Correlation in the of the process of cardiac ventricle intramural depolarization and distribution of cardioelectric field potentials of the dog Canis familiaris

Based on a multichannel synchronous mapping of heart electric potentials, the sequence in time of the ventricle myocardium depolarization was compared with dynamics of distribution of cardioelectric potentials on the body surface in a dog. The cardioelectric field on the dog body surface at the period of the initial ventricular activity has been shown to be characterized by the presence of two inversions of the mutual disposition of areas of positive and negative potentials. Contribution to formation of distribution of the cardioelectric potentials on the body surface at each moment of the period of initial ventricular activity was made by all myocardial layers involved by excitation.     

Cardiac function of the diabetic renovascular hypertensive rat: effects of insulin and thyroid hormone treatment

The influences of hypertension and hypothyroidism on diabetic cardiomyopathy are not clear. We studied this problem further by characterizing the effects of chronic triiodothyronine (T3) treatment on cardiac performance of diabetic renovascular hypertensive (RVH) rats. Hypertension was effected by clipping the left renal artery of Wistar-Kyoto (WKY) rats, and diabetes was induced 2 weeks later by streptozotocin (STZ; 55 mg/kg i.v.). The WKY strain was selected because it is relatively resistant to the cardiodepressant effects of diabetes, so that the influence of superimposed hypertension would be more apparent. Performance of working Krebs-Henseleit buffer perfused hearts was quantified by measuring left ventricular pressure and flow characteristics. The results showed that renovascular clipping caused a marked hypertension and left ventricular hypertrophy (LVH) but had no effect on perfused heart performance after 10 weeks. They also showed that diabetes during the final 8 weeks (i) caused a marked impairment in the performance of perfused hearts ex vivo of hypertensive rats but had no measurable effect in the normotensive WKY, (ii) had no effect on arterial pressure of either the normotensive or the hypertensive rats but reduced heart rate of hypertensive animals in vivo, and (iii) caused equivalent hyperglycemia, hypoinsulinemia, and hypothyroidism (depressed serum T3 and T4 levels) of hypertensive and normotensive rats. Treatment of diabetic RVH rats with T3 (10 micrograms.kg-1.day-1) in vivo was nearly as effective as insulin therapy (10 U.kg-1.day-1) in preventing the cardiac dysfunction ex vivo and was as effective as insulin therapy in preventing the bradycardia in vivo and the decline loss.(ABSTRACT TRUNCATED AT 250 WORDS)     

Correlation in time of the process of cardiac ventricle intramural depolarization and of distribution of cardioelectric field potentials of the dog <Emphasis Type="Italic">Canis famjliaris</Emphasis>

Based on a multichannel synchronous mapping of heart electric potentials, the sequence in time of the ventricle myocardium depolarization was compared with dynamics of distribution of cardioelectric potentials on the dog body surface. The cardioelectric field on the dog body surface at the period of the initial ventricular activity has been shown to be characterized by the presence of two inversions of the mutual disposition of areas of positive and negative potentials. Contribution to formation of distribution of the cardioelectric potentials on the body surface at each moment of the period of initial ventricular activity was made by all myocardial layers involved in excitation.     

Cardiac electric field on the epicardial and body surfaces during the period of depolarization and repolarization of ventricular myocardium in pikes

Body surface and ventricular epicardial potential distributions during the electrocardiographic QRST interval were studied in pikes with the aid of potential mapping. The earliest epicardial activation was observed at the posterior base near the atrioventricular orifice. The areas of the earliest repolarization were found at the apex and the posterior base, whereas the area of the latest repolarization was detected at the anterior base. In the initial period of the QRS, the minimum was developed in the middle third of the right lateral body surface, and the maximum in the middle third of the ventral body surface. The body surface potential distribution during the ST-Twas characterized by the clear-cut negative potential zone in the cranial ventral area with the rest of the body surface having positive potentials, a pattern being largely unchanged throughout the period of the T-wave. The ventricular epicardial repolarization sequence differed from the activation sequence. The ventricular epicardial depolarization and repolarization sequences as well as epicardial potential distributions are expressed in the cardiac electric field on the body surface during the QRS and ST-T complexes.     

Effects of regression of cardiac hypertrophy on myocardial contractility and ventricular myosin isoenzymes

The effects of regression of cardiac hypertrophy on myocardial contractility and ventricular myosin isoenzymes were investigated in rats with renovascular hypertension. Six-week-old male Wistar rats were made hypertensive by constriction of one renal artery with a silver clip. Regression of cardiac hypertrophy was induced following the lowering of blood pressure by nephrectomy on the affected side 5–6 weeks after constriction of the renal artery and was maintained for 5–6 weeks. In contrast, myocardial hypertrophy was induced by 10–11 weeks of the hypertensive state. Isometric developed tension of isolated left ventricular papillary muscles was measured, while they were being perfused with Tyrode solution. Left ventricular myosin isoenzymes were separated by pyrophosphate gel electrophoresis. The ventricular to body weight ratio of the nephrectomized group was significantly lower than that of the hypertensive group, although it was greater than that of age-matched normal control rats. There were no significant differences in the isometric developed tension among three groups, the nephrectomized, hypertensive, and normal control rats. However, dT/dtmax tended to decrease in the hypertensive rats and recovered to normal in the nephrectomized rats. The left ventricular myosin isoenzyme pattern was shifted toward VM-3 in hypertensive rats and was shifted back toward VM-1 again in nephrectomized rats.     

Polyamine levels and diamine oxidase activity in hypertrophic heart of spontaneously hypertensive rats and of rats treated with isoproterenol

Polyamine levels and diamine oxidase (EC 1.4.3.6) activity were studied in hypertrophic heart of spontaneously hypertensive rats as well as in the heart of Wistar rats during the development and regression of cardiac hypertrophy induced by isoproterenol administration. In spontaneously hypertensive rats, putrescine content and diamine oxidase activity were higher than those found in normotensive Kyoto-Wistar control rats. During the development of cardiac hypertrophy induced by isoproterenol, there was an increase in polyamine content and diamine oxidase activity. The administration of cycloheximide or actinomycin D prevented the increase in diamine oxidase activity during the first 24 h after isoproterenol administration, demonstrating that the rise in diamine oxidase activity was due to synthesis of new enzyme. Following the cessation of isoproterenol treatment, cardiac hypertrophy regressed and polyamine levels and diamine oxidase activity diminished toward control values. The administration of aminoguanidine to isoproterenol-treated rats caused in the heart an inhibition of diamine oxidase activity that led to an increase in putrescine level beyond the values found in animals given isoproterenol alone. The results suggest that the enhancement of diamine oxidase activity plays a role in the regulation of putrescine level in hypertrophic heart.     

钙调神经磷酸酶在肾血管性高血压大鼠心肌肥厚发展中的作用

本文观察了钙调神经磷酸酶(calcineurin,CaN)在肾血管性高血压大鼠肥厚心肌中的表达和活性以及CaN抑制剂——环孢菌素A(cyclosporine A,CsA)对逆转心肌肥厚的影响。利用两肾一夹肾血管性高血压大鼠心肌肥厚模型,观察大鼠心肌肥厚程度、CaN mRNA和蛋白质表达及CaN活性的改变。结果显示:大鼠左室重与胫骨长度的比值和光镜下心肌细胞横截面积在两肾一夹2月和3月组都较相应假手术组增高(P<0.05),CsA组大鼠左室重与胫骨长度比值、心肌细胞横截面积较两肾一夹2月和3月组均显著下降(P<0.05),与假手术组无显著性差异。大鼠心肌CaN mRNA和蛋白质表达及CaN活性在两肾一夹2月和3月组均高于相应假手术组(P<0.05),在CsA组低于两肾一夹2月和3月组(P<0.05)。这些结果提示,CaN参与肾血管性高血压大鼠心肌肥厚发展,抑制CaN活性可逆转心肌肥厚。     

Deficient prolylcarboxypeptidase gene and protein expression in left ventricles of spontaneously hypertensive rats (SHR)

Prolylcarboxypeptidase (PRCP), an endothelial cell membrane serine peptidase that inactivates angiotensin II and activates pre-kallikrein, is thought to have anti-hypertensive and anti-proliferative roles in cardiovascular homeostasis. We hypothesized that PRCP function may be altered in heart tissue under conditions that predispose to left ventricle hypertrophy (LVH) in rats. We therefore used real-time PCR and western-blotting to examine the mRNA and protein expression of PRCP in the hearts of spontaneously hypertensive rats (SHR) at pre-hypertensive (5-week-old) and hypertensive (16-week-old) stages compared with age-matched hypertensive (2 kidney-1 clip; 2K-1C) rats and normotensive Wistar rats. PRCP mRNA expression was significantly reduced in hearts of 5- and 16-week-old SHR compared with age-matched Wistar controls, 2K-1C hypertensive rats and sham-operated normotensive rats. There were no significant differences in the PRCP mRNA and protein expression levels in hearts from hypertensive renovascular and sham-operated normotensive rats. Prolonged treatment of SHR with the AT₁ receptor antagonist losartan (40 mg/kg, gavage for 8 weeks) reduced the left ventricular weight/body weight ratio (LVW/BW), as well as the mRNA expression of collagen type 1, collagen type 3 and MMP9 in left ventricular tissue, without affecting PRCP gene and protein expression. Our results suggest that diminished PRCP gene and protein expression might be constitutionally involved in the SHR phenotype. In addition, since neither the development of arterial hypertension in the 2K-1C model nor its successful treatment in SHR altered PRCP gene and protein expression in heart tissue, it appears unlikely that PRCP function is regulated by the renin–angiotensin system or by afterload conditions.     

Spatiotemporal characteristics of the heart electrical field in the period of ventricular depolarization in athletes training endurance and strength

As a result of hemodynamic and structural changes occurring in the heart of athletes under the influence of systematic physical loads, the myocardial electrical activity changes, which is reflected on the electric field formed on the body surface. The electrical activity of the heart during ventricular depolarization at rest was studied in the highly skilled athletes training to develop physical characteristics (endurance and strength) by the method of electrocardiotopography. The studied athletes had similar patterns of movement of zones of positive and negative cardiac electrical potentials and location of extrema as well as the total depolarization duration but showed significant distinctions in (1) the amplitude of the maximum negative extremum; (2) the time of the beginning and end of the first inversion; (3) the duration of the second inversion, the initial stage, and the stability period between inversions; and (4) the relative position of positive and negative cardiopotential zones.     

Time correlation of the cardiac electric field on the body surface and depolarization sequences in the pigeon heart ventricle epicardium

Multifocal depolarisation of the pigeon ventricle's epicardium was revealed. A time inversion correlation was found between cardiac electrical field's positive and negative areas on the body surface and the multifocal depolarisation of the ventricle epicardium, during the period of initial ventricular activity.     

Influence of ovariectomy on cardiac oxidative stress in a renovascular hypertension model

The aim of this study was to evaluate the potential influence of endogenous ovarian hormones on cardiac oxidative stress in renovascular hypertension. Female Wistar rats (N = 10 per group) were divided among 4 groups: (i) normotensive control; (ii) hypertensive control; (iii) normotensive ovariectomized; and (iv) hypertensive ovariectomized rats. To induce hypertension, 2-kidney 1-clip (2K1C) Goldblatt's method was followed. Blood pressure (BP) was enhanced (25%) in 2K1C and it was not further altered in hypertensive ovariectomized animals. Lipid peroxidation (measured by thiobarbituric acid reactive substances; TBARS) increased in heart homogenates after ovariectomy (253%) and was additionally augmented when associated with hypertension (by 28%). Superoxide dismutase and catalase activities were similar in both hypertensive groups. Hypertension enhanced glutathione peroxidase activity (75%), but the association with ovariectomy prevented this change. Total radical trapping antioxidant potential (TRAP) decreased in hypertensive rats (34%) and was recovered when associated with ovariectomy. However, this adaptation seems not to be sufficient to avoid the increased oxidative damage in ovariectomized hypertensive animals. These results suggest a protective role for physiological ovarian hormones in the cardiac oxidative stress induced by 2K1C hypertension.     

Depressor effect of diabetes in the spontaneously hypertensive rat: associated changes in heart performance

Effects of streptozotocin-induced diabetes (8 weeks) on the performance of perfused hearts from spontaneously hypertensive (SH) rats were compared with effects on normotensive Wistar-Kyoto (WK) and Sprague-Dawley (SD) rat hearts. Diabetes markedly decreased systolic arterial pressure (SAP) of SH rats in vivo but did not affect SAP of either of the normotensive strains. Diabetes also reduced heart size of SH and normotensive rats and reversed absolute left ventricular hypertrophy (wall-to-lumen ratios and left-to-right ventricular weight ratios) of SH rats. Heart perfusion at the end of the 8-week period revealed that diabetes (i) reduced hydraulic work at high pressure loads and efficiency of contraction (work/mu LO2 consumed) of SH rat hearts but not of WK or SD hearts, and (ii) depressed left ventricular pulse pressure development (LVPP) and contractility (LV + dP/dt) of SH hearts more extensively than it reduced these variables in either of the normotensive control groups. Effects of diabetes which were similar in hypertensive and normotensive hearts were reductions in stroke work at high volume loads and depressions in LV-dP/dt. Attendant hypothyroidism probably contributed to the reductions in SAP, heart size, LVPP, LV+ and -dP/dt, and stroke work but not to the decreased efficiency or reversal of hypertrophy of SH rat hearts. Malnutrition of SH rats, like hypothyroidism, also decreased heart size without reversing hypertrophy but had no effect on SAP and only reduced LV-dP/dt. The results show that diabetes reversed hypertrophy and selectively reduced contraction efficiency, contractility, and LVPP of SH hearts, but otherwise the effects of diabetes in hypertensive and normotensive rat strains were similar to each other.(ABSTRACT TRUNCATED AT 250 WORDS)     

Somatosympathetic reflex in rats with various models of arterial hypertension

Spontaneous and reflex activities of sympathetic nerve were compared in animals with arterial hypertension of different aetiology. Reflex discharges elicited by single-shock stimulation of afferent fibres were recorded. In acute experiences on anaesthetized rats with renovascular and spontaneous (SHR) model of arterial hypertension, electric basal and evoked activity (somatosympathetic reflex) in cervical sympathetic trunk were recorded. It is shown, that the spontaneous electric activity in sympathetic nerve of hypertensive rats is larger than spontaneous activity of normotensive control animals. The somatosympathetic reflex in hypertensive rats differs from that of control animals. In rats with renovascular model of hypertension, the reflex magnitude is reduced, and in the SHR the reflex is increased. Time characteristics of the reflex in hypertensive rats differed among them. It is suggested that functional activities of the brain stem in rats with different arterial hypertension model are unequal.     

Nitrendipine and other calcium entry blockers (calcium antagonists) in hypertension

Nitrendipine is a calcium antagonistic 1,4-dihydropyridine derivative with a pronounced antihypertensive activity in animal experiment. Similar to other calcium entry blockers, nitrendipine decreases blood pressure by lowering the elevated peripheral vascular resistance. However, its long-term effect differs from that of vasodilators such as hydralazine and minoxidil. In contrast to vasodilators, nitrendipine reduces heart hypertrophy in various forms of experimental hypertension in rats. Nitrendipine is highly effective in normalizing blood pressure, reducing heart hypertrophy, and preventing mortality in salt-related hypertension (two-kidney renal hypertension, salt-induced hypertension in Dahl rats), which are rather refractory to the effect of vasodilators. Nitrendipine reduces renovascular resistance in spontaneously hypertensive rats but has no effect on that of normotensive rats. In conscious renal hypertensive dogs, nitrendipine decreases blood pressure more than does hydralazine. The reflex tachycardia is more pronounced after hydralazine than after nitrendipine; blood pressure decrease is greater and the duration of the effect is longer than that of nifedipine. Nitrendipine is thus predicted as an effective drug for antihypertensive monotherapy.     

Effect of experimental obesity and subsequent weight reduction upon circulating atrial natriuretic peptide

The effect of obesity and weight reduction upon circulating concentrations of atrial natriuretic peptide was assessed in an experimental model of the disease. Obese rats weighing in excess of 750 g were compared with formerly obese animals subjected to a 15-week period of caloric restriction resulting in a 40% reduction in body weight. Mean adipocyte size was significantly reduced with weight loss, as was estimated body fat. Mean arterial blood pressure remained normotensive for both groups, but a significant reduction in heart rate was associated with weight reduction. Circulating atrial natriuretic peptide was significantly elevated in the lean rats, which also exhibited decreased plasma renin activity and a negative sodium balance. Analysis of heart to body weight ratios implied that an obesity-associated, volume-induced cardiac hypertrophy remained even after the normalization of body fat. These results suggest that the diuresis and natriuresis accompanying weight reduction may be facilitated by atrial natriuretic peptide, which was elevated in part due to a persistent left ventricular hypertrophy following the transition from the obese to lean condition.     

Regional blood flows and cardiac hemodynamics in renovascular and mineralocorticoid hypertensive rats

Regional blood flows and cardiac hemodynamics were studied in 3 models of hypertensive rats: one-kidney DOC-saline, one-kidney, one-clip and two-kidney, one-clip hypertension and in normotensive control rats. All hypertensive models were characterized by increased peripheral vascular resistance and normal cardiac output. Coronary and cerebral blood flows varied among the hypertensive models but did not significantly differ from the normotensive rats. However, coronary blood flow of one-kidney, one-clip rats (8.4 +/- 1.3 ml X min-1 X g-1) was significantly higher than that of the two-kidney one-clip rats (6.5 +/- 1.2 ml X min.-1 X g-1, P less than 0.05). Cerebral blood flow of DOC-saline rats was lower than that of two-kidney one-clip or one-kidney one-clip renovascular rats. Renal blood flows of the unclipped kidney of two-kidney renovascular rats (3.77 +/- 0.85 ml X min-1 X g-1) and DOC-saline rats (2.95 +/- 0.83 ml X min-1 X g-1) were significantly lower than those of normotensive rats (5.92 +/- 1.16 ml X min-1 X g-1, P less than 0.05). In conclusion, although vascular resistance becomes elevated in all models of experimental hypertension, regional vascular resistance and blood flow distribution may differ depending on the vasoconstrictor mechanisms that participate in each model.     

Induction of heme oxygenase produces load-independent cardioprotective effects in hypertensive rats.

Although heme oxygenase (HO) has been suggested to be involved in the regulation of cardiovascular function through production of carbon monoxide (CO), the pathophysiological significance of HO in hypertensive organ damage remains unknown. We examined the effects of inducing HO-1 mRNA by stannous chloride (SnCl2) on cardiac hypertrophy in stroke-prone spontaneously hypertensive rats (SHR-SP/Izm). Chronic administration of SnCl2 resulted in a significant decrease in left ventricular (LV) weight/body weight ratio and LV brain natriuretic peptide (BNP) mRNA levels as a marker of cardiac hypertrophy and a significant increase in LV HO-1 mRNA levels and LV cGMP contents in SHR-SP/Izm, while there was no significant change in systemic blood pressure. These results provide the first evidence that induction of HO in the heart attenuates cardiac hypertrophy in load-independent mechanism in genetically hypertensive rats.     

Normalization of the calcineurin pathway underlies the regression of hypertensive hypertrophy induced by Na+/H+ exchanger-1 (NHE-1) inhibition

Na+/H+ exchanger-1 (NHE-1) inhibition induces cardiac hypertrophy regression and (or) prevention in several experimental models, although the intracellular events involved remain unclarified. We aimed to determine whether the calcineurin/NFAT pathway mediates this effect of NHE-1 inhibitors. Spontaneously hypertensive rats (SHR) with cardiac hypertrophy were treated with the NHE-1 inhibitors cariporide and BIIB723 for 30 days. Wistar rats served as normotensive controls. Their hearts were studied by echocardiography, immunoblotting, and real-time RT-PCR. Cytoplasmic Ca2+ and calcineurin Abeta expression were measured in cultured neonatal rat ventricular myocytes (NRVM) stimulated with endothelin-1 for 24 h. NHE-1 blockade induced cardiac hypertrophy regression (heart mass/body mass=3.63+/-0.07 vs. 3.06+/-0.05 and 3.02+/-0.13 for untreated vs. cariporide- and BIIB723-treated SHR, respectively; p<0.05) and decreased myocardial brain natriuretic peptide, calcineurin Abeta, and nuclear NFAT expressions. Echocardiographic evaluation demonstrated a reduction in left ventricular wall thickness without changes in cavity dimensions or a significant decrease in blood pressure. NHE-1-inhibitor treatment did not affect myocardial stiffness or endocardial shortening, but increased mid-wall shortening, suggesting that a positive inotropic effect develops after hypertrophy regression. Cariporide normalized the increased diastolic Ca2+ and calcineurin Abeta expression observed in ET-1-stimulated NRVM. In conclusion, our data suggest that inactivation of calcineurin/NFAT pathway may underlie the regression of cardiac hyper-trophy induced by NHE-1 inhibition.     

Formation of Cardioelectric Field on the Body Surface at a Period of Activation of Ventricular Myocardium in the Chicken Gallus domesticus

Spatial and temporal non-uniform and polyfocal depolarization of the subendocardial, intramural, and subepicardial layers of the ventricle myocardium in the chicken have been established experimentally. Different depth and time of formation of activation centers in the ventricular myocardium provide the appearance of groups of multiple depolarization foci on the epicardial surface of the ventricles. During the initial ventricular activity the cardioelectric field (CEF) on the chicken body surface is characterized by three periods of the dynamics of distribution of potentials: (1) the period of their gradual changes reflecting the electrical activity of excitation foci in the subendocardial, intramural, and subepicardial ventricular layers of myocardium on CEF; (2) the period of inversion consisting of an alteration of the mutual arrangement of the positive and negative CEF areas, this alteration corresponding in time to polyfocal depolarization of the epicardial surface of the ventricles; (3) the period of stability, during which the arrangement of the positive and negative CEF regions does not change, which is due to depolarization of multiple myocardium zones at the final phase of the heart ventricle activation.     

Myocardial hypertrophy of normotensive Wistar-Kyoto rats

In our studies with spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Wistar rats, we observed normotensive WKY rats with cardiac hypertrophy determined by a greater left ventricular (LV) mass (LVM)-to-body weight (BW) ratio (LVM/BW) than that of normotensive Wistar rats. Thus we compared the following parameters in SHR, WKY, and Wistar rats: LVM/BW, cell capacitance as index of total surface area of the myocytes, length, width, and cross-sectional area of cardiac myocytes, LV collagen volume fraction, and myocardial stiffness. The LVM/BW of WKY (2.41 +/- 0.03 mg/g, n = 41) was intermediate between SHR (2.82 +/- 0.04 mg/g, n = 47) and Wistar rats (1.98 +/- 0.04 mg/g, n = 28). A positive correlation between blood pressure and LVM was found in SHR, whereas no such relationship was observed in WKY or Wistar rats. Cell capacitance and cross-sectional area were not significantly different in SHR and WKY rats; these values were significantly higher than those of Wistar rats. The cell length was smaller but the width was similar in WKY compared with SHR. Papillary muscles isolated from the LV of WKY and SHR were stiffer than those from Wistar rats. Consistently, a greater level of myocardial fibrosis was detected in WKY and SHR compared with Wistar rats. These findings demonstrate blood pressure-independent cardiac hypertrophy in normotensive WKY rats.