Biomedical subjects

M I Talan

Publications and source records attributed to M I Talan.

At least 19 recordsLinked to original sources

PubMed1999

Cold acclimation-induced increase of systolic blood pressure in rats is associated with volume expansion.

To investigate the mechanisms of cold-induced hypertension, the systolic blood pressure (SBP) and average daily water consumption were measured weekly in 6-month-old male Wistar rats; they were subsequently acclimated to thermoneutrality (26 degrees C for 7 weeks), to cold temperature (6 degrees C for 9 weeks), and then again reacclimated to 26 degrees C for 5 weeks. Circulating plasma volume and whole blood viscosity were measured in subgroups of rats at the end of acclimation to 26 degrees C after 2 days, after 1, 6, and 8 weeks of cold, and after 2 and 5 weeks of rewarming. The control values obtained at the end of thermoneutral period were: SBP = 130.8 +/- 18.6 mm Hg, plasma volume = 41.9 +/- 4.64 mL/kg, whole body viscosity at shear rate of 22.5 per sec = 6.7 +/- 0.48 cps, and daily water consumption = 42.25 +/- 16.81 mL. After 48 h of cold exposure there was almost a 50% increase in plasma volume that persisted to a lesser degree throughout the whole period of cold exposure (P < .05). After 2 weeks of cold exposure the daily water consumption increased and SBP began to increase. After 6 weeks of cold exposure the SBP was 30 mm Hg above that of the control level (P < .001) and was accompanied by a 25% increase in whole blood viscosity (P < .05). At the end of 8 weeks of cold exposure the plasma volume was 56.8 +/- 9.51 mL/ kg and the whole blood viscosity was 8.0 +/- 1.79 cps at the 22.5 per sec shear rate. During the 5 weeks of rewarming the elevation of SBP and increased whole blood viscosity persisted, whereas the increased daily water consumption and expanded plasma volume returned to normal. Therefore, the acclimation to cold is accompanied by the development of a volume-associated hypertension, which is sustained after rewarming without volume expansion.

Acclimatization↗

PubMed1998

The effect of exercise training in cold on shivering and nonshivering thermogenesis in adult and aged C57BL/6J mice.

To understand the mechanisms of improvement of cold-induced heat production in aged mice following exercise training, the relative contributions of shivering and nonshivering thermogenesis to cold-induced metabolic responses were assessed in adult and aged C57BL/6J male mice, which inhabited sedentarily at room temperature, or were subjected either to a regimen of moderate intensity exercise training at 6 degrees C, or to sedentary repeated exposures to the same temperature. The main findings were that (1) aged mice had greater cold-induced nonshivering thermogenesis, but lower shivering than adult mice; (2) exercise training in a cold environment enhanced cold-induced nonshivering thermogenesis in adult mice, but suppressed it in aged animals; (3) exercise training in a cold environment increased shivering thermogenesis in both age groups, but this increase was much greater in aged mice; (4) the increase of cold-induced shivering thermogenesis was mainly responsible for increased cold tolerance in aged mice after exercise training in a cold environment.

Aging↗

PubMed1997

Metabolic costs of mounting an antigen-stimulated immune response in adult and aged C57BL/6J mice.

Animals must balance their energy budget despite seasonal changes in both energy availability and physiological expenditures. Immunity, in addition to growth, thermoregulation, and cellular maintenance, requires substantial energy to maintain function, although few studies have directly tested the energetic cost of immunity. The present study assessed the metabolic costs of an antibody response. Adult and aged male C5BL/6J mice were implanted with either empty Silastic capsules or capsules filled with melatonin and injected with either saline or keyhole limpet hemocyanin (KLH). O2 consumption was monitored periodically throughout antibody production using indirect calorimetry. KLH-injected mice mounted significant immunoglobulin G (IgG) responses and consumed more O2 compared with animals injected with saline. Melatonin treatment increased O2 consumption in mice injected with saline but suppressed the increased metabolic rate associated with an immune response in KLH-injected animals. Melatonin had no effect on immune response to KLH. Adult and aged mice did not differ in antibody response or metabolic activity. Aged mice appear unable to maintain sufficient heat production despite comparable O2 production to adult mice. These results suggest that mounting an immune response requires significant energy and therefore requires using resources that could otherwise be allocated to other physiological processes. Energetic trade-offs are likely when energy demands are high (e.g., during winter, pregnancy, or lactation). Melatonin appears to play an adaptive role in coordinating reproductive, immunologic, and energetic processes.

Aging↗

PubMed1997

Central neural correlates of learned heart rate control during exercise: central command demystified.

To identify the brain areas involved in central command, four monkeys were trained to attenuate the tachycardia of exercise while different brain sites affecting heart rate (HR) were simultaneously stimulated electrically. Among 24 brain sites located mostly in the limbic structures, we have identified four types of control systems that mediate cardiovascular and motor behavior during exercise. One system increases HR equivalently during both exercise and operantly controlled HR, whereas another increases HR during both tasks and abolishes operant HR control. In the third system, the effect of brain stimulation on HR is attenuated during exercise and during exercise with operantly controlled HR. The fourth system increases HR in both tasks, but its effect is significantly attenuated during operant HR control. We believe that this last system, which includes the mediodorsal nucleus, nucleus ventralis anterior, and cingulate cortex, plays a significant role in central command.

Animals↗

PubMed1996

Sympathetic outflow to interscapular brown adipose tissue in cold acclimated mice.

C57BL/6J male mice were subjected to a cold acclimation procedure which consisted of three consecutive cold stress tests: 3-h partial restraint at 6 degrees C at 2-wk intervals. During the week following the last cold stress test, each animal previously subjected to the cold acclimation procedure, and an additional group of naive mice (animals that never had been exposed to an environment below room temperature) were anesthetized with urethan, paralyzed with vecuronium bromide, artificially ventilated, and subjected to cold stimulation for approximately 16 min. Electrical impulse activity from one of the fine sympathetic nerves entering the interscapular brown adipose tissue was recorded before and during cold stimulation, until body temperature dropped 8 degrees C below control level. Sympathetic outflow increased significantly during cold stimulation in all mice. Animals that did not achieve cold acclimation in three repeated cold stress tests (they demonstrated less cold tolerance in the last test) had lower sympathetic nervous outflow to brown adipose tissue at room temperature and during cold stimulation than mice that had achieved cold acclimation. In fact, sympathetic nervous outflow to brown adipose tissue in mice that had failed to show cold acclimation was similar to that of naive mice. These findings indicate that the sympathetic nervous system plays a primary role in cold acclimation.

Acclimatization↗

PubMed1996

Cold acclimation-associated changes in brown adipose tissue do not necessarily indicate an increase of nonshivering thermogenesis in C57BL/6J mice.

We have reported previously that a cold acclimation procedure (3-hr partial restraint at 6 degrees C, repeated 3 times at 2-week intervals) usually improves the cold tolerance of adult C57BL/6J mice. Those mice that did not improve their cold tolerance had lower cold-induced sympathetic nervous outflow to the interscapular brown adipose tissue (IBAT), suggesting a failure in the mechanisms of nonshivering thermogenesis. To understand the origin of this failure, this study was intended to measure nonshivering thermogenesis in mice that did not improve their cold tolerance after the cold acclimation procedure. After being subjected 3 times to a partial restraint at 6 degrees C, mice were anesthetized with urethane, immobilized with vecuronium bromide, and placed on artificial ventilation. The VO2 and VCO2 in expired air were measured and metabolic heat production (MHP) was calculated while body temperature was artificially lowered to 7.5 degrees C below control level. In a separate group of mice, the total amount and concentration of mitochondrial uncoupling protein, thermogenin (UCP), in IBAT was measured immediately after completion of the cold-acclimation procedure. The concentration and the amount of UCP in the mitochondria of IBAT was significantly higher in all mice that had been presented to the cold acclimation procedure, regardless of its outcome, than in mice that had never been exposed to an environment below room temperature (NAIVE). MHP increased significantly during body cooling in all mice. However, MHP before and during cold stimulation in mice that did not improve their cold tolerance as a result of the cold-acclimation procedure was significantly lower than the MHP of animals in which cold tolerance was improved, and was not different from MHP of the NAIVE group. Therefore, in mice in which cold tolerance did not improve after repeated cold exposure, the anatomical and biochemical changes in brown adipose tissue typical of cold acclimation were not associated with a cold-induced increase in MHP. We infer that the expression of UCP in brown adipose tissue is a necessary, but not sufficient, attribute of cold acclimation. Cold acclimation, measured as increased cold tolerance, occurs only if synthesis of UCP in BAT is associated with an increased cold-induced response of the sympathetic nervous system.

Acclimatization↗

PubMed1996

The effect of exercise training on cold tolerance in adult and old C57BL/6J mice.

In order to ascertain the effect of aging on cross-adaptation between exercise training and cold tolerance, we studied cold tolerance in adult and old C57BL/6J male mice before and after 6 weeks of an exercise regimen of moderate intensity. There were two age groups of 32 mice each, including 12-month-old (adult) and 24-month-old (aged) mice equally divided into control and exercise groups. The exercise consisted of daily runs on a treadmill (1 hr/day, 5 days/week) for 6 weeks, while the control mice spent the same time on a stationary treadmill. All mice were subjected to a cold stress test (3-hr partial restraint at 6 degrees C) prior to and following the designated regimen. The results revealed a statistically significant interaction between age and exercise training. In adult mice, exercise resulted in a reduction of cold-induced heat production and weakening of cold tolerance, while in aged mice, the opposite effect was observed; i.e., an increase in cold-induced heat production accompanied by greater cold tolerance. However, only the attenuating effect on cold tolerance of adults was statistically significant. The results of our experiments do not support the existence of cross-adaptation between exercise training and cold tolerance. They indicate, however, that exercise training affects the cold tolerance in adult and old mice through different physiological mechanisms.

Adaptation, Physiological↗

PubMed1996

Overnight heart rate and cardiac function in patients with dual chamber pacemakers.

Animal data indicate that chronic, overnight pacing at normal evening heart rates impairs cardiac function. We examined the relationship of pacing rate and cardiac function in nine patients with dual-chamber pacemakers. We investigated two, 3-week pacing regimens (80 and 50 ppm: DDD mode) in a cross-over design. Doppler echocardiograms were performed at 1700 hours (PM) and 0600 hours (AM) at the end of each regimen. Ventricular function and preload decreased overnight (PM vs AM) with both pacing regimens. Compared to the morning values, the ratio of preejection to ejection time (PEP/ET) rose (0.43 vs 0.46), while the mean velocity of circumferential fiber shortening (Vcf) fell (1.16 cm/s vs 1.11 cm/s). Stroke volume (SV) (61 mL vs 53 mL) and ejection fraction (EF) also fell (0.56 vs 0.53) in the morning. End-diastolic volume (EDV) (94 mL vs 88 mL) decreased in the morning, as did the ratio of passive to active filling (E/A) (1.06 vs 0.96). Isovolumic relaxation time (91 ms vs 101 ms) increased overnight at both pacing rates. Systolic function decreased at 80 ppm relative to 50 ppm at both times of day. SV fell (54 mL vs 61 mL), while both EDV (92 mL vs 90 mL) end-systolic volume (ESV) increased (43 mL vs 40 mL). Contractility measured by Vcf (1.09 cm/s vs 1.18 cm/s) and PEP/ET (0.49 vs 0.41) was reduced at 80 ppm. The heart needs to rest at night by slowing its rate of contraction. Pacing at 80 ppm impairs systolic and diastolic ventricular function compared to 50 ppm. Longer term consequences of ostensibly physiological pacing rates merit inquiry, particularly in those with preexisting cardiac dysfunction.

Adult↗

PubMed1994

Sympathetic nervous activity to brown adipose tissue increases in cold-tolerant mice.

Brown adipose tissue (BAT) is thought to be responsible for increased heat production in cold-acclimated rodents. We measured sympathetic nerve activity (SNA) in interscapular BAT (IBAT) during cold stimulation in cold-acclimated C57BL/6J mice (ACCLI). Cold acclimation was achieved (cold tolerance was increased) by repeated exposure to cold stress every other week for 3 weeks. We compared SNA in these animals with SNA in mice that had no previous cold stress experience (naive). During the test, mice were anesthetized by urethane and isoflurane and were paralyzed with vecuronium bromide. Sympathetic nerve activity was recorded directly from one of the fine nerves to IBAT. The animal's body caudal to the pelvic area was covered with a plastic bag containing a slurry of ice water to decrease colonic temperature 7 degrees C below control level, which took approximately 20 min. Interscapular BAT-SNA increased during cold stress in both groups, but ACCLI mice had higher IBAT-SNA during cold stress than naive mice. These findings confirmed the hypothesis that during the acute cold exposure, cold-acclimated mice have greater sympathetic outflow to BAT adipocytes.

Acclimatization↗

PubMed1994

Effect of exercise on cold tolerance and metabolic heat production in adult and aged C57BL/6J mice.

Two groups of adult (12-mo-old) and two groups of aged (24-mo-old) C57BL/6J male mice were subjected to a standardized cold stress test (3-h partial restraint at 6 degrees C). One group from each age group was tested in the morning, and the other was tested in the afternoon. Half of the mice were subjected to running exercise on a treadmill during 1 h before the cold stress test. The other half were placed on a nonoperational treadmill for 1 h before the cold stress test. One hour of exercise resulted in improvement of cold tolerance during the subsequent cold exposure in both age groups but only during afternoon testing. Improvement in cold tolerance was not accompanied by an elevation of cold-induced metabolic heat production in adult mice. Metabolic heat production in aged mice showed only modest elevation. The discrepancy between improvement in cold tolerance and lack of elevation of metabolic heat production suggests that the primary mechanism for augmentation of cold tolerance after exercise in the afternoon is an improvement in cold-induced vasoconstriction of skin vessels, which is probably normally compromised in the afternoon.

Age Factors↗

PubMed1993

Aged C57BL/6J mice respond to cold with increased sympathetic nervous activity in interscapular brown adipose tissue.

Aged, male C57BL/6J mice produce less heat than adults during cold, which may lead to a reduced ability to maintain core temperature, but the underlying mechanisms of the decreased heat production in aged mice are still unclear. We measured sympathetic nervous activity (SNA) to interscapular brown adipose tissue (IBAT) in aged mice and compared this activity with that of adults. Mice were anesthetized by urethane and isoflurane, and SNA was recorded from one of the fine nerves to IBAT. The animal's body caudal to the pelvic area was covered with a plastic bag containing iced-water to decrease colonic temperature 7 degrees C below control over 20 minutes. SNA to IBAT (IBAT-SNA) increased during cold in both groups, but aged mice had higher IBAT-SNA before and during cold. These findings indicate that neither the ability of aged mice to detect cold nor their ability to generate sympathetic outflow to BAT is deficient.

Adipose Tissue, Brown↗

PubMed1993

Morning increase in whole blood viscosity: a consequence of a homeostatic nocturnal haemodynamic pattern.

In a series of studies, we have shown that in non-human primates there is a consistent overnight fall in cardiac output and central venous pressure, and a rise in total peripheral resistance. This haemodynamic pattern is associated with a higher haematocrit level in the morning suggesting that these changes in the circulation are homeostatic adjustments to a nighttime fall in plasma volume. The present study was designed to test the hypothesis that in the morning whole blood viscosity also is higher. Whole blood viscosity was measured at shear rates of 450, 225, 90, 45, and 22.5 s-1 in each of six monkeys, on four occasions, at 2-week intervals, at 17.00 and 09.00 h the next morning. The average haematocrit was 4.2% higher in the morning than in the previous evening (P < 0.01). Viscosity decreased monotonically at progressively higher shear rates but was always significantly higher in the morning than in the evening (P < 0.01 at all shear rates). When viscosity was adjusted by covarying for haematocrit level, the morning/evening differences became non-significant. However, the morning/evening differences in linear trend of shear stress as a function of shear rate persisted. These findings add further support to our hypothesis that the nocturnal haemodynamic pattern in non-human primates is related to a reduction in plasma volume, and they also suggest that the morning rise in haematocrit is a major contributing factor to the elevated viscosity.

Animals↗

PubMed1993

Role of postural status in the nocturnal hemodynamic patterns of nonhuman primates.

We compared the nocturnal hemodynamic patterns of seven tethered monkeys (Macaca mulatta) with those of seven chaired animals to determine whether the overnight changes are comparable in the two conditions. In both groups, we found a consistent hemodynamic pattern characterized by an overnight fall in cardiac output and central venous pressure and a rise in total peripheral resistance that maintained blood pressure homeostasis. The pattern of overnight change occurred despite major differences in response levels: cardiac output and central venous pressure were significantly elevated, and total peripheral resistance was significantly reduced at all times (from 1800 to 1200 h the following day) in the chaired animals relative to the tethered animals. This difference was probably due to an expanded plasma volume in the chaired animals, because stroke volume was also significantly elevated. Because the nocturnal hemodynamic pattern occurred under both conditions, it is likely that it is a stable biologic effect, which is probably related to an overnight loss in fluid volume that is not replaced in animals that sleep throughout the night.

Animals↗

PubMed1992

Overnight increases in haematocrit: additional evidence for a nocturnal fall in plasma volume.

Our previously published studies with monkeys describe a characteristic nocturnal haemodynamic pattern consisting of a monotonic decline in cardiac output and central venous pressure, and a concomitant rise in total peripheral resistance. These findings led us to hypothesize that there is a reduction in total plasma volume during the night. Since a fall in plasma volume should cause an increase in haemoglobin and plasma protein concentration, we designed this experiment to test the hypothesis that haematocrit levels would be significantly greater in the morning than in the evening. In a study of five monkeys, the levels of haematocrit were measured at 1700 h and at 0900 h the next morning for 14 days. The average morning haematocrit levels were 6.5% higher than the average evening values. Lower plasma volume and possibly greater blood viscosity could contribute to the pathophysiology of the morning increase in the incidence of 'silent' ischaemia and catastrophic vascular events such as sudden cardiac death, myocardial infarctions and strokes in man.

Animals↗

PubMed1992

Effect of nocturnal atrial demand cardiac pacing on diurnal hemodynamic patterns.

Heart rate (HR), stroke volume (SV), intra-arterial blood pressure, and central venous pressure were recorded on a beat-to-beat basis, 18 h/day (1800-1200 h the following day), for approximately 2 mo in four monkeys (Macaca mulatta). Cardiac output, left ventricular work, and total peripheral resistance were derived from these primary measurements. During the 1st mo we measured these parameters under control conditions, and during the 2nd mo the animals were studied while HR was paced by atrial demand pacing sufficient to prevent the normal nocturnal fall in HR (approximately 10 beats/min above the fastest hourly average rate recorded during the control condition). The main hypothesis of this study was that when HR is prevented from falling, SV, which normally does not fall overnight, would fall; this hypothesis was confirmed. In addition, we observed that, during the period of pacing, relative to the control period, SV was approximately 14% greater during the early evening and 4% lower during the early morning; total peripheral resistance was similar during the early evening but was 13% higher by morning. Throughout the night, systolic pressure was approximately 4% greater, diastolic pressure was 17% higher, central venous pressure was 43% greater, and left ventricular work was 27% higher. These findings show that when HR is prevented from falling overnight by atrial demand pacing, even to a relatively modest degree, there can be very significant sustained changes in cardiovascular function.

Animals↗

PubMed1992

Systematic nocturnal atrial demand pacing results in high-output heart failure.

Beat-to-beat parameters of heart rate (HR), intra-arterial blood pressure (BP), central venous pressure, and derived indexes of cardiac output and total peripheral resistance were recorded 18 h/day (from 1800 to 1200 h the following day) in four monkeys (Macaca mulatta) during 20 control days followed by 20 days of atrial demand pacing. The pacing rate was set at approximately 10 beats/min above the fastest hourly average HR recorded during the control period, i.e., sufficient to prevent the normal nocturnal fall in HR. Nocturnal pacing resulted in progressive weekly increases in central venous BP and arterial BP. Analyses of levels and diurnal trends in hemodynamic parameters and cardiac function curves across consecutive 5-day periods of nocturnal pacing revealed a hemodynamic pattern characteristic of high-output heart failure, which progressively increased (week by week) during the early morning hours (0500-0700). Sustained elevated left ventricular work resulting from the prevention of a nocturnal fall in HR may have been responsible for the reduction in cardiac function seen in this experimental model.

Animals↗

PubMed1991

Autonomic blockade does not prevent learned heart rate attenuation during exercise.

Each of three monkeys was operantly conditioned to slow its heart, to exercise (lift weights) and to attenuate the tachycardia of exercise by combining these two skills. Each was further tested during beta-adrenergic blockade (atenolol), combined alpha-adrenergic blockade (prazosin) and beta-adrenergic blockade, or cholinergic blockade (methylatropine). During all experiments heart rate, stroke volume, intraarterial blood pressure, O2 consumption, and CO2 production were recorded on a beat-to-beat basis. Each animal was able to attenuate the tachycardia of exercise under each of the drug conditions, indicating that "central command" is not the expression of fixed, cardiovascular and pulmonary reflexes elicited by somato-motor commands, but rather is an adaptive behavior, determined by environmental contingencies and mediated by cardiovascular and pulmonary as well as somato-motor commands. The ability of the animals to perform with greater cardiac efficiency during the combined exercise and heart rate slowing task relative to the exercise-only task was not affected by sympathetic blockade; however, parasympathetic blockade did reduce cardiac efficiency.

Animals↗

PubMed1991

Cold tolerance and metabolic heat production in male C57BL/6J mice at different times of day.

Nine-month-old male C57BL/6J mice were subjected to three-hour cold stress tests (partial restraint at 6 degrees C) at 9:00 a.m. or at 1:00 p.m. Tests were repeated three times at two-week intervals at the same time of day. Body temperature was measured by colonic thermoprobe, and metabolic heat production was measured by indirect calorimetry during each test. All mice showed habituation to repeated cold exposures (an improvement of cold tolerance across tests) due to an increase in metabolic heat production. The levels of metabolic heat production were similar during morning and afternoon testing; however, mice tested in the afternoon had consistently poorer cold tolerance, which indicated increased heat loss. Increased heat loss in mice of similar body weight and presumably similar body composition, suggests that there is less effective cold-induced skin vasoconstriction during the afternoon. We hypothesize that the compromised skin vasomotor response during the afternoon cold exposure results from competing effects of vasodilation due to local autoregulation stimulated by a circadian reduction of cardiac output during the sleep phase, and vasoconstriction due to the cold stress.

Animals↗