Vascular Impedance Research Articles

Blood flow measurements of neovascularization in tubal pregnancy

In a retrospective study the results of vagino- and colour flow Doppler sonography of 23 tubal pregnancies verified by surgery were documented. Due to the neovascularisation in the trophoblast tissue the vascular impedance was elevated in all cases. The mean value of all pulsatility indices was 0.85 +/- 0.2. The direct signs of tubal pregnancy were seen in only 20 cases with vaginosonography alone. The combination of vagino- and colour flow Doppler sonography offers the chance of an earlier detection (5th week of pregnancy) of a tubal pregnancy.

Divergent Effects of Ephedrine and Phenylephrine on Cardiovascular Hemodynamics of Near-Term Fetal Sheep Exposed to Hypoxemia and Maternal Hypotension

Erkinaro, T.; Mäkikallio, K.; Acharya, G.; Päkkilä, M.; Kavasmaa, T.; Huhta, J.C.; Alahuhta, S.; Räsänen, J. Author Information

Arterial transfer functions: background, applications and reservations

Use of arterial transfer functions in modern medicine stems from the pioneering work of McDonald, Taylor and Womersley in London’s St Bartholomew’s Hospital in the 1950s. Womersley [1], an applied mathematician, showed that the nonlinearities in the equations of motion for fluid in elastic tubes were sufficiently small to be neglected to a first approximation. McDonald and Taylor [2], with the benefit of this background, expressed pressure and flow waves in the frequency domain, and related corresponding frequency components (harmonics) of pressure and flow waves to describe transfer functions – of pressure and flow at the same site (vascular impedance) – and to describe pressure relationships at different sites (pressure propagation). This concept expanded resistance of a vascular bed (as the ratio of mean pressure/mean flow) and of a mean pressure gradient along a segment or network of arteries, so that other arterial properties including elasticity, momentum and wave reflection could be embraced together with vascular resistance [3–6].

Is it time to add aortic isthmus evaluation to the repertoire of Doppler investigations for placental insufficiency?

Is it time to add aortic isthmus evaluation to the repertoire of Doppler investigations for placental insufficiency?

70: Low-dose aspirin reduces uteroplacental vascular impedance during the first half of pregnancy in IVF/ICSI patients: A randomized placebo-controlled study

We hypothesized that low-dose aspirin improves uteroplacental hemodynamics in unselected IVF/ICSI subjects when medication is started concomitantly with controlled ovarian hyperstimulation. Thirty-five pregnant women who had undergone IVF/ICSI and had been randomized to receive 100 mg aspirin (n = 15) or placebo (n = 20) daily starting on the first day of controlled ovarian hyperstimulation were included in this study. There were 4 twin pregnancies in aspirin group and 3 in placebo group. Altogether, 19 fetuses were exposed to aspirin and 23 fetuses to placebo. Doppler ultrasonography was performed at 6+, 10+, 13+ and 18+ gestational weeks. Uterine (UtA) and spiral artery pulsatility index (PI) values were calculated and bilateral UtA notch was noted. Subplacental arcuate artery PI values were obtained at 6+ and 10+ weeks. Umbilical artery PI values and mean velocity were calculated at 10+, 13+ and 18+ weeks. At 6+ weeks, arcuate artery PIs were lower (p = 0.02) in aspirin group (1.71±0.43) compared to placebo group (2.34±0.61). At 18+ weeks, right (p = 0.026) and left (p = 0.044) UtA PIs were lower in aspirin group (0.79±0.37 and 0.87±0.35) than in placebo group (1.14±0.43 and 1.20±0.49). At 18+ weeks, bilateral UtA notch tended (p = 0.06) to be more common in placebo group (40%) than in aspirin group (13%). Umbilical artery PIs and mean velocity did not differ significantly between the groups. Low-dose aspirin reduced uteroplacental vascular impedance in early and mid pregnancy in unselected IVF/ICSI patients when medication was started concomitantly with controlled ovarian hyperstimulation. This may reflect improved throphoblastic invasion and remodeling of spiral arteries. Aspirin did not affect umbilicoplacental circulation during the first half of pregnancy.

Ophthalmic artery Doppler as a measure of severe pre-eclampsia

Objective To identify differences in orbital flow behavior in mild and severe pre-eclamptic women compared with healthy pregnant women, demonstrated by ophthalmic artery Doppler indexes. Methods Ophthalmic artery Doppler indexes of 20 mild and 20 severe pre-eclamptic women were compared with 51 healthy pregnant women. Right and left eye Doppler index means were evaluated and the resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV), end diastolic velocity (EDV), and peak ratio (PR) were calculated. Results Statistically significant differences were observed between PR, PSV, and EDV ( P = 0.0009, P = 0.0020, P = 0.0001) ophthalmic artery Doppler in a comparison of women with mild and severe pre-eclampsia. Statistically significant differences were seen between all Doppler indexes of the study group and healthy pregnant women. Ophthalmic PR, PSV, and EDV were significantly higher in severe pre-eclamptic cases but other index parameters did not show any difference. An elevation of diastolic and systolic flow occurred when pre-eclampsia became severe. Conclusion Orbital vascular impedance reduction with orbital hyperperfusion was present in severe pre-eclamptic women compared with mild pre-eclamptic and healthy pregnant women. Ophthalmic Doppler is a novel parameter that may be useful in the diagnosis of severe pre-eclampsia.

Pulmonary vascular input impedance is a combined measure of pulmonary vascular resistance and stiffness and predicts clinical outcomes better than pulmonary vascular resistance alone in pediatric patients with pulmonary hypertension

Pulmonary vascular resistance (PVR) is the current standard for evaluating reactivity in children with pulmonary arterial hypertension (PAH). However, PVR measures only the mean component of right ventricular afterload and neglects pulsatile effects. We recently developed and validated a method to measure pulmonary vascular input impedance, which revealed excellent correlation between the zero harmonic impedance value and PVR and suggested a correlation between higher-harmonic impedance values and pulmonary vascular stiffness. Here we show that input impedance can be measured routinely and easily in the catheterization laboratory, that impedance provides PVR and pulmonary vascular stiffness from a single measurement, and that impedance is a better predictor of disease outcomes compared with PVR. Pressure and velocity waveforms within the main pulmonary artery were measured during right heart catheterization of patients with normal pulmonary artery hemodynamics (n = 14) and those with PAH undergoing reactivity evaluation (49 subjects, 95 conditions). A correction factor needed to transform velocity into flow was obtained by calibrating against cardiac output. Input impedance was obtained off-line by dividing Fourier-transformed pressure and flow waveforms. Exceptional correlation was found between the indexed zero harmonic of impedance and indexed PVR (y = 1.095x + 1.381, R2 = 0.9620). In addition, the modulus sum of the first 2 harmonics of impedance was found to best correlate with indexed pulse pressure over stroke volume (y = 13.39x - 0.8058, R2 = 0.7962). Among a subset of patients with PAH (n = 25), cumulative logistic regression between outcomes to total indexed impedance was better (R(L)2 = 0.4012) than between outcomes and indexed PVR (R(L)2 = 0.3131). Input impedance can be consistently and easily obtained from pulse-wave Doppler and a single catheter pressure measurement, provides comprehensive characterization of the main components of RV afterload, and better predicts patient outcomes compared with PVR alone.

OP01.05: A notch in the uterine artery during pregnancy is a sign of increased placental vascular resistance and not a reflection of increased peripheral vascular impedance

Total vascular resistance (dyne s/cm5) 1623 (1287–3125) 1163 (944–1785) 0.008 Stroke volume (mL) 69 (36–81) 67 (57–86) 0.95 Cardiac output (L/min) 5.40 (4.4–7.0) 6.1 (4.0–8.1) 0.08 Ejection fraction (%) 69 (64–83) 71 (65–79) 0.59 Midwall fractional shortening (% of predicted value) 118 (94–126) 122 (106–140) 0.04 Isovolumetric relaxation time (ms) 78 (50–90) 60 (45–75) 0.006 24 h ambulatory heart rate (bpm) 74 (61–82) 79 (76–92) 0.003 24 h ambulatory systolic blood pressure (mmHg) 117 (104–136) 106 (101–121) 0.031 24 h ambulatory diastolic blood pressure (mmHg) 75 (65–88) 66 (56–73) 0.012 24 h ambulatory mean arterial pressure (mmHg) 87 (79–104) 79 (72–87) 0.016

Effects of levosimendan on acute pulmonary embolism-induced right ventricular failure*

Repeated episodes of pulmonary embolism can persistently increase pulmonary arterial pressure and depress right ventricular contractility. We investigated the effects of levosimendan on right ventricular-pulmonary arterial coupling in this model of right ventricular failure. Prospective, controlled, randomized animal study. University research laboratory. Fourteen anesthetized piglets. Repeated acute pulmonary embolisms were induced with autologous blood clots to induce persistent right ventricular failure. Animals were randomly assigned to a control or levosimendan group. Levosimendan 20 microg/kg was administered in 10 mins followed by 0.2 microg/kg/min or same volumes of isotonic saline. Pulmonary artery distal resistance and proximal elastance by pressure-flow relationships and vascular impedance were measured. We noted right ventricle contractility by the end-systolic pressure-volume relationship (Ees), pulmonary artery effective elastance by the end-diastolic to end-systolic relationship (Ea), and right ventricular-pulmonary arterial coupling efficiency by the Ees/Ea ratio. The gradual pulmonary artery embolism increased pulmonary artery resistance and elastance, increased Ea from 1.01 +/- 0.17 to 5.58 +/- 0.37 mm Hg/mL, decreased Ees from 1.75 +/- 0.12 to 1.29 +/- 0.20 mm Hg/mL, and decreased Ees/Ea from 1.74 +/- 0.20 to 0.24 +/- 0.09. Compared with placebo, levosimendan decreased pulmonary arterial elastance and characteristic impedance. Right ventricular-pulmonary arterial coupling was restored by both an increase in right ventricular contractility and a decrease in right ventricular afterload. A gradual increase in pulmonary artery pressure induced by pulmonary embolism persistently worsens pulmonary artery hemodynamics, right ventricular contractility, right ventricular-pulmonary arterial coupling, and cardiac output. Levosimendan restores right ventricular-pulmonary arterial coupling better than placebo, because of combined pulmonary vasodilation and increased right ventricular contractility.

Approach to patients with heart failure and pulmonary hypertension

Pulmonary hypertension (PH), defined as a mean pulmonary artery pressure greater than 25 mm Hg, is not a diagnosis, but rather the physiologic consequence of the interaction between pulmonary blood flow, pulmonary vascular impedance, and downstream pulmonary venous pressure. The diagnosis and appropriate treatment of PH in patients with or without heart failure (HF) requires an understanding of the underlying pathogenesis, whether it be due to increased pulmonary venous pressure, increased pulmonary vascular resistance (PVR), increased pulmonary blood flow, or a combination thereof. Furthermore, an explanation for the underlying cause must also be sought. For example, a rise in pulmonary venous pressure may relate primarily to an increase in left ventricular end-diastolic pressure in a patient with a known cardiomyopathy; however, it may be complicated by severe mitral regurgitation. Similarly, an increased PVR may reflect reactive changes in the pulmonary vasculature due to long-standing pulmonary venous hypertension, concomitant hypoxemia/hypercapnia, or it may be the harbinger of chronic thromboembolic disease. It is imperative that reversible causes of PH be considered. Although most often diagnosed by Doppler echocardiography, full hemodynamic characterization of PH requires right heart catheterization to measure biventricular filling pressures and PVR. Integration of invasive pulmonary hemodynamics with an assessment of right ventricular function is essential to appreciate the clinical and prognostic significance of PH of an individual patient. Right heart catheterization is not practically feasible in all patients with HF and PH; however, at a minimum it should be performed in patients with a Doppler-estimated pulmonary artery pressure greater than 60 mm Hg, those who present clinically with predominant right HF, significant mitral valve disease, and in particular, patients with impaired right ventricular function.

Effects of an aging vascular model on healthy and diseased hearts

The vitamin D(3) and nicotine (VDN) model is a model of isolated systolic hypertension (ISH) due to arterial calcification raising arterial stiffness and vascular impedance similar to an aged and stiffened arterial tree. We therefore analyzed the impact of this aging model on normal and diseased hearts with myocardial infarction (MI). Wistar rats were treated with VDN (n = 9), subjected to MI by coronary ligation (n = 10), or subjected to a combination of both MI and VDN treatment (VDN/MI, n = 14). A sham-treated group served as control (Ctrl, n = 10). Transthoracic echocardiography was performed every 2 wk, whereas invasive indexes were obtained at week 8 before death. Calcium, collagen, and protein contents were measured in the heart and the aorta. Systolic blood pressure, pulse pressure, thoracic aortic calcium, and end-systolic elastance as an index of myocardial contractility were highest in the aging model group compared with MI and Ctrl groups (P(VDN) < 0.05, 2-way ANOVA). Left ventricular wall stress and brain natriuretic peptide (P(VDNxMI) = not significant) were highest, while ejection fraction, stroke volume, and cardiac output were lowest in the combined group versus all other groups (P(VDNxMI) < 0.05). The combination of ISH due to this aging model and MI demonstrates significant alterations in cardiac function. This model mimics several clinical phenomena of cardiovascular aging and may thus serve to further study novel therapies.

The Reliability of Pulse Contour-Derived Cardiac Output During Hemorrhage and After Vasopressor Administration

Reliable measurement of cardiac output (CO) is important in the critically ill. Pulse contour-derived CO (PCCO) has been evaluated during stable hemodynamics, but is sensitive to changes in vascular tone and has not been validated under conditions of changing hemodynamics. Furthermore, PCCO requires calibration for the individual vascular impedance by transpulmonary thermodilution CO (TPCO), and the required frequency of recalibration to maintain accurate measurements, especially during changing conditions, has not been confirmed. We compared PCCO measurements of CO with TPCO and continuous and bolus pulmonary artery CO (CCO and BCO, respectively) during conditions of uncontrolled hemorrhage and resuscitation with norepinephrine. Thirteen pigs were anesthetized and instrumented for determination of CO by BCO and CCO, respectively, as well as bolus TPCO and PCCO. Uncontrolled hemorrhage was accomplished by liver incision. When mean arterial blood pressure was <25 mm Hg, or heart rate declined progressively to <20% of its peak value, vasopressor therapy was started. TPCO and BCO were performed after induction of anesthesia and 15 min after start of therapy, and PCCO and CCO were obtained repeatedly. CO measurements were compared using Bland-Altman analysis. Mean arterial blood pressure, CO and systemic vascular resistance decreased after hemorrhage (P < 0.001 and <0.01, respectively). Bias and limits of agreement between CCO and PCCO (0.54 L/min; 1.46 L/min) increased after hemorrhage (-3.49; 6.12) and further deteriorated after norepinephrine administration (-8.01; 9.9). After recalibration, bias and limits of agreement returned to -0.51 and 1.28. PCCO needs frequent recalibration during hemorrhage and after vasopressor administration.

Human cardiovascular dose–response to supplemental oxygen

The aim of the study was to examine the central and peripheral cardiovascular adaptation and its coupling during increasing levels of hyperoxaemia. We hypothesized a dose-related effect of hyperoxaemia on left ventricular performance and the vascular properties of the arterial tree. Oscillometrically calibrated arterial subclavian pulse trace data were combined with echocardiographic recordings to obtain non-invasive estimates of left ventricular volumes, aortic root pressure and flow data. For complementary vascular parameters and control purposes whole-body impedance cardiography was applied. In nine (seven males) supine, resting healthy volunteers, aged 23-48 years, data was collected after 15 min of air breathing and at increasing transcutaneous oxygen tensions (20, 40 and 60 kPa), accomplished by a two group, random order and blinded hyperoxemic protocol. Left ventricular stroke volume [86 +/- 13 to 75 +/- 9 mL (mean +/- SD)] and end-diastolic area (19.3 +/- 4.4 to 16.8 +/- 4.3 cm(2)) declined (P < 0.05), and showed a linear, negative dose-response relationship to increasing arterial oxygen levels in a regression model. Peripheral resistance and characteristic impedance increased in a similar manner. Heart rate, left ventricular fractional area change, end-systolic area, mean arterial pressure, arterial compliance or carbon dioxide levels did not change. There is a linear dose-response relationship between arterial oxygen and cardiovascular parameters when the systemic oxygen tension increases above normal. A direct effect of supplemental oxygen on the vessels may therefore not be excluded. Proximal aortic and peripheral resistance increases from hyperoxaemia, but a decrease of venous return implies extra cardiac blood-pooling and compensatory relaxation of the capacitance vessels.

Divergent effects of ephedrine and phenylephrine on cardiovascular hemodynamics of near‐term fetal sheep exposed to hypoxemia and maternal hypotension

We hypothesized that the administration of ephedrine and phenylephrine for maternal hypotension modifies cardiovascular hemodynamics in near-term sheep fetuses. At 115-136 days of gestation, chronically instrumented, anesthetized ewes with either normal placental function or increased placental vascular resistance after placental embolization were randomized to receive boluses of ephedrine (n = 12) or phenylephrine (n = 12) for epidural-induced hypotension after a short period of hypoxemia. Fetal cardiovascular hemodynamics were assessed by Doppler ultrasonography at baseline, during hypotension and after vasopressor treatment. During hypotension, fetal PO(2) decreased and proximal branch pulmonary arterial and pulmonary venous vascular impedances increased. Additionally, in the embolized fetuses, the time-velocity integral ratio between the antegrade and retrograde blood flow components of the aortic isthmus decreased. These parameters were restored to baseline conditions by ephedrine but not by phenylephrine. With phenylephrine, weight-indexed left ventricular cardiac output and ejection force decreased in the non-embolized fetuses, and the proportion of isovolumetric contraction time of the total cardiac cycle was elevated in the embolized fetuses. After exposure to hypoxemia and maternal hypotension, ephedrine restored all fetal cardiovascular hemodynamic parameters to baseline. Phenylephrine did not reverse fetal pulmonary vasoconstriction or the relative decrease in the net forward flow through the aortic isthmus observed in fetuses with increased placental vascular resistance. Moreover, fetal left ventricular function was impaired during phenylephrine administration.

Effect of Continuous and Pulsatile Flow Left Ventricular Assist on Pulsatility in a Pediatric Animal Model of Left Ventricular Dysfunction: Pilot Observations

Pediatric ventricular assist devices are being developed that can produce pulsatile flow (PF) or continuous flow (CF). An important aspect of choosing between these two modes is understanding the consequences of each mode on pediatric vascular pulsatility. Differences in vascular pulsatility generated by PF and CF operation of the 3-inch pediatric cardiopulmonary assist system (pCAS, Ension, Inc., Pittsburgh, PA) were investigated while providing left atrium-to-aorta left ventricular assist (LVA), using an infant animal model of left ventricular dysfunction. Hemodynamic data were digitally recorded with the pCAS providing LVA at incremental flow rates while operating in continuous mode, pulsatile mode at 100 bpm, and pulsatile mode at 140 bpm. These data were used to calculate vascular input impedance (Zart), energy equivalent pressure, and surplus hemodynamic energy as indices of pulsatility for partial (50% of maximum) and maximum LVA flow. Both CF and PF LVA by the pCAS resulted in favorable hemodynamic rectification of left ventricular dysfunction while generating equivalent flows. PF LVA maintained a greater degree of pulsatility compared with CF, as evidenced by increasing energy equivalent pressure and a lesser drop in surplus hemodynamic energy with increasing pCAS flow. Differences in Zart modulus and phase were indiscernible. The selection of flow mode may have long-term consequences on Zart and end-organ perfusion affecting clinical outcomes in pediatric patients.

Quantification of Pulsatility as a Function of Vascular Input Impedance: An In Vitro Study

The physiological benefits of pulsatility generated by ventricular assist device (VAD) support continue to be heavily debated as application of VAD support has been expanded to include destination and recovery therapies. In this study, the relationship between input impedance (Zart) and vascular pulsatility during continuous flow (CF) or pulsatile flow (PF) VAD support was investigated. Hemodynamic waveforms were recorded at baseline failure and with 50%, 75%, and 100% CF or PF VAD support for nine different Zart test conditions (combination of three different resistance and compliance settings) in a mock circulatory system simulating left ventricular failure. High-fidelity hemodynamic pressure and flow waveforms were recorded to calculate mean arterial pressure (MAP), Zart, energy equivalent pressure (EEP), and surplus hemodynamic energy (SHE) as metrics for quantifying vascular pulsatility. MAP and EEP were elevated with increasing resistance whereas SHE was reduced with increasing compliance. Vascular pulsatility was restored with increasing PF VAD support, but diminished by up to 90% with increasing CF VAD support. The nonpulsatile energy component (MAP) of the pressure waveform is dependent on resistance whereas the pulsatile energy component (SHE) is dependent on compliance. The impact of Zart and vascular pulsatility on patient recovery with VAD support warrants further investigation.

89: Systemic vascular input impedance in humans, calves, and pigs: Clinical implications with medical devices and xenotransplantation

89: Systemic vascular input impedance in humans, calves, and pigs: Clinical implications with medical devices and xenotransplantation

Vascular pulsatility in patients with a pulsatile- or continuous-flow ventricular assist device

We sought to investigate differences in indices of pulsatility between patients with normal ventricular function and patients with heart failure studied at the time of implantation with continuous-flow or pulsatile-flow left ventricular assist devices. Eight patients with normal ventricular function and 22 patients with heart failure were studied. A high-fidelity aortic and left ventricular pressure catheter was inserted retrograde through the aortic valve into the left ventricle, and transit-time flow probes were placed on the aorta and device outflow graft. Hemodynamic waveforms were recorded at native heart rate before cardiopulmonary bypass and over a range of device flow rates controlled by adjusting beat rate or rpm. These data were used to calculate vascular input impedance and 2 indices of vascular pulsatility: energy-equivalent pressure and surplus hemodynamic energy. At low support levels, pulsatile support restored surplus hemodynamic energy to within 2.5% of normal values, whereas continuous support diminished surplus energy by more than 93%. At high support levels, pulsatile support augmented surplus energy by 49% over normal values, whereas continuous support further diminished surplus energy by 97%. Pulsatile support diminished vascular impedance from baseline failure values, whereas continuous support increased impedance. Vascular impedances at baseline for patients undergoing pulsatile and continuous support and during pulsatile support revealed normal vascular compliance, whereas impedance during continuous support indicated a loss of compliance (or "stiffening") of the vasculature. These results suggest that selection of device type and flow rate can influence vascular pulsatility and input impedance, which might affect clinical outcomes.

Effects of levosimendan versus dobutamine on pressure load-induced right ventricular failure*

A transient increase in pulmonary arterial (PA) pressure can persistently depress right ventricular (RV) contractility. We investigated the effects of dobutamine and levosimendan on RV-PA coupling in this model of RV failure. Prospective, controlled, randomized animal study. University research laboratory. Fifteen anesthetized dogs. Transient (90-min) PA constriction to induce persistent RV failure. Random assignment to dobutamine 5 and 10 microg/kg/min or levosimendan 12 microg/kg for 10 mins followed by 0.1 and 0.2 microg/kg/min. We measured PA distal resistance and proximal elastance by pressure-flow relationships and vascular impedance. We measured RV contractility by the end-systolic pressure-volume relationship (Ees), PA effective elastance by the end-diastolic to end-systolic relationship (Ea), and RV-PA coupling efficiency by the Ees/Ea ratio. PA constriction persistently increased PA resistance and elastance, increased Ea from 0.95 +/- 0.07 to 3.01 +/- 0.28 mm Hg/mL, decreased Ees from 1.17 +/- 0.09 to 0.58 +/- 0.07 mm Hg/mL, and decreased Ees/Ea from 1.26 +/- 0.09 to 0.22 +/- 0.03 (p < .05). Dobutamine did not affect pulmonary hemodynamics, markedly increased RV contractility, and improved RV-PA coupling. Levosimendan decreased PA resistance and elastance, increased RV contractility, and restored RV-PA coupling. Compared with dobutamine, levosimendan decreased RV afterload and therefore better restored RV-PA coupling at similar inotropic state. A transient increase in PA pressure persistently worsens PA hemodynamics, RV contractility, RV-PA coupling, and cardiac output. Levosimendan restores RV-PA coupling better than dobutamine because of similar inotropic effects and additional pulmonary vasodilatory effects.

Fetal middle cerebral to uterine artery pulsatility index ratios in normal and pre‐eclamptic pregnancies

To calculate the normal range for the fetal middle cerebral artery (MCA)/uterine artery pulsatility index (PI) ratio in the third trimester of pregnancy and to assess its value, compared with that of the MCA/umbilical artery PI ratio, in predicting an unfavorable outcome of pregnancies complicated by pre-eclampsia. Doppler blood flow velocimetry of the uterine and umbilical arteries and fetal MCA was performed. We calculated the ratios between 1) the PI of the MCA and the mean PI value of both uterine arteries and 2) the PI of the MCA and the PI of the umbilical artery. All women were examined at or beyond 26 weeks of gestation. A cross-sectional study of 231 normal pregnancies was conducted to construct the reference range. Values below the 5th percentile or an MCA/umbilical artery PI ratio lower than 1.08 were defined as brain-sparing. A further 115 pregnancies with pre-eclampsia (50 mild and 65 severe) were assessed prospectively and the results were related to perinatal outcome. The accuracy of MCA/uterine artery and MCA/umbilical artery PI ratios for prediction of unfavorable pregnancy outcome was compared. Normal MCA/uterine artery PI ratios decreased with advancing gestational age. Redistribution of the fetal circulation indicated by a low MCA/uterine artery PI ratio was seen in 30% of the mild (n=15) and 46% of the severe (n=30) pre-eclamptic cases. There was a significant difference between those without and those with signs of brain-sparing, respectively, in mean birth weight (2456.0 vs. 1424.5 g), gestational age at delivery (35.6 vs. 31.3 weeks) and gestational age at the time of examination (34.9 vs. 30.9 weeks). Furthermore, there was a significantly higher rate of small-for-gestational-age (SGA) neonates (57.8% vs. 25.7%), preterm delivery (100% vs. 81.8%) and Cesarean section (90.7% vs. 66.7%) in cases with an MCA/uterine artery PI ratio below the 5th percentile. However, there was no difference between the groups in the rate of low 5-min Apgar scores, admission to the neonatal intensive care unit, or deliveries before 34 weeks. The MCA/uterine artery and MCA/umbilical artery PI ratios were similar in the prediction of adverse perinatal outcome. Both ratios were better at predicting the outcome of pregnancy than were signs of increased vascular impedance in either the umbilical or uterine arteries. Normal MCA/uterine artery PI ratio decreases with gestational age. Abnormally low MCA/ uterine artery PI ratios are related to unfavorable pregnancy outcome. The predictive value of the MCA/uterine artery PI ratio is similar to that of the MCA/umbilical artery PI ratio.