Determination of the hemodynamic significance of coronary artery stenoses of intermediate severity.
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Blood Flow Velocity↗
Biomedical subjects
J Segal
Publications and source records attributed to J Segal.
Alterations of phasic coronary artery flow velocity in humans during percutaneous coronary angioplasty.
BACKGROUND AND OBJECTIVES: Studies using Doppler catheters to assess blood flow velocity and vasodilator reserve in proximal coronary arteries have failed to demonstrate significant improvement immediately after coronary angioplasty. Measurement of blood flow velocity, flow reserve and phasic diastolic/systolic velocity ratio performed distal to a coronary stenosis may provide important information concerning the physiologic significance of coronary artery stenosis. This study was designed to measure these blood flow velocity variables both proximal and distal to a significant coronary artery stenosis in patients undergoing coronary angioplasty. METHODS: A low profile (0.018-in.) (0.046-cm) Doppler angioplasty guide wire capable of providing spectral flow velocity data was used to measure blood flow velocity, flow reserve and diastolic/systolic velocity ratio both proximal and distal to left anterior descending or left circumflex coronary artery stenosis. These measurements were made in 38 patients undergoing coronary angioplasty and in 12 patients without significant coronary artery disease. RESULTS: Significant improvement in mean time average peak velocity was noted in distal coronary arteries after angioplasty (before 19 +/- 12 cm/s; after 35 +/- 16 cm/s; p less than 0.01). Increases in proximal average peak velocity after angioplasty were less remarkable (before 34 +/- 18 cm/s; after 41 +/- 14 cm/s; p = 0.04). Mean flow reserve remained unchanged after angioplasty both proximal (1.5 +/- 0.5 vs. 1.6 +/- 1; p greater than 0.10) and distal (1.6 +/- 1 vs. 1.5 +/- 0.8; p greater than 0.10) to a coronary stenosis. Before angioplasty, mean diastolic/systolic velocity ratio measured distal to a significant stenosis was decreased compared with that in normal vessels (1.3 +/- 0.5 vs. 1.8 +/- 0.5; p less than 0.01). After angioplasty, distal abnormal phasic velocity patterns generally returned to normal, with a significant increase in mean diastolic/systolic velocity ratio (1.3 +/- 0.5 vs. 1.9 +/- 0.6; p less than 0.01). Phasic velocity patterns and mean diastolic/systolic velocity ratio measured proximal to a coronary stenosis were not statistically different from values in normal vessels (1.8 +/- 0.8 vs. 1.8 +/- 0.5; p greater than 0.10) and did not change significantly after angioplasty (1.8 +/- 0.8 vs. 2.13 +/- 0.9; p greater than 0.10). CONCLUSIONS: Flow velocity measurements may be performed distal to a coronary stenosis with the Doppler guide wire. Phasic velocity measurements made proximal to a coronary stenosis differed from those in the distal coronary artery. Both proximal and distal flow reserve measurements made immediately after angioplasty were of limited utility. Changes in distal flow velocity patterns and diastolic/systolic velocity ratio appeared to be more relevant than the hyperemic response in assessing the immediate physiologic outcome of coronary angioplasty.
Angioplasty, Balloon, Coronary↗
Placement of anterior cervical instrumentation without intraoperative radiography.
Adequate fixation with several commonly used anterior cervical plate systems requires that the screws penetrate both the anterior and posterior cortices of the vertebral bodies. This report emphasizes the shortcomings of plain film and fluoroscopic examinations in confirming screw position through the posterior vertebral cortex in three patients with lower cervical trauma or tumor. These cases and radiographs of isolated vertebrae from the cervicothoracic region demonstrate the inadequacy of plain film/fluoroscopy for determination of the position of anterior cervical plate screws in relation to the posterior cortex. Only axial images such as those obtained with computed tomography are able to show the exact relationship of the screws to the posterior cortical curvature in C7 and T1.
Adolescent↗
Validation of a Doppler guide wire for intravascular measurement of coronary artery flow velocity.
BACKGROUND: An improved intravascular ultrasonic Doppler device could aid the clinical assessment of coronary hemodynamics. We evaluated a new device consisting of a 12-MHz piezoelectric transducer integrated onto the tip of a 0.018-in. flexible, steerable angioplasty guide wire. METHODS AND RESULTS: Doppler spectra were recorded in model tubes with pulsatile blood flow and in-line electromagnetic flowmeter. In four straight tubes (i.d., 0.79-4.76 mm), the time average of spectral peak velocity (APV) was linearly related to blood flow (QEMF) (r2 greater than or equal to 0.98 for each tube). A Doppler-derived quantitative flow estimate (QD) was calculated as the product of vessel cross-sectional area and mean velocity, with mean velocity estimated as 0.5 x APV. The slope of QD versus QEMF for the four tubes was near unity. APV was less accurate in a 7.94-mm straight tube and in tortuous segments. In four dogs, the left circumflex coronary artery (LCx) was perfused from the femoral artery via a cannula with in-line electromagnetic flowmeter. Good-quality signals were obtained in proximal and distal LCx vessels 3.3-1.2 mm in diameter. APV varied linearly with QEMF (r2 greater than or equal to 0.99 in the cannula, r2 = 0.93-0.99 in proximal LCx, and r2 = 0.86-0.99 in distal LCx). QD was calculated by quantitative angiography to determine proximal LCx diameter. For all dogs combined, the slope of QD versus QEMF was 0.95 in the cannula and 0.85 in the proximal LCx. CONCLUSIONS: The Doppler guide wire measures phasic flow velocity patterns and linearly tracks changes in flow rate in small, straight coronary arteries. It should facilitate measurement of phasic coronary flow velocity during coronary angiography and angioplasty.
Animals↗
[Primary cholesteatoma of the external auditory meatus].
Primary cholesteatoma of the external auditory meatus is a rare condition manifested by erosion of the external auditory meatus due to the development of a noncleansing pocket lined by squamous epithelium. The salient features of the disease are: unilateral protracted otalgia and purulent otorrhea in an elderly patient. 2 cases are presented, aged 64 and 80 years, both men, diagnosed by otomicroscopy and CT scan. Treatment is either conservative, by local cleansing of the pocket in the outpatient clinic, or surgical, by wide excision of the pocket and necrotic bone, then covering the area with temporal fascia. When the disease is detected early, treatment is simpler and shorter, and the outcome better.
Aged↗
Continuous determination of cardiac output using a flow-directed Doppler pulmonary artery catheter.
A newly developed, flow-directed, Doppler pulmonary artery catheter that uses multiple ultrasonic transducers to measure instantaneous and continuous cardiac output was evaluated in 20 patients undergoing cardiac and vascular surgical procedures. Cardiac output was determined using the product of the average velocity and the area of the main pulmonary artery. Pulmonary artery area was obtained from measurements of diameter via ultrasound transit time, and average velocity of blood flow was determined from the Doppler shift frequency. Two hundred thirty-eight simultaneous Doppler catheter and thermodilution cardiac output measurements were obtained preoperatively, intraoperatively, and during postoperative recovery. Catheter indwelling time varied from 18 through 94 hours (mean +/- SD, 40 +/- 19 hours) with 2 to 26 (mean +/- SD, 12 +/- 6) sets of triplicate cardiac output measurements obtained per patient. Doppler catheter cardiac output correlated well with thermodilution (r = 0.76, slope or m = 0.87, and SEE = 0.05 with P = 0.0001) and mean predictive error (bias) appeared clinically insignificant (bias +/- SD, -0.13 +/- 0.79 L/min). Accurate, continuous monitoring of instantaneous and mean cardiac output appears possible with use of this Doppler pulmonary artery catheter system.
Blood Flow Velocity↗
[Condylomata acuminata during pregnancy].
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Antineoplastic Combined Chemotherapy Protocols↗
Effect of anesthesia on cardiac function and response in the perfused rat heart.
In the present study we have examined the effect of the general anesthetic agent sodium pentobarbital (given i.p. to the intact animal) on the hemodynamic function of the isolated perfused heart and its response to treatments which affect calcium transsarcolemmal influx: extracellular calcium concentration and thyroid hormone. Perfused hearts (modified Langendorff system) isolated from anesthetized rats were found to respond differently to the two aforementioned effectors than hearts excised from non-anesthetized animals. Hearts of the two groups demonstrated a gradual increase in inotropic activity in response to step-wise increase in calcium concentration in the perfusion medium. However, cardiac contractility and the pattern of the response to the gradual increase in calcium concentration were different. At the lower Ca2+ concentrations of 0.5 and 1.0 mM, inotropic activity (left ventricular systolic pressure (LVP) and +dP/dt values) of hearts from anesthetized animals was significantly greater (P less than 0.05) than that of hearts from non-anesthetized animals: LVP values (mmHg, mean +/- S.E.M.) in hearts from anesthetized an non-anesthetized rats were: at 0.5 mM Ca2+, 19 +/- 3 and 9 +/- 2; and at 1.0 mM, 103 +/- 12 and 76 +/- 6, respectively. At the higher Ca2+ concentrations, hearts from anesthetized animals demonstrated maximal LVP at 1.75 mM calcium (139 +/- 9 mmHg), whereas the LVP values in hearts from non-anesthetized animals continued to increase throughout all the Ca2+ concentrations employed. A similar pattern of response was observed for +dP/dt values.(ABSTRACT TRUNCATED AT 250 WORDS)
Anesthesia, General↗
Instantaneous and continuous cardiac output in humans obtained with a Doppler pulmonary artery catheter.
A new Doppler pulmonary artery catheter was used to measure instantaneous and continuous cardiac output in both an in vitro model and in 44 patients undergoing cardiac catheterization. Cardiac output was calculated with use of the Doppler catheter-determined instantaneous space-average velocity and the ultrasonically determined instantaneous vessel area. Doppler flow and thermodilution were compared with electromagnetic flow in the in vitro model and with Fick cardiac output in patients. Doppler catheter-determined flow was highly predictive of electro-magnetic flow in the pulsatile flow model (r = 0.99, slope [m] = 1.01 and SEE = 0.05) and appeared comparable to thermodilution measurements (r = 1.00, m = 1.03 and SEE = 0.02). In patients undergoing cardiac catheterization, Doppler catheter-determined cardiac output appeared to modestly underestimate Fick cardiac output (r = 0.82, m = 0.80 and SEE = 0.09; mean error +/- SEM = -0.26 +/- 0.14 liters/min). However, predictive accuracy was comparable to simultaneously obtained thermodilution measurements (r = 0.85, m = 1.07 and SEE = 0.10; mean error +/- SEM = 0.61 +/- 0.16 liters/min). This new Doppler catheter system utilizes multiple ultrasound transducers to provide angle-independent measurements of vessel diameter and instantaneous velocity within the main pulmonary artery, resulting in a more accurate assessment of Doppler-derived cardiac output. In addition, useful information concerning hemodynamic variables such as peak flow, acceleration, deceleration, stroke work and pulmonary impedance may be derived.
Adult↗
Thyroid hormone action at the level of the plasma membrane.
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Animals↗
Calcium is the first messenger for the action of thyroid hormone at the level of the plasma membrane: first evidence for an acute effect of thyroid hormone on calcium uptake in the heart.
The thyroid hormone T3 produced a very rapid and transient increase in 45calcium uptake by freshly isolated rat heart slices, which was seen already 15 sec after the addition of the hormone, reached a maximum at 30 sec, and then progressively declined and returned to control values after 10 min. This effect of T3 was independent of extracellular calcium, concentration related (evident at a physiological concentration of 10 pM, reached maximum of about 75% above control at 1 nM, and was smaller at greater concentrations), and thyroid hormone specific, as judged from the order of potency of several thyroid hormone analogs: L-T3 greater than L-T4 greater than or equal to D-T3 greater than 3'-isopropyl-3,5-L-diiodothyronine greater than D-T4 greater than 3,5-L-diiodothyronine greater than r-L-T3 greater than D,L-thyronine. The inorganic calcium channel blockers La3+, Cd2+, and Mn2+ inhibited, in a concentration-related fashion, basal and T3-induced increases in 45Ca uptake in the cardiac slices. The organic calcium channel blockers verapamil, nifedipine, and diltiazem were without effect, indicating that in the quiescent cardiac slice the effect of T3 on 45Ca uptake is independent of sarcolemmal depolarization. Additional studies demonstrated that the stimulatory effect of T3 on 2-deoxyglucose uptake by the cardiac slices required extracellular calcium and was inhibited by the calcium channel blockers La3+, Cd2+, and Mn2+. The present study provides conclusive evidence for two central issues: that calcium is the first messenger for the prompt, plasma membrane-mediated action of thyroid hormone to increase cellular sugar uptake, and that thyroid hormone produces an acute increase in calcium uptake by the heart, an effect that is demonstrable at physiological concentrations and is thyroid hormone specific and, therefore, points to a physiological relevance for this action.
Animals↗
In vivo effect of 3,5,3'-triiodothyronine on calcium uptake in several tissues in the rat: evidence for a physiological role for calcium as the first messenger for the prompt action of thyroid hormone at the level of the plasma membrane.
Calcium has been shown in vitro to serve as the first messenger for the rapid effect of thyroid hormone at the level of the plasma membrane. In the present study the physiological relevance of this mechanism is examined in the whole animal. To this end, the effect of T3 on 45calcium uptake and sugar [2-deoxyglucose (2-DG]) uptake, an effect that requires extracellular calcium, and the influence of calcium blockers thereon were measured in ventricles, atria, diaphragm, fat, and liver in the rat. In the first three tissues, T3 produced comparable changes in 45Ca uptake and 2-DG uptake (T3 increased 2-DG uptake in fat, where 45Ca uptake was undetected, and had no effect in liver); this activity was blocked by the calcium channel blocker cadmium. The effect of T3 on 45Ca uptake, like its effect on the in vivo uptake of 2-DG described previously, was biphasic and time related; at physiological doses of 0.01 and 0.1 micrograms/100 g BW, T3 increased 45Ca uptake, whereas at greater (pharmacological) doses of 1 and 100 micrograms/100 g BW, T3 was without effect or inhibited 45Ca uptake. In ventricles and atria, the stimulatory effect of T3 on 45Ca uptake was very rapid [within 2 min, at which time it was at or near maximum (50-90% above control] and then declined gradually and was not seen after 10-20 min. Of the several calcium blockers employed, verapamil (organic) and cadmium (inorganic) were found to be the most effective. Verapamil and cadmium produced a rapid, transient, and dose-related inhibition of 45Ca uptake in the tissues examined (except fat tissue where, under the experimental conditions employed, 45Ca uptake was undetected). Verapamil, given iv (200 micrograms/100 g BW) or ip (1 mg/100 g BW), reduced tissue 45Ca uptake by 50-90% within 2 or 10 min, respectively, and then its inhibitory effect diminished rapidly and was not seen after 20-30 min. Cadmium, given iv (was ineffective when given ip) produced a rapid and dose-related decrease in 45Ca uptake, being most effective (40-90% inhibition) 1-10 min after its administration. Cadmium (1 mg/100 g BW) injected into the tail vein 2 min before T3 produced a comparable inhibition of the stimulatory effect of T3 on 45Ca uptake and 2-DG uptake. Verapamil did not change the T3 effect.(ABSTRACT TRUNCATED AT 400 WORDS)
Adipose Tissue↗
3,5,3'-tri-iodothyronine enhances sugar transport in rat thymocytes by increasing the intrinsic activity of the plasma membrane sugar transporter.
We have shown that 3,5,3'-tri-iodothyronine (T3) produces a prompt increase in sugar transport in rat thymocytes by increasing the maximal velocity without changing the Michaelis-Menten constant of the plasma membrane sugar transport system. To elucidate further the mechanism of this effect, we have now assessed the influence of T3 on the number and affinity of sugar transporters in thymocytes, measured as the sugar (2-deoxyglucose; dGlc)-displaceable binding of cytochalasin B. Cytochalasin B inhibited in a dose-related manner the uptake of dGlc by rat thymocytes with inhibition constant values of 0.19 and 0.22 mumol/l in the presence and absence of T3 respectively. Binding of cytochalasin B by the sugar-displaceable sites was rapid and saturable, demonstrating a single class of sites having an apparent dissociation constant of 0.33 +/- 0.02 (S.D.) mumol/l and maximal binding capacity of 3.73 +/- 0.48 pmol/20 x 10(6) cells (11.2 +/- 1.4 x 10(4) sites/thymocyte). In the rat thymocyte, sugar transporters were found to be located in two major subcellular pools, the plasma membrane and microsomes, the latter being about twice the size of the former. In these subcellular compartments, as well as in the intact cell, binding of [3H]cytochalasin B by the sugar-displaceable sites constituted about 40% of total cytochalasin B binding. 3,5,3'-Tri-iodothyronine in concentrations that stimulated uptake of dGlc by thymocytes had no effect on [3H]cytochalasin B binding (total and sugar-displaceable) in the intact cell and in the plasma membrane and microsomal compartments, nor did it influence the affinity and number of sugar transporters.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Stimulation of calcium-ATPase activity by 3,5,3'-tri-iodothyronine in rat thymocyte plasma membranes. A possible role in the modulation of cellular calcium concentration.
We have previously demonstrated that 3,5,3'-tri-iodo-L-thyronine (T3) produces a very rapid and transient increase in calcium uptake and cytoplasmic free calcium concentration in the rat thymocyte, and have postulated that Ca2+-ATPase may contribute to the overall effect of T3 on cellular calcium metabolism. In the present study, we show that in the rat thymocyte, T3 increased plasma membrane Ca2+-ATPase activity. This effect of T3 was very rapid, seen at 30 s after the addition of the hormone, and was concentration-related, evident at a physiological concentration as low as 1 pM. Evaluation of the effect of several thyronine analogues on Ca2+-ATPase activity revealed the following order of potency: D-T3 greater than or equal to 3'-isopropyl-L-T2 = L-T3 = L-T4 = D-T4 greater than L-rT3 greater than 3,5-L-T2 greater than DL-thyronine. Studies with the calmodulin antagonist trifluoperazine demonstrated that thymocyte Ca2+-ATPase activity and its stimulation by T3 are influenced by calmodulin. Other studies showed that several adrenergic agents, agonists and antagonists, had no effect on thymocyte Ca2+-ATPase activity and its stimulation by T3. From these and previous observations, we would suggest that in the rat thymocyte, the T3-induced increase in Ca2+-ATPase activity, which enhances the expulsion of calcium from the cell, plays a role in the diminution and transiency of the stimulatory effect of T3 on thymocyte calcium metabolism.
Animals↗
Acute effect of thyroid hormone on the heart: an extranuclear increase in sugar uptake.
The thyroid hormone 3,5,3'-triiodo-L-thyronine (T3) produced a rapid increase in [3H]2-deoxyglucose (2-DG) uptake by freshly isolated rat heart slices in vitro, an effect that was evident after 1 min of pre-incubation with the hormone. This stimulatory effect of T3 was dose-related; the lowest effective concentration was 1 pM and maximal effect of about 80% above control was seen at 1 nM. Studies with several thyroid hormone analogues revealed that L-T3 was the most effective analogue which was followed in a decreasing order of potency by L-T4 = D-T3 greater than D-T4 greater than 3,5-L-T2 greater than rT3 greater than DL-thyronine. Further, the T3-induced increase in 2-DG uptake was independent of new protein synthesis because it was not blocked by the protein synthesis inhibitor cycloheximide under conditions in which [3H] leucine incorporation was inhibited by approximately 95%. Evaluation of the mechanism through which T3 exerts this action revealed that the uptake of 2-DG and 3-0-methyl-D-glucose (30MG) by heart slices was saturable, but that of L-glucose was not, and that T3 produced a similar increase in the uptake of both 2-DG and 30MG but failed to change L-glucose uptake. Saturation curve analysis of 2-DG and 30 MG uptake revealed that T3 increased Vmax values but had no effect on Km values. Moreover, T3, which promoted total 2-DG uptake rate, had no effect on the proportionate phosphorylation rate of 2-DG to 2-DG-6-phosphate by hexokinase. From this study it is concluded that thyroid hormone produces a direct and acute effect on the heart. This prompt effect of T3 to increase sugar uptake by heart slices, owing to the increase in the Vmax of the sugar transport system, is extranuclear in nature, is thyroid hormone specific, and has a physiologic relevance.
3-O-Methylglucose↗
Calmodulin modulates thymocyte adenylate cyclase activity through the guanine nucleotide regulatory unit.
We have previously demonstrated in rat thymocyte plasma membranes that adenylate cyclase activity and its stimulation by 3,5,3'-triiodothyronine (T3) are influenced by calmodulin, and that these effects of calmodulin require calcium. In the present study, the mechanism by which calmodulin exerts its action was examined, in situ, in fresh plasma membranes isolated from rat thymocytes. Adenylate cyclase activity was potentiated by guanyl nucleotides, NaF and forskolin. Calmodulin did not affect basal adenylate cyclase activity. However, calmodulin influenced the guanyl nucleotide- and forskolin-stimulated adenylate cyclase activity, but had no effect on the fluoride-stimulated enzyme activity. This was evident from experiments with inhibitors of calmodulin: trifluoperazine, calmidazolium, and antibodies against calmodulin. The three inhibitors did not change basal adenylate cyclase activity, but all produced a marked decrease in the guanyl nucleotide- and forskolin-stimulated adenylate cyclase activity. The inhibitory effect of all three agents was reversed completely by the addition of calmodulin. The three inhibitors, however, failed to affect the fluoride-stimulated adenylate cyclase activity. In addition, T3, like the calmodulin inhibitors, did not change basal adenylate cyclase activity, increased the guanyl nucleotide- and forskolin-stimulated enzyme activity, but had no effect on the fluoride-stimulated enzyme activity. From these results I suggest that in the rat thymocyte calmodulin activation, and thereby T3 stimulation of the calcium-sensitive adenylate cyclase system is mediated through the guanine nucleotide regulatory unit.
Adenylyl Cyclases↗
Instantaneous and continuous cardiac output obtained with a Doppler pulmonary artery catheter.
A newly developed, flow-directed, Doppler pulmonary artery catheter, capable of measuring instantaneous and continuous cardiac output, was evaluated in both an in vitro pump model and an animal model. Quantitative flow was calculated with use of the instantaneous, space-average velocity (obtained from the velocity profile) and the instantaneous area (obtained from the vessel diameter) and compared with electromagnetic flow. Additionally, simultaneous thermodilution flow measurements were obtained. Doppler catheter-determined flow was highly predictive of electromagnetic flow in both continuous and pulsatile pump models (r2 = 0.98, slope or m = 1.04, SEE = 0.44; and r2 = 0.97, m = 1.04 and SEE = 0.33, respectively). Thermodilution was less predictive and appeared to underestimate electromagnetic flow in both the continuous and the pulsatile model (r2 = 0.99, m = 0.91, SEE = 0.20 and r2 = 0.95, m = 0.84 and SEE = 0.34, respectively). In the animal model, Doppler catheter-determined cardiac output appeared to modestly underestimate electromagnetic flow (r2 = 0.80, m = 0.87, SEE = 0.61). However, Doppler determinations of flow remained more accurate than did simultaneous thermodilution measurements (r2 = 0.73, m = 0.79, SEE = 0.72). Accurate, continuous and instantaneous cardiac output measurements appear possible with use of a flow-directed, Doppler pulmonary artery catheter. This catheter system also provides instantaneous diameter measurements and mapping of instantaneous velocity profiles within the main pulmonary artery and may lead to more accurate Doppler-derived assessment of cardiac output in humans.
Animals↗
Evidence that an increase in cytoplasmic calcium is the initiating event in certain plasma membrane-mediated responses to 3,5,3'-triiodothyronine in rat thymocytes.
The present studies were undertaken to explore further the mechanism by which T3 increases adenylate cyclase activity and the uptake of the sugar analog 2-deoxyglucose (2-DG) in freshly isolated rat thymocytes. In studies of cells preloaded with the fluorescent probe quin-2, whose fluorescence intensity increases linearly with increases in cytoplasmic free calcium concentration [( Ca2+]i), we have now demonstrated that T3 increases [Ca2+]i in thymocytes suspended in buffer containing 1 mM Ca2+. This effect was extremely prompt, becoming evident much less than 1 min after the addition of T3 and reaching maximal values in about 5-8 min. The subsequent time course of the T3 effect was obscured by an increase in fluorescence intensity in control thymocytes not exposed to T3, beginning after about 8 min of incubation. However, the T3 effect, after reaching its peak, appeared to remain stable for about 5 min and then to decline, abating completely in 18-30 min. No effect of T3 on [Ca2+]i was observed when thymocytes were suspended in Ca2+-free medium. The effect of T3 on [Ca2+]i was concentration dependent, and as with its actions on thymocyte adenylate cyclase activity, cAMP concentration and 2-DG uptake, the lowest effective concentration of T3 was 1 nM. Among several thyronine analogs studied, L-T3 was the most potent, followed in decreasing order of potency by L-T4, D-T3, 3,5-diiodo-3'-isopropyl-L-thyronine, and D-T4. rT3, 3,5-diiodo-L-thyronine, and D,L-thyronine were without effect. l-Alprenolol alone (10 microM) produced a modest increase in thymocyte [Ca2+]i, but, as it does with the effect of T3 on cellular cAMP concentration and 2-DG uptake, it markedly inhibited or abolished the stimulatory effect of T3 on [Ca2+]i. From these observations we conclude that T3 initiates the increase in thymocyte [Ca2+]i by enhancing the influx of extracellular calcium, though the possibility that it also releases calcium from an intracellular calcium pool cannot be excluded. Since the effects of T3 on thymocyte adenylate cyclase activity, cAMP concentration, and 2-DG uptake occur subsequent to these effects on calcium metabolism and require the presence of Ca2+ in the extracellular fluid, we suggest that an increase in [Ca2+]i, due at least partly to an influx of extracellular calcium, is the initiating event in these plasma membrane-mediated responses of the rat thymocyte to T3.
Adenylyl Cyclases↗