Renal studies in the hypothyroid rat

Whole kidney clearance studies were performed on 27 hypothyroid rats (H) and 25 euthyroid littermate rats (C). Absolute glomerular filtration rate (GFR) was less in hypothyroid rats (1.02 versus 1.39 ml/min), but when factored by body surface area (BSA) the two groups were comparable ($\text{GFR}\text{BSA}\text{= 2.26 versus 2.24 μl}\text{/min/sq/cm}$). Absolute and fractional (per GFR) sodium clearance was greater in the hypothyroid animals ($\text{C}{}_{\mathrm{Na}}\text{GFR:H}\text{= 0.36, C = 0.11, p < 0.001}$), but total electrolyte (Na⁺ + K⁺) excretion and clearance were comparable. End proximal tubular fluid (TF) micropuncture collections in 20 animals revealed no change in fractional reabsorption ($\text{TF}\text{P}$ inulin) in hypothyroid rats ($\text{TF}\text{P}$ insulin, 2.5 versus 2.7), but showed a decrease in single nephron GFR (Vo, 17 versus 36 nl/min) and absolute reabsorption (11 versus 20 nl/min). Hypothyroidism is associated with a decrease of sodium reabsorption at nephron sites distal to the convoluted proximal tubule. With ad libitum electrolyte and water intake most rats can maintain themselves in volume-sodium balance, but an occasional animal may display this distal leak syndrome in the extreme. One such rat had a urinary sodium concentration U_Na of 147 mEq/liter and a urinary flow rate of 56.0 μl/min (H = 3.33, C = 1.39). In addition, its hydropenic normal end proximal $\text{TF}\text{P}$ inulin mean of 2.7 confirmed the inability of the proximal nephron to compensate for this late leak. This rat's plasma sodium was 128 mEq/liter (H = 147, C = 148), dilutional hyponatremia. These renal problems are similar to those reported in man and suggest that the rat is an appropriate model for the study of human hypothyroidism.     

Impaired 3,5,3'-triiodothyronine (T3) production in diabetic patients.

Serum concentrations of thyroxine (T₄), 3,5,3′-triiodothyronine (T₃), and 3,3′,5′-triiodothyronine (RT₃) were measured in 50 patients with diabetes mellitus. The mean concentrations of serum T₄, T₃, and RT₃ were 8.5 ± 3.7 (SD) μg/dl, 134 ± 41 ng/dl, and 30 ± 13 ng/dl, respectively, which were not significantly different from values of 33 normal control subjects. The serum $\text{T}{}_3\text{T}{}_4$ ratio showed a significant inverse correlation with the level of fasting blood sugar (FBS) (p < 0.01). Turnover studies were carried out in seven normal control subjects and in 5 insulin-independent diabetic patients on T₄ replacement. T₄ turnover was similar in both groups. The T₃ metabolic clearance rate of the diabetic patients was also normal (20.7 ± 4.0 liter/day/70 kg), but the T₃ disposal rate was reduced when compared to that of normal control subjects (17.0 ± 5.6 vs. 40.6 ± 4.8 μg/day). The RT₃ metabolic clearance rate (80.6 ± 20.2 vs. 105.0 ± 14.0 liter/day/70 kg) and the RT₃ disposal rate (29.4 ± 10.8 vs. 49.4 ± 11.6 μg/day) were both reduced in the diabetic patients. In five other diabetic patients on 3 wk of oral T₄ replacement, the serum $\text{T}{}_3\text{T}{}_4$ ratio was below the normal range (0.0059 ± 0.0041 vs. 0.0152 ± 0.0011) and remained unchanged during insulin infusion during 10 hr. The $\text{T}{}_3\text{T}{}_4$ ratio increased but remained below the normal range after 10 days of dietary and insulin treatment (0.0083 ± 0.0032; p < 0.05). Our results suggest that T₃ production from peripheral T₄ monodeiodination is impaired in uncontrolled diabetic patients. This impairment in T₃ production is correlated with the impairment of glucose utilization.     

The effect of short-term feeding of a high carbohydrate diet on HDL subclasses in normal subjects

Plasma HDL concentrations are effected by several perturbations, including certain dietary manipulations. In this study we have examined the effects of a one week ingestion of an isocaloric, fat-free, high-carbohydrate diet (CHO >80% of calories) on the concentrations and compositions of plasma HDL subclasses. Eleven healthy normolipidemic volunteers (6 females, 5 males) took part in this study. Blood samples for lipoprotein analyses were drawn before and at the end of the dietary period and analyzed for lipoprotein lipid and apoprotein concentrations. Lipoproteins also were characterized by zonal ultracentrifugation. Our results show the following significant changes at the end of the dietary period: plasma concentrations of VLDL-TG, VLDL-cholesterol and total VLDL mass increased, whereas plasma concentrations of LDL-cholesterol, LDL mass and HDL-cholesterol and HDL mass, decreased. Plasma concentrations of apoprotein A₁ decreased (from 133.3 ± 7.7 to 108.1 ± 8.6; mean ± S.E.M., p < 0.0004), and apoprotein A₂ concentrations remained unchanged. This resulted in a drop in plasma ratio of $\text{ApoA}{}_1\text{ApoA}{}_2$ (p < 0.03). Since it has been shown that $\text{ApoA}{}_1\text{ApoA}{}_2$ ratio is higher in HDL₂ than HDL₃, we examined the concentrations of these two subfractions, employing rate-zonal ultracentrifugation for their isolation. One week of ingestion of the study diet was followed by consistent decreases in HDL₂ mass (from 84 ± 15 to 44 ± 16 mg/dl, mean ± S.E.M.), with inconsistent changes in HDL₃ mass, (from 254 ± 18 to 222 ± 13 mg/dl) resulting in significant decreases in $\text{HDL}{}_2\text{HDL}{}_3$ mass ratio. Lipid analyses of these subfractions did not demonstrate major compositional changes. The alterations noted could be due to decreased HDL production, at least in part, but alterations in the interconversions of lipoproteins also could have played a role. The falls in HDL₂ on a diet which should be “antiatherogenic” illustrate the difficulty of assessing the atherogenicity of any given diet solely by the changes it produces in the levels of circulating lipoproteins.     

Triiodothyronine and thyroxine content of desiccated thyroid tablets

Triiodothyronine (T₃) and thyroxine (T₄) were measured by radioimmunoassay in Pronase hydrolysates of four lots each of 1- and 2-grain tablets of desiccated thyroid (Thyroid, Armour) and thyroglobulin (Proloid, Warner-Chilcott). The methodology used was verified by studies of tablets containing known quantities of T₄ and T₃. One grain of desiccated thyroid contained 12 ± 1 and 64 ± 3 μg (mean ± SD) of T₃ and T₄ per tablet, respectively ($\text{T}{}_4\text{T}{}_3$ molar ratio, 4.3). A 1-grain tablet of thyroglobulin contained 16 ± 2 and 55 ± 5 μg of T₃ and T₄, respectively with a $\text{T}{}_4\text{T}{}_3$ ratio of 2.9. Two-grain tablets generally contained twice the quantity of T₃ and T₄ in the 1-grain preparations. The variation in T₃ and T₄ content between the four lots of each tablet strength for each product was 10% or less. These estimates of T₃ and T₄ content are 1.5- to 2-fold greater than those previously published. This difference probably results from the more sophisticated methodology now available which does not require chromatographic separation of T₃ and T₄ or iodometry. Using calculations based on published estimates of T₄ and T₃ absorption and of the $\text{T}{}_3\text{T}{}_4$ potency ratio, it would appear that the T₃ content of desiccated thyroid and thyroglobulin provide approximately 39% and 51%, respectively, of the thyromimetic activity of these two medications.     

Hepatic lymph flow and protein concentration during intravenous saline infusion and intestinal fluid absorption

A simple procedure for the collection of the postnodal and prenodal hepatic lymph in the rats under pentobarbital anesthesia is described. Lymph flow (J_L) from the main hepatic lymph duct (postnodal), protein concentration in both the lymph (C_L) and plasma (C_P), and the $\text{C}{}_{\mathrm{<mtext>L</mtext>}}\text{C}{}_{\mathrm{<mtext>P</mtext>}}$ ratio were 0.22 ± 0.1 ml/kg of body weight · hr (0.66 ± 0.3 ml/100 g wet liver wt · hr), 4.3 ± 0.5 and 6.2 ± 0.3 g%, and 0.69 ± 0.1 (mean ± SE), respectively. There was no significant difference in C_L between prenodal and postnodal lymph in the fasted or unfasted rats. During intestinal fluid absorption with an increase in intestinal J_L, postnodal hepatic J_L or C_L did not change. During intravenous saline infusion with lowering of plasma oncotic pressure, there was a small increase in prenodal J_L (by ～160%) with some decrease (by 16%) in $\text{C}{}_{\mathrm{<mtext>L</mtext>}}\text{C}{}_{\mathrm{<mtext>P</mtext>}}$ ratio but a much larger increase in postnodal J_L (by ～700%) with a significant decrease (by 55%) in $\text{C}{}_{\mathrm{<mtext>L</mtext>}}\text{C}{}_{\mathrm{<mtext>P</mtext>}}$ ratio. The results demonstrate that both flow and protein concentration of the postnodal lymph differ greatly from that of the prenodal lymph due to modification during transit through the lymph node. The small increase of the prenodal J_L with negligible change in $\text{C}{}_{\mathrm{<mtext>L</mtext>}}\text{C}{}_{\mathrm{<mtext>P</mtext>}}$ ratio during saline infusion suggests that oncotic pressure grandient plays a minor or insignificant role in the transsinusoidal fluid transport in the liver.     

Effect of fluocarbon exchange transfusion on myocardial infarction size in dogs

Fluosol DA (20% ), a perfluocarbon with high oxygen solubility, was administered by concurrent exchange transfusion (30 ml/kg) to anesthetized open-chested adult greyhounds (n = 9) 1 hour after left anterior descending coronary ligation. Mechanical ventilation using 100% oxygen was used throughout the experiment. A second similar group (n = 9) received 0.9% normal saline solution (30 ml/kg), and a third group (n = 9) received no further intervention. Systemic, right atrial, and left atrial pressures were not altered by the exchange transfusion. Monastryl blue dye was injected through the left atrial line at 6 hours after ligation to define the area of myocardium at risk (A_R); the animals were then killed and the heart was excised. The left ventricle was sliced at 5 mm intervals and stained using triphenyltetrazolium chloride, defining areas of necrosis (a_n). The ratio of $\text{A}{}_{\mathrm{N}}\text{A}{}_{\mathrm{R}}$ and total left ventricular mass were then compared with the use of planimetry.The results were as follows: the $\text{A}{}_{\mathrm{N}}\text{A}{}_{\mathrm{R}}$ ratio in the 9 control animals was 90 ± 2 (mean ± standard error of the mean); in the 9 animals who received saline solution it was 88 ± 2; and in the animals who received Fluosol it was 67 ± 4 (p < 0.01 compared with control; p < 0.001 compared with the saline group).Fluocarbon exchange transfusion may reduce infarct size when administered after coronary occlusion.     

Dog lymph flow in increased capillary permeability states

The lung lymph flow rate ($\text{Q}\text{?}{}_{\mathrm{<mtext>L</mtext>}}$) is increased in edema caused by an increase in lung microvascular permeability. This increase in $\text{Q}\text{?}{}_{\mathrm{<mtext>L</mtext>}}$ could be caused by either a decrease in the effective resistance of the lymph vessels (R_L), or by an increase in the effective lymph driving pressure (P_L), or by a change in both R_L and P_L. We estimated P_L and R_L from the linear relationship between $\text{Q}\text{?}{}_{\mathrm{<mtext>L</mtext>}}$ and the pressure at the outflow end (P_O) of five cannulated dog lung lymph vessels ($\text{R}{}_{\mathrm{<mtext>L</mtext>}}\text{=}\text{?ΔP}{}_{\mathrm{<mtext>O</mtext>}}\text{Δ}\text{Q}\text{?}{}_{\mathrm{<mtext>L</mtext>}}$ and P_L = the P_O at which $\text{Q}\text{?}{}_{\mathrm{<mtext>L</mtext>}}\text{= 0}$). We increased lung microvascular permeability by giving the dogs 100 mg/kg of alloxan and found that $\text{Q}\text{?}{}_{\mathrm{<mtext>L</mtext>}}$ increased from 24.5 ± 8.9 μl/min to 112 ± 41 μl/min (mean ± SD). R_L decreased from 0.35 ± 0.12 to 0.11 ± 0.04 cm H₂O min/μl and P_L increased from 8.5 ± 1.5 to 15.9 ± 2.7 cm H₂O. We then increased the capillary pressures from 18.3 ± 3.8 to 41.3 ± 7.3 cm H₂O and $\text{Q}\text{?}{}_{\mathrm{<mtext>L</mtext>}}$ increased to 169.9 ± 47.8 μl/min. P_L increased by an additional 6.3 cm H₂O but R_L decreased by only an additional 0.02 cm H₂O min/μl. These results show that the $\text{Q}\text{?}{}_{\mathrm{<mtext>L</mtext>}}$ vs P_O relationship is changed in edema secondary to an increase in microvascular permeability, and that this change can be represented as changes in R_L and P_L. In terms of these parameters, $\text{Q}\text{?}{}_{\mathrm{<mtext>L</mtext>}}$ increased in edema as a result of a decrease in R_L and an increase in P_L.     

Management of adults with congenital bidirectional cardiac shunts,cyanosis, and pulmonary vascular obstruction: Successful operative repair in 3 patients

Patients with congenital cardiac shunts in whom marked functional disability, cyanosis and pulmonary arterial hypertension develop have been considered inoperable or at exceedingly high risk. Three adult patients, 2 with atrial septal defect (ASD) and 1 with patent ductus arteriosus (PDA), presented with New York Heart Association class IV symptoms, bidirectional shunting with cyanosis, polycythemia, severe pulmonary hypertension, and increased pulmonary vascular resistance. Pulmonary arterial pressure did not decrease in response to administration of 100% oxygen in any patient, and 2 had lung biopsy results showing advanced pulmonary vascular obstruction. While a right-to-left shunt caused cyanosis in all patients, the net shunt was left to right ($\text{Q}{}_{\mathrm{p}}\text{Q}{}_{\mathrm{s}}\text{> 1}$) and the resistance ratio $\text{(}\text{R}{}_{\mathrm{p}}\text{R}{}_{\mathrm{s}}\text{) <0.5}$. All 3 patients survived operation, became acyanotic with normal hematocrit, and are in functional class I or II a mean of 36 months post-operatively. At repeat cardiac catheterization, pulmonary arterial pressure and resistance had decreased substantially.This high-risk group of patients with bidirectional shunts, in whom cyanosis due to pulmonary vascular obstruction and polycythemia develop and who appear to be at very high operative risk, should still be considered for surgical correction if the usual criteria for operability exist: net left-to-right $\text{Q}{}_{\mathrm{p}}\text{Q}{}_{\mathrm{s}}$ and $\text{R}{}_{\mathrm{p}}\text{R}{}_{\mathrm{s}}\text{<0.50}$.     

Immunoassay for avian pancreatic polypeptide and applications in chickens

A specific radioimmunoassay for avian pancreatic polypeptide (APP) is described. At an antiserum dilution of 1:50,000 the assay is usable over a range of 0.02 to 1.25 ng APP per tube. At the lowest level of standard, cumulative within-assay variance at the 95% confidence level was ±6.58% and at the highest level was ±16.68%. Cumulative between-assay variance ±2.7 to ±5.0% over the same range. Fifty percent displacement of ¹²⁵I-APP occurred at 0.45 ng APP per tube. Recovery of APP added to chicken plasma was ±5.0% except at levels near 20 ng/ml where estimates of APP content were 10–15% high. Dilution curves paralleled the standard curves except at high APP content. The immunoassay detected APP in acid alcohol extracts of chicken pancreas and duodenum. No APP could be detected in other organs. The disappearance from plasma of APP injected intravenously into chickens could be fitted to a two-compartment model with $\text{T}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$ values of 2.45 and 8.28 min, respectively.     

The effect of oscillatory flow on the release reaction and aggregation of human platelets

The effect of variable shear rate on the thrombin-induced release of [¹⁴C]serotonin from human platelets was investigated by subjecting washed suspensions containing 5 × 10⁵ cells/μl to laminar oscillatory flow at 37°C in 1-meter lengths of 1.57-mm polyethylene tubing. The suspensions were prepared at 37°C in Tyrodes-albumin containing apyrase to avoid desensitization of the platelets by released ADP. After flow, the sheared sample and a control, incubated at rest at 37°C, were stirred with thrombin at concentrations of 0.04 units/ml (threshold at which aggregation just occurred) and 0.02 units/ml, and the ¹⁴C-activity in the supernatant measured after centrifugation.At time-averaged wall shear rates $\text{G}\text{(R}{}_0\text{) = 2350}\text{sec}{}^{\mathrm{?1}}$ and 20 min shear, there was no significant release of [¹⁴C]serotonin due to flow alone. However, in 53 experimental runs the mean release at 0.02 and 0.04 units/ml exceeded that in the paired controls by 6.1%(±1.4%, SE) and 10.1%(±1.3%) of the total activity in the suspension. The increase in serotonin release was not significant at $\text{G}\text{(R}{}_0\text{) < 1300}\text{sec}{}^{\mathrm{?1}}$.The synergistic effects of flow were also noted when [Ca²⁺] was increased from 4 to 12 mEq, and in the presence of ASA (1 mg/ml), release being less inhibited in the sheared samples. When adrenaline (2.5 μM) was added, the serotonin release, which increased by 26.4%(±3.8%) in 17 controls at the lower thrombin level, was further enhanced by 10.9%(±2.6%) in the paired sheared samples. However, when adrenaline was added after oscillatory flow, the reverse occurred, the sheared samples releasing 8.5% less than the controls.Studies in the aggregometer showed that the rate and extent of aggregation in the sheared samples was a little lower than that in the controls.     

QTQS2 ratio as an index of autonomic tone changes

The effects of changes in sympathetic tone on $\text{QT}\text{QS}{}_2$ ratio were studied in 10 healthy subjects aged 21 to 24 years. The subjects underwent a bicycle ergometer exercise, a tilt test, a decrease in carotid transmural pressure induced by means of pneumatic neck chamber, an i.v. injection of phenylephrine. A phonocardiogram and ECG were simultaneously recorded at a paper speed of 100 mm/s to evaluate QT and QS₂ intervals in each test. In basal conditions, the $\text{QT}\text{QS}{}_2$ ratio was less than 1, whereas it increased progressively during the physical exercise and became greater than 1 at peak exercise. Both the upright position and the increase in neck-tissue pressure induced a significant increase in the $\text{QT}\text{QS}{}_2$ ratio as compared with the basal values, whereas i.v. administration of phenylephrine reduced significantly the $\text{QT}\text{QS}{}_2$ ratio. These results demonstrate that those stimuli which induce a rise in adrenergic activity may increase the $\text{QT}\text{QS}{}_2$ ratio. In contrast, the reflex inhibition of the adrenergic activity induced by phenylephrine is accompanied by a reduction in $\text{QT}\text{QS}{}_2$ ratio. Therefore, the $\text{QT}\text{QS}{}_2$ ratio might represent a reliable index of sympathetic cardiac tone.     

Synthesis of glucose in human thrombocytes

Net synthesis of carbohydrates could be demonstrated at a rate of $\text{12 μ}\text{mole/hr}\text{10}{}^{11}$ cells by incubating human thrombocytes in a buffered solution in the presence of 20 mM pyruvate and 2.5 mM ATP. Moreover, incorporation of isotopic carbon from pyruvate-2-¹⁴C into carbohydrates was measured to occur at a rate of $\text{0.7 μ}\text{mole/hr}\text{10}{}^{11}$ cells in the absence of added ATP and of $\text{2.2 μ}\text{mole/hr}\text{10}{}^{11}$ cells in the presence of 7.5 mM ATP. The addition of 20 mM pyruvate and of increasing amounts of ATP (up to 7.5 mM) were shown to have a sparing effect on carbohydrate utilization. On the other hand, increasing the cell concentration from 3.3 × 10⁸ to 16.5 × 10⁸ cells/ml in the incubation medium resulted in an increase of glucose uptake from the medium. It is concluded that thrombocytes are capable of synthesizing carbohydrates from pyruvate.     

Rest and exercise hemodynamics in children before and after aortic valvotomy

The rest and exercise hemodynamics in children with congenital valvar aortic stenosis were studied before and after aortic valvotomy. Eighteen patients were studied at rest; ten of the 18 patients were also studied during supine leg exercise using a bicycle ergometer.Aortic valvotomy resulted in a significant reduction in the mean left ventricular-aortic pressure gradient and in peak left ventricular systolic pressure with an increase in aortic valve area in most patients. There was an associated increase in the subendocardial blood flow assessed indirectly by the $\text{DPTI ×}\text{O}{}_2{}^{\mathrm{c}}\text{SPTI}$ ratio. There was a minor increase in the degree of aortic insufficiency in most patients.Although, in general, there was significant hemodynamic improvement, three of the 18 patients still had significant residual stenosis after surgery and another four patients had a major increase in aortic insufficiency. The three patients with residual obstruction and one of the four patients with moderate to severe aortic insufficiency still had a $\text{DPTI ×}\text{O}{}_2{}^{\mathrm{c}}\text{SPTI}$ ratio of less than 10, suggesting possible residual subendocardial ischemia. Also, the increased left ventricular end-diastolic pressures (LVEDP) present in nearly 50% of the patients before surgery did not change significantly after surgery. Three patients showed an actual increase in LVEDP after surgery.Before surgery, the left ventricular systolic pressure and mean gradient increased on exercise, but this increase was proportionately less than the increase in cardiac output, so that calculated aortic valve area increased on exercise. The $\text{DPTI ×}\text{O}{}_2{}^{\mathrm{c}}\text{SPTI}$ ratio decreased significantly on exercise, suggesting an increase in myocardial ischemia. Successful surgery resulted in a reduction in left ventricular systolic pressure and mean left ventricular-aortic gradient on exercise, and in improvement in the subendocardial blood flow as assessed by the $\text{DPTI ×}\text{O}{}_2{}^{\mathrm{c}}\text{SPTI}$ ratio.In general, children with severe aortic stenosis have relatively normal cardiac function on exercise. Some children did show a reduction of stroke index on exercise in spite of rising LVEDP. However, stroke work index increased in all of our children. Adult studies have shown many patients with decrease in stroke work index relative to LVEDP on exercise.The results of pre- and postoperative rest and exercise hemodynamics may be useful in evaluating results of surgery; the postoperative hemodynamic evaluation including the use of $\text{DPTI ×}\text{O}{}_2{}^{\mathrm{c}}\text{SPTI}$ ratio provides additional useful information which can be used in making decisions concerning exercise activity after surgery.     

Progressive transmural electrographic,myocardial potassium ion/sodium ion ratio and ultrastructural changes as a function of time after acute coronary occlusion

The progressive transmural electrographic, biochemical and ultrastructural changes as a function of time after acute coronary occlusion were systematically assessed in eight dogs. Transmural plunge electrodes with poles 1 mm apart were placed in the ischemic and nonischemic zones, and coronary occlusion was maintained for 4 hours. Transmural full thickness biopsy specimens were obtained from each zone for electron microscopy before, and 1 and 4 hours after occlusion. Endocardial and epicardial layers were also obtained for assessment of myocardial potassium ion (K⁺) and sodium ion (Na⁺) concentrations. Before coronary occlusion, local Q waves were recorded an average depth of 1.0 ± 0.34 mm from the endocardial surface. After 1 hour of occlusion, Q waves appeared at an average depth of 3.8 ± 0.67 mm and progressed to a depth of 5.2 ± 0.7 mm at 2 hours, 6.2 ± 0.5 mm at 3 hours and 7.0 ± 0.5 mm at 4 hours. After 1 hour, ultrastructural changes of early ischemia, including a decrease in glycogen and mild mitochondrial swelling, were seen in the endocardial layer; the epicardial layer showed normal morphologic features. After 4 hours, the endocardial layer showed well developed ischemic changes marked by the loss of mitochondrial cristae, vacuolization, the appearance of amorphous mitochondrial densities, an increase in interfibrillary space and the appearance of I bands. In contrast, the epicardial layer at this time showed only early ischemic changes. At the end of 4 hours, the endocardial layer showed a marked decrease in myocardial K⁺ concentration and an increase in Na⁺ concentration leading to complete reversal of the $\text{K}{}^{\mathrm{+}}\text{Na}{}^{\mathrm{+}}$ ratio (0.7 ± 1.0; P < 0.001). In the epicardial layer, a smaller decrease in K⁺ concentration and an increase in Na⁺ concentration occurred, resulting in a diminution but not a reversal of the $\text{K}{}^{\mathrm{+}}\text{Na}{}^{\mathrm{+}}$ ratio (1.4 ± 0.2; P < 0.005).Thus, the dynamic evolution of an acute myocardal infarction involves a sequential progression from endocardium to epicardium as a function of time, resulting in an epicardial “border zone” in the early stages after acute coronary occlusion.     

Hormonal regulation of iodine accumulation in ovary and thyroid of Japanese quail

Clearance of radioiodide by thyroid and ovary was studied in female Japanese quail which had been injected with thyrotropin (TSH) or one of several gonadotropins. TSH stimulated effective clearance ($\text{C}{}_{\mathrm{<mtext>e</mtext>}}\text{m}$) of radioiodide by the thyroid by factors of 7 and 12; TSH injection increased $\text{C}{}_{\mathrm{<mtext>e</mtext>}}\text{m}$ by the ovary to a limited extent, possibly due to contamination with gonadotropin. Follicle-stimulating hormone produced the most marked increase in $\text{C}{}_{\mathrm{<mtext>e</mtext>}}\text{m}$ by the smallest sized developing oocytes and total ovary. Prolactin was the only other gonadotropin to exhibit any effect on $\text{C}{}_{\mathrm{<mtext>e</mtext>}}\text{m}$ of radioiodide by the ovary.     

Margination of leukocytes in blood flow through small tubes

Leukocyte margination in the vessels of the microcirculation has been attributed to a flow-dependent interaction with red cells. To determine the extent of this effect, experiments with human blood were done in 100- to 180-μm tubes to detect changes in cell distribution as a function of hematocrit and flow rate. Using a flow visualization technique, the leukocyte concentration distribution was determined in 45% ghost cell suspensions. Migration of cells toward the wall was observed at centerline velocities > 1 mm sec^?1 and increased with increasing flow rate. The effect was probably due to a more rapid inward migration of ghosts than leukocytes because of fluid inertia and cell density differences. Experiments were therefore carried out in whole blood at hematocrits from 20 to 60%, measuring the number concentration of leukocytes and erythrocytes within the tube, n_t, and comparing it to that in the infusing reservoir, n₀, (Fahraeus effect). At mean tube shear rates $\text{G}\text{< 100}\text{sec}{}^{\mathrm{?1}}\text{,}\text{n}{}_{\mathrm{<mtext>t</mtext>}}\text{n}{}_0\text{< 1}$ for both leukocytes and erythrocytes showing net migration of cells away from the wall, although at nearly all hematocrits there was an enrichment of leukocytes relative to erythrocytes in the tubes. At $\text{G}\text{< 50}\text{sec}{}^{\mathrm{?1}}\text{,}\text{n}{}_{\mathrm{<mtext>t</mtext>}}\text{n}{}_0$ remained < 1 for erythrocytes but increased to > 1 for leukocytes showing migration toward the wall, the increase being greatest at 20% hematocrit in the 100-μm tubes. The nature of the effect was revealed by cine films which showed that, as the flow rate decreased, erythrocytes formed rouleaux which migrated inward creating a core and displacing leukocytes to the periphery. In control experiments using washed blood cells in phosphate buffer-albumin, $\text{n}{}_{\mathrm{<mtext>t</mtext>}}\text{n}{}_0\text{< 1}$ for both leukocytes and erythrocytes at all $\text{G}$ and hematocrits, and leukocytes were now depleted relative to erythrocytes in the tubes, i.e., the leukocytes were more axially distributed. Cine films of washed blood confirmed that, in the absence of rouleaux, no significant inward migration of erythrocytes occurred.     

Accumulation of radioiodine in thyroids of chicks of the obese strain with hereditary thyroiditis and of their parental strain

The Obese strain of chicks exhibits hereditary thyroiditis (at about 2 weeks of age) which is followed by a syndrome of severe hypothyroidism.K_b (min^?1), the fraction of thyroidal radioiodide which was protein bound per minute for initially short intervals (up to 30 min) after injection of ¹³¹I in the parental control strain, was 0.32 up to 4 days after hatching but rose thereafter and varied from 0.90 to 1.47 from 1 to 6 weeks of age. In the Obese chicks K_b was 0.06–0.14 up to 4 days after hatching and rose to about 1.0 at 1 week of age. Beginning at 3 weeks of age those Obese chicks which exhibited a more severe degree of thyroiditis (lymphocytic infiltration) had K_b values which continued to decrease from 0.025 to ～0 at 6 weeks of age. Obese chicks with less severe thyroiditis at this time had K_b values which rose from 2.2 at 2 weeks of age to 3.0 at 3–4 weeks, then decreased to 1.12 at 6 weeks of age.Values for $\text{C}{}_{\mathrm{<mtext>e</mtext>}}\text{m}$, effective clearance of radioiodide by the thyroid from the serum, in the parental strain rose from 2.05 at 2 days after hatching to 4.4 at 1 week, held at about 5.0 from 2–4 weeks then dropped to 2.2–2.9 until 6 weeks. $\text{C}{}_{\mathrm{<mtext>e</mtext>}}\text{m}$ in the Obese birds was 0.09–0.48 until 4 days of age, then rose to 1.7–2.1 at 1 week. Obese chicks with severe thyroiditis showed values of $\text{C}{}_{\mathrm{<mtext>e</mtext>}}\text{m}$ of 0.015 at 3 weeks which further decreased to about 0 at 6 weeks. Obese birds with less severe thyroiditis showed $\text{C}{}_{\mathrm{<mtext>e</mtext>}}\text{m}$ of 3.3 to 6.8 between 3 and 6 weeks of age.Changes in K_b and $\text{C}{}_{\mathrm{<mtext>e</mtext>}}\text{m}$ were temporally correlated inversely with severity of lymphocytic infiltration of the thyroid.     

Cell population kinetics in tadpole limb epidermis during thyroxine-induced,spontaneous, and prolactin-inhibited metamorphosis

Immersion of Rana pipiens tadpoles in 30 μg/liter thyroxine for 1 to 4 days revealed a sequence of changes in basal epidermal cell labeling index and growth fraction different at Stages III to IV than at Stages IX to XI. Little stage specificity was shown, however, in thyroxine-induced changes in cell cycle parameters, which included fluctuations in the duration of the S phase and increase in the length of $\text{G}{}_1\text{+}\text{1}\text{2}\text{M}$. Similar cell cycle changes occurred in spontaneous metamorphic climax. Prolactin treatment of Stages V to VI tadpoles (10 μg/day for 15 days) showed that prolactin, like thyroxine, affects cell proliferation in the limb epidermis primarily by controlling the size of the proliferative pool. Prolactin-thyroxine antagonism was indicated when $\text{G}{}_2\text{+}\text{1}\text{2}\text{M}$ lengthened after prolactin treatment whereas this phase shortened in some instances when thyroxine was administered.     

Calcium ion effects on the rising phases of action potentials obtained from guinea-pig papillary muscles at different potassium concentrations

In guinea-pig papillary muscles, action potentials, rates of rise ($\text{v}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$ and conduction velocities were measured at various potassium concentrations. An increase in potassium reduced $\text{v}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$ in an S-shaped relation to the membrane potential but conduction velocity was influenced differently. At 18 to 20 mm K₀⁺, the rising phase often included a remainder of the fast depolarization and $\text{v}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$ showed two peaks; the first peak could be abolished by TTX (10^?6m), the second peak by D600 (1 μg/ml, 1 Hz). The $\text{v}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$ (second peak) of the rising phase of the slow responses as well as overshoot and amplitude was clearly correlated (r = 0.99) to the log of Ca₀²⁺. The increase in Ca₀²⁺ concentration caused an elevation of both overshoot and amplitude of 34.22 mV per decade. In contrast, the $\text{v}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$ of the first peak was correlated to the linear Ca₀²⁺ concentration. At K₀⁺ 20 mm increase of Ca₀²⁺ led to a marked increase of the first and Na⁺-dependent peak of $\text{v}\text{?}$. This $\text{v}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$ was increased 4.23 times by a Ca₀²⁺ increase from 2.5 to 10 mm. Accordingly, impaired conduction due to 20 mm K₀⁺ was almost normalized by 10 mm Ca₀²⁺. A Ca₀²⁺-increase (2.5 to 10 mm) shifted the curve of Na⁺-inactivation by 4.26 mV in the depolarization direction and reduced $\text{v}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$ at normal membrane potential. The results confirm the dependence of the rising phase and the overshoot of slow responses to the log Ca₀²⁺ but indicate strong and simultaneous Ca₀²⁺-effects on recovery of the Na⁺-system which may add to or even dominate the overall changes in $\text{v}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$ of slow responses.     

Platelet aggregation in Poiseuille flow: II. Effect of shear rate

Using a double infusion technique described in the previous paper, the effect of shear rate, G, on platelet aggregation was studied in citrated platelet-rich plasma in Poiseuille flow over a range of mean linear flow rates, $\text{u}{}_3$ from 50 to 1500 μm sec^?1 corresponding to $\text{G}$ from 2 to 54 sec^?1. At 1 μm ADP, aggregates were formed at all $\text{u}{}_3$ and, except at the lowest flow rate, both the degree of aggregation (net fraction of cells in aggregates, A′) and size of the aggregates increased with distance down the tube. The degree of aggregation was both time and shear rate-dependent. Over the first 10 sec, A′ appeared to be independent of the mean transit time indicating that the collision capture efficiency decreased with increasing G. Thereafter, A′ increased with increasing shear rate leading to the formation of an appreciable number of aggregates >10 cells at $\text{G}\text{> 24}\text{sec}{}^{\mathrm{?1}}$. Small aggregates initially formed near the tube wall and, as they grew in size, migrated toward the axis as their rotation was physically impeded by the wall. In addition, the values of A′ in cPRP from five female donors were significantly greater than those from five male donors.