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PubMed2002

Continuous and intermittent cardiac output measurement: pulmonary artery catheter versus aortic transpulmonary technique.

BACKGROUND: Cardiac output (CO) can be measured intermittently by bolus thermodilution methods in the pulmonary artery (COpa) or in the aorta (COart). A continuous thermodilution method (CCO) and a method for continuous estimation using the arterial pulse wave (PCCO) are also available. METHODS: We compared two methods of intermittent CO measurements in patients during liver transplantation: COpa, regarded as the current clinical standard, and an aortic transpulmonary thermodilution technique (COart) performed with the PiCCO system. We also compared CCO and PCCO. Measurements were made in 62 patients at three stages: after the induction of anaesthesia, after caval clamping phase, and at the end of surgery. We used Bland-Altman and correlation analysis. RESULTS: We found close agreement between the techniques. Mean bias between COart and COpa and PCCO and CCO was 0.15 (2SD of differences between methods=1.74) litre min(-1) and -0.03 (1.75) litre min(-1), respectively. Mean bias between CCO and COpa and PCCO and COpa was 0.02 (1.48) litre min(-1) and 0.04 (1.69) litre min(-1), respectively. CONCLUSIONS: Measurement with the aortic transpulmonary thermodilution technique gives continuous and intermittent values that agree with the pulmonary thermodilution method.

Adult↗
PubMed1978

Cardiac output and regional blood flow following trauma.

The changes in cardiac output (Q), regional blood blow (Qr) and regional vascular resistance, and arterial pressure were studied in rats subjected to moderate (LD0) or severe (LD50) traumatic shock. Q and Qr were determined using microspheres at 15, 60 and 180 min posttrauma. Arterial pressure decreased in both groups at 15 min and recovered by 3 hr after sublethal (LD0) trauma, while arterial pressure did not return to control levels after LD50 trauma. Q decreased in both groups at 15 min and returned to control only in the LD0 trauma group by 3 hr. Cerebral, coronary, and hepatic arterial flows and resistances were maintained in both groups. Renal, intestinal, and splenic flows decreased and resistances increased in both groups by 15 min and returned to control levels by 3 hr only in the LD0 trauma group. Total hepatic and hepatic portal flows decreased at 60 min and returned to control levels at 3 hr after LD0 trauma, while there was significant depression in these parameters 3 hr after LD50 trauma. Therefore, sublethal and severe trauma resulted in early redistribution of flow favoring the coronary, cerebral, and hepatic arterial beds. However, renal, intestinal, splenic, and portal flows remained depressed only in severely traumatized rats, suggesting that continued hypoperfusion is a factor in the multiple organ failure and death following severe traumatic injury.

Animals↗
PubMed2001

Relations of stroke volume and cardiac output to body composition: the strong heart study.

BACKGROUND: Although cardiac output (CO) plays the vital role of delivering nutrients to body tissues, few data are available concerning the relations of stroke volume (SV) and CO to body composition in large population samples. METHODS AND RESULTS: Doppler and 2D echocardiography and bioelectric impedance in 2744 Strong Heart Study participants were used to calculate SV and CO and to relate them to fat-free body mass (FFM), adipose mass, and demographic variables. Both SV and CO were higher in men than women and in overweight than normal-weight individuals, but these differences were diminished or even reversed by normalization for FFM or body surface area. In both sexes, SV and CO were more strongly related to FFM than adipose mass, other body habitus measures, arterial pressure, diabetes, or age. In multivariate analyses using the average of Doppler and left ventricular SV to minimize measurement variability, FFM was the strongest correlate of SV and CO; other independent correlates were adipose mass, systolic pressure, diabetes, age, and use of digoxin and calcium channel and beta-blockers. CONCLUSIONS: In a population-based sample, SV and CO are more strongly related to FFM than other variables; increased FFM may be the primary determinant of increased SV and CO in obesity.

Adipose Tissue↗
PubMed1984

Cardiac output and redistribution of organ blood flow in hypermetabolic sepsis.

Cardiac output (CO) and the distribution of blood flow were studied in chronically catheterized conscious rats during sustained (4 days) sepsis. Septicemia was induced by intraperitoneal administration of a pooled fecal inoculum, and tissue blood flow and CO were determined daily with 15-micron radioactive microspheres. Mean arterial blood pressure (MABP, 113 +/- 2 mmHg), CO (244.5 +/- 11.4 ml X min-1 X kg-1), and total peripheral resistance (TPR, 1.36 +/- 0.07 mmHg X ml-1 X min) were stable in control rats over the 4 days postinoculation. Septic animals showed a consistent tachycardia with MABP significantly reduced only on days 3 and 4 (86 +/- 4 mmHg). A hyperdynamic response to sepsis was indicated by an elevated CO (27%) and similarly reduced TPR on day 2. The calculated stroke volume averaged 0.22 +/- 0.01 ml/beat and did not vary over time or between the two groups. There was a 40-70% increase in blood flow to the heart, spleen, adrenal glands, and small intestine, and a greater than sixfold increase in hepatic arterial blood flow. The sustained elevation of coronary blood flow, observed in septic animals, was independent of myocardial work and is consistent with impaired myocardial function. Pancreas, stomach, and skeletal muscle blood flow was consistently compromised (24, 39, and 52%, respectively) during sepsis. Blood flow in other organs remained unchanged over time. Sepsis-induced changes in the fractional distribution of blood flow to various organs were similar to those described for absolute flow. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2002

Role of the autonomic nervous system in the reduced maximal cardiac output at altitude.

After acclimatization to high altitude, maximal exercise cardiac output (QT) is reduced. Possible contributing factors include 1) blood volume depletion, 2) increased blood viscosity, 3) myocardial hypoxia, 4) altered autonomic nervous system (ANS) function affecting maximal heart rate (HR), and 5) reduced flow demand from reduced muscle work capability. We tested the role of the ANS reduction of HR in this phenomenon in five normal subjects by separately blocking the sympathetic and parasympathetic arms of the ANS during maximal exercise after 2-wk acclimatization at 3,800 m to alter maximal HR. We used intravenous doses of 8.0 mg of propranolol and 0.8 mg of glycopyrrolate, respectively. At altitude, peak HR was 170 +/- 6 beats/min, reduced from 186 +/- 3 beats/min (P = 0.012) at sea level. Propranolol further reduced peak HR to 139 +/- 2 beats/min (P = 0.001), whereas glycopyrrolate increased peak HR to sea level values, 184 +/- 3 beats/min, confirming adequate dosing with each drug. In contrast, peak O(2) consumption, work rate, and QT were similar at altitude under all drug treatments [peak QT = 16.2 +/- 1.2 (control), 15.5 +/- 1.3 (propranolol), and 16.2 +/- 1.1 l/min (glycopyrrolate)]. All QT results at altitude were lower than those at sea level (20.0 +/- 1.8 l/min in air). Therefore, this study suggests that, whereas the ANS may affect HR at altitude, peak QT is unaffected by ANS blockade. We conclude that the effect of altered ANS function on HR is not the cause of the reduced maximal QT at altitude.

Acclimatization↗
PubMed1990

[Interobserver and spontaneous variability of Doppler echocardiography measured cardiac output in children with congenital heart defects].

Doppler-derived cardiac output (CO) measurements were performed on 2 consecutive days in 30 children with surgically corrected congenital heart diseases. The children formed three subgroups of 10 patients each according to age (group 1 = less than 1 year, 2 = 1-5 years, 3 = greater than 5 years). Pulsed Doppler recordings were carried out over pulmonary and aortic valves using standard projections. All recordings were "blindly" evaluated by two independent investigators. In each age group day-to-day and interobserver variability were assessed for CO, cross-sectional area of the vessel (A), time-velocity integral (I), and heart rate (HR). Day-to-day variability for CO ranged between 20% and 33% depending on age and sampling site. The corresponding variabilities for A, I, and HR were 19-35%, 14-23%, and 9-11%, respectively. Spontaneous variability did not differ significantly between the three age groups. Interobserver variabilities for CO, I, A, and HR were 13-40%, 14-32%, 20-55%, and 1-3%, respectively. A of the aorta in group 1 and aortic I in group 3 were significantly different (p less than 0.05) for both observers. None of the remaining parameters, measured by both observers, were significantly different. CO and I revealed a higher interobserver variability (p less than 0.01) for infants (group 1) than for older children, when determined over the pulmonary valve. In addition, interobserver variability of aortic cross-sectional area was significantly increased (p less than 0.01) for the young age group (group 1). We conclude that there is a considerable spontaneous and interobserver variability of Doppler-derived CO measurements in pediatric patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve↗
PubMed1989

Effect of infused adenosine on cardiac output and systemic resistance in normal subjects.

1. The purine nucleoside adenosine relaxes smooth muscle in vitro and is a vasodilator in animals, but its effects on cardiac output and systemic vascular resistance have not been measured in normal conscious human subjects. 2. We have studied the effects of infused adenosine in doses of 0.005, 0.03 and 0.07 mg kg-1 min-1 on pulmonary blood flow and systemic vascular resistance in eight healthy volunteers, using a non-invasive, inert gas method and mass spectrometry. 3. At a dose of 0.07 mg kg-1 min-1, there was a rise in effective pulmonary blood flow (which is approximately equivalent to cardiac output) of 0.52 +/- 0.08 l min-1 m-2 (mean +/- s.e. mean) and a fall in estimated systemic vascular resistance of 357 +/- 44 dyn s cm-5. Despite this marked systemic vasodilation, there was no significant change in mean heart rate. 4. The effects of this dose of adenosine were maximal 2 min after starting the infusion, and had disappeared within 5 min of stopping it. 5. Adenosine may be therapeutically useful in the reduction of left ventricular afterload, where the absence of reflex tachycardia may be advantageous. We suggest that adenosine in doses of 0.03 mg kg-1 min-1 should be evaluated as a selective pulmonary vasodilator.

Adenosine↗
PubMed1985

Determination of cardiac output at rest and during exercise by carbon dioxide rebreathing method in obstructive airway disease.

We evaluated the accuracy of the CO2 rebreathing method (CO2rb) for measuring cardiac output at rest and during steady-state exercise in 15 patients (mean +/- SD age, 59.7 +/- 7.5 yr) with obstructive airway disease. At rest, there was a significant correlation between direct Fick and CO2rb methods using measured arterial PCO2 (r = 0.70; p = 0.002), but not with using end-tidal PCO2 (r = 0.38; p = NS). During exercise, there was greater correlation with CO2rb using arterial PCO2 (r = 0.79; p = 0.001) than using end-tidal PCO2 (r = 0.63; p = 0.007) compared with the direct Fick determination. Correlation between the CO2rb and direct Fick methods was greater with moderate air-flow obstruction (n = 6) than with severe airway disease (n = 9), and the CO2rb method was more accurate during exercise than at rest. The CO2rb method using either end-tidal or arterial PCO2 underestimated the direct Fick measurement in 13 of 15 patients at rest, which may reflect inadequate equilibration between alveolar and oxygenated mixed venous PCO2. However, no consistent error was observed during exercise when higher CO2 production and an increased venoarterial PCO2 difference would diminish potential inaccuracies. We concluded that the CO2rb technique is an acceptable method for measuring cardiac output during exercise in patients with moderate and severe obstructive airway disease as long as arterial PCO2 is directly measured rather than estimated from end-tidal PCO2.

Aged↗
PubMed1987

[Noninvasive measurement of cardiac output using two-dimensional Doppler echocardiography and analysis of sources of error].

The purpose of this study was (1) to analyze the factors responsible for errors in the two-dimensional Doppler echographic measurements of cardiac output (C.O.) and (2) to establish a noninvasive method for measuring C.O. The subjects were 50 cardiac patients who had neither aortic valve disease nor intracardiac shunts. The C.O. was calculated using the following formula: C.O. (l/min) = mean flow velocity (cm/sec) x pi(aortic ring diameter/2)2 (cm2) x 60/10(3) Left ventricular ejection flow velocity was recorded in the center of the aortic ring from the apical approach. Mean velocity was calculated by integration of instantaneous mean velocity in the ejection phase divided by the cardiac cycle length, and was corrected by the Doppler incident angle. The inner diameter of the aortic ring was measured in the parasternal long-axis view at the time of the maximum ejection flow velocity. The following results were obtained: 1. Sources of error in the measurement of cardiac output. 1) Accuracy of instantaneous mean velocity calculating circuit: This calculating circuit was accurate in model experiments using pulsatile flow. 2) Effect of high-pass filter: In model circuits, application of high-pass filter overestimated flow velocity. The higher the cut-off frequency of the high-pass filter, the larger the overestimation. This was probably due to the parabolic flow velocity profile in the circuit. 3) Flow velocity profile in the aortic ring: The flow velocity profile seemed to be flat in the aortic ring except near the anterior aortic wall. Therefore, the effect of the high-pass filter was considered to be negligible in case of clinical application. 4) The effects of shift and size of sample volume: The location of sample volume relative to the aortic valve ring shifted about 7 mm during systole. However, the shift and size of sample volume seemed to have little effect on the measured C.O., because the flow velocity profile was nearly flat in the aortic ring. 5) Ultrasound beam incident angle: From a practical viewpoint, it was necessary to set an incident angle of less than 50 degrees for minimizing the error. We were able to set the angle within 50 degrees in all but one of patients. 6) Diameter of the aortic ring: Two-dimensional echographic measurement of the aortic ring diameter was not so accurate; it seemed to become a major source of error in the calculation of C.O.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

[Value of coronary reperfusion in cases of very low cardiac output following coronary artery bypass grafts].

From January 1986 to December 1988, 244 patients had a coronary artery revascularization at St Joseph Hospital. Four patients (1.8%) died in post operative time (less than 30 days). None died directly from cardiogenic shock. Five patients had a severe low cardiac output (2 h to 48 h post-op) and needed cardiac resuscitation. These patients were immediately taken to the operating room. The coronary bypasses were explored (2 technical errors corrected), the metabolic disorders were treated and a coronary reperfusion was done with the Buckberg's technique. All the patients could be weaned from cardiopulmonary bypass, two with intra aortic balloon pumping. One patient died of digestive complication the 10th postoperative day. The four other patients survived and are in good clinical condition. The severe low cardiac output after coronary revascularization can be reversible with resuscitation in operating room, short assistance, and coronary reperfusion.

Aged↗
PubMed1990

Negative effect of insufflation on cardiac output and pulmonary blood volume.

In 14 anaesthetized young pigs the changes in pulmonary blood flow and pulmonary blood volume (Qp) during mechanical ventilation were quantified. Ventilation was performed at 10 cycles per min and tidal volume (VT) was adjusted to an arterial PCO2 of about 40 mmHg (5.3 kPa). In 4 animals, 7 ventilatory cycles with an inspiratory pause (IP) of 7.2 s but different tidal volumes were inserted at intervals of 5 min to determine the decrease in Qp (delta Qp) from the differences between right ventricular (Qs,rv) and left ventricular (Qs,lv) stroke volume, and to relate delta Qp to VT. We measured pressure in the aorta (Pao), central veins (Pcv), right and left ventricles (Prv, Plv) pericardium (Pit), and trachea (PT). Blood flow was measured electromagnetically (EM) in the pulmonary artery (Q'pa) and aorta (Q'ao). Stroke volumes were derived from the EM-flow curves. In the other 10 experiments, Qs,lv was derived from the aortic pulse contour. Beat-to-beat analyses of Qs,rv and Qs,lv and blood pressures during the normal ventilatory cycles and those with an IP revealed the following: 1) The end-expiratory RV output and LV output were constant and were defined as baseline values. 2) The accumulated decrease in Qs,rv during insufflation caused a mean deficit in cardiac output of 10.3 +/- 3.2% (s.d.), n = 135; the same was found for Qs,lv, indicating the pulse contour as a useful method to estimate the variations in cardiac output during a ventilatory cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1999

Comparison of cardiac output assessed by pulse-contour analysis and thermodilution in patients undergoing minimally invasive direct coronary artery bypass grafting.

OBJECTIVE: To investigate the precision and accuracy of continuous pulse contour cardiac output (PCCO) compared with intermittent transcardiopulmonary (TCPCO) and pulmonary artery thermodilution (TDCO) measurements in patients undergoing minimally invasive coronary bypass surgery (MIDCAB). DESIGN: Prospective, controlled, clinical study. SETTING: University hospital. PARTICIPANTS: Twelve patients undergoing MIDCAB. INTERVENTIONS: Thirty-six measurements of PCCO and thermodilution cardiac output (CO) were simultaneously performed after the start of surgery, during bypass grafting, and at the end of surgery. TCPCO and TDCO were simultaneously assessed by three injections of ice-cold saline randomly spread over the respiratory cycle. The pulse contour device was initially calibrated with an additional set of aortic thermodilution measurements. MEASUREMENTS AND MAIN RESULTS: Absolute values of CO ranged between 1.6 and 9.2 L/min. A close agreement among the three techniques was observed at all measurements. Mean bias between PCCO and TDCO and TCPCO was 0.003 L/min (2 SD of differences between methods = 1.26 L/min) and 0.27 L/min (2 SD of differences between methods = 1.16 L/min), respectively. The correlation coefficients were r2 = 0.90 for TCPCO versus PCCO and r2 = 0.88 for TDCO versus PCCO. CONCLUSION: The results of the present study show that compared with thermodilution CO, pulse contour analysis enables accurate measurement of continuous CO in patients undergoing MIDCAB.

Cardiac Output↗
PubMed1980

Transcutaneous Doppler method of measuring cardiac output--II. Noninvasive measurement by transcutaneous Doppler aortic blood velocity integration and M mode echocardiography.

In 15 patients with acute myocardial infarction (group I) and in 14 patients undergoing routine cardiac catheterization (group II) cardiac output values obtained by multiplying the 1 minute sum of the systolic integral of aortic blood flow velocity by the average systolic diameter of the aortic root were compared with values obtained with the thermodilution and Fick methods, respetively. Patients in group I were studied under various hemodynamic conditions, whereas those in group II were studied in the baseline state conditions, whereas those in group II were studied in the baseline state only. In group I, the correlation between the two methods was excellent (r values ranged from 0.96 to 0.99) except in one severely anemic patient whose Doppler signals were noisy, but at heart rates exceeding 150 beats/min it was not as good. In group II, the correlatin between the two methods was r = 0.96 with a standard error of the estimate of 0.226 liter. The Doppler method is totally noninvasive and is useful for monitoring changes in cardiac output in patients with acute myocardial infarction.

Adult↗
PubMed1991

NG-monomethyl-l-arginine (NMA) restores arterial blood pressure but reduces cardiac output in a canine model of endotoxic shock.

Previous studies have suggested that NMA or similar inhibitors of nitric oxide synthesis from L-arginine reverses or prevents the hypotension associated with endotoxin administration. We wanted to determine if vascular and cardiac responses to NMA support the idea that inhibitors of nitric oxide synthesis might be useful in the treatment of septic shock. Pentobarbital-anesthetized beagle dogs were administered endotoxin for 2 hours at a dose of 250 ng/kg/min. This resulted in reductions in systemic vascular resistance (34% decrease) and mean arterial pressure (25% decrease). Administration of NMA (30 mg/kg, IV) caused large and sustained increases in mean arterial pressure and systemic vascular resistance, and a large decrease in cardiac output and femoral arterial blood flow. Although NMA restored arterial pressure, the large and sustained fall in cardiac output suggests that the cardiovascular action of NMA is detrimental to dogs treated with endotoxin.

Animals↗
PubMed1997

Cardiopulmonary interactions after Fontan operations: augmentation of cardiac output using negative pressure ventilation.

BACKGROUND: The low-output state is the chief cause of morbidity and mortality after Fontan operations. An alternative hemodynamic tool would be a welcome addition for these patients, who are typically resistant to conventional therapeutic measures. METHODS AND RESULTS: The hemodynamic effects of conversion from conventional intermittent positive pressure ventilation (IPPV) to cuirass negative pressure ventilation (NPV) was investigated in nine acute postoperative Fontan patients on the pediatric intensive care unit and nine anesthetized patients undergoing cardiac catheterization in the convalescent phase after Fontan operations. Pulmonary blood flow was measured using the direct Fick method during IPPV and after a brief period of NPV. In one subgroup of patients, pulmonary blood flow was measured again after reinstitution of IPPV, and in a second subgroup, pulmonary blood flow was measured after an extended period of NPV. A brief period of NPV increased pulmonary blood flow from 2.4 to 3.5 L x min(-1) x /m(-2), with a mean increase of 42%. Pulmonary blood flow continued to improve, with a total increase of 54% after an extended period of NPV. Values fell toward baseline after reinstitution of IPPV. Heart rate was unchanged during NPV, and the improvement in pulmonary blood flow was achieved by an increase in stroke volume from 25 mL/m2 to 37 mL/m2. CONCLUSIONS: Through improvement of the stroke volume alone, NPV brought about a marked increase in the pulmonary blood flow and, hence, cardiac output of Fontan patients. An improvement in cardiac output of this order, and by this mechanism, is currently unmatched by any therapeutic alternatives.

Adolescent↗
PubMed1992

Loss of cerebral regulation during cardiac output variations in focal cerebral ischemia.

Focal cerebral ischemia was induced in anesthetized macaque monkeys by unilateral middle cerebral artery occlusion. The effect of blood volume expansion by a colloid agent and subsequent exsanguination to baseline cardiac output (CO) on local cerebral blood flow (CBF) was measured by the hydrogen clearance technique in both ischemic and nonischemic brain regions. Cardiac output was increased to maximum levels (159% +/- 92%, mean +/- standard error of the mean) by blood volume expansion with the colloid agent hetastarch, and was then reduced a similar amount (166% +/- 82%) by exsanguination during the ischemic period. Local CBF in ischemic brain regions varied directly with CO, with a correlation coefficient of 0.89 (% change CBF/% change CO), while CBF in nonischemic brain was not affected by upward or downward manipulations of CO. The difference in these responses between ischemic and nonischemic brain was highly significant (p less than 0.001). The results of this study show a profound loss of regulatory control in ischemic brain in response to alterations in CO, thereby suggesting that blood volume variations may cause significant changes in the intensity of ischemia. It is proposed that CO monitoring and manipulation may be vital for optimum care of patients with acute cerebral ischemia.

Animals↗
PubMed1987

Renal fraction of cardiac output cleared of radioactive indicator in 99Tcm-DTPA gamma camera renography.

The renal images recorded during 1 to 2 1/2 min postinjection in 99Tcm-DTPA gamma camera renography were used for determination of the total cleared renal fraction (TCRF) of cardiac output with respect to the radioactive indicator. The left and right cleared renal fractions of cardiac output were determined directly, i.e., assessment of single-kidney uptake function within a few minutes postinjection was also possible. TCRF was proportional to the glomerular filtration rate (GFR) determined by the 51Cr-EDTA plasma clearance in a group of 23 subjects with GFR in the interval 15 to 130 ml/min/1.73 m2. The slope of the regression line of TCRF against GFR was in agreement with the theoretical estimate for it. GFR could be predicted from TCRF with a standard error of estimate from 4 to 15 ml/min/1.73 m2 for values of GFR in the above interval. Intra-observer variability of TCRF was unbiased and varied between 4% (normal GFR) and 9% (decreased GFR). TCRF is proposed to represent an alternative to renal clearance for evaluation of renal uptake function.

Cardiac Output↗
PubMed2002

Increased cerebral blood flow after brain arteriovenous malformation resection is substantially independent of changes in cardiac output.

Brain arteriovenous malformation (BAVM) resection can result in an acute increase in cerebral blood flow (CBF) of unclear etiology. This observational study investigated the relationship between changes in CBF and cardiac output (CO) in patients undergoing microsurgical resection of BAVMs. In 20 patients undergoing a BAVM resection during an isoflurane-based anesthesia, we measured CBF and systemic cardiovascular parameters immediately before and after BAVM resection. CBF was measured on the hemisphere ipsilateral to the lesions and on the contralateral side, using intravenous cold 133Xe washout. Cardiac output was measured using thermodilution technique via a pulmonary artery catheter. There was an increase in global CBF after resection (25 +/- 8 versus 31 +/- 13 mL/100 g/min, preresection versus postresection, mean +/- SD, P =.002), ipsilateral CBF (25 +/- 8 versus 31 +/- 13 mL/100 g/min, P =.002), and contralateral CBF (24 +/- 7 versus 30 +/- 13 mL/100 g/min, P =.003). There was no change in CO, mean systemic arterial pressure, central venous pressure, or pulmonary artery diastolic pressure. The change in CBFGLOBAL was not correlated with changes in CO (r =.154, P =.517). BAVM resection resulted in global increases in CBF that was not substantially related to changes in CO or other systemic parameters.

Adult↗