Principles underlying the assessment of ventricular and myocardial work and power capacity.
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Animals↗
Biomedical subjects
R Jacob
Publications and source records attributed to R Jacob.
Haemodynamic effects of amrinone in the anaesthetized pig.
The vasodilator and inotropic actions of amrinone were investigated in mini-pigs under pentobarbitone anaesthesia. Left ventricular volume was determined angiocardiographically under afterload and isovolumetric conditions. Furthermore, aortic flow, left ventricular pressure and aortic pressure were measured. In some of the animals, the beta-adrenergic receptors were blocked with propranolol prior to the administration of amrinone. Without blockade of the beta-receptors, amrinone (2 mg kg-1) caused a significant reduction in mean aortic pressure. Due to less end-diastolic ventricular filling, stroke volume decreased, and thus ejection fraction remained constant. Since heart rate increased under amrinone, cardiac output remained constant. At the same time, the maximum rate of pressure rise increased, despite less end-diastolic ventricular filling. After blockade of the beta-adrenergic receptors, aortic pressure, end-diastolic ventricular filling, and stroke volume also decreased with amrinone. In contrast, heart rate remained practically constant, so that cardiac output declined. The maximum rate of pressure rise also declined due to less end-diastolic ventricular filling. It can be concluded from these results that, in situ, the primary action of amrinone occurs on vascular smooth muscle and that a positive inotropic activity with a normal dosage of amrinone is only an indirect outcome of reflex activation of the sympathetic system. Analysis of isovolumetric mechanograms and the ejection phase does not indicate a direct positive inotropic effect of amrinone. In the failing heart, however, beneficial effects can be expected, since the maxima curves follow a flatter course. Thus a reduction in afterload can lead to a significant increase in stroke volume, provided that aortic pressure does not fall below the critical coronary perfusion pressure.
Amrinone↗
Somatoform disorder in a psychiatric setting. Systematic comparisons with depression and anxiety disorders.
Somatoform disorder (SD) is recognized as an important clinical entity in general medicine although its psychiatric nature is insufficiently appreciated. Its prevalence and descriptive validity among psychiatric patients have not been investigated. These two aspects of SD are examined by comparing it with depressive and anxiety disorders, both of which include somatic symptoms and often are confounded with it. A semistructured evaluation procedure applied in a naturalistic clinical setting yielded a diagnosis and ratings of a large array of symptoms. The relative rarity of SD stands out, as well as the unique way in which it tends to be used in diagnostic formulations of psychiatric patients seeking evaluation and care. These results may reflect these patients' reluctance to seek psychiatric care and to define their problems as mental, as well as the bias of clinicians working in psychiatric settings geared to looking for traditional psychopathology. The distinguishing symptoms of SD vis-à-vis depressive and anxiety syndromes are outlined. These symptoms suggest that SD patients resemble depressives, but harbor traits that reflect personality and interpersonal difficulties. However, rater bias may have influenced these results as well.
Adult↗
Biliary catabolism of glutathione and differential reabsorption of its amino acid constituents.
Biliary excretion of glutathione, free amino acids, and total amino acids (after acid hydrolysis) was measured in hepatic bile collected from guinea pigs, rabbits, and dogs anesthetized with pentobarbital sodium. In controls, the concentration of glutathione in bile was less than 20 microM in all three species. However, when hepatic gamma-glutamyltransferase activity was decreased by retrograde intrabiliary infusion of the irreversible inhibitor acivicin (AT-125; 20 mumol/kg), there was a marked increase in biliary glutathione excretion (in mumol glutathione equivalents.kg body wt-1.h-1) from 0.10 +/- 0.04 to 2.2 +/- 0.6 in guinea pigs, from 0.014 +/- 0.013 to 2.5 +/- 1.9 in rabbits, and from an undetectable level (less than 0.001) to 0.11 +/- 0.05 in dogs. Amino acid analysis of bile revealed that the concentration of glutathione's constituent amino acids (free glutamate, cystine, and glycine) in control bile samples from these three species were quite low and were not affected by AT-125. However, acid hydrolyzates of these same bile samples revealed an unusually high degree of amino acid conjugation. Glutamate (0.06-0.5 mM), cystine (0.2-1.1 mM), and glycine (1.7-2.8 mM) constituted the overwhelming majority of total amino acids in hydrolyzed bile from controls. After AT-125, concentrations of total glutamate and cystine were elevated in hydrolyzed bile, while concentrations of all other amino acids remained the same. Thus glutathione is avidly secreted into bile in the guinea pig, rabbit, and dog but is almost quantitatively broken down within the biliary tree. Subsequently, the glutamate and cysteine moieties derived from catabolism of glutathione must be partially reabsorbed either as peptides, conjugates, or free amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)
Absorption↗
Splanchnic amino acid and glucose metabolism during amino acid infusion in dogs.
With the organ-balance technique, we studied amino acid and glucose metabolism by hepatic and extrahepatic splanchnic tissues in awake dogs in the postabsorptive state and during a 3-h intravenous amino acid infusion. Dogs received a high (1.4 g/kg body wt, n = 5) or low (0.7 g/kg body wt, n = 8) dose of amino acids. In four of the latter dogs, the dose was delivered into a mesenteric vein. During the basal period there was a net removal of gluconeogenic amino acids (particularly alanine), but not branched-chain amino acids, and a net production of glucose by the liver in all dogs. During this time there was a net removal of glucose and production of alanine by the extrahepatic splanchnic tissues. During either high- or low-dose amino acid infusion, net hepatic glucose release increased; despite this, arterial plasma glucose declined due to an increase in tissue glucose uptake at extrasplanchnic sites. The net amount of glucogenic amino acids removed by the liver during high-dose (9.1 +/- 1.0 mmol.kg-1.3 h-1) and low-dose (4.8 +/- 0.6 mmol.kg-1.3 h-1) infusion equaled or exceeded the infused load of these amino acids. In addition, the liver contributed to the net disposal of branched-chain amino acids during high-dose (536 +/- 147 mumol.kg-1.3 h-1) and low-dose (341 +/- 70 mumol.kg-1.3 h-1) infusion. During high-dose infusion, extrahepatic splanchnic tissues participated in the net removal of branched-chain amino acids (436 +/- 162 mumol.kg-1.3 h-1) but not glucogenic amino acids, and net alanine production continued (410 +/- 91 mumol.kg-1.3 h-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acids↗
Effect of chronic diabetes on myocardial fuel metabolism and insulin sensitivity.
To assess the effect of chronic insulin-deficient diabetes on myocardial fuel substrate metabolism in vivo, we measured the myocardial balance of glucose, free fatty acids (FFAs), and amino acids in nine postabsorptive conscious dogs 4-6 wk after treatment with streptozocin. The acute effect of insulin on the myocardial balance of these same substrates was measured in six dogs by use of the euglycemic insulin clamp technique. To further examine the effect of insulin on heart amino acid balance, we studied three additional dogs given a constant infusion of amino acids during the insulin clamp to blunt the insulin-induced hypoaminoacidemia. In these dogs, the fasting plasma glucose concentration was markedly elevated (258 +/- 3 mg/dl). In the basal period, there was no significant glucose uptake by the heart [arterial vs. coronary sinus concentration difference (delta) = 1.0 +/- 2.0 mg/dl]; furthermore, physiologic hyperinsulinemia did not stimulate glucose uptake (delta = 2.0 +/- 2.5 mg/dl). Postabsorptively, arterial FFAs were elevated (1550 +/- 320 microM) in diabetic animals, and there was a significant net extraction of FFAs by the heart (net uptake 26 +/- 9 mumol/min; extraction ratio 30 +/- 8%). During the insulin clamp, arterial FFAs declined (645 +/- 240 microM), as did heart FFA uptake (11 +/- 6 mumol/min), and the net extraction ratio for FFAs was unchanged (30 +/- 7%). Similarly, the arterial branched-chain amino acid (BCAA) concentration was elevated in the postabsorptive state, and there was a significant myocardial uptake of these amino acids and of alanine.(ABSTRACT TRUNCATED AT 250 WORDS)
Alanine↗
An isotopic method for measurement of muscle protein synthesis and degradation in vivo.
In eight anaesthetized post-absorptive dogs we measured the concentration and specific radioactivity of phenylalanine and leucine in arterial and femoral-venous plasma, together with hindlimb flow during a continuous infusion of L-[ring-2,6-3H]phenylalanine and [1-14C]leucine. The femoral-venous plasma concentration was greater than arterial for both phenylalanine and leucine (P less than 0.05 for each). Despite net amino acid release there was a significant removal of both labelled phenylalanine and labelled leucine. Consequently, a significant dilution of specific radioactivity was observed between artery and vein for both radio-tracers. The uptake of leucine from the arterial circulation by the hindlimb exceeded by 2.6-fold that of phenylalanine; the measured molar ratio of leucine to phenylalanine in hindlimb muscle protein averaged 2.4 +/- 0.1. Since phenylalanine is neither synthesized nor degraded by muscle tissue, the measured removal of tracer and the dilution of tracer specific radioactivity across the hindlimb can be used to estimate rates of phenylalanine incorporation into, and release from, tissue protein. The estimated rate of protein synthesis by hindlimb averaged 644 +/- 250 nmol of phenylalanine/min. This was exceeded by the rate of tissue protein degradation (987 +/- 285 nmol of phenylalanine/min). The present results demonstrate that the dilution of the specific radioactivity of labelled phenylalanine can be readily measured across dog hindlimb. This measurement, coupled with an estimate of tissue blood flow, can provide a readily measured, non-destructive, method for estimation of protein turnover in specific muscle beds in vivo. Measurements can be made repeatedly over time in a single experiment, allowing the study of factors which regulate protein turnover. The method developed here in dogs can be readily extended to clinical studies.
Amino Acids↗
Chronic cardiac reactions. I. Assessment of ventricular and myocardial work capacity in the hypertrophied and dilated ventricle.
The end-systolic and end-diastolic pressure-volume or stress-length curves define the margins of the various conceivable courses of pressure-volume or stress-length loops. Although the end-systolic pressure-volume and stress-length relations of isovolumetric and afterloaded contractions are not entirely identical, the area between isovolumetric maxima- and end-diastolic minima curves in the pressure-volume or stress-length diagram can be taken as a measure of potential ventricular and myocardial work under different yet defined mechanical conditions. The normalized stress-length area, as derived from the left ventricular pressure-volume diagram and myocardial mass, renders a rational basis for global quantitative evaluation of myocardial work capacity. The area obtained is independent of ventricular mass and size and as such is invaluable for assessing hypertrophied and/or dilated hearts, and thus interindividual comparison of myocardial contractile capability based on physical principles. However, this measure should be supplemented by considering time dependent parameters (e.g. maximum rate of stress development as a function of end-diastolic stress). The principle set here for evaluating ventricular and myocardial performance should always be borne in mind, especially when referring to more empirical parameters.
Animals↗
Chronic cardiac reactions. II. Mechanical and energetic consequences of myocardial transformation versus ventricular dilatation in the chronically pressure-loaded heart.
Mechanical and energetic consequences of myocardial transformation and of ventricular configuration on the other were separately analysed. The considerations were realized on representative samples of normotensive rats and spontaneously hypertensive rats (SHR) in compensated stages, as well as in SHR in a state of congestive cardiac failure. Cardiac dynamic measurements were performed under Urethane anaesthesia and open chest conditions. Myosin isoenzyme pattern was determined by pyrophosphate gel electrophoresis. Energetic calculations were based on oxygen consumption data, measured in a specified heart-lung model. In the compensated stage of SHR the concentric type of left ventricular hypertrophy with renormalized systolic auxotonic wall stress predominated. The process of cardiac hypertrophy was associated with a shift in the myosin isoenzyme pattern towards the "slow" VM-3. Myocardial transformation did not significantly reduce myocardial performance and pumping ability, but caused a decrease in oxygen consumption as related to developed stress and LV weight. Thus, the efficiency of the hypertrophied ventricle of SHR was improved. However, due to the moderate effect of isoenzyme pattern redistribution for total energy turnover and the limited adaptive reserve of normotensive controls, the extent of improvement was small. In SHR with congestive heart failure, myocardial contractility was severely impaired, when structural dilatation of the left ventricle had set in. Reduced myocardial contractility could not be explained solely on the basis of a shift in the myosin isoenzyme pattern. Both impaired myocardial contractility and structural dilatation contributed to reduced ventricular performance. Myocardial transformation, along with its energy economizing effect, failed to compensate for unfavorable energetic consequences of structural dilatation and therefore the reduced ventricular efficiency is assumed to be another deleterious factor in the dilated failing heart.
Animals↗
Chronic cardiac reactions. III. Factors involved in the development of structural dilatation.
The significance of various factors for the development of structural dilatation in the chronically pressure-loaded and failing heart were evaluated. The investigations were performed on male rats with renal (Goldblatt II) and spontaneous (Aoki-Okamoto) hypertension at different stages of haemodynamic overload. Two groups of SHR were submitted to intermittent feeding (SHR IF); one group received additionally the beta-blocking agent atenolol (50 mg/kg b.w.; SHR IF + beta Bl.). Haemodynamic measurements were carried out under open chest conditions. Myosin isoenzyme pattern, hydroxyproline concentration and circulating blood volume were determined. Transformation to slower myocardium per se, induced by IF, did not lead to significant change in ventricular configuration. After additional blockade of beta-adrenergic receptors there were indications of unfavourable development of left ventricular configuration. Inhibition of hypertrophic mass increase due to curtailed adrenergic stimulation could be an influential factor in the development of dilatation. Further investigations, however, are required to establish the relationship between the adrenergic system, on the one hand, and degree of hypertrophy as well as structural dilatation of the ventricle, on the other hand. The established marked increase in hydroxyproline concentration of the dilated ventricle of SHR in congestive failure is consistent with the assumption of a causal link between the degree of fibrosis and structural dilatation. Observations on rats with aorto-caval shunt and Goldblatt II rats with eccentric hypertrophy and corresponding increase in filling potential or circulating blood volume indicate a correlation between the latter and ventricular size. Thus, we assume that curtailed protein synthesis, fibrosis and regulatory processes related to water and electrolyte balance, but not myocardial transformation per se, play a role in the development of structural dilatation. The relative contribution of each factor, however, may depend on the experimental model that is used.
Animals↗
Chronic cardiac reactions. IV. Effect of drugs and altered functional loads on cardiac energetics as inferred from myofibrillar ATPase and the myosin isoenzyme population.
A major determinant of myocardial energetics is the ATPase activity of myofibrils. In order to account for chronic changes in myofibrillar ATPase, the state equation of the intertropomyosin-interaction model of Tawada et al. was extended by introducing the rates of cross-bridge cycling of myofibrils composed of V-1 or V-3 and the concentration of the myosin isoenzymes. Cross-bridge cycling rates of 1.0 or 0.7 were derived for myofibrils composed of V-1 or V-3, respectively. Ca2+ responsiveness and positive co-operativity were not significantly affected by the myosin isoenzymes. Redistribution of the myosin isoenzyme population and thus altered myocardial energetics was observed following administration of various drugs and as a result of different functional loads. Besides thyroid hormones, catecholamines had a marked influence on myosin. Reducing the adrenergic drive by administration of atenolol, guanethidine or reserpine led to a shift in the direction of V-3. Since serum T3 levels were not significantly reduced by these interventions, the drugs act most probably at the organ level. The functional states responsible for the increase in the proportion of V-3 (pressure load, intermittent feeding, schedule-induced stress) also did not affect circulating T3 in a manner that could entirely explain the redistribution. Hypertrophy-induced dilution of sympathetic nerve fibres or reduced adrenergic responsiveness most likely play a role in the redistribution. An increase in the proportion of V-1 was observed following swimming exercise but not, however, after spontaneous or enforced running. In the swim-exercised rats, T3 was markedly reduced. Thus, the trigger reactions linked most probably to the high adrenergic drive during swimming have to overcome the lower T3 level. It is concluded that myocardial energetics can be decisively altered by a variety of drugs and functional loads, whereby the trigger reactions leading to an altered gene expression of myosin cannot be accounted for entirely by altered circulating T3 but most probably involve the adrenergic system.
Adenosine Triphosphatases↗
Implications of myocardial transformation for cardiac energetics.
The influence of isoenzyme pattern of myosin on cardiac energetics was investigated in a modified in situ heart-lung preparation in the rat. Chronic pressure load (spontaneous hypertension, aortic stenosis, Goldblatt hypertension), intermittent feeding, and swim-training elicited redistribution in the concentration of alpha chains of myosin ranging from 18 to 94%. The influence of isoenzyme pattern of myosin on cardiac energetics could be quantitatively assessed by extrapolation of the regression line of oxygen and substrate consumption related to tension time index. Fast myocardium with 100% alpha chains had an ATP and oxygen consumption which exceeded that of slow myocardium with 0% alpha chains by about 60%. This corresponds well to the state of activity of myofibrillar ATPase of fast myocardium which also exceeds that of slow myocardium by about 50%. Furthermore it could be shown that acute increase in the ATPase activity depends on the isoenzyme pattern of myosin. Under the influence of catecholamines the oxygen consumption related to tension time index increased by 30-40% in fast myocardium, whereby in a myocardium with 40% alpha chains no increase in oxygen consumption per unit tension time index was observed, when catecholamines were applied.
Adenosine Triphosphatases↗
Subacute and long term effect of swimming training on blood pressure in young and old spontaneously hypertensive rats.
The effects of swimming training (three weeks' training with the duration increasing up to a maximum of 180 min per day, at a water temperature of 36 degrees C) on arterial blood pressure were studied in 4, 11, and 18 month old spontaneously hypertensive rats. In addition, in the 11 month old rats the change in blood pressure after individual exercise was determined. The significance of a training induced loss of body weight in lowering blood pressure was assessed by pair feeding of sedentary age matched spontaneously hypertensive rats. Blood pressure was reduced by approximately 50 mmHg within 8-10 days, except in the oldest rats, which tolerated the physical activity poorly and had, if any, only a moderate fall in blood pressure. It was possible to distinguish between subacute transient effects lasting for not more than one day and long term effects. Blood pressures were 20-25 mmHg lower after individual swimming routines than those before exercise when measured on the ninth day of the training programme. On cessation of training, blood pressures approached those of sedentary rats within two weeks. It seems that the loss of body weight was of minor importance in lowering blood pressure under these experimental conditions.
Aging↗
Effects of sodium-potassium pump inhibition and low sodium on membrane potential in cultured embryonic chick heart cells.
1. When the Na+-K+ pump of cultured embryonic chick heart cells was inhibited by addition of ouabain with or without removal of external K+, the membrane potential rapidly depolarized to -40 mV and the Na+ content approximately doubled within 3 min. 2. After this, exposure to an [Na+]o of 27 mM caused a fall in Na+ content, a gain in Ca2+ content and a hyperpolarization. The hyperpolarization was approximately 25 mV in a [K+]o of 0 or 5.4 mM after 3 min of pump inhibition. After approximately 10 min of pump inhibition, the same hyperpolarization was observed in a [K+]o of 5.4 mM but in K+-free solution the hyperpolarization increased to approximately 44 mV. 3. Varying [K+]o during the 10 min period of Na+-K+ pump inhibition showed that the increase in hyperpolarization was associated with the period of exposure to K+-free solution rather than the [K+]o at the time of lowering [Na+]o. 4. Changes in Na+ and Ca2+ content induced by exposure to an [Na+]o of 27 mM in K+-free solution were similar at 3 and 10 min. This and the above observations suggest that the increased hyperpolarization was due to an increased membrane resistance. 5. 10 mM-Cs+ reduced the low-[Na+]o hyperpolarization by 26% but did not significantly affect the movements of Na+ and Ca2+. 1 mM-La3+ reduced the low-[Na+]o hyperpolarization by 15%: it also totally blocked the rise in Ca2+ content and partially blocked the fall in Na+ content. 1 mM-Ba2+ reduced the low-[Na+]o hyperpolarization by 20%. 6. Raising [Ca2+]o from 2.7 to 13.5 mM produced similar but smaller hyperpolarizations (approximately 6 mV after 3 min pump inhibition). High [Ca2+]o caused a rise in Ca2+ content but no significant drop in Na+ content. The hyperpolarization in high [Ca2+]o was insensitive to verapamil (20 microM) and 10 mM-Cs+. 7. We conclude from the disparities between the magnitudes of the hyperpolarizations and the changes in ion contents that Na+-Ca2+ exchange cannot be unequivocally identified as electrogenic solely from the low-[Na+]o hyperpolarizations.
Animals↗
Electrogenic sodium-calcium exchange in cultured embryonic chick heart cells.
1. The membrane potential (Em) of cultured chick embryonic heart cells depolarized to -36 mV after inhibition of the Na+-K+ pump by 0.1 mM-ouabain in a [K+]o of 24 mM: this was accompanied by a rise in Na+ content of approximately 65% in 3 min. Lowering [Na+]o to 27 mM then caused a fall in Na+ content, a rise in Ca2+ content and a small hyperpolarization of approximately 5 mV. The fall in Na+ content indicated a movement of Na+ which was in the opposite direction to the Na+ electrochemical gradient (a countergradient movement). 2. In the presence of 10 mM-Cs+ or 1 mM-Ba2+ the hyperpolarization was approximately 10 or approximately 30 mV, respectively. A 30 mV hyperpolarization took Em negative to the reversal potentials for K+, and Cl- as measured by ion-selective micro-electrodes. 3. The decay of the intracellular Na+ activity alpha iNa, in an [Na+]o of 27 mM followed a simple exponential time course (time constant, 36 s). The initial rate depended on the value to which [Na+]o was lowered in a manner suggesting a simple competitive inhibition of the exchange by external Na+. 4. The low-[Na+]o hyperpolarization was unaffected by amiloride (0.1 or 1 mM) or verapamil (20 microM). Both La3+ (1 mM) and Mn2+ (20 mM) blocked the hyperpolarization sufficiently to prevent Em hyperpolarizing negative to the reversal potentials for K+, Na+ and Cl-. 5. Re-establishing [Na+]o caused a rise in Na+ content and a countergradient drop in Ca2+ content. The effects of verapamil (20 microM), amiloride (0.1 and 1 mM), dichlorobenzamil (0.1 mM), quinidine (1 mM), Mn2+ (20 mM) and La3+ (1 mM) were tested on the movements of Na+ and Ca2+ both during exposure to an [Na+]o of 27 mM and on re-establishing [Na+]o. The only consistent and substantial effects were the attenuation by La3+ and Mn2+ and Ca2+ movements during exposure to an [Na+]o of 27 mM. However, neither La3+ nor Mn2+ affected the movements of Na+ and Ca2+ on re-establishing [Na+]o. 6. We conclude that cultured embryonic chick heart cells contain a Na+-Ca2+ exchange evidenced by the ability to cause movements of Na+ and Ca2+ which are counter to their respective electrochemical gradient and which are accompanied by downhill movements of the counter ion.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Free calcium in isolated chick embryo heart cells measured using quin2 and fura-2.
Cytosolic free calcium (Cai) was measured using quin2 and fura-2 in isolated chick embryo heart cells. Account was taken of extracellular quin2 and fura-2 (which could not be entirely washed away) by adding Mn. Shortly after loading with quin2, Cai was 49 nM (n = 7) but then rose continuously at a rate varying between 13 and 88%/h. By varying the time between cell isolation and quin2 loading, it was ascertained that the loading was causing the rise in Cai. In one set of experiments, Cai was stable in time and the apparent Cai increased steadily from 55 to 179 nM as dye loading (quin2 or fura-2) was decreased from 1 mM to 5 microM. We conclude that although quin2 and fura-2 are useful for comparing Cai levels and determining whether Cai changes as a result of certain maneuvers, they do not provide an absolute measure of Cai in isolated embryonic heart cells.
Aminoquinolines↗
(Na + K + 2Cl) cotransport in cultured embryonic chick heart cells.
The coupled movements of Na, K, and Cl were studied in cultured chick embryonic heart cells using ion-selective microelectrodes. Movements of K and Cl in response to changes in extracellular [K] ([K]o) showed a furosemide-sensitive coupled process. The movement of Na was then studied. Lowering extracellular [Na] ([Na]o) to 27 mM caused a decrease in intracellular Cl activity (aicl). Upon restoring [Na]o to 143 mM, Cl was taken up against its electrochemical gradient (delta mu Cl). In Cl-free solution, cells lost Na against delta mu Na and simultaneously lost Cl. Upon restoring extracellular [Cl] ([Cl]o), Cl was taken up against delta mu Cl; this was accompanied by an uptake of Na. The Cl uptake was 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS)-insensitive (0.1 mM) but inhibited by removing Nao. Both Cl and Na uptakes were potentiated by raising [K]o from 5.4 to 15 mM, and Na uptake was diminished by lowering [K]o to 1 mM. In all experiments, Cl and Na movements were furosemide (0.3 mM) or bumetanide-sensitive (0.1 mM). Removal of Nao, with resultant depletion of intracellular [Na] ([Na]i), blocked the furosemide or bumetanide-sensitive Cl loss or uptake upon exposure to zero or 133 mM [K]o + SITS (0.1 mM), respectively. These results suggest that cultured heart cells possess an electroneutral (Na + K + 2Cl) cotransport.
4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
Functional significance of contractile proteins in cardiac hypertrophy and failure.
The functional significance of alterations in contractile proteins was investigated in the chronically overloaded left ventricle of Goldblatt rats and spontaneously hypertensive rats (SHRs). Congestive cardiac insufficiency occurring in late stages of pressure overload is associated with impaired contractility, as well as significant structural dilatation. Only in the event of extreme dilatation, however, would pumping failure occur in the presence of intact myocardial contractile capability. The transformation toward a slower myocardium is associated with a reduced rate of Ca2+ uptake by the sarcoplasmic reticulum. Transformation influences ventricular and myocardial working capacity to a much lesser extent than do the velocity parameters of contraction. Although a fairly homogeneous VM-3 pattern is typical for ventricles when cardiac failure is experimentally induced, extreme myocardial transformation, as such, does not cause congestive failure. With cardiac insufficiency, left ventricular volume, systolic wall stress, and hydroxyproline concentration are overproportionately increased, as related to VM-3 content, whereas noradrenaline content is decreased. This is consistent with the assumption that myocardial transformation is not necessary for the development of these alterations. Myocardial transformation may be promoted by structural dilatation. Extreme transformation, however, should, in turn, decrease contractility, contributing to cardiac failure. A considerable decrease in contractility indirectly causes depletion of the catecholamine stores. The energy-saving effect of myocardial transformation toward a slower muscle cannot compensate for the unfavorable effects of a substantial degree of ventricular dilatation.
Animals↗