Maja Elstad

Respiratory sinus arrhythmia: opposite effects on systolic and mean arterial pressure in supine humans

1 Are arterial blood pressure fluctuations buffered or reinforced by respiratory sinus arrhythmia (RSA)? There is still considerable debate about this simple question. Different results have been obtained, triggering a discussion as to whether or not the baroreflexes are responsible for RSA. We suspected that the measurements of different aspects of arterial pressure (mean arterial pressure (MAP) and systolic pressure (SP)) can explain the conflicting results. 2 Simultaneous recordings of beat‐to‐beat MAP, SP, left cardiac stroke volume (SV, pulsed ultrasound Doppler), heart rate (HR) and respiration (RE) were obtained in 10 healthy young adults during spontaneous respiration. In order to eliminate HR variations at respiratory frequency we used propranolol and atropine administration in the supine and tilted positions. Respiration‐synchronous variation in the recorded variables was quantified by spectral analysis of the recordings of each of these variables, and the phase relations between them were determined by cross‐spectral analysis. 3 MAP fluctuations increased after removing heart rate variations in both supine and tilted position, whereas SP fluctuations decreased in the supine position and increased in the head‐up tilted position. 4 RSA buffers respiration‐synchronous fluctuations in MAP in both positions. However, fluctuations in SP were reinforced by RSA in the supine and buffered in the tilted position.

Hypothermia is not neuroprotective after infection-sensitized neonatal hypoxic-ischemic brain injury

BACKGROUND Therapeutic hypothermia (HT) is the standard treatment after perinatal hypoxic-ischemic (HI) injury. Infection increases vulnerability to HI injury, but the effect of HT on lipopolysaccharide (LPS) sensitized HI brain injury is unknown. DESIGN/METHODS P7 rat pups were injected either with vehicle or LPS, and after a 4h delay they were exposed to left carotid ligation followed by global hypoxia inducing a unilateral stroke-like HI injury. Pups were randomized to the following treatments: (1) vehicle treated HI-pups receiving normothermia treatment (NT) (Veh-NT; n=30); (2) LPS treated HI-pups receiving NT treatment (LPS-NT; n=35); (3) vehicle treated HI-pups receiving HT treatment (Veh-HT; n=29); or (4) LPS treated HI-pups receiving HT treatment (LPS-HT; n=46). Relative area loss of the left/right hemisphere and the areas of hippocampi were measured at P14. RESULTS Mean brain area loss in the Veh-NT group was 11.2±14%. The brain area loss in LPS-NT pups was 29.8±17%, which was significantly higher than in the Veh-NT group (p=0.002). The Veh-HT group had a significantly smaller brain area loss (5.4±6%), when compared to Veh-NT group (p=0.043). The LPS-HT group showed a brain area loss of 32.5±16%, which was significantly higher than in the Veh-HT group (p<0.001). LPS-HT group also had significantly smaller size of the left hippocampus, which was not found in other groups. LPS-sensitization significantly decreased the sizes of the right, unligated-hemispheres, independent of post-HI treatment. CONCLUSIONS Therapeutic hypothermia is not neuroprotective in this LPS-sensitized unilateral stroke-like HI brain injury model in newborn rats. Lack of neuroprotection was particularly seen in the hippocampus. Pre-insult exposure to LPS also induced brain area loss in the unligated hemisphere, which is normally not affected in this model.

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.

Cerebral Resistance Index is less predictive in hypothermic encephalopathic newborns

Aim:  Neonatal hypoxic‐ischaemic encephalopathy (HIE), if severe, may involve cerebral vasoparalysis. In HIE, Pourcelot’s cerebral vascular resistance index (RI) below 0.55 (by Doppler ultrasound) from published literature at normothermia predicted poor outcome with a positive predictive value (PPV) of 84%. The aim of this study was to re‐assess RI as a predictor of outcome in HIE during hypothermia.

Respiratory variations in pulmonary and systemic blood flow in healthy humans

Cardiovascular oscillations are tightly coupled to respiration. Respiratory sinus arrhythmia (RSA) is an important part of heart rate variability with unknown function. Stroke volumes from the right (r‐SV) and left (l‐SV) side of the heart are assumed to vary differently with respiration, but have not previously been recorded non‐invasively and simultaneously in humans. The present study introduces an improved technique for capturing respiratory variations in r‐SV.

Low-frequency fluctuations in heart rate, cardiac output and mean arterial pressure in humans: what are the physiological relationships?

Objective Cardiovascular variability is a complex physiological phenomenon associated with the outcome of cardiovascular diseases. Blood pressure oscillations may cause cardiovascular complications, which, however, are also claimed to have antihypertensive effects. The physiological understanding is limited. This study evaluates whether oscillations in heart rate (HR) and cardiac output (CO) buffer fluctuations at approximately 0.1 Hz in arterial blood pressure (Mayer waves). Method We recorded mean arterial pressure (MAP), left cardiac stroke volume (SV), and HR in 10 healthy humans during autonomic blockade in supine and tilted (30 degrees) position. Variability in the cardiovascular variables at 0.04–0.15 Hz and phase angles (time lags) between the variables were calculated by spectral analysis. Results Fluctuations in cardiovascular variables at 0.1 Hz decreased after removal of HR variability (HRV) by propranolol and atropine in the supine position. Tilting from supine did not change fluctuations in MAP or total peripheral resistance (TPR), whereas variations in CO decreased. Variations in CO remained decreased in tilt after atropine compared to supine control, whereas variations in MAP and in TPR were unchanged. HRV were in phase with oscillations in CO. Variations in CO were in inverse phase with variations in TPR. Conclusion TPR oscillations produce fluctuations in MAP at 0.1 Hz. HRV produces CO variations, but CO variations do not efficiently buffer MAP variations during supine rest and mild ortostasis. Both feedback and feedforward mechanisms are responsible for the interaction between HR and MAP.

Hypothermia makes cerebral resistance index a poor prognostic tool in encephalopathic newborns.

Background: Severe neonatal encephalopathy (NE) of hypoxic-ischaemic origin may cause death or life-long disability. Acute encephalopathy may also affect cerebrovascular control. Pourcelots cerebrovascular resistance index (RI) ≤0.55 was predictive of poor outcome in normothermic NE infants. Recent studies have questioned its predictive power during therapeutic hypothermia (HT). Objective: To assess the predictive power of RI during HT and after rewarming. Methods: 45 infants with NE treated with HT for 72 h had their RI calculated during early (median 11 h) and late (median 62 h) cooling and after rewarming (median 89 h). Poor outcome was defined as death or abnormalities on day 10 magnetic resonance imaging shown to predict severe neuromotor disability. Results: RI ≤0.55 during cooling did not differentiate between good and poor outcome (late cooling, p = 0.08), but was powerful after rewarming (p = 0.004). RI ≤0.55 predicted true poor outcome in 43% (95% confidence interval (CI): 12, 80) during late cooling and in 100% (95% CI: 31, 100) after rewarming. RI >0.55 predicted good outcome in 86% (95% CI: 69, 95) during late cooling and in 89% (95% CI: 74, 96) after rewarming. Conclusions: Low RI is not predictive of poor outcome during HT in NE infants, but regains the predictive power seen in normothermic infants after rewarming.

Model simulations of cardiovascular changes at the onset of moderate exercise in humans.

We have tested whether the cardiovascular changes at the onset of exercise could be simulated only by an increase in the baroreflex set point and locally induced vasodilatation in the exercising muscles. The mathematical model consists of a heart, a linear elastic arterial reservoir and two parallel resistive vascular beds. The arterial baroreflex loop is modelled by three separate time domain processing objects, each with its own gain, time constant and delay. These are intended to simulate the action of a sympathetic signal to the peripheral vascular bed, a parasympathetic signal to the heart and a sympathetic signal to the heart. We used this model with previously published experimental data to estimate the unknown parameters in the reflex control loop. In all 10 subjects and in the global averaged response, the short‐term cardiovascular responses were adequately simulated by using individual sets of parameters in the model. An increase in the baroreflex set point and locally induced vasodilatation in the exercising muscles can explain almost all of the cardiovascular changes in the recorded variables (mean arterial pressure, RR interval and stroke volume) at the onset of exercise.

Heart rate variability and stroke volume variability to detect central hypovolemia during spontaneous breathing and supported ventilation in young, healthy volunteers

Cardiovascular oscillations exist in many different variables and may give important diagnostic and prognostic information in patients. Variability in cardiac stroke volume (SVV) is used in clinical practice for diagnosis of hypovolemia, but currently is limited to patients on mechanical ventilation. We investigated if SVV and heart rate variability (HRV) could detect central hypovolemia in spontaneously breathing humans: We also compared cardiovascular variability during spontaneous breathing with supported mechanical ventilation.Ten subjects underwent simulated central hypovolemia by lower body negative pressure (LBNP) with >10% reduction of cardiac stroke volume. The subjects breathed spontaneously and with supported mechanical ventilation. Heart rate, respiratory frequency and mean arterial blood pressure were measured. Stroke volume (SV) was estimated by ModelFlow (Finometer). Respiratory SVV was calculated by: 1) SVV% = (SVmax - SVmin)/SVmean during one respiratory cycle, 2) SVIntegral from the power spectra (Fourier transform) at 0.15-0.4 Hz and 3) SVV_norm = (√SVIntegral)/SVmean. HRV was calculated by the same methods.During spontaneous breathing two measures of SVV and all three measures of HRV were reduced during hypovolemia compared to baseline. During spontaneous breathing SVIntegral and HRV% were best to detect hypovolemia (area under receiver operating curve 0.81). HRV% ≤ 11% and SVIntegral ≤ 12 ml(2) differentiated between hypovolemia and baseline during spontaneous breathing.During supported mechanical ventilation, none of the three measures of SVV changed and two of the HRV measures were reduced during hypovolemia. Neither measures of SVV nor HRV were classified as a good detector of hypovolemia.We conclude that HRV% and SVIntegral detect hypovolemia during spontaneous breathing and both are candidates for further clinical testing.

Responses in acral and non-acral skin vasomotion and temperature during lowering of ambient temperature.

Arteriovenous anastomoses (AVA) in acral skin (palms and soles) have a huge capacity to shunt blood directly from the arteries to the superficial venous plexus of the extremities. We hypothesized that acral skin, which supplies blood to the superficial venous plexus, has a stronger influence on blood flow adjustments during cooling in thermoneutral subjects than does non-acral skin. Thirteen healthy subjects were exposed to stepwise cooling from 32 °C to 25 °C and 17 °C in a climate chamber. Laser Doppler flux and skin temperature were measured simultaneously from the left and right third finger pulp and bilateral upper arm skin. Coherence and correlation analyses were performed of short-term fluctuations at each temperature interval. The flux from finger pulps showed the synchronous spontaneous fluctuations characteristic of skin areas containing AVAs. Fluctuation frequency, amplitude and synchronicity were all higher at 25 °C than at 32 °C and 17 °C (p<0.02). Bilateral flux from the upper arm skin showed an irregular, asynchronous vasomotor pattern with small amplitudes which were independent of ambient temperature. At 32 °C, ipsilateral median flux values from the right arm (95% confidence intervals) were 492 arbitrary units (au) (417, 537) in finger pulp and 43 au (35, 60) in upper arm skin. Flux values gradually decreased in finger pulp to 246 au (109, 363) at 25 °C, before an abrupt fall occurred at a median room temperature of 24 °C, resulting in a flux value of 79 au (31, 116) at 17 °C. In the upper arm skin a gradual fall throughout the cooling period to 21 au (13, 27) at 17 °C was observed. The fact that the response of blood flow to ambient cooling is stronger in acral skin than in non-acral skin suggests that AVAs have a greater capacity to adjust blood flow in thermoneutral zone than arterioles in non-acral skin.