Distribution pattern of sudanophilic plaques in the descending thoracic and proximal abdominal human aorta.

The localization of sudanophilic plaques around the intercostal ostia and the origin of the superior mesenteric and coeliac artery was examined in 38 human aortae. The perimeter of the opened aorta and the outline of each sudanophilic plaque were digitized and computerized. By means of a special program the results were displayed as progressive contour lines connecting points with an equal frequency of plaques. This study shows that the sudanophilic plaques have a distinct spatial distribution both in the thoracic and abdominal aorta. Around the intercostal ostia peak frequency of plaques is found just proximal to the lower lip of the ostia. In the bifurcation of both the superior mesenteric and coeliac artery the plaques are present on the outer walls while the inner walls and the apex itself are free of plaques.

Localization of atherosclerotic lesions in the bifurcation of the main left coronary artery.

The detailed distribution of atherosclerotic lesions in the branching region of the left main coronary artery in man was studied. Tissue cubes of the hearts, containing the left coronary arteries, were removed, and 1.5-mm-thick parallel and consecutive slices were cut perpendicular to the main coronary artery. Histological sections of the slices were stained and photographed. Drawings of the cross-sections of the arteries, including information about thickness of the intima and borders of the atherosclerotic lesions, were fed into a computer, scaled and analyzed. Casts were made of the left main coronary bifurcation from additional hearts. The curvature of the arteries and the angles of the bifurcation were measured. Atherosclerotic lesions have a distinct pattern with a high frequency on the outer walls of the bifurcation and at the inner curvature downstream from the bifurcation. The extent of intimal thickening and the occurrence of atherosclerotic lesions were mostly in agreement.

Sequential or fixed sample trial design? A case study by stochastic simulation.

The properties of Wilcoxon's rank sum test for fixed sample size and a Wilcoxon-type two-sample sequential test have been illustrated and compared by means of stochastic simulation. Data from a real fixed sample trial have been used, both for resampling from the original data, and for construction of an idealized theoretical distribution. The sequential and the fixed sample test obtain equal power, but the sequential test mostly includes considerably fewer patients to reach a conclusion, i.e. the mean and median number of patients included are both much lower than the fixed sample size. Under the hypotheses only a small fraction of the simulation runs exceed the fixed sample size. These findings exemplify results obtained in theoretical analyses and simulation studies covering a wide range of distributions. In our opinion sequential tests have obvious advantages and are in many cases better alternatives than fixed sample tests in clinical trials.

Arm and leg blood pressures--are they really so different in newborns?

Controversy still exists over differences between upper and lower limb blood pressures (BP) in neonates. We measured upper arm and calf systolic (S) and diastolic (D) BP and heart rate (HR) using 2 Dinamap 847 instruments simultaneously every half minute for several measurement periods of 5-10 min. Nine healthy term newborns were studied in active (AS) and quite (QS) sleep on post-natal days 1 and 5. The results were examined using unbalanced analyses of variance. Arm SBP was 62.3 +/- 1.6 mmHg and DBP 35.5 +/- 1.0 mmHg on day 1 in AS and QS. Calf values were not significantly different but were slightly higher (by 2-3 mmHg) in AS. Arm SBP and DBP rose by 8.5 and 5 mmHg, respectively, between days 1 and 5 but calf pressures rose less. Calf SBP and DBP were significantly lower (by 4.6 and 3.4 mmHg, respectively) than the arm values in QS on day 5. Arm SBP and DBP were dependent on post-natal age but not on sleep state while calf SBP and DBP and HR were dependent on both. Mean HR rose with age from 114 to 117.6 bpm in QS and from 118.6 to 122.4 bpm in AS. Our non-invasive BP measurements were similar to available invasive data. We postulate that differences in arm and calf vasoreactivity account for the different dependence on sleep state and for the unequal changes in arm and calf BE from days 1 to 5.

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.

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.

Recording of short-term finger blood pressure changes induced by an arterial occlusive thigh cuff: comparison between the modified oscillometric and Finapres techniques.

Blood pressure recordings obtained by the volume clamp method (Finapres monitor, Ohmeda, USA) were compared with measurements by using a novel modification of the oscillometric method (UT9201 beat-to-beat monitor, University of Tartu, Estonia). Step changes in total peripheral resistance were introduced in 11 healthy volunteers by rapid inflation to the suprasystolic pressure of bilateral thigh cuffs during a rhythmical exercise with the quadriceps muscles and simultaneously performed handgrip compression. The provoked short-term changes in mean arterial pressure (MAP) were similarly tracked by both devices. The agreement between the methods was better for MAP rise than drop. The group-averaged difference UT9201 minus Finapres did not exceed 1.2 mmHg (NS, p = 0.46) after cuff successive inflation but yielded 3.8 mmHg (significant, p < 0.05) after cuff successive deflation.

Improved method for cardiac output determination in man using ultrasound Doppler technique.

An existing ultrasound Doppler method for measuring cardiac output has been improved and refined, partly by locating the sampling volume higher up in the aorta while still using the aortic ring size as the effective transverse flow area. The basis for using this technique is the approximately rectangular systolic velocity profile in the aortic orifice in physiologically and anatomically normal subjects, and the fact that this profile velocity is conserved as the maximum velocity in the ascending aorta for some 3 to 4 cm above the valves. This higher location of the sampling volume improves Doppler signal quality, and does not reduce the accuracy of the method, as can be confirmed in each experimental subject. Together with automatic computer-based online signal analysis, the technique employed enables us to make continuous long-term beat-to-beat measurements of cardiac output in subjects without aortic valve disease or grossly deforming disease of the aortic root.

Stroke volume decreases during mild dynamic and static exercise in supine humans.

AIM: The contributions of cardiac output (CO) and total peripheral resistance to changes in arterial blood pressure are debated and differ between dynamic and static exercise. We studied the role stroke volume (SV) has in mild supine exercise. METHODS: We investigated 10 healthy, supine volunteers by continuous measurement of heart rate (HR), mean arterial blood pressure, SV (ultrasound Doppler) and femoral beat volume (ultrasound Doppler) during both dynamic mild leg exercise and static forearm exercise. This made it possible to study CO, femoral flow (FF) and both total and femoral peripheral resistance beat-by-beat. RESULTS: During a countdown period immediately prior to exercise, HR and mean arterial pressure increased, while SV decreased. During mild supine exercise, SV decreased by 5-8%, and most of this was explained by increased mean arterial pressure. Dynamic leg exercise doubled femoral beat volume, while static hand grip decreased femoral beat volume by 18%. FF is tightly regulated according to metabolic demand during both dynamic leg exercise and static forearm exercise. CONCLUSION: Our three major findings are, firstly, that SV decreases during both dynamic and static mild supine exercise due to an increase in mean arterial pressure. Secondly, femoral beat volume decreases during static hand grip, but FF is unchanged due to the increase in HR. Finally, anticipatory responses to exercise are apparent prior to both dynamic and static exercise. SV changes contribute to CO changes and should be included in studies of central haemodynamics during exercise.

Hypothermia during laparotomy can be prevented by locally applied warm water and pulsating negative pressure.

BACKGROUND: Conflicting results have been obtained when using heat and constant negative pressure applied to the arm to induce re-warming in patients with mild hypothermia due to surgery. We hypothesized that pulsating negative pressure would increase skin blood flow and thus heat transfer. The purpose of this study was to compare a new method of applying heat and pulsating negative pressure to the skin with conventional forced-air warming for preventing perioperative hypothermia. METHODS: Twenty patients undergoing prolonged laparotomy for gastric surgery were randomized into two groups. One group (SM) received hospital standard method: forced-air warming, 43 degrees C (Bair Hugger) on the thoracic and upper arm surface. The other group (NM) received the new method: warm water and pulsating negative pressure treatment applied in a transparent acrylic cylinder (50 x 16 cm) on one arm. The cylinder was circulated with water at 42.5 degrees C, leaving an air pocket inside the device. Pulsating pressure between 0 and -40 mm Hg was generated in the air pocket inside the cylinder. RESULTS: Two groups of 10 patients were studied. Warming was started shortly after induction of general anaesthesia. The two methods performed similarly during the first 60 min, with a mean 0.7 degrees decrease in core temperature. The tympanic temperature curve in NM group then increased and returned to baseline (37 degrees C) by 120 min. The temperature of SM group increased more slowly, reaching 36 degrees C by 120 min (P < 0.05). CONCLUSION: Warm water and pulsating negative pressure was significantly better at treating hypothermia during laparotomy than forced-air warming.

On the transmission of information through sensory neurons.

Information about muscle length is transmitted to the cerebellum from muscle spindle receptors through the dorsal spinocerebellar tract (DSCT). The "transinformation" about muscle length in single DSCT fibers was calculated from steady-state spike trains by two different methods, assuming that the decoding mechanisms use a frequency code. By the first method, the number of distinguishable muscle lengths (and thus the transiformation) was determined from the rate of convergence of the mean frequency of firing (with increasing number of intervals). The observation time necessary to estimate the mean frequency of the impulse train with a certain accuracy was independent of the stretch level, even though the number of intervals necessary to make this estimate was different at high and low levels of stretch. By the second method an input frequency-output frequency matrix was calculated. The transinformations and the rate of transinformation was then calculated from this matrix. There was an acceptable agreement in the estimates of transinformation by the two methods. The rates of transinformation are significantly increased by the particular time structure of the discharge patterns of the nerve cells. Consequently, the loss of information due to the synaptic coupling is appreciably reduced.

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.

Summation of excitation and inhibition in a second order sensory neuron investigated by computer simulation.

Dorsal spinocerebellar tract (DSCT) neurones adequately activated by primary afferents from the muscle spindles in one muscle in the hindleg of the cat, is regularly inhibited by primary afferents from other muscles. The inhibitory input causes a constant reduction in firing frequency independent of the excitatory drive of the cell. In a simple model the effects of presynaptic inhibition and of postsynaptic inhibition with different time course of the inhibitory action, have been explored. Within the scope of this model, only postsynaptic inhibition with a very long time-constant could explain the experimental results. It is suggested that the inhibitory action is transmitted to the DSCT-cell through a number of synapses distributed over the dendrites.

Skin blood flow in humans as a function of environmental temperature measured by ultrasound.

We have measured the blood velocities in arteries supplying the skin in humans both in areas with arteriovenous anastomoses (AVA) and in skin areas without AVA in different temperature situations by means of a pulsed, bidirectional doppler ultrasound instrument. The instrument measures the time average of the instantaneous mean of the blood velocities present in a cross-section of a vessel. So long as the cross-sectional area of the vessel is constant, this average velocity is proportional to volume flow. We observe rapid and large fluctuations in blood velocities in arteries supplying skin areas with AVA in a comfortably warm environment. These fluctuations are substantially larger and more rapid than described by previous authors who have used plethysmograph methods. The blood velocities are more constant both at higher and lower environmental temperatures. There are no similar fluctuations in blood velocity in arteries supplying skin areas without AVA.

Firing behaviour in a stochastic nerve membrane model based upon the Hodgkin-Huxley equations.

A nerve membrane model with a two-state pore system was investigated by computer simulation in the uniform (space-clamped) case. Both sodium and potassium conducting pores were modelled, each pore having four independent gates which switched randomly between the open and the closed position, governed by the assumed rate constants. Each pore conducted only when all the gates were open. The model was based upon the Hodgkin-Huxley equations for the giant axon in squid, and in the limit of an infinite number of pores it was identical to these. The firing behaviour of this model as a function of the number of pores and the injected current were investigated. The mean firing frequency and the distribution of interspike intervals were mainly used in the presentation of the results. It was found that for pore numbers less than about 20 000 the main effects due to a finite number of pores were a lowering of the current threshold for firing and a more linear frequency current relationship relative to that of the original H-H equations. For higher pore numbers an increase in the current threshold and a pronounced burst firing close to the threshold were found.

Transfer properties of the slowly adapting stretch receptor of the crayfish abdomen.

The slowly adapting stretch receptor in the abdomen of freshwater crayfish (Astacus fluviatilis) was investigated to determine its properties under dynamic conditions. An in situ preparation was used; the necessary dissection did not involve the receptor organ or its immediate surroundings. Sinusoidal variations in the angle of flexion in the joint to which the receptor organ was connected, were generated by a feed-back controlled stretcher. Nerve spiked recorded from the axon of the receptor neurone and information about angle of flexion in the joint obtained by position transducers, were fed into a computer. Fourier transforms were performed on both input and output data to determine the amplitude of the 0. and 1. harmonic together with the phase of the 1. harmonic. The receptor organ was investigated for linearity up to 1.5 degrees input amplitude, and proved to be surprisingly linear within this range. In addition, the transfer function of the receptor organ was determined by stimulating it with small-amplitude sinusoidals with different frequencies. With a steady flexion of 35-40 degrees in the joint, the gain of the receptor organ increased 5-6 times when the modulation frequency of the input signal was increased from 0.1 to 5 cycles/s. A maximum in gain was constantly found at about 5 cycles/s, with a rapid fall towards 0 when the modulation frequency was increased further. A change in phase lead from positive (leading output) to negative with change in sign about 1 cycle/s was also found. These results resemble the results found by investigators of isolated preparations. A "hold" property is probably a part of the overall property of the receptor organ together with an element of Maxwell type. An element of the form h(s) = ksn with n approximately 0.45 is also a part of the transfer function of the receptor organ, although the physiological parallel to this element is uncertain.

Reflex inhibition of the slowly adapting stretch receptors in the intact abdomen of the crayfish.

The reflex inhibition of abdominal stretch receptors in crayfish was studied by controlled passive flexion of individual abdominal joints. The results are very similar to those obtained by electrical or mechanical stimulation of individual stretch receptors in immobilized abdomens. Reflex effects from posterior to anterior abdominal segments are somewhat stronger than in the opposite direction. Flexion of one abdominal joint excites the stretch receptors of that joint and inhibits the stretch receptors in neighbouring abdominal segments. Without reflex inhibition flexion of one abdominal joint excites the stretch receptors in several abdominal segments.

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.

Thermoregulatory fluctuations in heart rate and blood pressure in humans: effect of cooling and parasympathetic blockade.

The spontaneous fluctuations in acral skin blood flow, mean blood pressure (MAP), and heart rate (HR) were studied in 9 healthy supine volunteers in a thermoneutral and in a cool environment, and after parasympathetic blockade by atropine. In skin areas with a high density of arteriovenous anastomoses (AVAs), there were large, spontaneous fluctuations in blood flow in a thermoneutral environment. The fluctuations were nearly abolished in a cool environment, while they seemed unaffected by atropine administration. Power spectral analysis demonstrated a reduction in HR and MAP variability in the low- and mid-frequency (LF) (< 0.15 Hz) band after cooling, and a prominent reduction in HR variability in both the LF and the high-frequency (HF) (< 0.15 Hz) band after atropine administration. A sudden drop in skin vascular conductance was accompanied by diphasic HR changes and an increase in MAP. After atropine administration, the initial HR acceleration was delayed and reduced in magnitude. The secondary HR deceleration, which probably represents baroreceptor modulation, was abolished. Atropine administration caused a delayed, but augmented increase in MAP, which was probably related to the loss of baroreceptor control of HR. The presence of an autonomic rhythm, consisting of sympathetic vasoconstrictor impulses to skin AVAs, connected with reciprocal sympathetic and vagal impulses to the heart, is indicated. The HR changes were mainly determined by vagal activity. The rhythmic changes in skin blood flow, HR and MAP were suppressed in a cool environment.