Kristin Lossius

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.

Heart rate response to transient chemoreceptor stimulation in term infants is modified by exposure to maternal smoking.

Modulation of heart rate (HR) during transient hyperoxia, hypoxia, and hypercapnia was studied in 46 healthy term infants on 103 occasions (postnatal d 2 to 82). Twenty-three infants had smoking mothers (median, 11 cigarettes/d). Transient chemoreceptor stimuli (100% O2, 15% O2, or 3% CO2) were presented repeatedly during quiet sleep. Beat-by-beat HR and breath-by-breath ventilation were recorded continuously. The coherently averaged HR and ventilation responses to each stimulus were calculated for each infant at each age. Outcome variables (HR change from baseline to end of stimulation, maximum HR change, and time to half-maximum) were analyzed by ANOVA. Overall, HR declined during hyperoxia (median change, 4.2 beats/min) and rose during hypoxia (median change, 4.2 beats/min) and hypercapnia (median change, 4.6 beats/min). The percentage change in HR was positively correlated with the percentage change in ventilation (p < 0.001). Increasing number of cigarettes smoked by the mother was correlated with deeper HR declines and smaller HR rises (p = 0.02). For the population as a whole, the HR response lagged 3.8 s behind the ventilatory response during hyperoxia and hypoxia (p < 0.001), whereas during hypercapnia there was no significant lag. The lag in HR response in the smoke-exposed group was 2.5 s greater than that in the control group for all three stimuli (p = 0.001), and the difference increased with the number of cigarettes smoked by the mother (p < 0.01). Both pulmonary reflexes and the type of the chemoreceptor stimulus seemed to influence HR. Maternal smoking affected the magnitude and time-course of the HR response in a dose-dependent manner.

Development of Ventilatory Response to Transient Hypercapnia and Hypercapnic Hypoxia in Term Infants

Whereas peripheral chemoreceptor oxygen sensitivity increases markedly after birth, previous studies of ventilatory responses to CO2 in term infants have shown no postnatal development. However, the hypercapnic challenges applied have usually been long-term, which meant that the effect of central chemoreceptors dominated. Oscillatory breathing, apneas, and sighs cause transient Pco2 changes, probably primarily stimulating peripheral chemoreceptors. We wanted to assess whether the immediate ventilatory responses to step changes in inspired CO2 and O2 in term infants undergo postnatal developmental changes. Twenty-six healthy term infants were studied during natural sleep 2 d and 8 wk postnatally. Ventilatory responses to a randomized sequence of 15 s hypercapnia (3% CO2), hypoxia (15% O2), and hypercapnic hypoxia (3% CO2 + 15% O2) were recorded breath-by-breath using a pneumotachometer. Response rate, stimulus-response time, and response magnitude were analyzed with ANOVA after coherent averaging. Response rate increased with age by 30% (hypercapnia), 318% (hypoxia), and 302% (hypercapnic hypoxia). Response rate during hypercapnic hypoxia exceeded rate during hypercapnia plus rate during hypoxia in wk 8, but not on d 2. Time to half-maximum response decreased by 3.4 s with age for the two hypercapnic stimuli but was unchanged for hypoxia. Response magnitude was unchanged for hypercapnia, but increased for the two hypoxic stimuli. In conclusion, an interaction between the effects of hypercapnia and hypoxia on ventilatory response rate emerged between postnatal d 2 and wk 8 in term infants. Concomitantly, stimulus-response time to hypercapnic stimuli declined markedly. The development of a prompt response to transient hypercapnia may be important for infant respiratory stability.

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.

Postnatal changes in mechanisms mediating acetylcholine-induced relaxation in piglet femoral arteries

We studied the nitric oxide-cGMP pathway in endothelium-dependent relaxation in femoral arterial rings from piglets at different postnatal ages. Responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were examined in phenylephrine-precontracted rings from newborn (10-22-h) and 7 d(7-10-d)-old piglets. Relaxant responses were investigated in endothelium-denuded rings and endothelium-intact controls, and in endothelium-intact rings incubated with the nitric oxide synthase (NOS) inhibitor NG-monomethyl-L-arginine acetate (L-NMMA), indomethacin, or the superoxide anion generator 6-anilinoquinoline-5,8-quinone(LY83583). Arterial rings from both age groups relaxed to a similar degree in response to ACh. Relaxation in rings from newborn piglets was insensitive to NOS inhibition by L-NMMA, whereas in artery rings from 7-d-old piglets, the relaxant response was significantly inhibited by L-NMMA. Incubation with LY83583 gave an inhibition of ACh-induced relaxation very similar to that of L-NMMA. Incubation with indomethacin had no significant effect on ACh-induced relaxation in either age group. Artery rings from both age groups relaxed 100% to SNP; the 7-d-old group was more sensitive than the newborn. NOS inhibition potentiated SNP-induced relaxation in both groups, but the potentiating effect was of greater magnitude in the newborn. Our results indicate a difference in the mechanism(s) underlying ACh-induced relaxation in the femoral artery from newborn and 7-d-old piglets, with an intact relaxant response in rings from the newborn despite NOS inhibition. The SNP results indicate a down-regulated soluble guanylate cyclase in the newborn, possibly related to a difference in basal NO release between the two age groups.

A causal relationship between fluctuations in thermoregulatory skin perfusion and respiratory movements in man.

The relationship between regular respiration with normal tidal volume and spontaneous fluctuations in blood flow through skin arteriovenous anastomoses (AVAs) was investigated. Laser Doppler measurements from skin areas known to contain arteriovenous anastomoses, ultrasound Doppler measurements from the radial artery and respiratory movements were recorded simultaneously in 7 supine human subjects in a thermoneutral environment. The phase relationship between respiration and the onset of sudden arteriovenous anastomoses vasoconstrictions was calculated in each subject. A few seconds before a vasoconstriction, there was a clear tendency towards synchrony in the respiration recordings, indicating that some respiration-phase-dependent event precedes the vasoconstrictions. Since arteriovenous anastomoses constrictions are accompanied by specific changes in heart rate and blood pressure, our findings link respiration to low-frequency heart rate and blood-pressure variability in humans.

Connection between skin arteriovenous shunt flow fluctuations and heart rate variability in infants

Large, spontaneous fluctuations in blood flow to acral skin, caused by synchronous opening and closing of arteriovenous anastomoses (AVAs), have been demonstrated in adults in a thermoneutral environment. Individual AVA constrictions were accompanied by a diphasic heart rate (HR) response, indicating the presence of an autonomic rhythm which affected both skin AVA activity and heart rate variability. In the present study, 24 neonates were examined on day 2 (range 1-3 days) and re-examined at 14 weeks (11-17 weeks). The presence of rhythmic, synchronous fluctuations in laser Doppler flux in the palm of the hand and sole of the foot in 20 of 24 neonates strongly indicated the presence of functional skin AVA at birth. Both neonates and 3-month-old infants showed a diphasic HR response in association with cutaneous AVA constrictions. The infant response differed from the adult response mainly by the longer duration of the secondary bradycardia. This may reflect different properties of the baroreceptor reflex in infants and adults.

A method of assessing ventilatory responses to chemoreceptor stimulation in infants

Various methods of assessing infant chemoreceptor responses have been reported in the literature. However, equipment dead space, trigeminal stimulation and inherent respiratory variability may have affected the results. A method is presented which attempts to reduce the effect of these factors and thereby isolate the chemoreceptor response. Inspiratory gas was delivered into a lightweight face mask with a pliable rim, minimal dead space and a connected pneumotachograph. Ventilatory data were computed breath by breath. Computer‐controlled electromagnetic valves allowed instantaneous switching between air and different gas mixtures, repeated in a randomized sequence. In 18 healthy term neonates, the mask increased ventilation by 12% (95% confidence interval 6—18%), measured by calibrated strain‐gauge bands. The effect on respiratory frequency and tidal volume differed significantly between sleep states. Neonates were challenged with short‐lasting hyperoxia, mild hypoxia, rebreathing and mild hypercapnia. Coherent averaging of several ventilatory responses from each sleep state reduced the variability while maintaining a high time‐resolution. □Chemoreceptors, infant, respiration, respiratory dead space

Postnatal Development of Oxygen Sensitivity in Infants of Smokers and Non-Smokers - A Matched Control Study

Postnatal Development of Oxygen Sensitivity in Infants of Smokers and Non-Smokers - A Matched Control Study

The Relative Contribution of NO and EDHF to Acetylcholine-Induced Relaxation in Femoral Artery Rings from Newborn and 2 week old Piglets |[diams]| 350

In the pulmonary and mesenteric circulation, NO is known to be an important vasodilator during the period of postnatal transitional circulation. Little is known about the contribution of endothelium-derived hyperpolarizing factor(EDHF). We previously demonstrated that the NOS-inhibitor L-NMMA had little effect on ACh-mediated relaxation in femoral artery rings from newborn piglets, whereas it significantly inhibited relaxation in rings from 2 week old piglets. We therefore hypothesized that EDHF is more important than NO in mediating ACh-induced relaxation in newborn arteries, and that the relative importance of NO increases with age.