Long-pulse improved central electron confinement in the TCV tokamak with electron cyclotron heating and current drive.

Current profile tailoring by electron cyclotron heating (ECH) and current drive (ECCD) is used to improve central electron energy confinement in the TCV tokamak. Counter-ECCD on axis alone achieves this goal in a transient manner only. A stable scenario is obtained by a two-step sequence of off-axis ECH, which stabilizes magnetohydrodynamics modes, and on-axis counter-ECCD, which generates a flat or inverted current profile. This high-confinement regime, with central temperatures up to 9 keV (at a normalized beta(N) approximately 0.6), has been sustained for the entire duration of the heating pulse, or over 200 electron energy confinement times and 5 current redistribution times.

Augmented sympathetic response to bradykinin in the diabetic heart before autonomic denervation.

We studied whether diabetes mellitus affects the bradykinin (BK)-induced release of norepinephrine (NE) from rat cardiac sympathetic endings in situ. Three groups were studied. Group A (n=12) was rendered diabetic with streptozotocin (STZ), group B (n=13) received STZ and insulin, and group C (n=14) received citrate buffer only. NPH insulin was given to group B from day 7 after STZ. Atria were paced (3Hz) with rectangular voltage pulses at mechanical threshold intensity (0.15 V/cm). The release of NE was assessed through its effects on contractile force in the presence of atropine (1 micromol/L). Intensifying the field stimulation above the neural threshold ( approximately 0.4 V/cm) produced a graded positive inotropic effect that was due to the release of NE from sympathetic nerve endings. The additional effect of 0.1 micromol/L BK on the force of contraction was determined at half-maximal neural stimulation (ie, at approximately 0.65 V/cm). Then, after washing out BK and lowering the stimulation intensity to mechanical threshold, a cumulative dose-response curve for added NE was generated, allowing the positive inotropic effects of neural stimulation (with or without BK) to be expressed in terms of an equivalent inotropic concentration of added NE ([NE(eq)]). Neural stimulation, in the absence of BK, gave an [NE(eq)] of 32+/-3 nmol/L in group A, 44+/-6 nmol/L in group B, and 37+/-6 nmol/L in group C. BK increased [NE(eq)] by a factor of 6.2+/-0.9 in group A, 4.5+/-0.5 in group B, and 3.7+/-0.3 in group C. This factor was greater in group A than in group C but indistinguishable in groups B and C. Atria from normal and diabetic rats were incubated in (3)[H]NE for 60 minutes. Excess tracer was removed, and atria were stimulated during a series of 1-minute episodes at half-maximal neural stimulation to cause exocytotic (3)[H]NE release. BK augmented (3)[H]NE release in normal (n=4) and in diabetic (n=4) atria. This BK-induced increase of (3)[H]NE overflow (expressed as a fraction of tissue (3)[H]NE radioactivity) was 4 times greater in diabetic than in normal preparations. The response to BK in releasing sympathetic neurotransmitter is augmented in diabetic rats, recovering in a manner dependent on insulin.

Blood flow after retinal ischemia in cats.

PURPOSE: To determine the changes in blood flow in the cat retina after 1 hour of ischemia. METHODS: Blood flow in the retina and choroid of adult cats anesthetized with chloralose, acepromazine, and halothane was measured using sequential injections of radioactively labeled microspheres. Ischemia was induced by elevation of intraocular pressure above systolic arterial pressure. Measurements were carried out before (baseline) and during ischemia, and at 5, 10, 15, 60, 120, and 240 minutes after the return of ocular circulation. In another two series of cats, blood flow was measured at comparable time periods without ischemia (controls). Arterial blood gas tension, systemic arterial pressure, hematocrit, and anesthetic level were controlled in each experiment. RESULTS: Retinal blood flow was decreased to 6%, and choroidal blood flow to 0.6%, of baseline value during ischemia. Within 5 minutes of the return of ocular circulation, retinal blood flow was approximately 200% of baseline, and choroidal blood flow was 108% of baseline. Blood flow 1 hour after the return of ocular circulation was not significantly different from baseline. There was no late decrease in blood flow after the ischemic period. CONCLUSION: As does cerebral ischemia, retinal ischemia results in a hyperemic response but no delayed hypoperfusion. The mechanism of this effect is unknown.

The effects of enflurane on ocular blood flow.

Although general anesthesia is frequently chosen for eye surgery or experimental studies of ocular blood flow, there are few data available describing its effects on ocular blood flow. In a previous study in cats, we reported that enflurane produced significant increases in preretinal oxygen tension, indicating an increase in oxygen availability in the retina. To examine whether this effect was due to an increase in retinal or choroidal blood flow, we used radioactively labeled 15 microns microspheres of Ce 141, Sn 113, Ru 103, or Nb 95, to measure ocular blood flow in cats during enflurane anesthesia. In 10 adult cats, retinal blood flow measured 75 +/- 13, 90 +/- 9 and 88 +/- 11 ml x 100 g-1 x min-1 (mean +/- S.E.M.) at 0.5, 1.0, and 1.5 MAC enflurane, respectively (1 MAC is the concentration at which 50% of subjects do not move in response to a standardized stimulus). Corresponding values for choroidal blood flow were 1275 +/- 124, 876 +/- 106 and 842 +/- 102 ml x 100 g-1 x min-1 (mean +/- S.E.M.) at 0.5, 1.0, and 1.5 MAC enflurane, respectively. The decrease in choroidal blood flow was significant between 0.5 and 1.0 MAC. These results differ from those in our previous investigation of the effects of halothane on ocular blood flow. With halothane, retinal blood flow increased and choroidal blood flow decreased throughout the entire dose range (0.5, 1.0, and 1.5 MAC). We conclude that inhalational anesthetic agents produce significant but different effects upon ocular blood flow.

Vasoactive intestinal peptide enhances thyroidal iodide uptake during dietary iodine deficiency.

The presence of vasoactive intestinal peptide and neuropeptide Y in thyroid nerves and their effects on thyroid blood flow are well known. However, the effects of these two neuropeptides on the various processes involved in thyroid hormone biosynthesis and release have not been fully explored. We have now tested these two peptides for effects on an early step in thyroid hormone biosynthesis, namely iodide uptake, a process which is comprised of trapping and organification. In these experiments, we have used anesthetized adult male rats pretreated with thyroxine or fed a low iodine diet to increase thyroidal sensitivity. Vasoactive intestinal peptide significantly increased iodide uptake in rats fed an iodine deficient diet but not in those fed a normal iodine diet. This effect disappeared if animals were pretreated with propylthiouracil. Neuropeptide Y did not alter iodide uptake in rats on either the low or the high iodine diet, regardless of the presence or absence of propylthiouracil. The effect of vasoactive intestinal peptide on iodide uptake could be due to its influence on the organification of iodine, or on thyroid blood flow, or on both processes.

Compensatory changes in thyroid blood flow are only partially mediated by thyrotropin.

It has been shown that the compensatory growth of the thyroid gland and the compensatory increase in hormone secretion that occur after hemithyroidectomy are preceded by a dramatic increase in thyroid blood flow (BF). These alterations in the thyroid remnant may be due to the concomitant increase in plasma thyrotropin (TSH) concentrations. It has been suggested, however, that the compensatory thyroid growth may also involve a neural reflex. In this study we have investigated the role of TSH in mediating the compensatory alterations in thyroid BF and mass after subtotal thyroidectomy. Male Sprague-Dawley rats were anesthetized with ether for surgical or sham hemithyroidectomy. One-half of the hemithyroidectomized rats (HTX) received no further treatment; in the other one-half of the HTX rats (Clamp), plasma TSH levels were maintained at levels comparable with those in sham-operated animals by initiating constant thyroid hormone replacement beginning at the time of hemithyroidectomy. Plasma samples for TSH, 3,5,3'-triiodothyronine, and thyroxine radioimmunoassays were obtained 2, 7, 14, and 21 days after surgery. Thyroid BF was determined at 1, 2, and 3 wk after surgery by the reference sample version of the radioactive microsphere technique (141Ce, 15 microns diameter). Plasma TSH levels and thyroid lobe weight were significantly elevated in HTX rats but not in Clamp rats. Thyroid BF was markedly increased in HTX rats. Thyroid BF was also significantly increased in Clamp rats despite the suppression of the rise in plasma TSH concentration, but this increase was less than that in HTX rats. Neither hemithyroidectomy nor Clamp treatments had any effect on arterial blood pressure or BF to other tissues (e.g., kidney).(ABSTRACT TRUNCATED AT 250 WORDS)

Muscarinic modulation of the vasodilatory effects of vasoactive intestinal peptide at the rat thyroid gland.

In the thyroid gland, vasoactive intestinal peptide (VIP) and acetylcholine (ACh) are found in nerve fibers associated with secretory cells and blood vessels. We have, therefore, initiated studies to explore the actions of and interactions between cholinergic agents and VIP in the regulation of thyroid vascular conductance (VC). Thyroid and other organ blood flows were measured using radiolabelled (141Ce) microspheres injected directly into the left cardiac ventricle of anesthetized male rats. The mean systemic arterial pressure was monitored and used in the calculation of organ VC (blood flow/arterial pressure). Plasma TSH, T3, and T4 levels before and after infusions were measured by RIA. The acute administration of ACh (3 x 10(-8) mol/100 g BW) over 4 min increased thyroid VC, whereas nicotine (10(-7) mol/100 g BW) had no such effect. Circulating TSH and thyroid-hormone levels following ACh or nicotine were not different from those in vehicle-treated animals at 20 min or 2 h after infusion. This observation suggested that ACh acts through muscarinic receptors at the thyroid gland to increase VC. In order to extend these observations and to evaluate whether VIP might exert any of its thyroidal effects on VC via muscarinic receptors, we assessed the effects of ACh, methacholine chloride (MCC), and VIP in the presence and absence of the muscarinic receptor blocker atropine. Rats were treated intravenously with saline or atropine (3 mg/kg) 20 min before intravenous infusions of vehicle, ACh (3 x 10(-8) mol/100 g BW), MCC (5 x 10(-9) mol/100 g BW), or VIP (10(-11) mol/100 g BW).(ABSTRACT TRUNCATED AT 250 WORDS)

Helodermin, but not cholecystokinin, somatostatin, or thyrotropin releasing hormone, acutely increases thyroid blood flow in the rat.

In the present study, we investigated whether peptides located within the thyroid gland, but not directly found in nerve fibers associated with blood vessels, might influence thyroid blood flow. Specifically, we evaluated the effects of helodermin, cholecystokinin (CCK), somatostatin (SRIF) and thyrotropin releasing hormone (TRH) given systemically on thyroid blood flow and circulating thyroid hormone levels. Blood flows in the thyroid and six other organs were measured in male rats using 141Ce-labeled microspheres. Circulating thyrotropin (TSH) and thyroid hormone levels were monitored by RIA. Helodermin (10(-10) mol/100 g BW, i.v. over 4 min) markedly elevated thyroid blood flow (52 +/- 6 vs. 10 +/- 2 ml/min.g in vehicle-infused rats; n = 5). Blood flows to the salivary gland, pancreas, lacrimal gland and stomach (but not adrenal and kidney) were also increased during helodermin infusions. CCK, SRIF, and TRH were without effect on blood flows to the thyroid and other organs even though these peptides were tested at higher molar doses than helodermin. Helodermin, CCK, or SRIF did not affect thyroid hormone or plasma calcium levels. As expected however, plasma TSH and T3 levels were increased at 20 min and 2 h, respectively, following TRH infusions. Since helodermin shares sequence homology with VIP, we next compared the relative effects of these two peptides on thyroid and other organ blood flows. VIP (10(-11) mol/100 g BW, i.v.) was more potent in increasing blood flows to the thyroid, salivary gland, and pancreas than an equimolar dose of helodermin. This study shows that while helodermin, like VIP, has the ability to increase thyroid and other organ blood flows, it appears to be a less potent vasodilator.