Calcium oscillations in electrically non-excitable cells.
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Animals↗
Biomedical subjects
R Jacob
Publications and source records attributed to R Jacob.
Effects of a diet rich in Q-3 fatty acids on left ventricular geometry and dynamics in spontaneously hypertensive rats.
The aim of the present study was to investigate the chronic effects of a dietetic antihypertensive treatment on blood pressure, ventricular dynamics and geometry of the pressure loaded heart. Spontaneously hypertensive rats (SRH) received a standard diet enriched with 10% mackerel oil, containing 30% polyunsaturated Q-3 fatty acids, over a period of 70 days. As described previously the diet reduced blood pressure permanently by 40-50 mm Hg. Despite this reduction, the degree of left ventricular hypertrophy was only slightly (statistically insignificantly) reduced. This was probably a result of an increase in sympathetic tone as indicated by a raised pulse rate. On the other hand, the treatment prevented the development of eccentric hypertrophy, typical to the SHR, without changing the elastic material properties of the myocardium. Since the age-matched controls did not show significant degenerative alterations, protective effects at the level of myocardial tissue could not be demonstrated. Furthermore, future investigations need to investigate why myocardial contractility of the treated animals diminishes as observed in this study.
Animals↗
Left ventricular performance in rats with chronic cardiac overload due to arterio-venous shunt.
The effects of experimental arterio-venous shunt (AV shunt) on left ventricular dynamics and myocardial mechanics were investigated in female Wistar rats, weighing approx. 240 g. The main goal of the study was to characterize ventricular and myocardial working capacity and to estimate the significance of the various processes involved in cardiac adaptation to the altered loading conditions. Twelve weeks after operation, systemic blood pressure was slightly elevated in AV shunt rats as compared with age-matched controls, although total peripheral resistance (as related to a common aortic pressure) was significantly reduced. Heart rate and cardiac output were considerably increased. Despite marked left ventricular dilatation with increased end-diastolic and systolic wall stress, no signs of resting insufficiency were present. Left ventricular weight, end-diastolic volume and pressure, stroke volume, and ejection fraction were increased. The area between the curve of isovolumic maxima and the end-diastolic P-V curve (up to a defined end-diastolic pressure) and the normalized area between the isovolumic and end-diastolic stress-length curves as well as the maximum rate of stress development were augmented, even in the specimen with the highest degree of ventricular dilatation--despite a shift of the myosin isoenzyme pattern towards VM3. The study reveals that besides the change in ventricular mass and configuration, augmented preload is involved in cardiac adaptation to the altered hemodynamic state. Furthermore, there are indications of an intensified sympathetic stimulation of the heart. Transformation of the myocardium towards a slower muscle seems to be of minor functional significance under the conditions of the present experiments.
Adaptation, Physiological↗
Agonist-stimulated divalent cation entry into single cultured human umbilical vein endothelial cells.
1. The free cytoplasmic Ca2+ concentration ([Ca2+]i) can be measured using Fura-2 in superfused single human umbilical vein endothelial cells. When an endothelial cell is stimulated by a maximal dose of histamine (100 microM), [Ca2+]i rises to a peak and then falls back to a maintained plateau which is due to a stimulated Ca2+ influx. 2. If extracellular Ca2+ is replaced by 50 microM-Mn2+ then 100 microM-histamine causes a rise in [Ca2+]i accompanied by a fluorescence quench that signals the stimulated entry of Mn2+ into the cytoplasm. 3. If in Ca2(+)-free solution a cell is stimulated by 100 microM-histamine for 120 s to discharge the internal Ca2+ store, and then exposed to 50 microM-Mn2+ after removal of the histamine, a similar stimulated Mn2+ entry is seen. This quench is unaffected by readdition of histamine and is not seen if the store is refilled by exposure to 1 mM-extracellular Ca2+ for 180 s before exposure to the Mn2+. 4. The refilling of the internal store by exposure to 1 mM-Ca2+ and the stimulated entry of Mn2+ are both blocked by 2 mM-Ni2+. 5. If [Ca2+]i is stimulated to produce repetitive spikes by a low dose of histamine (0.3-1 microM) in nominally Ca2(+)-free solution containing Mn2+, then the stimulated quench is uniform and is not modulated by the [Ca2+]i spiking. 6. If the internal store is discharged by exposure to histamine in Ca2(+)-free solution and then refilled for a short period then the cell is in a state where the internal store is partly full to an extent that depends on the duration of the refilling. In such an experiment, the rate of Mn2+ influx may be estimated by measuring the rate of quench during a short exposure to 50 microM-Mn2+. The rate of Mn2+ entry varies inversely with the degree of fullness of the internal Ca2+ store. 7. If a similar experiment is repeated but with the fullness of the internal store being varied by varying the period of the initial exposure to 100 microM-histamine, with no refilling, the same inverse relationship between Mn2+ influx and fullness of the internal store is obtained. 8. These experiments show that Mn2+ enters human umbilical vein endothelial cells following agonist stimulation by a pathway that is controlled by the degree of fullness of the internal store; it does not, however, enter the cytoplasm by exactly the same route as Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS)
Action Potentials↗
The perioperative effects of oral premedication in children.
The pre- and postoperative effects of oral diazepam (0.5 mg/kg), trimeprazine (4 mg/kg), pentobarbitone (3 mg/kg) and a placebo were compared in a randomized double-blind clinical trial in 149 children, aged one to ten years, undergoing adenotonsillectomy. The anaesthetic was standardised and each patient received intraoperative intramuscular papaveretum (0.3 mg/kg). Preoperative sedation was assessed in the ward before transfer onto the theatre trolley, on leaving the ward, on arrival on the theatre floor, on arrival in the induction room and on induction of anaesthesia. There was no significant difference in sedation between the four drug groups except for the placebo group which had a significantly greater unsatisfactory rating at the stage of induction of anaesthesia (P = 0.001). There were no differences in waking times between the diazepam, pentobarbitone and placebo groups, but the trimeprazine group's waking times were significantly prolonged (P less than 0.001). However, the trimeprazine group exhibited significantly less distress in the recovery unit (P = 0.02) and had half the incidence of vomiting (P less than 0.001) than did the other premedication groups.
Adenoidectomy↗
A study of preoperative fasting in infants aged less than three months.
The effects of preoperative fasting on plasma glucose and gastric emptying was studied in 62 infants aged less than three months after a feed of either breast milk or an infant milk formula. Prior to induction of anaesthesia no infant was hypoglycaemic, defined as plasma glucose less than 2.2 mmol/l. Five per cent of infants had a significant volume of residual gastric contents. The mean intraoperative plasma glucose levels rose significantly and this was not influenced by the use of intravenous Hartmann's solution or low dose opioids. Infants in this age group tolerate three- to four-hour preoperative fasts well as no infant became hypoglycaemic intraoperatively. They demonstrate a hyperglycaemic response to the stress of anaesthesia and surgery, and may not need routine intraoperative glucose supplements although plasma glucose should still be monitored.
Acid-Base Equilibrium↗
Moyamoya disease.
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Anesthesia, Inhalation↗
Sunscreens: prevention by the ounce.
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Humans↗
Interaction of (Na + K + 2 Cl) cotransport and the Na/K pump in cultured chick cardiac myocytes.
We have recently reported the presence of an electroneutral (Na + K + 2 Cl) cotransport mechanism that is bumetanide-sensitive and maintains Cli above its electrochemical equilibrium in cultured chick heart cells. In steady state, (Na + K + 2 Cl) cotransport is inwardly directed and so contributes to the Na influx that must be counterbalanced by the activity of the Na/K pump to maintain Nai homeostasis. We now show that manipulating (Na + K + 2 Cl) cotransport by restoring Clo to a Cl-free solution indirectly influences Na/K pump activity because the bumetanide-sensitive recovery of aiNa to its control level and the accompanying hyperpolarization could be blocked by 10(-4)M ouabain. In another protocol, when the Na/K pump was reactivated by restoring Ko (from 0.5 mM to 5.4 mM) and removing ouabain, the recovery of aNa was attenuated by 10(-4)M bumetanide. The relatively slow rate of ouabain dissociation coupled with the activation of Na influx by (Na + K + 2 Cl) cotransport clearly establishes the interaction of these transport mechanisms in regulating Nai. Although (Na + K + 2 Cl) cotransport is electroneutral, secondary consequences of its activity can indirectly affect the electrophysiological properties of cardiac cells.
Animals↗
Influx of bivalent cations can be independent of receptor stimulation in human endothelial cells.
Stimulation of human umbilical-vein endothelial cells by agonists such as histamine or thrombin promotes an influx of Ca2+, causing an increase in cytoplasmic free Ca2+ ([Ca2+]i) that is dependent on the continued presence of both agonist and extracellular Ca2+. This influx can also be clearly detected by using Mn2+ as a marker for Ca2+ entry, since Mn2+ quenches fura-2 fluorescence. The internal stores can be discharged in nominally Ca2+-free solution by stimulation for a brief period by 100 microM-histamine, with the stimulation being terminated by addition of 20 microM of the H1 antagonist mepyramine. After this (i.e. in the continuous presence of antagonist) a stimulated bivalent-cation influx can still be detected, as evidenced by the following observations: (a) addition of Mn2+ produces a stimulated quench, (b) addition of Ca2+ produces a transient rise in [Ca2+]i, (c) addition of 1 unit of thrombin/ml produces a much attenuated response unless the cells are exposed for a short period to 1 mM extracellular Ca2+. These results imply that stimulated bivalent-cation influx may be a direct consequence of the discharge of the internal Ca2+ stores rather than a direct consequence of the presence of agonist.
Calcium↗
Use of manganese to discriminate between calcium influx and mobilization from internal stores in stimulated human neutrophils.
Stimulation of human neutrophils with f-met-leu-phe, platelet-activating factor, or leukotriene B4 resulted in an increase in [Ca2+]i. The [Ca2+]i rise was greater in the presence than absence of external Ca2+; the component that was dependent on external Ca2+ was blocked by Ni2+, or could be reconstituted by addition of external Ca2+ following discharge of the internal Ca2+ store. These measurements of [Ca2+]i responses provide only indirect evidence for agonist-stimulated Ca2+ entry, and here we have used an alternative approach to demonstrate directly agonist-stimulated divalent cation entry. In the presence of extracellular Mn2+, f-met-leu-phe, leukotriene B4, and platelet-activating factor stimulate a quench in fluorescence of fura-2-loaded human neutrophils. This quench was due to stimulated Mn2+ influx and was blocked by Ni2+. When Mn2+ was added in the continued presence of agonist, after discharge of the internal store of Ca2+, a stimulated quench was seen; this result shows that an elevated [Ca2+]i is not needed for the stimulation of Mn2+ entry. Depolarization by high [K+] or addition of the L-type Ca2+ channel agonist, BAY-R-5417, had little or no effect on either [Ca2+]i or Mn2+ entry. These results show that agonists stimulate divalent cation entry (Ca2+ or Mn2+) by a mechanism independent of changes in [Ca2+]i and unrelated to voltage-dependent Ca2+ channels.
Benzofurans↗
Calcium oscillations in non-excitable cells.
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Animals↗
Acute effects of insulin-like growth factor I on glucose and amino acid metabolism in the awake fasted rat. Comparison with insulin.
To elucidate the acute metabolic actions of insulin-like growth factor I (IGF-I), we administered a primed (250 micrograms/kg), continuous (5 micrograms/kg.min) infusion of human recombinant (Thr 59) IGF-I or saline to awake, chronically catheterized 24-h fasted rats for 90 min. IGF-I was also infused while maintaining euglycemia (glucose clamp technique) and its effects were compared to those of insulin. IGF-I infusion caused a twofold rise in IGF-I levels and a 75-85% decrease in plasma insulin. When IGF-I alone was given, plasma glucose fell by 30-40 mg/dl (P less than 0.005) due to a transient twofold increase (P less than 0.05) in glucose uptake; hepatic glucose production and plasma FFA levels remained unchanged. IGF-I infusion with maintenance of euglycemia produced a sustained rise in glucose uptake and a marked stimulation of [3-3H]glucose incorporation into tissue glycogen, but still failed to suppress glucose production and FFA levels. IGF-I also produced a generalized 30-40% reduction in plasma amino acids, regardless of whether or not hypoglycemia was prevented. This was associated with a decrease in leucine flux and a decline in the incorporation of [1-14C]leucine into muscle and liver protein (P less than 0.05). When insulin was infused in a dosage that mimicked the rise in glucose uptake seen with IGF-I, nearly identical changes in amino acid metabolism occurred. However, insulin suppressed glucose production by 65% and FFA levels by 40% (P less than 0.001). Furthermore, insulin was less effective than IGF-I in promoting glycogen synthesis. We conclude that (a) IGF-I produces hypoglycemia by selectively enhancing glucose uptake; (b) IGF-I is relatively ineffective in suppressing hepatic glucose production or FFA levels; and (c) IGF-I, like insulin, lowers circulating amino acids by reducing protein breakdown rather than by stimulating protein synthesis. Thus, IGF-I's metabolic actions in fasted rats are readily distinguished from insulin.
Amino Acids↗
Evidence that agonists stimulate bivalent-cation influx into human endothelial cells.
Human umbilical-vein endothelial cells stimulated with thrombin or histamine show an increase in [Ca2+]i (cytoplasmic free calcium concn.) that is maintained well above the basal pre-stimulated value as long as agonist and a source of extracellular Ca2+ are present. These results provide circumstantial evidence that agonists stimulate influx of Ca2+ across the plasma membrane and into the cytoplasm. Here, we have used Mn2+ as the extracellular bivalent cation which can bind to the fluorescent Ca2+ indicator fura-2 to quench its fluorescence completely. Human umbilical-vein endothelial cells were loaded with fura-2 and, in the presence of extracellular Mn2+, thrombin and histamine were shown to cause quenching of the intracellular dye. This result demonstrates conclusively that agonists can stimulate the influx of bivalent cations. Stimulated discharge of Ca2+ from intracellular stores and influx of Mn2+ were temporally resolved in the same cells to show that release of Ca2+ from intracellular stores clearly precedes influx. Influx of Mn2+ was also demonstrated when extracellular Mn2+ was added after agonist at a time when [Ca2+]i had fallen back to the basal value, showing that influx is not dependent on elevated [Ca2+]i.
Calcium↗
Repetitive spikes in cytoplasmic calcium evoked by histamine in human endothelial cells.
Measurement of cytoplasmic free calcium, [Ca2+]i, in single human endothelial cells has shown that low doses of the inflammatory mediator histamine evoke asynchronous repetitive spikes in [Ca2+]i whereas high doses cause a maintained elevated [Ca2+]i. We discuss possible regulatory mechanisms, and the potential physiological and pathological implications of such a frequency-modulated [Ca2+]i signalling system.
Calcium↗
Influence of a diet rich in fish oil on blood pressure, body weight and cardiac hypertrophy in spontaneously hypertensive rats.
The effects of a diet rich in fish oil on arterial blood pressure, body weight, left ventricular weight and heart rate have been investigated in 8 month old spontaneously hypertensive male rats (SHR) as compared to age-matched hypertensive controls. A diet containing 10% fish oil decreased blood pressure by about 40 mmHg within 20 days of starting the experiment, and this effect persisted over the observation period of 80 days. Permitting the animals free access to food, the body weight of the diet group increased by 25%. The degree of hypertrophy as evaluated by relating left ventricular weight to tibial length was significantly reduced (10%) in the diet fed group. Heart rate was increased by 53%. The study demonstrates that a diet rich in fish oil can lower arterial blood pressure over several weeks without a recognizable loss in function despite a considerable increase in body weight. It can be assumed that a more marked regression of left ventricular hypertrophy is counteracted by a reflex increase in sympathetic efferentation to the heart.
Animals↗
Principles underlying the assessment of ventricular and myocardial work and power capacity.
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Animals↗
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↗