compared with 6.2% in the control left ventricle. This increase in synthesis was reflected in both the myofibrillar and sarcoplasmic proteins. After 5 days the protein-synthesis rate decreased, but still remained significantly elevated above that in the control left ventricle by 24 days of stenosis.     

Optical mapping of chronotopography of excitation of the frog heart ventricle epicardial surface in sinus rhythm

Two points of early activation were shown on the surface of the frog Rana temporaria ventricle using optical mapping technique. These points are located on the left and right ventricular surface at equal distance from apex and base of the ventricle. The excitation approaches to epicardial ventricular surface at these points, and then it spreads all over the surface. Such pattern of epicardial activation is also shown in mammals where it is related to conduction system functioning. Thus, the precursor of conduction system seems to exist in the frog ventricle, too.     

Voltage-sensitive dye mapping in Langendorff-perfused rat hearts

An imaging system suitable for recordings from Langendorff-perfused rat hearts using the voltage-sensitive dye 4-[beta-[2-(di-n-butylamino)-6-naphthyl]vinyl]pyridinium (di-4-ANEPPS) has been developed. Conduction velocity was measured under hyper- and hypokalemic conditions, as well as at physiological and reduced temperature. Elevation of extracellular [K(+)] to 9 mM from 5.9 mM caused a slowing of conduction velocity from 0.66 +/- 0.08 to 0.43 +/- 0.07 mm/ms (35%), and reduction of the temperature to 32 degrees C from 37 degrees C caused a slowing from 0.64 +/- 0.07 to 0.46 +/- 0.05 mm/ms (28%). Ventricular activation patterns in sinus rhythm showed areas of early activation (breakthrough) in both the right and left ventricle, with breakthrough at a site near the apex of the right ventricle usually occurring first. The effects of mechanically immobilizing the preparation to reduce motion artifact were also characterized. Activation patterns in epicardially paced rhythm were insensitive to this procedure over the range of applied force tested. In sinus rhythm, however, a relatively large immobilizing force caused prolonged PQ intervals as well as altered ventricular activation patterns. The time-dependent effects of the dye on the rat heart were characterized and include 1) a transient vasodilation at the onset of dye perfusion and 2) a long-lasting prolongation of the PQ interval of the electrocardiogram, frequently resulting in brief episodes of atrioventricular block.