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Biomedical subjects

Y C Lin

Publications and source records attributed to Y C Lin.

At least 307 records · Page 17Linked to original sources

Isoproterenol infusion promotes nitrogen washout in rats under normobaric conditions.

Cardiac output and the rate of N2 elimination were measured simultaneously in unanesthetized rats during isobaric desaturation with 100% O2. Whole-body N2-washout curves for the rat are characterized by three compartment half times derived by exponential stripping, representing the slow, intermediate, and fast components of the system. During saline infusion (control) the respective half times for these compartments were 120, 15, and 2 min. Isoproterenol infusion increased cardiac output by 40% and the volume of N2 eliminated by 10% over a 2-h washout. More importantly, the half time of the slowest compartment decreased from 120 to 70 min. The intermediate compartment half time shortened from 15 to 13 min, while the fast compartment was unaffected. The decrease in slow compartment half time will contribute significantly to the shortening of the duration of stay during decompression. A plot of slow compartment rate constants vs. measured cardiac output (range 280-690 ml X min-1 X kg-1) demonstrated a linear relationship between perfusion and the tissue-blood gas exchange rate. The results indicate that enhanced cardiac output and generalized vasodilation shorten the time required to desaturate the slower body tissues. Various maneuvers or drugs that demonstrate similar cardiovascular responses should be beneficial during prolonged decompression procedures involved in saturation diving.

Animals↗

Disposition of N-vinyl-2-pyrrolidinone in the rat.

The disposition of N-[14C-vinyl]-2-pyrrolidinone was studied in male Sprague-Dawley rats following a single iv injection. Plasma levels of the intact compound dropped rapidly within the first 6 hours after dosing with a half life of 1.90 hours. Urinary excretion by 12 hours represented 74.9% of a 5 microCi dose while 18.7% was excreted into the bile by 6 hours. 14C-activity attributed to the intact compound was found to be less than 0.59% of the dose in the urine and less than 0.46% in the bile. Tissue distribution studies showed that the liver and small intestines and contents contained the highest accumulation of 14C-activity up to 6 hours after administration of N-[14C-vinyl]-2-pyrrolidinone. Urine analyses performed for metabolite elucidation indicated that 12% of the radioactivity dosed was incorporated into acetate and the major remaining portion in species which appeared to be water soluble acidic compounds.

Animals↗

Circulatory functions during immersion and breath-hold dives in humans.

An unusual circulatory state exists in humans immersed in water at or near 35 degrees C. This circulatory state is characterized by a persistent and elevated stroke index (SI) but heart rate (HR) changes little; hence an increased cardiac index (CI) results. In comparison of measurements in air and immersion in water up to the neck level that are based on the weighted averages of 45 subjects from 8 studies, SI increased by 29%, CI increased by 24%, and HR decreased by 6%. Evidence is presented to support the finding that the increase in stroke volume is a result of enhanced preload of the heart, and that alterations in afterload and contractility play an unimportant role in affecting cardiac performance during immersion in thermoneutral water up to the level of the neck. The circulatory state represents hyperperfusion, since there is no concurrent rise in metabolic demand or heat stress. To what extent this preexisting circulatory state affects the cardiovascular responses to breath-hold (BH) diving is in most part unknown. However, the BH bradycardiac responses are more potent in a natural setting than in the laboratory where the breath hold is performed with only face immersion in water. In contrast, in the natural setting, the divers perform BH dives while they are immersed up to the neck in cold water (much lower than 35 degrees C) and are exercising. It is desirable in future studies to compare systematically other aspects of circulatory responses to BH dives while immersed in water and while exercising.

Biomechanical Phenomena↗

Sertoli cells of the golden-mantled ground squirrel (Spermophilus lateralis): a model system for the study of shape change.

Sertoli cells of the ground squirrel (Spermophilus lateralis), a seasonal breeder, were examined by light and electron microscopy and their structure, particularly the organization of the cytoskeleton, was related to events that occur in the seminiferous epithelium during spermatogenesis. Among the events considered and described are the apical movement of elongate spermatids, withdrawal of residual cytoplasm from germ cells, transport of smooth endoplasmic reticulum (SER) between the base and apex of the Sertoli cells, and sperm release. These events are dramatically evident in this species because the seminiferous epithelium is thin, i.e., there are few germ cells, and both the germ cells and Sertoli cells are large. Sertoli cells of the ground squirrel have a remarkably well developed cytoskeleton. Microfilaments occur throughout the cell but are most evident in ectoplasmic specializations associated with junctions. Intermediate filaments occur around the nucleus, as a layer at the base of the cell, and adjacent to desmosome-like junctions with germ cells. Intermediate filaments, together with microtubules, are also abundant in regions of the cell involved with the transport of SER, in cytoplasm associated with elongate spermatids, and in processes that extend into the residual cytoplasm of germ cells. Our observations of ultrastructure are consistent with the hypothesis that Sertoli cell microtubules are involved with the movement of germ cells within the seminiferous epithelium, and further implicate these structures as possibly playing a role in the retraction of residual cytoplasm from germ cells and the intracellular transport of SER. The abundance and organization of intermediate filaments suggest that these cytoskeletal elements may also be involved with events that occur during spermatogenesis.

Animals↗

Cardiovascular functions during voluntary apnea in dogs.

We studied cardiovascular responses to apnea during voluntary snout immersion in conscious, chronically instrumented dogs. Voluntary snout immersion up to eye level for a duration of greater than 15 s ensured that the dog was engaged in active apnea. In a control apnea of 15-35 s, heart rate decreased by 43% from a control value of 104 beats/min. Changes in cardiac output paralleled those of heart rate. Mean aortic blood pressure did not vary during apnea, which, coupled with a reduced cardiac output, indicated a 65% increase in estimated total peripheral resistance compared with preapnea values. Treatment with atropine sulfate (0.2 mg/kg) eliminated the bradycardia response, but the peripheral vasoconstriction persisted. Treatment with propranolol (0.5 mg/kg) eliminated postapnea hypertension. Changes in myocardial contractility during apnea were observed by measuring hemodynamic parameters while maintaining a constant heart rate with cardiac pacing. Myocardial contractility was decreased during apnea as indicated by decreases in stroke volume (-13%), stroke work (-22%), cardiac output (-13%), left ventricular (dP/dt)max (-11%), and cardiac power (-24%). These changes were prevented by atropine treatment, indicating the depressed contractility was a result of vagus nerve activity. The circulatory adjustments in the dog during apnea are potential mechanisms for oxygen conservation, although the effectiveness is uncertain for the animal as a whole. It is clear that by appropriate reduction in cardiac power output, the heart itself plays an active role in conservation of limited oxygen during apnea.

Animals↗

Effects of hypercapnia, hypoxia, and rebreathing on heart rate response during apnea.

Five series of breath-hold (BH) experiments were conducted on eight male subjects with the purpose of partitioning the effects of apnea per se, hypercapnia, and hypoxia on the development and maintenance of BH bradycardia. All BH were 90 s in duration and were achieved by face immersion at room temperature. Of the five series of BH, one was a continuous BH and the remaining included rebreathing at 15-s intervals while the face remained immersed. Comparison of heart rate (HR) responses between the continuous BH with air and that interrupted every 15 s by rebreathing without improving the alveolar gas composition yields the attenuating effect of respiratory activity. The hypercapnic effect was calculated from the difference in HR responses between two series of BH with O2, in which hypoxia was not present and rebreathing was common to both; in one rebreathing was through a CO2 scrubber thus creating different alveolar CO2 levels in the two series. The effect of hypoxia was deduced by finding the difference between the total bradycardial response (continuous BH) and the summed effects of hypercapnia and apnea per se. By this procedure, it was found that apnea and hypoxia reduced the HR by 19 and 18%, respectively, from the pre-BH value, and hypercapnia increased HR by 6% from the pre-BH level, thus accounting for the total 31% reduction in HR in a continuous BH.

Adult↗

Effects of hypercapnia, hypoxia, and rebreathing on circulatory response to apnea.

Cardiovascular responses to cessation of respiration and to progressive hypoxia and hypercapnia were investigated noninvasively in eight male volunteers. A total of five 90-s breath holds (BH) with face immersion were performed by each subject. A continuous BH (BH-1) eliminated the circulatory effects of respiratory movements, BH with air (BH-3) or with O2 (BH-5) with rebreathing at 15-s intervals through a CO2 scrubber reduced the effect of hypercapnia, and BH with air (BH-2) or with O2 (BH-4) with rebreathing at 15-s intervals bypassing the CO2 scrubber produced hypercapnia with or without concomitant hypoxia. Mean arterial blood pressure rose continuously in BH-1 and BH-2 and to a much lesser degree in other BHs. Vasoconstriction was evident within 30 s of BH. Determined by impedance cardiograph, stroke volume (SV) rose by 33%, which was balanced out by a 30% reduction in heart rate (HR) from the pre-BH values, at the end of a continuous BH. A transient depression of cardiac output (CO) was observed at 30 and 60 s of BH-1. CO values were maintained at pre-BH levels throughout the BHs where progressive hypercapnia occurred (BH-2 and BH-4) but were depressed to a similar degree as BH-1 when hypercapnia was prevented (BH-3 and BH-5). Alveolar CO2 levels were found to be correlated linearly and positively with SV, HR, and CO. No such relationship existed between alveolar O2 levels and these hemodynamic parameters. Thus rebreathing and hypercapnia during BH prevented CO from falling during BH. It is reasoned that hypercapnia and consequent acidosis, through enhanced sympathoadrenal release of catecholamines, was responsible for the compensatory SV response.

Adult↗

Hyperbaric whole-body plethysmograph for rodents.

Described is a rodent size whole-body plethysmograph constructed of two concentric Plexiglas cylinders. Chamber temperature is controlled by circulating water of constant temperature between the cylinders, the entry gas also being preconditioned to a desired temperature. An aluminum plate partitions the chamber into an animal compartment (1.4 liters without the rat) and a transducer compartment (1.1 liters). Dynamic calibration indicates the system response is uniform between 60 and 270 cycles/min. Static calibration shows a linear correlation between the transducer output (in microV) and the calibration volume. Under hyperbaric conditions such linear correlation also exists, but the transducer outputs are greater for a given calibration volume. For a given volume of injection the transducer output is a linear function of log-ambient pressure. Respiratory variables measured with this plethysmograph are comparable to those reported in the literature both for 1 ATA and under hyperbaric conditions. The plethysmograph is also adaptable for measurement of oxygen consumption and CO2 production, under elevated ambient pressure. Caution for this application is given in regard to 1) the protracted time requirement for reaching a steady state, 2) accumulation of CO2 in the chamber, and 3) diminishing gas concentration of interest between the entering and existing gases, suggesting a trade-off in selecting chamber size, ventilation rate, and level of acceptable CO2 in the chamber.

Animals↗

Effects of age and 1,4,6-androstatriene-3,17-dione on activities of hCG-induced 19-hydroxylase and aromatase of rat testes.

The testicular aromatase activity was significantly increased by administration of hCG to 18-day old rats, but not increased in 29-day old rats. 1,4,6-Androstatriene-3,17-dione did not inhibit the in vitro conversion of testosterone to 19-hydroxytestosterone by the testicular cell-free homogenates of the hCG-treated 18-day old rats, but strongly suppressed production of estrogen from 19-hydroxyandrostenedione. On the other hand, the 19-hydroxylase activity of 18-day old rats stimulated by hCG was reduced to about 50% of the control value by SKF-525A, SU-4,885, SU-8,000 and SU-9,055 at their concentration of 10(-4) M. From our results, it is postulated that there are two distinct steps in the process of aromatization of testosterone, the one, the primary 19-hydroxylation which is inhibited by SKF-525A and SU-compounds, but not by 1,4,6-androstatriene-3,17-dione, and the other, aromatization of 19-hydroxylated androgen which is inhibited by both 1,4,6-androstatriene-3,17-dione and non-steroidal inhibitors.

Aging↗

Local thermodilution: a reliable technique for estimating renal blood flow in the rabbit.

1. A thermistor probe designed for determination of renal blood flow in rabbits, consisted of a fast-responding bead thermistor and an injection port which was also used to measure renal venous pressure between injections. 2. By an in vitro calibration system, actual measured flow (Qa) correlates well with the thermodilution calculated flow (Qc), where Qc = 0.99 Qa + 4.9 (r = 0.97, n = 42). 3. The renal blood flow (RBF) as determined by the thermodilution technique in 3 control groups was 53 +/- 3 (8), 60 +/- 6 (8), and 62 +/- 3 (3) ml/min/kidney or about 9% of the cardiac output. 4. Hypovolemia (-10%) reduced RBF by 19% from the control value, whereas, hypervolemia (+10%) did not alter RBF. 5. Smoke-induced apnea resulted in hypertension (+30%) and bradycardia (-39%), and was associated with changes in RBF (-55%) and renal vascular resistance (+183%). 6. We conclude that the local thermodilution technique is a relatively easy and reliable method for estimating RBF in rabbits.

Animals↗

Permissive role of the pituitary in the induction and growth of estrogen-dependent renal tumors.

Prolonged administration of estrogen to hamsters by implanted pellets induces not only renal adenocarcinomas but also enlarges pituitaries with hyperplastic and neoplastic changes, especially in the pars intermedia. The pituitaries of the diethylstilbestrol-implanted animals weigh 90 to 150 mg; those of control animals without diethylstilbestrol pellets weigh 7 to 12 mg. The enlarged pituitaries have 9.7 x 10(-10) M progesterone receptors compared to 0.75 x 10(-10) M in the controls. Castrated male hamsters were hypophysectomized, implanted with diethylstilbestrol pellets, fed laboratory chow ad libitum, and given 5% glucose in water to drink. New pellets were implanted every 3 months, and the animals survived for 12 to 15 months. At autopsy, none of the animals had a tumor. Sixty-two of 65 control castrated males with the same schedule of pellet implantation developed tumors. Hypophysectomized castrated males implanted with diethylstilbestrol pellets were given daily injections of 1 microgram each of follicle-stimulating hormone, luteinizing hormone, and prolactin; or with 0.9% NaCl solution. These animals survived for 12 to 15 months, but none developed kidney tumors. Other castrated males were hypophysectomized and implanted with diethylstilbestrol pellets, and 2 months later tumor tissues were transplanted under the kidney capsule. Eighty days later, no tumors were evident in the kidneys of these animals. Control castrated males were implanted with diethylstilbestrol pellets, and 2 months later tumor tissue was transplanted under the kidney capsule. Between 60 and 85 days later, 13 of the 15 controls had developed renal tumors. The concentrations of follicle-stimulating hormone, luteinizing hormone, and prolactin were measured by radioimmunoassays. The concentrations of circulating follicle-stimulating hormone and luteinizing hormone in animals with diethylstilbestrol implants decreased with time and, by 7 months, were similar to those in hypophysectomized animals. The concentration of prolactin in animals with diethylstilbestrol pellets increased with time and reached twice the value in the control animals without diethylstilbestrol pellets. These studies suggest that some factor secreted by the pituitary may be involved as a promoter or a cocarcinogen in the estrogen induction of kidney tumors.

Animals↗

Contribution of environmental factors in development of hyperbaric bradycardia.

Bradycardia has been observed in animals and humans upon exposure to various hyperbaric environments. However, the relative contribution of ambient pressure, gas density, inert gas species, and inspired O2 tension has not been defined. By means of cutaneous ECG leads, the heart rates of unanesthetized rats were recorded and compared in 11 separate thermo-neutral environments. Ambient pressures applied were 1, 3, and 10 ATA, O2 partial pressure PO2 ranged from 140 to 1,590 Torr, and gas densities were varied from 0.40 to 11.45 g/l, utilizing either N2-O2 or He-O2 mixtures. The exposure heart rates were averaged over a 30-min period and compared with a preceding control value obtained in 1 ATA normoxic He or N2. Significant bradycardia was associated with hyperoxia in environments containing either He or N2, with a magnitude proportional to log PO2. On the other hand, under normoxic conditions bradycardia was not observed despite the similar density, pressure, and inert gas components. It is concluded that hyperoxia is the most important variable of those considered in the development of hyperbaric bradycardia.

Air Pressure↗