Heterogeneity of the myocardium. Function of the left and right ventricle under normal and pathological conditions

A number of important differences can be found between the left ventricle (LV) and right ventricle (RV) of the heart under physiological conditions. In anatomy, the most important is probably the architecture of the atrioventricular valve and its annulus. The LV has a mitral valve (with two cusps) and a firm annulus, while the RV has a tricuspid valve with a greater total area, but relatively small cuspid areas, and an elastic annulus. The difference in the blood supply is important. Owing to high intramural pressure, the coronary flow in the wall of the LV occurs only during the diastole; in the RV it is limited only in the presence of a significant increase in intracavitary pressure. The LV myocardium is functionally "accustomed" to short-term marked changes in the systolic load (in extreme static exercise the arterial pressure rises for a short time to three times the normal value), while the RV is adapted to changes in the diastolic load (marked filling changes associated with deep breathing, for instance). The difference in the response to a long-term volume load is difficult to evaluate: between a defect of the interatrial septum and aortic insufficiency there are too many differences. A long-term pressure load seems to be tolerated better by the right ventricle: patients with severe pulmonary stenosis and a pressure six times higher than the physiological value have lived 25 years and patients with isolated corrected L-transposition of the great arteries can reach 35 years without any signs of impaired RV function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characteristic features of EchoCG parameters in men and women with different geometric configurations

An echocardiographic study of 190 subjects in the second period of adult age (108 women and 82 men) has been conducted. The absolute and relative sizes of the left ventricle (LV), left atrium (LA), right ventricle (RV), myocardium mass, and LV mass index were determined. Morphological changes in the heart detected by echocardiography (EchoCG) depended on the geometric configuration of the LV. The size of the RV was significantly increased in women with hypertrophy of the myocardium of the LV. All the EchoCG parameters with the exception of relative wall thickness (RWT) were gender-dependent. The gender-dependent differences in LV remodeling included higher values of LV mass index in men, different dynamics of the LV mass index (LVMI) in subjects with different geometric configurations of the LV, and more pronounced elevation of the index in women with eccentric hypertrophy of the LV (LV EG), in particular. The functional capacity of the heart was lower in men than in women.     

A comparative MudPIT analysis identifies different expression profiles in heart compartments

Cardiomyopathies indistinctly affect atrial and ventricular cardiac compartments with alterations of their mechanical and/or electrical activity. To understand the main mechanisms involved in these pathological alterations, a detailed knowledge of the physiology of the healthy heart is critical. In the present work, we utilize multidimensional protein identification technology to characterize the murine left ventricle (LV), right ventricle (RV), and atria (A) proteomes, identifying thousands of distinct proteins. Moreover, using multidimensional algorithm protein map tool, relative abundances of proteins among the heart chambers were investigated. In sum, we found 16 and 55 proteins were more abundant in LV compared to RV and A, respectively; 47 and 60 proteins were more abundant in RV than LV and A, respectively; and, 81 and 74 proteins were more abundant in A than LV and RV, respectively. This detailed characterization of myocardial compartment proteome represents an important advancement in the knowledge of heart physiology, and may contribute to the identification of key features underlying the onset of cardiomyopathy.     

Endotoxemia decreases matching of regional blood flow and O2 delivery to O2 uptake in the porcine left ventricle

Heterogeneity of regional coronary blood flow is caused in part by heterogeneity in O(2) demand in the normal heart. We investigated whether myocardial O(2) supply/demand mismatching is associated with the myocardial depression of sepsis. Regional blood flow (microspheres) and O(2) uptake ([(13)C]acetate infusion and analysis of resultant NMR spectra) were measured in about nine contiguous tissue samples from the left ventricle (LV) in each heart. Endotoxemic pigs (n = 9) showed hypotension at unchanged cardiac output with a fall in LV stroke work and first derivative of LV pressure relative to controls (n = 4). Global coronary blood flow and O(2) delivery were maintained. Lactate accumulated in arterial blood, but net lactate extraction across the coronary bed was unchanged during endotoxemia. When LV O(2) uptake based on blood gas versus NMR data were compared, the correlation was 0.73 (P = 0.007). While stable over time in controls, regional blood flows were strongly redistributed during endotoxin shock, with overall flow heterogeneity unchanged. A stronger redistribution of blood flow with endotoxin was associated with a larger fall in LV function parameters. Moreover, the correlation of regional O(2) delivery to uptake fell from r = 0.73 (P < 0.001) in control to r = 0.18 (P = 0.25, P = 0.009 vs. control) in endotoxemic hearts. The results suggest a redistribution of LV regional coronary blood flow during endotoxin shock in pigs, with regional O(2) delivery mismatched to O(2) demand. Mismatching may underlie, at least in part, the myocardial depression of sepsis.     

Effects of training on biochemical and functional properties of rodent neonatal heart

This study was undertaken to determine biochemical and functional (in vivo) adaptations of the rodent neonatal heart in response to a training program of endurance running. Ten day-old rats were progressively trained on a treadmill (final intensity, 21 m/min, 30% grade, 1 h/day) until 75 days of age. The training program induced 14, 57, and 24% increases in relative heart mass, skeletal muscle citrate synthase activity, and whole-body maximal O2 uptake, respectively (P less than 0.05). Cardiac myosin (ATPase) and Ca2+-regulated myofibril ATPase were both reduced by approximately 15% in trained vs. sedentary animals (P less than 0.05). In the majority of trained hearts examined, the myosin isozyme profile reflected an estimated 14 +/- 3% shift toward the V3 or low ATPase isozyme. Left ventricular functional indices during submaximal exercise, derived from a fluid-filled indwelling cannula, indicated that the trained animals maintained similar left ventricular (LV) systolic pressure, LV + the time derivative of pressure, and systemic arterial mean blood pressure compared with their sedentary counterparts. These functional parameters were maintained even though the trained animals performed with lower submaximal exercise heart rate. These findings suggest that maximal exercise capacity can be enhanced in neonatal rats even though the biochemical potential for ATP degradation in the cardiac contractile system is lowered. We speculate that the trend to maintain the myosin isozyme pattern further in the direction of the V3 isozyme in the trained neonatal rat heart may reflect a means to economize cross-bridge cycling while maintaining normal levels of ventricle performance at a given submaximal work load.     

The cost of energy and cardiovascular expenditure in basketball players during a game

Energy expenditure was evaluated for 6 Basket players while exercising on a cyclergometer. Oxygen consumption (VO2), pulmonary ventilation (VE), heart rate (HR), respiratory quotient (QR) and other parameters were estimated at various levels of load (25 Watt each step of 3 minutes duration), till to submaximal load of 175 Watt. The same subjects participate to a regular Basket game and their heart rate was continuously stored on a tape recorder (Holter). Arterial blood pressure was also taken whenever possible (timeout, etc). From the laboratory and field data, estimates were made for the oxygen consumption together with energy cost of the game. This can be assume a net value of 0.1339 Kcal X Kg-1 X min-1.     

The effect of vortex formation on left ventricular filling and mitral valve efficiency

A new mechanism for quantifying the filling energetics in the left ventricle (LV) and past mechanical heart valves (MHV) is identified and presented. This mechanism is attributed to vortex formation dynamics past MHV leaflets. Recent studies support the conjecture that the natural healthy left ventricle (LV) performs in an optimum, energy-preserving manner by redirecting the flow with high efficiency. Yet to date, no quantitative proof has been presented. The present work provides quantitative results and validation of a theory based on the dynamics of vortex ring formation, which is governed by a critical formation number (FN) that corresponds to the dimensionless time at which the vortex ring has reached its maximum circulation content, in support of this hypothesis. Herein, several parameters (vortex ring circulation, vortex ring energy, critical FN, hydrodynamic efficiencies, vortex ring propagation speed) have been quantified and presented as a means of bridging the physics of vortex formation in the LV. In fact, the diastolic hydrodynamic efficiencies were found to be 60, 41, and 29%, respectively, for the porcine, anti-anatomical, and anatomical valve configurations. This assessment provides quantitative proof of vortex formation, which is dependent of valve design and orientation, being an important flow characteristic and associated to LV energetics. Time resolved digital particle image velocimetry with kilohertz sampling rate was used to study the ejection of fluid into the LV and resolve the spatiotemporal evolution of the flow. The clinical significance of this study is quantifying vortex formation and the critical FN that can potentially serve as a parameter to quantify the LV filling process and the performance of heart valves.     

Arterial vasodilatory and ventricular diastolic reserves determine the stroke volume response to exercise in elderly female hypertensive patients

Elderly female hypertensives with arterial stiffening constitute a majority of patients with heart failure with preserved ejection fraction (HFpEF), a condition characterized by inability to increase cardiac stroke volume (SV) with physical exercise. As SV is determined by the interaction between the left ventricle (LV) and its load, we wished to study the role of arterial hemodynamics for exertional SV reserve in patients at high risk of HFpEF. Twenty-one elderly (67 ± 9 yr) female hypertensive patients were studied at rest and during supine bicycle stress using echocardiography including pulsed-wave Doppler to record flow in the LV outflow tract and arterial tonometry for central arterial pressure waveforms. Arterial compliance was estimated based on an exponential relationship between pressure and volume. The ratio of aortic pressure-to-flow in early systole was used to derive characteristic impedance, which was subsequently subtracted from total resistance (mean arterial pressure/cardiac output) to yield systemic vascular resistance (SVR). It was found that patients with depressed SV reserve (NoRes; reserve <15%; n = 10) showed decreased arterial compliance during exercise, while patients with SV reserve ≥15% (Res; n = 11) showed increased compliance. Exercise produced parallel increases in LV end-diastolic volume and arterial volume in Res patients while NoRes patients exhibited a lesser decrease in SVR and a drop in effective arterial volume. Poor SV reserve in elderly female hypertensives is due to simultaneous failure of LV preload and arterial vasodilatory reserves. Abnormal arterial function contributes to a high risk of HFpEF in these patients.     

Developmental changes of calcium transients and contractility during the cultivation of rat neonatal cardiomyocytes

In the normal myocardium matrix metalloproteinases (MMP) are present in the latent form. To examine whether MMP are activated following infarction or idiopathic dilated cardiomyopathy (DCM), we extracted and measured MMP activity in tissue derived from 7 explanted, failing human hearts due to either previous myocardial infarction (MI) or DCM. MMP activity in infarcted left ventricle (LV), noninfarcted IV and right ventricle (RV) from MI patients, as well as tissue from either ventricle of DCM patients, were compared to the activity of donor heart tissue. SDS-PAGE and dye-binding assays were used to determine total protein concentration, while collagenase activity was measured by SDS-PAGE type substrate gels embedded with type I gelatin (zymography). Accuracy of the zymographic technique was shown for tissue samples as small as 0.05 mg and was comparable to results obtained by a spectrophotometric method.. After normalization for total protein concentration, we found 3 ± 1 % collagenase activity in normal atrial tissue which could be activated to 80–90% by trypsin or plasmin, indicating that collagenase is normally inactive or in a latent form in human heart. In endo- and epimyocardium of infarcted LV on the other hand, collagenase activity was 85–95% and 10–20%, respectively, while 5–10% and 3–5%, respectively, in noninfarcted LV In DCM, collagenolytic activity in the endo and epimyocardium was 75 ± 5 and 35 ± 5% in the LV and 35 ± 7 and 20 ± 5% in the RV, respectively. Thus, in dilated failing human hearts secondary to previous MI or DCM, MMP activity is increased. This is particularly the case within the endomyocardium of the infarcted and noninfarcted portions of either ventricle with MI and in both ventricles in DCM. This suggests that an activation of collagenase throughout the myocardium may contribute to its remodeling that includes ventricular dilatation and wall thinning.This work was supported in part by NIH grant GM-48595 and by a Grant-In-Aid from the American Heart Association, Missouri Affiliate (92-10517).     

Induction of heat shock protein 72 in the failing heart is attenuated after an exposure to heat shock

Induction of heat shock protein (Hsp) 72 in the right ventricular muscle of the rat with heart failure following acute myocardial infarction (AMI) was examined. AMI was induced by the left coronary artery ligation (CAL). The animals at the 8th, but not 2nd, week after CAL revealed a decrease in cardiac output index (COI), suggesting that heart failure had developed by 8 weeks after CAL. Increases in the right ventricular developed pressure and the ratios of right ventricle/body weight and lung/body weight at the 2nd and 8th weeks showed the development of the right ventricular hypertrophy. After measurement of hemodynamic parameters, the hearts isolated from animals at the 2nd and 8th weeks after CAL (2w- and 8w-CAL hearts, respectively) were perfused and subjected to heat shock (at 42 degrees C, for 15 min) followed by 6-h perfusion. At the end of perfusion, Hsp72 content in the left ventricle without infarct area (viable LV) and the right ventricle (RV) was determined by the Western immunoblotting method. The production of myocardial Hsp72 in the viable LV and RV of the 2w-CAL heart increased after an exposure to heat shock. In contrast, induction of Hsp72 in the viable LV and RV of the 8w-CAL heart was blunted. The results suggest that the development of heart failure following AMI may result in a decrease in the ability for Hsp72 induction not only in the viable LV but also in the RV, leading to contractile dysfunction of the heart.     

Regional left ventricular myocardial contractility and stress in a finite element model of posterobasal myocardial infarction

Recently, a noninvasive method for determining regional myocardial contractility, using an animal-specific finite element (FE) model-based optimization, was developed to study a sheep with anteroapical infarction (Sun et al., 2009, "A Computationally Efficient Formal Optimization of Regional Myocardial Contractility in a Sheep With Left Ventricular Aneurysm," ASME J. Biomech. Eng., 131(11), p. 111001). Using the methodology developed in the previous study (Sun et al., 2009, "A Computationally Efficient Formal Optimization of Regional Myocardial Contractility in a Sheep With Left Ventricular Aneurysm," ASME J. Biomech. Eng., 131(11), p. 111001), which incorporates tagged magnetic resonance images, three-dimensional myocardial strains, left ventricular (LV) volumes, and LV cardiac catheterization pressures, the regional myocardial contractility and stress distribution of a sheep with posterobasal infarction were investigated. Active material parameters in the noninfarcted border zone (BZ) myocardium adjacent to the infarct (T(max_B)), in the myocardium remote from the infarct (T(max_R)), and in the infarct (T(max_I)) were estimated by minimizing the errors between FE model-predicted and experimentally measured systolic strains and LV volumes using the previously developed optimization scheme. The optimized T(max_B) was found to be significantly depressed relative to T(max_R), while T(max_I) was found to be zero. The myofiber stress in the BZ was found to be elevated, relative to the remote region. This could cause further damage to the contracting myocytes, leading to heart failure.     

Parasympathetic control of the heart. I. An interventriculo-septal ganglion is the major source of the vagal intracardiac innervation of the ventricles.

The locations, projections, and functions of the intracardiac ganglia are incompletely understood. Immunocytochemical labeling with the general neuronal marker protein gene product 9.5 (PGP 9.5) was used to determine the distribution of intracardiac neurons throughout the cat atria and ventricles. Fluorescence microscopy was used to determine the number of neurons within these ganglia. There are eight regions of the cat heart that contain intracardiac ganglia. The numbers of neurons found within these intracardiac ganglia vary dramatically. The total number of neurons found in the heart (6,274 +/- 1,061) is almost evenly divided between the atria and the ventricles. The largest ganglion is found in the interventricular septum (IVS). Retrogradely labeled fluorescent tracer studies indicated that the vagal intracardiac innervation of the anterior surface of the right ventricle originates predominantly in the IVS ganglion. A cranioventricular (CV) ganglion was retrogradely labeled from the anterior surface of the left ventricle but not from the anterior surface of the right ventricle. These new neuroanatomic data support the prior physiological hypothesis that the CV ganglion in the cat exerts a negative inotropic effect on the left ventricle. A total of three separate intracardiac ganglia innervate the left ventricle, i.e., the CV, IVS, and a second left ventricular (LV2) ganglion. However, the IVS ganglion provides the major source of innervation to both the left and right ventricles. This dual innervation pattern may help to coordinate or segregate vagal effects on left and right ventricular performance.     

Computer simulation of intraventricular flow and pressure gradients during diastole

A two-dimensional axisymmetric computer model is developed for the simulation of the filling flow in the left ventricle (LV). The computed results show that vortices are formed during the acceleration phases of the filling waves. During the deceleration phases these are amplified and convected into the ventricle. The ratio of the maximal blood velocity at the mitral valve (peak E velocity) to the flow wave propagation velocity (WPV) of the filling wave is larger than 1. This hemodynamic behavior is also observed in experiments in vitro (Steen and Steen, 1994, Cardiovasc. Res., 28, pp. 1821-1827) and in measurements in vivo with color M-mode Doppler echocardiography (Stugaard et al., 1994, J. Am. Coll. Cardiol., 24, 663-670). Computed intraventricular pressure profiles are similar to observed profiles in a dog heart (Courtois et al., 1988, Circulation, 78, pp. 661-671). The long-term goal of the computer model is to study the predictive value of noninvasive parameters (e.g., velocities measured with Doppler echocardiography) on invasive parameters (e.g., pressures, stiffness of cardiac wall, time constant of relaxation). Here, we show that higher LV stiffness results in a smaller WPV for a given peak E velocity. This result may indicate an inverse relationship between WPV and LV stiffness, suggesting that WPV may be an important noninvasive index to assess LV diastolic stiffness, LV diastolic pressure and thus atrial pressure (preload).     

Non-Invasive Determination of Left Ventricular Workload in Patients with Aortic Stenosis Using Magnetic Resonance Imaging and Doppler Echocardiography

Early detection and accurate estimation of aortic stenosis (AS) severity are the most important predictors of successful long-term outcomes in patients. Current clinical parameters used for evaluation of the AS severity have several limitations including flow dependency. Estimation of AS severity is specifically challenging in patients with low-flow and low transvalvular pressure gradient conditions. A proper diagnosis in these patients needs a comprehensive evaluation of the left ventricle (LV) hemodynamic loads. This study has two objectives: (1) developing a lumped-parameter model to describe the ventricular-valvular-arterial interaction and to estimate the LV stroke work (SW); (2) introducing and validating a new index, the normalized stroke work (N-SW), to assess the global hemodynamic load imposed on the LV. N-SW represents the global hemodynamic load that the LV faces for each unit volume of blood ejected. The model uses a limited number of parameters which all can be measured non-invasively using current clinical imaging modalities. The model was first validated by comparing its calculated flow waveforms with the ones measured using Cardiovascular Magnetic Resonance (CMR) in 49 patients and 8 controls. A very good correlation and concordance were found throughout the cycle (median root mean square: 12.21 mL/s) and between the peak values (r = 0.98; SEE = 0.001, p<0.001). The model was then used to determine SW using the parameters measured with transthoracic Doppler-echocardiography (TTE) and CMR. N-SW showed very good correlations with a previously-validated index of global hemodynamic load, the valvular arterial impedance (), using data from both imaging modalities (TTE: r = 0.82, SEE = 0.01, p<0.001; CMR: r = 0.74, SEE = 0.01, p<0.001). Furthermore, unlike , N-SW was almost independent from variations in the flow rate. This study suggests that considering N-SW may provide incremental diagnostic and prognostic information, beyond what standard indices of stenosis severity and provide, particularly in patients with low LV outflow.     

A Simulation of Human Heart Function

A simulation of the function of the human heart and heart muscle has been developed in the form of a digital computer code. For a given set of values for the input variables, realistic values of the cardiac output variables are predicted. A detailed discussion of the simulation and some results obtained from its application are presented. This simulation represents a unique combination of what was known in muscle mechanics, muscle thermodynamics, and of the structure, size, and shape of the heart, into an engineering model to improve the understanding of human heart muscle function. The left ventricle (LV) is treated as a thick-walled sphere whose wall is composed entirely of muscle fibers. Force-length velocity relationships are used to determine the tension in each fiber. The pressure in the LV is computed from fiber tension and fiber structure in the LV. A lumped-parameter simulation of the arterial tree provides a load impedance for the LV. Results are presented for simulation of normal human LV performance.     

Quantification of left and right ventricular kinetic energy using four-dimensional intracardiac magnetic resonance imaging flow measurements

We aimed to quantify kinetic energy (KE) during the entire cardiac cycle of the left ventricle (LV) and right ventricle (RV) using four-dimensional phase-contrast magnetic resonance imaging (MRI). KE was quantified in healthy volunteers (n = 9) using an in-house developed software. Mean KE through the cardiac cycle of the LV and the RV were highly correlated (r(2) = 0.96). Mean KE was related to end-diastolic volume (r(2) = 0.66 for LV and r(2) = 0.74 for RV), end-systolic volume (r(2) = 0.59 and 0.68), and stroke volume (r(2) = 0.55 and 0.60), but not to ejection fraction (r(2) < 0.01, P = not significant for both). Three KE peaks were found in both ventricles, in systole, early diastole, and late diastole. In systole, peak KE in the LV was lower (4.9 ± 0.4 mJ, P = 0.004) compared with the RV (7.5 ± 0.8 mJ). In contrast, KE during early diastole was higher in the LV (6.0 ± 0.6 mJ, P = 0.004) compared with the RV (3.6 ± 0.4 mJ). The late diastolic peaks were smaller than the systolic and early diastolic peaks (1.3 ± 0.2 and 1.2 ± 0.2 mJ). Modeling estimated the proportion of KE to total external work, which comprised ～0.3% of LV external work and 3% of RV energy at rest and 3 vs. 24% during peak exercise. The higher early diastolic KE in the LV indicates that LV filling is more dependent on ventricular suction compared with the RV. RV early diastolic filling, on the other hand, may be caused to a higher degree of the return of the atrioventricular plane toward the base of the heart. The difference in ventricular geometry with a longer outflow tract in the RV compared with the LV explains the higher systolic KE in the RV.     

Distinctive left-sided distribution of adrenergic-derived cells in the adult mouse heart

Adrenaline and noradrenaline are produced within the heart from neuronal and non-neuronal sources. These adrenergic hormones have profound effects on cardiovascular development and function, yet relatively little information is available about the specific tissue distribution of adrenergic cells within the adult heart. The purpose of the present study was to define the anatomical localization of cells derived from an adrenergic lineage within the adult heart. To accomplish this, we performed genetic fate-mapping experiments where mice with the cre-recombinase (Cre) gene inserted into the phenylethanolamine-n-methyltransferase (Pnmt) locus were cross-mated with homozygous Rosa26 reporter (R26R) mice. Because Pnmt serves as a marker gene for adrenergic cells, offspring from these matings express the β-galactosidase (βGAL) reporter gene in cells of an adrenergic lineage. βGAL expression was found throughout the adult mouse heart, but was predominantly (89%) located in the left atrium (LA) and ventricle (LV) (p<0.001 compared to RA and RV), where many of these cells appeared to have cardiomyocyte-like morphological and structural characteristics. The staining pattern in the LA was diffuse, but the LV free wall displayed intermittent non-random staining that extended from the apex to the base of the heart, including heavy staining of the anterior papillary muscle along its perimeter. Three-dimensional computer-aided reconstruction of XGAL+ staining revealed distribution throughout the LA and LV, with specific finger-like projections apparent near the mid and apical regions of the LV free wall. These data indicate that adrenergic-derived cells display distinctive left-sided distribution patterns in the adult mouse heart.     

Metabolic enzyme response in the pressure-overloaded heart of weanling and adult rats

Weanling and adult rats were subjected to left ventricular pressure overload induced by abdominal aortic constriction. At 5 days or 5 weeks postsurgery, the left ventricle (LV) was dissected, weighed, and metabolic marker enzyme activities (mumole/g/min) of tissue homogenates were measured. Enzymes representing glycolytic (phosphofructokinase (PFK] and mitochondrial (citrate synthase (CS) and malate dehydrogenase (MDH] metabolisms were evaluated. Five days of pressure overload had detectable, but statistically nonsignificant effects on left ventricles of both weanling and adult rats. Sustained pressure overload (5 weeks) increased LV weight by 52 and 39% in weanling and adult rats, respectively. PFK activity was 24 +/- 1 (mean +/- SE) in control weanlings and was unaltered in any of the other groups. LDH isoenzyme composition was estimated by substrate inhibition (ratio 0.33/10 mM pyruvate). With normal heart development, the LDH ratio increased from 1.89 +/- 0.06 to 2.03 +/- 0.08. Pressure overload had no influence on the adult LDH ratio. Developmental LDH responses were not observed in weanling LV after 5 weeks of aortic constriction (1.74 +/- 0.06). The product of CS activity and LV weight was used to estimate mitochondrial mass in the ventricle. Mitochondria accumulated at a rate of about 5% increase per day over the intervening 5-week period of normal heart growth. Pressure overload for 5 weeks in weanling rats elicited net accumulation of mitochondria at a rate of about 9% increase per day. Mitochondrial accumulation in the adapting adult rat heart amounted to less than 1% increase per day. The results indicate that qualitative and quantitative differences exist between young and adult animals in their heart enzyme adaptive responses to pressure overloading. Divergent metabolic adaptations may contribute to heart functional differences in the enlarged heart of weanlings and adults.     

Modification of the structural and functional response of the heart and systemic hemodynamics to the cardioselective β<Subscript>1</Subscript>-blockers in patients with arterial hypertension and adaptation to cold

We investigated the features of the structural and functional organization of the left heart (ventricle—LV, atrium—LA) and the state of systemic hemodynamics at rest and in response to a single dose of cardioselective β₁-blocker (BB) Egilok. We examined the patients with stage II (1–2 degrees) of arterial hypertension (AH); the study was performed in summer and winter in the northern regions of Russia. It was found that the process of adaptation to cold is accompanied by the inhibition of the pacemaker, a decrease in the rate of active diastolic blood filling of the LV and transaortic blood flow in the aortic root (VAo), an increase in the contractility of the LV posterior wall and interventricular septum (IVS). The negative chronotropic cardiac effect in these conditions results in the reduction of heart productivity per minute in 65% of cases. In winter we observed a more pronounced diastolic LV dysfunction and a decrease in the connectivity of active relaxation of LV posterior wall and LA walls with certain structural and functional cardiac parameters. In contrast to summer, in winter period BB causes a decrease in the active relaxation of LA walls and IVS and LA contractility, which leads to a decrease in the blood filling of passive and active LV. At the same time, LV systolic function (ejection fraction, VAo) and the rhythm and the performance of the heart (stroke volume and cardiac output) decreases; the hypotensive effect accompanied by an increase in peripheral vascular resistance is more pronounced. In winter, the effect of BB reduces the correlation between IVS and LV posterior wall contractions, but the feedback rate or passive to active LV diastolic hyperemia and after load increases. We suggest that in winter component “contractile apparatus” retains its the leading role in the organization of intracardiac response to the BB in patients with hypertension; in addition, new dominant components were formed: “contingency of the LV wall contraction with afterload” and “reverse contingency of early and late diastolic LV function.”