Cerebral blood flow response to cardiorespiratory oscillations in healthy humans.

Dynamic cerebral autoregulation (CA) characterizes the cerebral blood flow (CBF) response to abrupt changes in arterial blood pressure (ABP). CA operates at frequencies below 0.15 Hz. ABP regulation and probably CA are modified by autonomic nervous activity. We investigated the CBF response and CA dynamics to mild increase in sympathetic activity. Twelve healthy volunteers underwent oscillatory lower body negative pressure (oLBNP), which induced respiratory-related ABP oscillations at an average of 0.22 Hz. We recorded blood velocity in the internal carotid artery (ICA) by Doppler ultrasound and ABP. We quantified variability and peak wavelet power of ABP and ICA blood velocity by wavelet analysis at low frequency (LF, 0.05-0.15 Hz) and Mayer waves (0.08-0.12 Hz), respectively. CA was quantified by calculation of the wavelet synchronization gamma index for the pair ABP-ICA blood velocity in the LF and Mayer wave band. oLBNP increased ABP peak wavelet power at the Mayer wave frequency. At the Mayer wave, ABP peak wavelet power increased by >70 % from rest to oLBNP (p < 0.05), while ICA blood flow velocity peak wavelet power was unchanged, and gamma index increased (from 0.49 to 0.69, p < 0.05). At LF, variability in both ABP and ICA blood velocity and gamma index were unchanged from rest to oLBNP. Despite an increased gamma index at Mayer wave, ICA blood flow variability was unchanged during increased ABP variability. The increased synchronization during oLBNP did not cause less stable CBF or less active CA. Sympathetic activation seems to improve the mechanisms of CA.

Respiratory Sinus Arrhythmia is Mainly Driven by Central Feedforward Mechanisms in Healthy Humans.

Heart rate variability (HRV) has prognostic and diagnostic potential, however, the mechanisms behind respiratory sinus arrhythmia (RSA), a main short-term HRV, are still not well understood. We investigated if the central feedforward mechanism or pulmonary stretch reflex contributed most to RSA in healthy humans. Ventilatory support reduces the centrally mediated respiratory effort but remains the inspiratory stretch of the pulmonary receptors. We aimed to quantify the difference in RSA between spontaneous breathing and ventilatory support. Nineteen healthy, young subjects underwent spontaneous breathing and non-invasive intermittent positive pressure ventilation (NIV) while we recorded heart rate (HR, from ECG), mean arterial pressure (MAP) and stroke volume (SV) estimated from the non-invasive finger arterial pressure curve, end-tidal CO2 (capnograph), and respiratory frequency (RF) with a stretch band. Variability was quantified by an integral between 0.15-0.4 Hz calculated from the power spectra. Median and 95% confidence intervals (95%CI) were calculated as Hodges-Lehmann's one-sample estimator. Statistical difference was calculated by the Wilcoxon matched-pairs signed-rank test. RF and end-tidal CO2 were unchanged by NIV. NIV reduced HR by 2 bpm, while MAP and SV were unchanged in comparison to spontaneous breathing. Variability in both HR and SV was reduced by 60% and 75%, respectively, during NIV as compared to spontaneous breathing, but their interrelationship with respiration was maintained. NIV reduced RSA through a less central respiratory drive, and pulmonary stretch reflex contributed little to RSA. RSA is mainly driven by a central feedforward mechanism in healthy humans. Peripheral reflexes may contribute as modifiers of RSA.

Mathematical modelling of atrial and ventricular pressure-volume dynamics and their change with heart rate.

This paper presents mathematical models that can simulate the cardiovascular system of a healthy sheep under normal resting conditions in which the heart rate changes significantly. The models include several new modelling features that are introduced progressively. The contraction of the cardiac chambers is modelled using a time-dependent muscle force with constant elasticity instead of time dependent elasticity. A new hypothesis about the mechanical contraction of the atria generates realistic pressure volume (PV) loops. The inter-ventricular interaction is modelled as well. Additionally, hysteresis is incorporated in the aortic valve to produce an end-systolic reverse (negative) flow. Most of the model parameter values are based on previous literature data while time periods of delay, atrial and ventricular contraction are derived using experimental data from 14 sheep. We provide new relationships between contraction time and delay as a function of heart period. The effects of different aspects of our modelling on the mean cardiac output, stroke volume, ejection time, ejection fraction and PV loops are studied. Model outputs are compared with published experimental results where possible, and are within a wide range of physiological observations.

Internal Carotid Artery Blood Flow Response to Anesthesia, Pneumoperitoneum, and Head-up Tilt during Laparoscopic Cholecystectomy.

BACKGROUND: Little is known about how implementation of pneumoperitoneum and head-up tilt position contributes to general anesthesia-induced decrease in cerebral blood flow in humans. We investigated this question in patients undergoing laparoscopic cholecystectomy, hypothesizing that cardiorespiratory changes during this procedure would reduce cerebral perfusion. METHODS: In a nonrandomized, observational study of 16 patients (American Society of Anesthesiologists physical status I or II) undergoing laparoscopic cholecystectomy, internal carotid artery blood velocity was measured by Doppler ultrasound at four time points: awake, after anesthesia induction, after induction of pneumoperitoneum, and after head-up tilt. Vessel diameter was obtained each time, and internal carotid artery blood flow, the main outcome variable, was calculated. The authors recorded pulse contour estimated mean arterial blood pressure (MAP), heart rate (HR), stroke volume (SV) index, cardiac index, end-tidal carbon dioxide (ETCO2), bispectral index, and ventilator settings. Results are medians (95% CI). RESULTS: Internal carotid artery blood flow decreased upon anesthesia induction from 350 ml/min (273 to 410) to 213 ml/min (175 to 249; -37%, P < 0.001), and tended to decrease further with pneumoperitoneum (178 ml/min [127 to 208], -15%, P = 0.026). Tilt induced no further change (171 ml/min [134 to 205]). ETCO2 and bispectral index were unchanged after induction. MAP decreased with anesthesia, from 102 (91 to 108) to 72 (65 to 76) mmHg, and then remained unchanged (Pneumoperitoneum: 70 [63 to 75]; Tilt: 74 [66 to 78]). Cardiac index decreased with anesthesia and with pneumoperitoneum (overall from 3.2 [2.7 to 3.5] to 2.3 [1.9 to 2.5] l · min · m); tilt induced no further change (2.1 [1.8 to 2.3]). Multiple regression analysis attributed the fall in internal carotid artery blood flow to reduced cardiac index (both HR and SV index contributing) and MAP (P < 0.001). Vessel diameter also declined (P < 0.01). CONCLUSIONS: During laparoscopic cholecystectomy, internal carotid artery blood flow declined with anesthesia and with pneumoperitoneum, in close association with reductions in cardiac index and MAP. Head-up tilt caused no further reduction. Cardiac output independently affects human cerebral blood flow.

Respiratory pump maintains cardiac stroke volume during hypovolemia in young, healthy volunteers.

Spontaneous breathing has beneficial effects on the circulation, since negative intrathoracic pressure enhances venous return and increases cardiac stroke volume. We quantified the contribution of the respiratory pump to preserve stroke volume during hypovolemia in awake, young, healthy subjects. Noninvasive stroke volume, cardiac output, heart rate, and mean arterial pressure (Finometer) were recorded in 31 volunteers (19 women), 19-30 yr old, during normovolemia and hypovolemia (approximating 450- to 500-ml reduction in central blood volume) induced by lower-body negative pressure. Control-mode noninvasive positive-pressure ventilation was employed to reduce the effect of the respiratory pump. The ventilator settings were matched to each subject's spontaneous respiratory pattern. Stroke volume estimates during positive-pressure ventilation and spontaneous breathing were compared with Wilcoxon matched-pairs signed-rank test. Values are overall medians. During normovolemia, positive-pressure ventilation did not affect stroke volume or cardiac output. Hypovolemia resulted in an 18% decrease in stroke volume and a 9% decrease in cardiac output ( P < 0.001). Employing positive-pressure ventilation during hypovolemia decreased stroke volume further by 8% ( P < 0.001). Overall, hypovolemia and positive-pressure ventilation resulted in a reduction of 26% in stroke volume ( P < 0.001) and 13% in cardiac output ( P < 0.001) compared with baseline. Compared with the situation with control-mode positive-pressure ventilation, spontaneous breathing attenuated the reduction in stroke volume induced by moderate hypovolemia by 30% (i.e., -26 vs. -18%). In the patient who is critically ill with hypovolemia or uncontrolled hemorrhage, spontaneous breathing may contribute to hemodynamic stability, whereas controlled positive-pressure ventilation may result in circulatory decompensation. NEW & NOTEWORTHY Maintaining spontaneous respiration has beneficial effects on hemodynamic compensation, which is clinically relevant for patients in intensive care. We have quantified the contribution of the respiratory pump to cardiac stroke volume and cardiac output in healthy volunteers during normovolemia and central hypovolemia. The positive hemodynamic effect of the respiratory pump was abolished by noninvasive, low-level positive-pressure ventilation. Compared with control-mode positive-pressure ventilation, spontaneous negative-pressure ventilation attenuated the fall in stroke volume by 30%.

Cardiorespiratory interactions in humans and animals: rhythms for life.

The cardiorespiratory system exhibits oscillations from a range of sources. One of the most studied oscillations is heart rate variability, which is thought to be beneficial and can serve as an index of a healthy cardiovascular system. Heart rate variability is dampened in many diseases including depression, autoimmune diseases, hypertension, and heart failure. Thus, understanding the interactions that lead to heart rate variability, and its physiological role, could help with prevention, diagnosis, and treatment of cardiovascular diseases. In this review, we consider three types of cardiorespiratory interactions: respiratory sinus arrhythmia (variability in heart rate at the frequency of breathing), cardioventilatory coupling (synchronization between the heart beat and the onset of inspiration), and respiratory stroke volume synchronization (the constant phase difference between the right and the left stroke volumes over one respiratory cycle). While the exact physiological role of these oscillations continues to be debated, the redundancies in the mechanisms responsible for its generation and its strong evolutionary conservation point to the importance of cardiorespiratory interactions. The putative mechanisms driving cardiorespiratory oscillations as well as the physiological significance of these oscillations will be reviewed. We suggest that cardiorespiratory interactions have the capacity to both dampen the variability in systemic blood flow as well as improve the efficiency of work done by the heart while maintaining physiological levels of arterial CO2. Given that reduction in variability is a prognostic indicator of disease, we argue that restoration of this variability via pharmaceutical or device-based approaches may be beneficial in prolonging life.

Dynamic cerebral autoregulation is preserved during isometric handgrip and head-down tilt in healthy volunteers.

In healthy humans, cerebral blood flow (CBF) is autoregulated against changes in arterial blood pressure. Spontaneous fluctuations in mean arterial pressure (MAP) and CBF can be used to assess cerebral autoregulation. We hypothesized that dynamic cerebral autoregulation is affected by changes in autonomic activity, MAP, and cardiac output (CO) induced by handgrip (HG), head-down tilt (HDT), and their combination. In thirteen healthy volunteers, we recorded blood velocity by ultrasound in the internal carotid artery (ICA), HR, MAP and CO-estimates from continuous finger blood pressure, and end-tidal CO2 . Instantaneous ICA beat volume (ICABV, mL) and ICA blood flow (ICABF, mL/min) were calculated. Wavelet synchronization index γ (0-1) was calculated for the pairs: MAP-ICABF, CO-ICABF and HR-ICABV in the low (0.05-0.15 Hz; LF) and high (0.15-0.4 Hz; HF) frequency bands. ICABF did not change between experimental states. MAP and CO were increased during HG (+16% and +15%, respectively, P < 0.001) and during HDT + HG (+12% and +23%, respectively, P < 0.001). In the LF interval, median γ for the MAP-ICABF pair (baseline: 0.23 [0.12-0.28]) and the CO-ICABF pair (baseline: 0.22 [0.15-0.28]) did not change with HG, HDT, or their combination. High γ was observed for the HR-ICABV pair at the respiratory frequency, the oscillations in these variables being in inverse phase. The unaltered ICABF and the low synchronization between MAP and ICABF in the LF interval suggest intact dynamic cerebral autoregulation during HG, HDT, and their combination.

Respiration-related cerebral blood flow variability increases during control-mode non-invasive ventilation in normovolemia and hypovolemia.

PURPOSE: Increased variability in cerebral blood flow (CBF) predisposes to adverse cerebrovascular events. Oscillations in arterial blood pressure and PaCO2 induce CBF variability. Less is known about how heart rate (HR) variability affects CBF. We experimentally reduced respiration-induced HR variability in healthy subjects, hypothesizing that CBF variability would increase. METHODS: Internal carotid artery (ICA) blood velocity was recorded by Doppler ultrasound in ten healthy subjects during baseline, control-mode, non-invasive mechanical ventilation (NIV), i.e., with fixed respiratory rate, hypovolemia induced by lower body negative pressure, and combinations of these. ICA beat volume (ICABV) and ICA blood flow (ICABF) were calculated. HR, mean arterial blood pressure (MAP), respiratory frequency (RF), and end-tidal CO2 were recorded. Integrals of power spectra at each subject's RF ± 0.03 Hz were used to measure variability. Phase angle/coherence measured coupling between cardiovascular variables. RESULTS: Control-mode NIV reduced HR variability (-56%, p = 0.002) and ICABV variability (-64%, p = 0.006) and increased ICABF variability (+140%, p = 0.002) around RF. NIV + hypovolemia reduced variability in HR and ICABV by 70-80% (p = 0.002) and doubled ICABF variability (p = 0.03). MAP variability was unchanged in either condition. Respiration-induced HR and ICABV oscillations were in inverse phase and highly coherent (coherence >0.9) during baseline, but this coherence decreased during NIV, in normovolemia and hypovolemia (p = 0.01). CONCLUSION: Controlling respiration in awake healthy humans reduced HR variability and increased CBF variability in hypovolemia and normovolemia. We suggest respiration-induced HR variability to be a mechanism in CBF regulation. Maintaining spontaneous respiration in patients receiving ventilatory support may be beneficial also for cerebral circulatory purposes.

Oscillatory pattern of acral skin blood flow within thermoneutral zone in healthy humans.

The acral skin contains arteriovenous anastomoses, which probably is the main part of skin microcirculation for blood flow adjustments and thermoregulation in the thermoneutral zone. The objective was to investigate if an increase in sympathetic activation during cooling influences the oscillatory pattern of acral skin blood flow. We had measurements of bilateral acral skin blood flow (n = 12) during lowering of ambient temperature from 32 °C to 18 °C. We quantified the oscillatory pattern as the time averaged wavelet spectral powers, coherence and phase angles in three frequency intervals (0.01-0.02 Hz, 0.02-0.05 Hz and 0.05-0.08 Hz). The differences were tested by Wilcoxon signed rank sum method between adjacent intervals. The absolute fluctuations in laser Doppler flux at 0.01-0.02 Hz, 0.02-0.05 Hz and 0.05-0.08 Hz were similar at 32 °C and 25 °C, and decreased at 18 °C (p < 0.001). The relative fluctuations (amplitude of the fluctuations relative to median flux value) in laser Doppler flux at 0.01-0.02 Hz, 0.02-0.05 Hz and 0.05-0.08 Hz were higher at 25 °C and 18 °C as compared to 32 °C (p < 0.002). The coherence between the oscillations of signals from right and left finger tips was highest (median coherence > 0.89) at 25 °C, and lower at 32 °C and at 18 °C.The median phase angles between the flux signals from right and left finger tips were close to 0 radians. We found that the relative fluctuations in acral skin blood flow increased during vasoconstriction due to cooling. Wavelet analysis of acral skin blood flow oscillations could serve as a future clinical tool.

Cold-induced sympathetic tone modifies the impact of endothelium-dependent vasodilation in the finger pulp.

OBJECTIVE: In thermoneutral and cold subjects, the sympathetic nervous system regulates skin blood flow by adjusting frequency of the tonic vasoconstrictor impulses. However, the way these thermoregulatory impulses influence the vascular endothelium is not well known. We studied how the sympathetic nervous system influences endothelium-dependent vasodilation (EDV) caused by shear stress in skin containing arteriovenous anastomoses (AVAs) and arterioles in healthy subjects. METHODS: Thirteen healthy subjects were exposed to thermoneutral (29°C) and cold (22°C) ambient temperatures on separate days. EDV was induced by releasing suprasystolic pressure cuff applied to the forearm or third finger after 4min. Bilateral laser Doppler flux from the finger pulp, dorsal finger and dorsal wrist was measured together with ultrasound Doppler from the right radial artery. Absolute EDV response (EDV peak minus baseline) and normalized relative EDV response (ratio EDV peak/baseline) were calculated (median, 95% confidence interval). The relative EDV response reflect the size of EDV response independent of the baseline level and is thus used to compare the EDV responses in the finger pulp and wrist skin in the two temperature conditions. RESULTS: In finger pulp (dominated by AVAs), the absolute EDV response (flux, au) in thermoneutral (137.8 (67.5, 168.8)) and cold (130.3 (97.2, 154.9)) was the same (p=0.85), whereas the relative EDV response was significantly higher in cold (3.6 (2.5, 5.9)) than in thermoneutral (1.4 (1.1, 1.6), p=0.002). The same patterns were found in the radial artery. In the dorsal wrist (dominated by arterioles) the absolute EDV response (flux, au) was smaller in cold (30.9 (15.91, 38.0)) than in thermoneutral (52.1 (38.4, 57.8), p=0.04), whereas the relative EDV responses in cold (3.5 (2.3, 4.2)), and thermoneutral (2.3 (1.6, 2.7)) were equal (p=0.16). CONCLUSIONS: The relative EDV responses show that the impact of EDV on skin perfusion in cold conditions is significantly greater in the finger pulp than in wrist skin. However, the absolute EDV responses indicate that vascular smooth muscle relaxation during EDV is probably not affected by higher mild cold-induced sympathetic activity either in AVAs or in arterioles.

Resting-state high-frequency heart rate variability is related to respiratory frequency in individuals with severe mental illness but not healthy controls.

Heart rate variability (HRV) has become central to biobehavioral models of self-regulation and interpersonal interaction. While research on healthy populations suggests changes in respiratory frequency do not affect short-term HRV, thus negating the need to include respiratory frequency as a HRV covariate, the nature of the relationship between these two variables in psychiatric illness is poorly understood. Therefore, the aim of this study was to investigate the association between HRV and respiratory frequency in a sample of individuals with severe psychiatric illness (n = 55) and a healthy control comparison group (n = 149). While there was no significant correlation between HF-HRV and respiration in the control group, we observed a significant negative correlation in the psychiatric illness group, with a 94.1% probability that these two relationships are different. Thus, we provide preliminary evidence suggesting that HF-HRV is related to respiratory frequency in severe mental illness, but not in healthy controls, suggesting that HRV research in this population may need to account for respiratory frequency. Future work is required to better understand the complex relationship between respiration and HRV in other clinical samples with psychiatric diseases.

Internal carotid artery blood flow in healthy awake subjects is reduced by simulated hypovolemia and noninvasive mechanical ventilation.

Intact cerebral blood flow (CBF) is essential for cerebral metabolism and function, whereas hypoperfusion in relation to hypovolemia and hypocapnia can lead to severe cerebral damage. This study was designed to assess internal carotid artery blood flow (ICA-BF) during simulated hypovolemia and noninvasive positive pressure ventilation (PPV) in young healthy humans. Beat-by-beat blood velocity (ICA and aorta) were measured by Doppler ultrasound during normovolemia and simulated hypovolemia (lower body negative pressure), with or without PPV in 15 awake subjects. Heart rate, plethysmographic finger arterial pressure, respiratory frequency, and end-tidal CO2 (ETCO2) were also recorded. Cardiac index (CI) and ICA-BF were calculated beat-by-beat. Medians and 95% confidence intervals and Wilcoxon signed rank test for paired samples were used to test the difference between conditions. Effects on ICA-BF were modeled by linear mixed-effects regression analysis. During spontaneous breathing, ICA-BF was reduced from normovolemia (247, 202-284 mL/min) to hypovolemia (218, 194-271 mL/min). During combined PPV and hypovolemia, ICA-BF decreased by 15% (200, 152-231 mL/min, P = 0.001). Regression analysis attributed this fall to concurrent reductions in CI (ß: 43.2, SE: 17.1, P = 0.013) and ETCO2 (ß: 32.8, SE: 9.3, P = 0.001). Mean arterial pressure was maintained and did not contribute to ICA-BF variance. In healthy awake subjects, ICA-BF was significantly reduced during simulated hypovolemia combined with noninvasive PPV Reductions in CI and ETCO2 had additive effects on ICA-BF reduction. In hypovolemic patients, even low-pressure noninvasive ventilation may cause clinically relevant reductions in CBF, despite maintained arterial blood pressure.

Cardiac stroke volume variability measured non-invasively by three methods for detection of central hypovolemia in healthy humans.

PURPOSE: Hypovolemia decreases preload and cardiac stroke volume. Cardiac stroke volume (SV) and its variability (cardiac stroke volume variability, SVV) have been proposed as clinical tools for detection of acute hemorrhage. We compared three non-invasive SV measurements and investigated if respiration-induced fluctuations in SV may detect mild and moderate hypovolemia in spontaneously breathing humans. METHODS: Ten healthy subjects underwent experimental central hypovolemia induced by lower body negative pressure to -60 mmHg or onset of presyncopal symptoms. SV beat-to-beat was estimated simultaneously by ultrasound Doppler, finger arterial blood pressure curve and impedance cardiography. SVV was calculated by spectral analysis between 0.15 and 0.40 Hz. RESULTS: Relative changes in SV did not show significant differences between the methods. The SVV measured by ultrasound Doppler and arterial blood pressure curve decreased at -30 mmHg to 32 % (ultrasound Doppler: 95 % CI 18-47, arterial blood pressure curve: 95 % CI 21-43) and at maximal simulated hypovolemia to 23 % (ultrasound Doppler: 95 % CI 14-81) and 21 % (arterial blood pressure curve: 95 % CI 9-33) of baseline variability. The variability in cardiac stroke volume from the impedance cardiography did not change significantly during the simulated hypovolemia, to 88 and 76 % of baseline variability. CONCLUSION: Cardiac stroke volume estimated by ultrasound Doppler and by arterial blood pressure curve showed parallel variations beat-to-beat during simulated hemorrhage, whereas impedance cardiography did not appear to track beat-to-beat changes in cardiac stroke volume. The variability in cardiac stroke volume was decreased during mild and moderate hypovolemia and could be used for early detection of hypovolemia.

Heart rate response to therapeutic hypothermia in infants with hypoxic-ischaemic encephalopathy.

AIM OF THE STUDY: Neonatal encephalopathy (NE) of hypoxic-ischaemic origin may cause death or life-long disability which is reduced by therapeutic hypothermia (TH). Our objective was to assess HR response in infants undergoing TH after perinatal asphyxia. METHODS: We performed a retrospective case series, from a single-centre tertiary care NICU. We included ninety-two infants with NE of likely hypoxic-ischaemic origin, moderate or severe, treated with TH (n=60) or normothermia (n=32) who had 18 month outcome data and at least 12 HR recordings the first 24h after birth (1998-2010) Bristol, UK. Poor outcome was defined as death or severe disability. Data are reported as medians and 95% confidence intervals (CI). RESULTS: TH to 33.5°C decreased HR by 30bpm to 92bpm (95% CI: 88, 96) 12h after birth in infants with NE and good outcome as compared to infants treated at normothermia 118bpm (95% CI: 110, 130). Despite constant low rectal temperature, HR increased gradually during cooling from 36 to 72h to 97bpm (89, 106) approaching the normothermia group, 117bpm (96, 133). During TH, infants with poor outcome had higher HR at 12h after birth (112bpm, 95% CI: 92, 115) as compared to infants with good outcome (p=0.004). Inotropic support increased HR by 17bpm in infants with good outcome and by 22bpm in infants with poor outcome. CONCLUSIONS: In NE, TH decreases HR the first day of life. HR remained lower during TH, but increased during the last day of TH. Infants with poor outcome have higher HR.

Monitoring of cerebral blood flow during hypoxia-ischemia and resuscitation in the neonatal rat using laser speckle imaging.

Neonatal hypoxic-ischemic encephalopathy (HIE) is associated with alterations in cerebral blood flow (CBF) as a result of perinatal asphyxia. The extent to whichCBFchanges contribute to injury, and whether treatments that ameliorate these changes might be neuroprotective, is still unknown. Higher throughput techniques to monitorCBFchanges in rodent models ofHIEcan help elucidate the underlying pathophysiology. We developed a laser speckle imaging (LSI) technique to continuously monitorCBFin six postnatal-day 10 (P10) rats simultaneously before, during, and after unilateral hypoxia-ischemia (HI, ligation of the left carotid artery followed by hypoxia in 8% oxygen). After ligation,CBFto the ligated side fell by 30% compared to the unligated side (P < 0.0001). Hypoxia induced a bilateral 55% reduction inCBF, which was partially restored by resuscitation. Compared to resuscitation in air, resuscitation in 100% oxygen increasedCBFto the ligated side by 45% (P = 0.033). Individual variability inCBFresponse to hypoxia between animals accounted for up to 24% of the variability in hemispheric area loss to the ligated side. In both P10 and P7 models of unilateralHI, resuscitation in 100% oxygen did not affect hemispheric area loss, or hippocampalCA1 pyramidal neuron counts, after 1-week survival. ContinuousCBFmonitoring usingLSIin multiple rodents simultaneously can screen potential treatment modalities that affectCBF, and provide insight into the pathophysiology ofHI.

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.

Respiratory sinus arrhythmia stabilizes mean arterial blood pressure at high-frequency interval in healthy humans.

PURPOSE: Arterial blood pressure variations are an independent risk factor for end organ failure. Respiratory sinus arrhythmia (RSA) is a sign of a healthy cardiovascular system. However, whether RSA counteracts arterial blood pressure variations during the respiratory cycle remains controversial. We restricted normal RSA with non-invasive intermittent positive pressure ventilation (IPPV) to test the hypothesis that RSA normally functions to stabilize mean arterial blood pressure. METHODS: Ten young volunteers were investigated during metronome-paced breathing and IPPV. Heart rate (ECG), mean arterial blood pressure and left stroke volume (finger arterial pressure curve) and right stroke volume (pulsed ultrasound Doppler) were recorded, while systemic and pulmonary blood flow were calculated beat-by-beat. Respiratory variations (high-frequency power, 0.15-0.40 Hz) in cardiovascular variables were estimated by spectral analysis. Phase angles and correlation were calculated by cross-spectral analysis. RESULTS: The magnitude of RSA was reduced from 4.9 bpm(2) (95% CI 3.0, 6.2) during metronome breathing to 2.8 bpm(2) (95% CI 1.1, 5.0) during IPPV (p = 0.03). Variations in mean arterial blood pressure were greater (2.3 mmHg(2) (95% CI 1.4, 3.9) during IPPV than during metronome breathing (1.0 mmHg(2) [95% CI 0.7, 1.3]) (p = 0.014). Respiratory variations in right and left stroke volumes were inversely related in the respiratory cycle during both metronome breathing and IPPV. CONCLUSIONS: RSA magnitude is lower and mean arterial blood pressure variability is greater during IPPV than during metronome breathing. We conclude that in healthy humans, RSA stabilizes mean arterial blood pressure at respiratory frequency.

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.