Lars Walløe

Time course and magnitude of blood flow changes in the human quadriceps muscles during and following rhythmic exercise.

1. Pulsed bidirectional Doppler‐ultrasound equipment was used to measure changes in blood velocities in the femoral artery on a beat to beat basis for consecutive contraction and relaxation phases during voluntary rhythmic exercise of the quadriceps muscle group in man. 2. Rapid and large fluctuations of blood velocities were found, being high during relaxation and low during contraction phases. At the onset of contraction phase, negative velocities were present, indicating retrograde flow. During the rest of the contraction phase, forward flow occurred comparable to the resting flow level even at high loads. 3. Estimated maximal flow to the whole leg during relaxation phase, calculated from these blood velocity measurements and vessel diameter (measured with echo‐ultrasound equipment with high resolution) was in two of the subjects 3.32 l min‐1 (female) and 5.97 l min‐1 (male). When using computer tomography to estimate the volume of the quadriceps muscle group, the calculated maximum flow to this muscle group was 243 (female) and 257 (male) ml min‐1 100 ml muscle‐1. The time‐averaged flow during exercise to the whole leg was 1.51 l min‐1 (female) and 2.47 l min‐1 (male). The calculated time‐averaged flow to the quadriceps muscle group was 101 (female) and 98 (male) ml min‐1 100 ml muscle‐1. 4. The duration of post‐contraction hyperaemia following such rhythmic exercise of up to 6 min duration and up to 75% maximum voluntary contraction was never in excess of 150 s.

Height, weight and menarcheal age of Oslo schoolchildren during the last 60 years

Every 5th year since 1920 the heights and weights of all Oslo schoolchildren (aged 7 to 18 years) have been measured, and the measurements processed centrally. For ages between 8 and 14 the mean height increased by about 4 cm per decade between 1920 and 1940 for both sexes. A drop of about 1.5 cm occurred during World War II, followed by a rapid catch-up. Since 1950, height has increased only moderately. A weight increase of between 1.5 kg (8 years old) and 3.5 kg (13 years old) per decade before 1940 was followed by a drop during the war equivalent to somewhat less than one decades gain. A rapid catch-up after the war was followed by a slight decrease since 1950, especially for ages above puberty. A stable difference in the social composition of the eastern and western districts of Oslo allowed comparison of the trends for lower and higher social strata. Before the war, children from higher strata were taller than children from lower strata, but this difference has now practically disappeared. Children from the higher strata weighed more until about 1955, but later those from the lower strata weighed markedly more, especially during adolescence. The difference in menarcheal age between social strata was examined in 1928, 1952, 1970 and 1975. The time trend parallels that for weight: menarcheal age was lowest among higher strata until the 1950s, but after that the lower strata experienced the lowest menarcheal age.

Fluctuations in blood flow to acral skin in humans: connection with heart rate and blood pressure variability.

1. Spontaneous fluctuations in blood flow in arteries supplying acral skin were investigated with Doppler ultrasound in human subjects. Finger blood pressure, heart rate (HR) and cardiac output were measured simultaneously and noninvasively. 2. Synchronous fluctuations in flow were found in arteries supplying the hands and feet. The fluctuations were larger and more rapid than the flow variations which have been demonstrated with other methods. The magnitude of the total flow fluctuations in the hands and feet was estimated to be 5‐10% of cardiac output in resting subjects. This range of flow fluctuations is made possible by spontaneous opening and closing of skin arteriovenous anastomoses (AVAs). 3. The fluctuations in skin blood flow were accompanied by inverse fluctuations in mean blood pressure (MAP). The power spectra of skin vascular conductance and MAP both contained maximum intensity at low frequencies, below 0.15 Hz, with high coherence. 4. The central circulatory events connected with the skin blood flow fluctuations were calculated from the experimental data with the use of transfer function analysis. There was a rise in HR, cardiac output and MAP starting 1‐4 s before a cutaneous vasoconstriction. This indicates that the HR and MAP responses are not only passive effects of changes in peripheral resistance, but are the result of a simultaneous activation of the peripheral vascular and cardiac efferent branches of the autonomic nervous system. The HR and MAP responses are then modified, probably by baroreceptor activation.

Dynamics and dimensions of cardiac output changes in humans at the onset and at the end of moderate rhythmic exercise.

1. An improved Doppler ultrasound technique was used to measure stroke volume (SV) and cardiac output (CO) on a beat‐to‐beat basis in a group of supine humans before, during and after periods of standardized, rhythmic exercise, involving the quadriceps muscle groups on both sides. The development of CO on such bouts of exercise was compared to Doppler ultrasound records of the simultaneous femoral arterial flow (FF) response. 2. Records of CO at rest revealed spontaneous fluctuations around a mean level, with differences between the minimal and maximal values of the order of 1 l min‐1. The mean CO level at rest again varied considerably from one day to another and from test run to test run. 3. Upon start of exercise an immediate and rapid increase in heart rate (HR) and CO took place. The entire increase, the size of which varied appreciably from test run to test run, was completed within 10‐15 s. No or only minor changes were seen in the mean SV level during the exercise periods. 4. The time course of the increase in FF was indistinguishable from that of the increase in CO, which occurred without any detectable delay relative to the changes in FF. These closely parallel developments indicate a tight regulatory coupling between the two types of flow changes. 5. In the majority of tests the total and two‐sided increase in FF seen in the steady‐state situation in the last part of an exercise period was significantly larger than the recorded increase in CO. This discrepancy implies that some redistribution of flow from tissues other than the working muscles might take place, even at this moderate level of work. 6. Upon the end of exercise a striking but transient increase in CO occurred, resulting from an increase in SV concomitant with a maintained HR. In the course of five to eight post‐exercise cardiac cycles about 100 extra milliliters of blood were expelled from the heart. This cardiac outflow overshoot was found to occur during a post‐exercise fall in mean arterial blood pressure (MAP).

Climate-driven introduction of the Black Death and successive plague reintroductions into Europe

Significance The second plague pandemic in medieval Europe started with the Black Death epidemic of 1347–1353 and killed millions of people over a time span of four centuries. It is commonly thought that after its initial introduction from Asia, the disease persisted in Europe in rodent reservoirs until it eventually disappeared. Here, we show that climate-driven outbreaks of Yersinia pestis in Asian rodent plague reservoirs are significantly associated with new waves of plague arriving into Europe through its maritime trade network with Asia. This association strongly suggests that the bacterium was continuously reimported into Europe during the second plague pandemic, and offers an alternative explanation to putative European rodent reservoirs for how the disease could have persisted in Europe for so long. The Black Death, originating in Asia, arrived in the Mediterranean harbors of Europe in 1347 CE, via the land and sea trade routes of the ancient Silk Road system. This epidemic marked the start of the second plague pandemic, which lasted in Europe until the early 19th century. This pandemic is generally understood as the consequence of a singular introduction of Yersinia pestis, after which the disease established itself in European rodents over four centuries. To locate these putative plague reservoirs, we studied the climate fluctuations that preceded regional plague epidemics, based on a dataset of 7,711 georeferenced historical plague outbreaks and 15 annually resolved tree-ring records from Europe and Asia. We provide evidence for repeated climate-driven reintroductions of the bacterium into European harbors from reservoirs in Asia, with a delay of 15 ± 1 y. Our analysis finds no support for the existence of permanent plague reservoirs in medieval Europe.

Abnormal Thermoregulatory Responses in Adolescents With Chronic Fatigue Syndrome: Relation to Clinical Symptoms

OBJECTIVES. Chronic fatigue syndrome is a common and disabling disease of unknown etiology. Accumulating evidence indicates dysfunction of the autonomic nervous system. To further explore the pathophysiology of chronic fatigue syndrome, we investigated thermoregulatory responses dependent on catecholaminergic effector systems in adolescent patients with chronic fatigue syndrome. PATIENTS AND METHODS. A consecutive sample of 15 patients with chronic fatigue syndrome aged 12 to 18 years and a volunteer sample of 57 healthy control subjects of equal gender and age distribution were included. Plasma catecholamines and metanephrines were measured before and after strong cooling of 1 hand. Acral skin blood flow, tympanic temperature, heart rate, and mean blood pressure were measured during moderate cooling of 1 hand. In addition, clinical symptoms indicative of thermoregulatory disturbances were recorded. RESULTS. Patients with chronic fatigue syndrome reported significantly more shivering, sweating, sudden change of skin color, and feeling unusually warm. At baseline, patients with chronic fatigue syndrome had higher levels of norepinephrine, heart rate, epinephrine, and tympanic temperature than control subjects. During cooling of 1 hand, acral skin blood flow was less reduced, vasoconstrictor events occurred at lower temperatures, and tympanic temperature decreased more in patients with chronic fatigue syndrome compared with control subjects. Catecholamines increased and metanephrines decreased similarly in the 2 groups. CONCLUSIONS. Adolescent patients with chronic fatigue syndrome have abnormal catecholaminergic-dependent thermoregulatory responses both at rest and during local skin cooling, supporting a hypothesis of sympathetic dysfunction and possibly explaining important clinical symptoms.

Breast-feeding practice in Norway 1860–1984

Data from birth records with information on previously born children from 3 maternity hospitals in Norway have been used to study the trend in breastfeeding practice from 1860-1984. During the period the % of women breastfeeding for at least 1 week was remarkably high above 90%. The results show a fairly stable duration of breastfeeding up until 1920 at least 3 months in approximately 80% of the women. After that year the distribution of the duration of breastfeeding changed dramatically. The shortest durations were found in the late 1960s when only about 30% lactated for 3 months or more. The duration then increased quickly so that at the beginning of the 1980s about 80% of the women were again breastfeeding for at least 3 months. By multiple regression methods the relationships of several independent variables to the duration of breastfeeding were investigated. Married women lactated for 1.5-3 months longer than unmarried the difference being largest before 1920. 1st-born children were breast-fed for a little shorter time than 2nd and later-born children. Until World War II women of lowest social strata had the longest durations of breastfeeding and then the situation was reversed women of highest social strata continuing the longest. (authors modified)

Development of oxygen sensitivity in infants of smoking and non-smoking mothers.

AIMS To assess the effect of prenatal cigarette smoke exposure on the postnatal resetting of oxygen sensitivity in term infants. METHODS 15 healthy term infants of smoking mothers (median 10 cigarettes/day) and 16 controls were studied during quiet sleep 1, 3, and 10 days and 10 weeks postnatally. Strain-gauge respiratory trace was continuously recorded. Repeated 15-s challenges with 100% O2 and 15% O2 were presented in randomised order through a face mask. A median of six hyperoxic and six hypoxic challenges per recording were obtained. Breath-by-breath ventilation in a time-window from 20 s before onset of stimulus to 60 s after was extracted. For each infant at each age, the normalised coherently averaged response to hyperoxia and hypoxia was calculated. Mean ventilation at end of the 15-s stimulus was analysed with ANOVA, as were parameters describing a function fitted to each averaged response. RESULTS During air breathing, smoke-exposed infants had higher respiratory rates and lower tidal volumes than controls. Nicotine concentration in infant hair, measured by gas chromatography, was positively correlated with maternal level of smoking. A long-term development in oxygen sensitivity was demonstrated in both groups. However, neither the time-course nor the magnitude of O2 responses was affected by maternal smoking. Overall, hyperoxia reduced ventilation by 6.3% at day 1, 13.2% at day 3, 29.6% at day 10, and 40.0% at week 10. Transient hypoxia increased ventilation by 3.5%, 3.2%, 6.4%, and 8.8%, respectively, at the four ages studied.

Perfusion of the human finger during cold-induced vasodilatation.

We have investigated the effect of severe local cooling on the vasomotor activity of the arteriovenous anastomoses (AVAs) and other finger vessels. The right third finger was subjected to local cooling (3 degrees C) for 30-45 min in 21 healthy, thermoneutral subjects. Blood velocity in the third finger arteries of both hands was simultaneously recorded using ultrasound Doppler, and skin temperature and laser-Doppler flux from the pulp of the cooled finger were also recorded. The results demonstrate that the initial cold-induced vasoconstriction during severe local cooling involves constriction of the AVAs as well as the two main arteries supplying this finger. During cold-induced vasodilatation (CIVD), the maximum velocity values were not significantly different from those before cooling. Furthermore, the velocity fluctuations in the cooled finger were in most subjects found to be synchronous with the velocity fluctuations in the control finger. This indicates that the large blood flow to the finger and the high skin temperature during CIVD are caused by relaxation of the smooth muscle cells of the AVAs.We have investigated the effect of severe local cooling on the vasomotor activity of the arteriovenous anastomoses (AVAs) and other finger vessels. The right third finger was subjected to local cooling (3°C) for 30-45 min in 21 healthy, thermoneutral subjects. Blood velocity in the third finger arteries of both hands was simultaneously recorded using ultrasound Doppler, and skin temperature and laser-Doppler flux from the pulp of the cooled finger were also recorded. The results demonstrate that the initial cold-induced vasoconstriction during severe local cooling involves constriction of the AVAs as well as the two main arteries supplying this finger. During cold-induced vasodilatation (CIVD), the maximum velocity values were not significantly different from those before cooling. Furthermore, the velocity fluctuations in the cooled finger were in most subjects found to be synchronous with the velocity fluctuations in the control finger. This indicates that the large blood flow to the finger and the high skin temperature during CIVD are caused by relaxation of the smooth muscle cells of the AVAs.

Cardiovascular responses to tilting in healthy newborn babies

It has been suggested that newborn infants have immature baroreceptor responses and they are unable to maintain their blood pressure (BP) by appropriate reflex peripheral vasoactivity and heart rate (HR) changes in response to tilting. We have measured simultaneously upper arm and calf systolic and diastolic BP and HR every 30 s using an oscillometric method (Dinamap 847) in quiet and active sleep in 9 term babies. Measurements were performed continuously with 5-min periods in each of three positions; horizontal, 30 degrees head up and 30 degrees head down tilt. The results were analysed using unbalanced analyses of variance and multivariate regression. All responses were proportional to the angle of the tilt. The observed values were very close to those predicted from the model. HR increased and decreased by 3.25 beats/min (bpm) on 30 degrees up and down tilting respectively and by twice this amount when tilting through 60 degrees. Arm systolic and diastolic BP both decreased by 1.3 mmHg when tilting through 60 degrees from down to up and increased correspondingly with down-tilting. Calf systolic BP changed appropriately for the change in hydrostatic pressure (+7.37 mmHg with 30 degrees up tilting), but diastolic BP rose only by 60% of this value. The results showed no individual variation, were independent of day, sleep state, the number of tilts, the starting value of the BP and the direction of the previous tilt. This study shows that the healthy newborn has a well developed baroreceptor reflex.