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Biomedical subjects

M I Talan

Publications and source records attributed to M I Talan.

At least 19 recordsLinked to original sources

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

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

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

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

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

Hemodynamic and respiratory concomitants of learned heart rate control during exercise.

Each of three monkeys was trained to slow its heart, to exercise (lift weights), and to attenuate the tachycardia of exercise by combining these two skills. During all experiments, heart rate, stroke volume, intra-arterial blood pressure, O2 consumption, and CO2 production were recorded on a beat-to-beat basis. All animals reliably attenuated the tachycardia of exercise, indicating that this expression of central command is, at least in part, a learned motor skill. Double-product (heart rate X systolic pressure) was attenuated during combined sessions relative to exercise only sessions, and heart rate was always lower at similar levels of cardiac output, indicating that under the combined conditions, animals were performing with better cardiac efficiency at comparable levels of mechanical effort. Analyses of O2 consumption, CO2 production, and respiratory quotient (the ratio of CO2 production to O2 consumption) suggested that the animals also might have been delivering more O2 to their working muscles during combined sessions.

Animals

Diurnal variations in central venous pressure.

We analysed the haemodynamic patterns of seven monkeys (Macaca mulatta) during a one-month period during which we monitored beat-to-beat levels of heart rate, stroke volume, intra-arterial pressure and central venous pressure 7 days/week, 18 h/day. We replicated an earlier finding that cardiac output falls and total peripheral resistance rises throughout the night: the fall in cardiac output was mediated by a fall in heart rate since stroke volume did not change; and the rise in peripheral resistance reflected a homeostatic adjustment to the fall in cardiac output since blood pressure was stable throughout the night although it fell early in the evening. In addition, we have shown for the first time that central venous pressure also falls throughout the night; this occurs even in the presence of alpha- and beta-adrenergic sympathetic blockade. Since stroke volume does not change overnight this indicates that the nocturnal fall in cardiac output is not due to a shift of blood volume into the venous compartment. These findings support our hypothesis that there is a nocturnal decline in plasma volume.

Animals

Cardiovascular responses as behavior.

Exercise is a ubiquitous, biologically and clinically significant behavior. Although the somatomotor responses are generally regarded as "behavior," the cardiovascular adjustments that accompany these responses are generally considered to be reflexes that are elicited by neurally mediated stimuli and metabolites arising from working muscles. We report experimental evidence that monkeys can be trained to exercise, to slow heart rate, and to combine these two skills. Furthermore, some animals will emit more physical work at slower heart rates (at comparable levels of cardiac output) and lower left ventricular work during the combined condition relative to an exercise-only condition. Thus, these findings show that the cardiovascular and somatomotor responses of exercise can be dissociated and that both sets of responses should be considered behaviors. Also included are results that show these animals can perform these behaviors during sympathetic or vagal blockade. These findings are further evidence that the cardiovascular adjustments to exercise are, in part, learned behaviors because they show that the behavior--attenuation of the tachycardia of exercise--is not a reflex that is specifically tied to any neuroeffector system; rather, this behavior is emitted to achieve a contingent reward, and the nervous system will use whatever mechanisms are available to attain that consequence.

Animals

Nocturnal hemodynamic patterns in dogs.

Several species which have a single daily wake-sleep cycle show a progressive fall in cardiac output and rise in total peripheral resistance during sleep, a cardiovascular response which may reflect a progressive decrease in plasma volume. The present study showed that no such progressive overnight changes in cardiac output or total peripheral resistance occur in the dog, a carnivore which tends to be awake and to drink intermittently during the night. Progressive overnight bradycardia (-12.7 +/- 3.1%) and compensatory increase in stroke volume (14.8 +/- 6.0%) were observed in this species, however. These findings are consistent with the view that differences between primates and carnivores in overnight hemodynamic function are related to species differences in sleep and ingestive behavior.

Animals

Metabolic heat production during repeated testing at 24 degrees C and 6 degrees C in adult and aged male C57BL/6J mice: the effect of physical restraint before cold stress.

Adult (9-14 month) and aged (29-31 month) male C57BL/6J mice were subjected to 3 baseline tests (BASE), 3 cold tests (COLD), or 3 baseline immediately followed by cold tests (BASE/COLD). All tests consisted of partial restraint, and baseline tests were at 24 degrees C for 1 h while cold tests were at 6 degrees C for 3 h. All tests were started at 0900 and were repeated every 2 weeks. Mice were weighed before each test and colonic temperature, O2 consumption, and CO2 production were measured every 4 min for the duration of the test. Mean metabolic heat production during baseline and/or cold and slopes of colonic temperature over time during cold were calculated for each animal. Metabolic heat production at 24 degrees C in both BASE and BASE/COLD was the same in aged mice as adults, however, at degrees C BASE/COLD adult mice increased metabolic heat production compared to 24 degrees C, while aged mice produced a similar amount of heat at both 6 degrees C and 24 degrees C. When comparing metabolic heat production at 6 degrees C between COLD and BASE/COLD mice, adult COLD mice demonstrate an habituation to repeated cold exposure accompanied by increasing heat production, while BASE/COLD adults produce higher heat in all 3 cold exposures. The authors suggest that this is due to a priming of heat production in adults by restraint before the cold. In aged mice, neither COLD nor BASE/COLD groups demonstrate habituation, but BASE/COLD mice produce more heat than COLD during cold exposure, again indicating baseline priming of heat production. The data imply that aged mice have an impairment in specific cold-induced thermogenesis, while their abilities to produce heat in response to restraint-induced sympathetic activation remains intact.

Aging

Metabolic heat production during repeated cold stress in adult and aged male C57BL/6J mice.

Adult and aged male C57BL/6J mice were subjected to three consecutive 3-hour cold stress tests (partial physical restraint at 6 degrees C), repeated 2 weeks apart. Body mass and colonic temperature were measured before each test, and colonic temperature, O2 consumption, and CO2 production were measured during cold exposure. The slopes of colonic temperature and heat production and the mean metabolic heat production were calculated for each animal. Adult mice showed stronger cold tolerance compared to aged mice and also exhibited habituation to cold exposure (improvement of cold tolerance with repeated tests). Mean metabolic heat production during cold exposure was greater in adult mice, and only adults demonstrated significant increases across tests in both metabolic heat production and slope of metabolic heat production over time. We hypothesize that reduced cold tolerance in aged mice is related mainly to a decrease in metabolic heat production. Increased metabolic heat production in subsequent tests in adults is a probable mechanism for habituation to repeated cold exposure.

Aging

An improved method for recording blood pressure in the tethered monkey.

Existing tethering systems intended for continuous recording of blood pressure incur two major problems: 1) vertical movements of the animal in the cage produce a significant error in measured pressure introduced by the change in distance between the pressure transducer and the highest point of the infusion system and 2) the necessity for repeated zero adjustment of the pressure transducer requires sedation of the animal and disconnection of the catheter. Continuous infusion and a one-way valve in the infusion line in proximity to the pressure transducer will eliminate the error of measurement related to vertical movement of the animal. A remotely controlled, two-way solenoid valve can close the catheter line and open the pressure transducer to atmospheric pressure, thereby permitting repeated zero adjustment without sedation of the animal and disconnection of the catheter. Eliminating the need to disconnect the catheter will significantly reduce the risk of adventitious infection.

Animals

Effect of electrical stimulation of "rewarding" areas of the hypothalamus on habituation and dishabituation to repeated mild cold exposures in C57BL/6J mice.

Four groups of 12-month-old C57BL/6J male mice had chronic electrodes implanted in the median forebrain bundle. In three groups the "rewarding" property of electrical stimulation was determined during a single 30-min session of self-stimulation (ISS) before the beginning of the experiment. In the fourth group this test was postponed until the end of experiment. Every two weeks for 12 weeks all animals were subjected to repeated 3-hr cold stress tests consisting of partial physical restraint at an ambient temperature of 10 degrees C. The time interval between tests No. 3 and No. 4 was intentionally delayed up to four weeks. During the 4-week interval, animals of one of the groups tested for ISS remained in their home cages; mice of the second ISS-tested group received daily 30-min sessions of brain stimulation; and animals of the third ISS-tested group were placed daily for 30 min in the experimental chamber where they had been tested for ISS previously but received no brain stimulation. Animals of the fourth group, which were not tested for ISS prior to the experiment, also were placed daily in the experimental chamber without brain stimulation. Repeated cold testing resulted in improvement of cold tolerance (decrease of the rate of decline of colonic temperature during cold exposure) in the second and third tests relative to the first cold test in all groups (cold habituation).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effect of sympathetic blockade on diurnal variation of hemodynamic patterns.

Heart rate, stroke volume, and intra-arterial blood pressure were monitored continuously in each of four monkeys, 18 consecutive h/day for several weeks. The mean heart rate, stroke volume, cardiac output, systolic and diastolic blood pressure, and total peripheral resistance were calculated for each minute and reduced to hourly means. After base-line data were collected for approximately 20 days, observation was continued for equal periods of time under conditions of alpha-sympathetic blockade, beta-sympathetic blockade, and double sympathetic blockade. This was achieved by intra-arterial infusion of prazosin, atenolol, or a combination of both in concentration sufficient for at least 75% reduction of response to injection of agonists. The results confirmed previous findings of a diurnal pattern characterized by a fall in cardiac output and a rise in total peripheral resistance throughout the night. This pattern was not eliminated by selective blockade, of alpha- or beta-sympathetic receptors or by double sympathetic blockade; in fact, it was exacerbated by sympathetic blockade, indicating that the sympathetic nervous system attenuates these events. Because these findings indicate that blood volume redistribution is probably not the mechanism mediating the observed effects, we have hypothesized that a diurnal loss in plasma volume may mediate the fall in cardiac output and that the rise in total peripheral resistance reflects a homeostatic regulation of arterial pressure.

Animals

Learned control of systolic blood pressure raising and lowering in rhesus monkeys.

Three male monkeys (Macaca mulatta) were operantly conditioned to raise and lower systolic blood pressure (SP). All animals were trained in three stages: first to lower, then to raise systolic pressure, and finally to alternate these two behaviors. All monkeys learned the task and performed reliably in all stages. Diastolic pressure (DP) usually paralleled systolic pressure but changed much less than SP. Heart rate (HR) always fell below baseline in lowering sessions, and in two of the three animals during raising sessions as well. These findings support our earlier results which showed that monkeys could learn to control heart rate. This animal model should permit detailed studies of the hemodynamic mechanisms mediating learned control of systolic pressure.

Animals

Habituation and dishabituation to repeated mild cold exposures in C57BL/6J mice.

Every two weeks for 12 weeks four groups of C57BL/6J male mice, initially 12 months old, were subjected to three-hour cold stress tests, which consisted of a partial physical restraint at an ambient temperature of 10 degrees C. The control group experienced six consecutive tests; one experimental group skipped the cold exposure during test No. 4 but was physically restrained at room temperature; the other two experimental groups omitted test No. 4. One of these groups spent the four weeks between test No. 3 and test No. 5 in their home cages, while the other was subjected to daily, 30-minute sessions of electrical stimulation of the hypothalamus through electrodes implanted in the "rewarding" area of the medial forebrain bundle. All animals in this group showed self-stimulating behavior in the test session which preceded cold stress test No. 1. During test No. 3, all four groups showed an improvement of cold tolerance relative to their first tests; body mass and colonic temperature prior to cold exposure remained unchanged. The two experimental groups that were not exposed to cold during test No. 4 and did not receive brain stimulation, demonstrated a significant worsening of cold tolerance during the subsequent test. Their body mass and baseline colonic temperatures did not change. The control group and the group which was subjected to brain stimulation during the interval between tests No. 3 and No. 5 did not demonstrate any changes in cold tolerance. These data demonstrated habituation to repeated mild cold exposures and dishabituation after interruption of cold exposures.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance

Diurnal patterns of hemodynamic performance in nonhuman primates.

Heart rate, stroke volume, and intra-arterial blood pressures were monitored continuously in each of four monkeys for 18 consecutive hours, 5 days/wk, for several weeks. Mean heart rate, stroke volume, cardiac output, systolic and diastolic pressure, and total peripheral resistance were calculated each minute, and these averages were analyzed further to yield hourly means and intercorrelations. The main findings from the analyses of mean levels were that cardiac output fell throughout the night and that peripheral resistance rose during the same interval so that arterial pressure fell only slightly; the highest levels of peripheral resistance and lowest levels of cardiac output were recorded between 0500 and 0700. Furthermore, the levels of these responses during the remainder of the morning were higher (peripheral resistance) and lower (cardiac output) than those recorded in the evening.

Animals

Effects of voluntary and forced exercise on thermoregulation and survival in aged C57BL/6J mice.

To evaluate the effect of exercise on thermoregulation in senescent animals, three groups of male C57BL/6J mice aged 28-30 months were tested for cold tolerance, defined as the rate of decline in colonic temperature during 3 h exposure to 10 degrees C ambient temperature. Following this test, the mice were exposed to one of the following exercise conditions: forced exercise on a treadmill for 60 min daily at a rate of 5 m/min; continuous access to voluntary exercise in wheel-activity cages, which resulted in a mean rate of 1.1 m/min; or no expressed exercise with 60 min daily placement on the non-activated treadmill. After 3 weeks, assessment of cold tolerance was repeated. A combined mortality rate of 36% was observed in the exercise groups for this period, while there were no deaths in the non-exercised group. The high mortality rate among exercised animals indicated that these regimens were hazardous for aged mice. Moreover, between tests the non-exercised group exhibited a 0.6 degree C increase in body temperature and 38% improvement in cold tolerance which could be interpreted as a normal adaptation for repeated cold exposure. In contrast, no significant change in either of these variables was observed among survivors in the exercise groups. Thus, introduction of these exercise regimens in senescent mice decreased survival and did not improve the age-related impairment in thermoregulation.

Adaptation, Physiological