Per Lav Madsen

Near-infrared oximetry of the brain.

Near-infrared (IR) light easily penetrates biological tissue, and the information offered by in vivo spectroscopy of cerebral oxygenation is detailed and comes with a high temporal resolution. Near-IR light spectroscopy (NIRS) reflects cerebral oxygenation during arterial hypotension, hypoxic hypoxaemia and hypo- and hypercapnia. As determined by dual-wavelength NIRS, the cerebral O2 saturation integrates the arterial O2 content and the cerebral perfusion, and as established for skeletal muscle, NIRS obtains information on tissue oxygenation and metabolism beyond that obtained by venous blood sampling. Caveats of cerebral NIRS include insufficient light shielding, optode displacement and a sample volume including muscle or the frontal sinus mucous membrane. The relative influence from the extracranial tissue is minimized by optode separation and correction for an extracranial sample volume, or both. The natural pigment melatonin and also water are of little influence to spectroscopic analysis of cerebral oxygenation, whereas bilirubin systematically lowers ScO2 and attenuates the detection of changes in cerebral oxygenation. By NIRS, reduction of cytochrome oxidase is demonstrated during hypoxic hypoxaemia and head-up tilt-induced arterial hypotension, but the changes are small. In the clinical setting, NIRS offers useful information in patients with both systemic and local cerebral circulatory impairment, for example, during cranial trauma, surgery on the cerebral arteries, orthostasis and acute heart failure. Whereas mapping of the brain circulation is needed for jugular venous sampling to reflect either global or local oxygenation, the determination of cerebral oxygenation by NIRS has the advantage of localized monitoring of the cerebral cortex.

Muscle Tensing During Standing: Effects on Cerebral Tissue Oxygenation and Cerebral Artery Blood Velocity

Background and Purpose— When standing up causes dizziness, tensing of the leg muscles may alleviate the symptoms. We tested the hypothesis that leg tensing improves orthostatic tolerance via enhanced cerebral perfusion and oxygenation. Methods— In 10 healthy young adults, the effects of leg tensing on transcranial Doppler–determined middle cerebral artery (MCA) mean blood velocity (Vmean) and the near-infrared spectroscopy–determined frontal oxygenation (O2Hb) were assessed together with central circulatory variables and an arterial pressure low-frequency (LF) (0.07 to 0.15 Hz) domain evaluation of sympathetic activity. Results— Standing up reduced central venous pressure by (mean±SEM) 4.3±2.6 mm Hg, stroke volume by 49±7 mL, cardiac output by 1.9±0.4 L/min, and mean arterial pressure at MCA level by 9±4 mm Hg, whereas it increased heart rate by 30±4 beats per minute (P <0.05). MCA Vmean declined from 67±4 to 56±3 cm/s, O2Hb decreased by 7±2.8%, and LF spectral power increased (P <0.05). Leg tensing increased central venous pressure by 1.4±2.7 mm Hg and cardiac output by 1.8±0.4 L/min with no significant effect on blood pressure, whereas heart rate decreased by 11±3 beats per minute (P <0.05). MCA Vmean increased to 63±3 cm/s and O2Hb increased by 2.1±2.6%, whereas LF power declined (P <0.05). Within 2 minutes after leg tensing, these effects had disappeared. Conclusions— During standing, tensing of the leg muscles attenuates a reduction in cerebral perfusion and oxygenation as it stabilizes central circulatory variables and reduces sympathetic activity.

Ageing Is Associated with a Prolonged Fever Response in Human Endotoxemia

ABSTRACT The purpose of this study was to investigate whether an age-associated impaired acute-phase response exists. Nine healthy elderly volunteers (median, 66 years; range, 61 to 69 years) and eight young controls (median, 24 years; range, 20 to 27 years) were given an intravenous bolus of endotoxin (2 ng/kg). The rectal temperature was monitored continuously, and blood samples for cytokine measurements were obtained before endotoxin administration as well as 0.5, 1, 1.5, 2, 3, 4, 8, 12, and 24 h after the injection. The elderly subjects showed a more prolonged fever response compared to the young controls. Levels of tumor necrosis factor alpha (TNF-α), soluble TNF receptors (sTNFR-I), interleukin-6 (IL-6), IL-8, IL-10, and IL-1 receptor antagonist (IL-1ra) in plasma increased markedly following endotoxin administration in both groups. The elderly group showed larger initial increases in TNF-α and sTNFR-I levels and prolonged increased levels of sTNFR-I. Monocyte concentrations decreased in both groups, with the elderly group showing a more rapid decrease and a slower subsequent increase than did the young group. Furthermore, the elderly group had a more rapid increase in C-reactive protein levels than did the young group. In conclusion, ageing is associated with an altered acute-phase response including initial hyperreactivity, prolonged inflammatory activity, and prolonged fever response.

Interference of Cerebral Near-infrared Oximetry in Patients with Icterus

Near-infrared spectrophotometry assesses cerebral oxygen saturation (ScO2) based on the absorption spectra of oxygenated and deoxygenated hemoglobin and the translucency of biological tissue in the near-infrared band. In patients with icterus, however, bilirubin can potentially hinder cerebral oximetry. In 48 patients undergoing orthotopic liver transplantation, we related total plasma bilirubin to ScO2 as determined from spectrophotometry with wavelengths of 733 and 809 nm. Before surgery, ScO2 was 59% (15%–78%) (median with range) and bilirubin was 71 (6–619) &mgr;mol/L with a negative correlation (r = −0.72;P < 0.05). The 95% prediction interval included the lowest measurable ScO2 of 15% at a bilirubin level of 370 &mgr;mol/L. During reperfusion of the grafted liver, the ScO2 increased by 7% (−8% to 17%) (P < 0.05), and bilirubin did not influence this increase. In one patient, the ScO2 remained below 15% despite a decrease in bilirubin from 619 to 125 &mgr;mol/L, suggesting that tissue pigmentation deposits also absorb light. In conclusion, bilirubin dampens the spectrophotometry-determined cerebral oxygen saturation at 733 and 809 nm. A bilirubin level of 370 &mgr;mol/L, tissue pigment deposits, or both, may render determination of cerebral oxygen saturation impossible. Even at high bilirubin values, changes in cerebral perfusion may be visible. Implications In 48 patients undergoing liver transplantation, the interference of icterus on cerebral oximetry by near-infrared light was investigated. Bilirubin absorbed the near-infrared light and lowered the measured cerebral oxygen saturation. Even at high bilirubin values, changes in cerebral oxygenation, as seen during reperfusion of the grafted liver, may be visible.

Central and Peripheral Blood Flow During Exercise With a Continuous-Flow Left Ventricular Assist DeviceClinical Perspective

Background— End-stage heart failure is associated with impaired cardiac output (CO) and organ blood flow. We determined whether CO and peripheral perfusion are maintained during exercise in patients with an axial-flow left ventricular assist device (LVAD) and whether an increase in LVAD pump speed with work rate would increase organ blood flow. Methods and Results— Invasively determined CO and leg blood flow and Doppler-determined cerebral perfusion were measured during 2 incremental cycle exercise tests on the same day in 8 patients provided with a HeartMate II LVAD. In random order, patients exercised both with a constant (≈9775 rpm) and with an increasing pump speed (+400 rpm per exercise stage). At 60 W, the elevation in CO was more pronounced with increased pump speed (8.7±0.6 versus 8.1±1.1 L · min−1; mean±SD; P=0.05), but at maximal exercise increases in CO (from 7.0±0.9 to 13.6±2.5 L · min−1; P<0.01) and leg blood flow [0.7 (0.5 to 0.8) to 4.4 (3.9 to 4.8) L · min−1 per leg; median (range); P<0.001] were similar with both pumping modes. Normally, middle cerebral artery mean flow velocity increases from ≈50 to ≈65 cm · s−1 during exercise, but in LVAD patients with a constant pump speed it was low at rest (39±14 cm · s−1) and remained unchanged during exercise, whereas in patients with increasing pump speed, it increased by 5.2±2.8 cm · s−1 at 60 W (P<0.01). Conclusions— With maximal exercise, the axial-flow LVAD supports near-normal increments in cardiac output and leg perfusion, but cerebral perfusion is poor. Increased pump speed augments cerebral perfusion during exercise.

Central and Peripheral Blood Flow During Exercise With a Continuous-Flow Left Ventricular Assist Device Constant Versus Increasing Pump Speed: A Pilot Study

Background— End-stage heart failure is associated with impaired cardiac output (CO) and organ blood flow. We determined whether CO and peripheral perfusion are maintained during exercise in patients with an axial-flow left ventricular assist device (LVAD) and whether an increase in LVAD pump speed with work rate would increase organ blood flow. Methods and Results— Invasively determined CO and leg blood flow and Doppler-determined cerebral perfusion were measured during 2 incremental cycle exercise tests on the same day in 8 patients provided with a HeartMate II LVAD. In random order, patients exercised both with a constant (≈9775 rpm) and with an increasing pump speed (+400 rpm per exercise stage). At 60 W, the elevation in CO was more pronounced with increased pump speed (8.7±0.6 versus 8.1±1.1 L · min−1; mean±SD; P=0.05), but at maximal exercise increases in CO (from 7.0±0.9 to 13.6±2.5 L · min−1; P<0.01) and leg blood flow [0.7 (0.5 to 0.8) to 4.4 (3.9 to 4.8) L · min−1 per leg; median (range); P<0.001] were similar with both pumping modes. Normally, middle cerebral artery mean flow velocity increases from ≈50 to ≈65 cm · s−1 during exercise, but in LVAD patients with a constant pump speed it was low at rest (39±14 cm · s−1) and remained unchanged during exercise, whereas in patients with increasing pump speed, it increased by 5.2±2.8 cm · s−1 at 60 W (P<0.01). Conclusions— With maximal exercise, the axial-flow LVAD supports near-normal increments in cardiac output and leg perfusion, but cerebral perfusion is poor. Increased pump speed augments cerebral perfusion during exercise.

The decrease of cardiac chamber volumes and output during positive-pressure ventilation

Positive-pressure ventilation (PPV) is widely used for treatment of acute cardiorespiratory failure, occasionally at the expense of compromised cardiac function and arterial blood pressure. The explanation why has largely rested on interpretation of intracardiac pressure changes. We evaluated the effect of PPV on the central circulation by studying cardiac chamber volumes with cardiac magnetic resonance imaging (CMR). We hypothesized that PPV lowers cardiac output (CO) mainly via the Frank-Starling relationship. In 18 healthy volunteers, cardiac chamber volumes and flow in aorta and the pulmonary artery were measured by CMR during PPV levels of 0, 10, and 20 cmH2O applied via a respirator and a face mask. All cardiac chamber volumes decreased in proportion to the level of PPV. Following 20-cmH2O PPV, the total diastolic and systolic cardiac volumes (±SE) decreased from 605 (±29) ml to 446 (±29) ml (P < 0.001) and from 265 (±17) ml to 212 (±16) ml (P < 0.001). Left ventricular stroke volume decreased by 27 (±4) ml/beat; heart rate increased by 7 (±2) beats/min; and CO decreased by 1.0 (±0.4) l/min (P < 0.001). From 0 to 20 cmH2O, right and left ventricular peak filling rates decreased by -146 (±32) and -187 (±64) ml/s (P < 0.05) but maximal emptying rates were unchanged. Cardiac filling and output decrease with increasing PPV in healthy volunteers. The decrease is seen even at low levels of PPV and should be taken into account when submitting patients to mechanical ventilation with positive pressures. The decrease in CO is fully explained by the Frank-Starling mechanism.

Left atrial and ventricular function during dobutamine and glycopyrrolate stress in healthy young and elderly as evaluated by cardiac magnetic resonance

The aim of this study is to describe phasic volume changes of the left atrium (LA) in healthy young and elderly subjects at rest and during pharmacological stress (PS). LA maximum size is related to cardiovascular mortality. LA has passive, active, and conduit function for left ventricular (LV) filling. We hypothesized that changes in LV compliance from normal aging are reflected in LA volume changes and that PS will augment these differences. We enrolled twenty young (20-30 yr) and twenty elderly (60-70 yr) healthy subjects and measured their LV and LA volumes by cardiac magnetic resonance imaging at rest and during dobutamine and glycopyrrolate stress. We identified LA minimum, maximum, and middiastolic volumes and the volume before atrial contraction. LA emptying volumes were calculated as LA passive and active emptying volumes and LA conduit volume. We also calculated LV peak filling rates (LVPFRs). Both at rest and during PS, LA maximum and minimum volumes were similar in the groups, whereas middiastolic volume was higher in the elderly. During PS, a marked decrease in LA passive emptying function and a corresponding increase in LA active emptying function were seen in the elderly but not in the young. At rest, LVPFR was lower in the elderly, and during PS this difference was augmented. The aging heart has reduced LVPFR, which is reflected in reduced LA passive and compensatory increased LA active volumetric contribution to LV stroke volume. These age-related differences are evident at rest and highly augmented during both dobutamine and glycopyrrolate stress.

Cardiac remodelling and function with primary mitral valve insufficiency studied by magnetic resonance imaging

AIMS Evaluation of patients with primary mitral valve insufficiency (MI) is best supported by quantitative measures. Cardiovascular magnetic resonance imaging (CMR) offers flow and cardiac chamber volume quantification. We studied cardiac remodelling with CMR to determine MI regurgitation volumes (MIVol) related to severe MI. METHODS AND RESULTS In total, 24, 20, and 28 patients determined to have mild, moderate, and severe primary MI, respectively, were studied. Combining cine stacks with phase-contrast velocity mapping across the ascending aorta, CMR-determined MIVol was reproducibly obtained as the difference between left ventricular (LV) stroke volume and aortic forward flow (Aoflow). With increasing MI severity, MIVol, left heart volumes, and pulmonary venous diameters increased (P < 0.01). Severe MI with LV end-systolic diameter of 40 mm was signified by MIVol >40 mL, MI regurgitant fraction >0.30, LV end-diastolic volume (LVEDV(i)) >108 mL m(-2), and a total left heart volume >188 mL m(-2) with dilated pulmonary veins and a LVEDV/right ventricular EDV ratio >1.2. In severe MI, LV ejection fraction was unaffected, but the Aoflow and the peak ejection rate indexed to LVEDV were lowered (P < 0.05). In surgical patients, the MIVol correlated to the decrease in LV dimension after valve surgery (P < 0.02). CONCLUSION CMR provides a reproducible quantitative technique for evaluation of MI, as MIVol and cardiac chamber volumes can be held against diagnostic cut-off values. The Aoflow and peak ejection rate indexed to LVEDV may reveal early LV systolic dysfunction in patients with severe MI. Severe MI is related to lower MI regurgitation volume and fraction than previously believed.

Circulating immunoreactive proANP(1–30) and proANP(31–67) responses to acute exercise

The circulating immunoreactive atrial natriuretic peptide (C-terminal; alpha-ANP) increases during exercise to become suppressed in the first hours of the recovery. The response of the N-terminal ANP fragments to acute exercise is not known while proANP (31-67) appears to be elevated with chronic exercise. We evaluated the plasma concentrations of the N-terminal ANP fragments (1-30) and (31-67) in oarsmen (n=10) before and after two acute exercise bouts separated by 5 h. As control, measurements were made on a day with no exercise (n=12). At rest, the concentrations of proANP(1-30) and proANP(31-67) were 344+/-42 and 810+/-172 pmol x l(-1), respectively. Half an hour after the first exercise bout, proANP(1-30) was elevated (to 404+/-48 pmol x l(-1); P<0.05) and decreased below the pre-exercise level (to 316+/-41 pmol x l(-1); P<0.05) 4 h into the recovery period. Also, 30 min after the second exercise session, the concentration of proANP(1-30) was elevated to 408+/-45 pmol x l(-1) (P<0.05) and the pre-exercise level was re-established on the following morning. Thus, proANP(1-30), rather than proANP(31-67), responded to acute exercise. These results suggest that atrial distension and, therefore, the central blood volume changes markedly in athletes during a day with repeated exercise bouts.