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Technique for using video microscopy and indicator dilution for repeated measurements of cardiac output in small animals.

BACKGROUND: The authors developed an indicator dilution technique for small animals to repeatedly determine cardiac output and blood volume without cardiac instrumentation or blood sampling. METHODS: Observations were made in the hamster (N = 32, 70 mg/kg pentobarbital) cremaster using in vivo fluorescence videomicroscopy. Fluorescein isothiocyanate-conjugated bovine serum albumin (10 mg/ml) was injected as a bolus dose (right jugular) while video recording the light intensity in a 20-microm arteriole (intensified charge-coupled device [CCD] camera at fixed gain). The intensity signal was analyzed over time (background subtracted) and calibrated to the dye concentration. The ex vivo calibration was performed using a constant optical path length (20 microm) and a range of dye and hematocrit concentrations. In vivo tube hematocrit was determined using standard methods with fluorescently labeled erythrocytes. Thus, quenching of the fluorescence signal by hemoglobin was corrected for the calibration, and the plasma space in the arteriole was determined. The steady state dye concentration measured by the light intensity at 2 min was not different from the dye concentration found by direct spectrophotometric analysis of the plasma. RESULTS: Cardiac index was calculated as milliliters of blood per minute per kilogram body weight. The calculated cardiac index was 359 +/- 18 ml.min(-1).kg(-1), which is not different from the reported values for hamsters. Cardiac output was increased twofold when enough intravenous nitroprusside or nitroglycerine was injected to decrease mean arterial pressure from 90 to 70 mmHg. Cardiac output was elevated during dobutamine infusion (16 microg.kg(-1).min(-1)) and decreased during esmolol infusion (50, 75.kg(-1).min(-1)). Blood volume determined from the steady state dye concentrations was 6.2 +/- 0.5 ml/100 g body weight, within the normal range for hamsters. CONCLUSIONS: Fluorescent dye dilution and video microscopy can be used to repeatedly determine cardiac output or blood volume in small animals.

Animals↗

Effects of sympathetic blockade and splenectomy on cardiac output response to muscular work in dogs.

The effects of splenectomy and sympathetic blockade on cardiac output (Q) response to mild to moderate exercise were studied in chloralose-anesthetized vagotomized dogs during electrically-induced muscular work, which increased oxygen consumption (VO2) 4- to 5-fold. Splenectomy reduced the exercise factor (deltaQ/deltaVO2 ratio) from 5.86 +/- 0.43 (SE) to 3.30 +/- 0.34 (p less than 0.001), while left nephrectomy had no effect. The exercise factor was not affected by beta-adrenoceptor blockade produced by propranolol or practolol, but was reduced by mecamylamine. The spleen did not increase cardiac output by displacing blood into the general circulation because pulmonary artery wedge pressure did not change during exercise in normal dogs. Furthermore, cardiac output was increased 35 +/- 6% after intraportal infusion of splenic venous blood obtained during exercise, whereas arterial blood infusion increased cardiac output only 10%. We conclude that the cardiac output rise during exercise in part is caused by the inotropic action of a splenic noncatecholamine substance, which is released by sympathetic stimulation.

Animals↗

Measurement of cardiac output by cine computed tomography.

High-speed computed transmission tomography (cine CT) is a new noninvasive technique that may be useful for the rapid, accurate quantitation of cardiac function. The capability of cine CT to assess cardiac output was examined 10 mongrel dogs as an initial step in validating this method. After the dogs were anesthetized, femoral arterial pressure and pulmonary artery thermodilution catheters were inserted. After intravenous injection of a bolus of contrast medium, cine CT scans were performed in the flow mode, in which 50-ms scans were triggered electrocardiographically at end-diastole at 8 levels during sequential cardiac cycles. Scans and thermodilution measurements of cardiac output were obtained at rest and during altered hemodynamic states induced by separate infusions of dobutamine and phenylephrine. Time-density analysis was performed over the left ventricular cavity and curves were fitted to the CT flow data by gamma-variate analysis. Using the Stewart-Hamilton equation established for indicator dilution techniques, the cardiac output was calculated. The results established a direct linear correlation (r = 0.92) between cine CT cardiac output and thermodilution cardiac output over a wide range of cardiac outputs (1.5 to 6.3 liters/min). This study demonstrates that cine CT can provide a reliable estimate of cardiac output noninvasively using contrast medium as an indicator in dogs.

Cardiac Output↗

Noninvasive cardiac output monitoring during exercise stress test.

A computerized continuous wave Doppler instrument was used to monitor changes in cardiac output during symptom limited supine bicycle exercise in 41 individuals. Eight (19%) had technically unsatisfactory Doppler signals. Of the remaining 33 patients, 21 had clinical and 18 had angiographic evidence of coronary artery disease (group 1) and 12 age-matched asymptomatic subjects served as controls (group 2). In eight group 1 patients, cardiac output determined simultaneously by Doppler and thermodilution technique correlated well at rest and peak exercise (Y = 1.71x + 0.69, SEE = 0.57, r = 0.86, P less than 0.001). During exercise, group 1 patients increased their cardiac output from 5.2 +/- 1 to 6.9 +/- 1.4 (mean +/- SD), group 2 subjects increased their cardiac output from 5.5 +/- 1.3 to 10.9 +/- 2. Group 1 patients, when compared to group 2 control subjects, had a lesser increase in cardiac output (34% versus 103%, P less than 0.05), a shorter duration of exercise (6.1 versus 9.7 mins, P less than 0.05) and a lower double product (172 +/- 18 versus 211 +/- 27, P less than 0.05). This new Doppler technique provides reasonably accurate estimates of cardiac output at rest and on moderate exercise in selected patients. In selected clinical situations, it may be a valuable addition to other measurements that are usually determined during exercise.

Cardiac Output↗

Non-invasive measurement of cardiac output in patients with acute lung injury using the carbon dioxide rebreathing method.

STUDY OBJECTIVE: To compare measurement of cardiac output by the CO2 rebreathing method with the thermodilution cardiac output technique in mechanically ventilated patients with acute lung injury. DESIGN: Prospective study comparing two methods of cardiac output measurement in 22 consecutive patients with acute lung injury. SETTING: Intensive care unit of a university hospital. PATIENTS: Twenty-two mechanically ventilated patients with acute lung injury monitored with systemic and pulmonary artery catheters. MEASUREMENTS AND RESULTS: Cardiac output was determined using both the thermodilution technique and an indirect CO2 Fick method. Veno-arterial CO2 content difference was calculated from an estimated mixed venous CO2 tension obtained by an equilibrium CO2 rebreathing method and measured arterial CO2 tension. Carbon dioxide pressure was converted to content using the equation of the CO2 dissociation curve described by McHardy. A wide range of cardiac index was studied from 2.7-5.7 l/min/m2. There was a significant correlation between thermodilution and CO2 rebreathing methods (r2 = 0.82, p < 0.01). The mean difference between the CO2 rebreathing method and thermodilution was 0.05 l/min/m2, with a standard deviation for the bias of 0.38 l/min/m2. CONCLUSION: Our results suggest that the CO2 rebreathing method may be a reliable non-invasive technique to determine cardiac output in mechanically ventilated patients with acute lung injury.

Carbon Dioxide↗

Instantaneous and continuous cardiac output in humans obtained with a Doppler pulmonary artery catheter.

A new Doppler pulmonary artery catheter was used to measure instantaneous and continuous cardiac output in both an in vitro model and in 44 patients undergoing cardiac catheterization. Cardiac output was calculated with use of the Doppler catheter-determined instantaneous space-average velocity and the ultrasonically determined instantaneous vessel area. Doppler flow and thermodilution were compared with electromagnetic flow in the in vitro model and with Fick cardiac output in patients. Doppler catheter-determined flow was highly predictive of electro-magnetic flow in the pulsatile flow model (r = 0.99, slope [m] = 1.01 and SEE = 0.05) and appeared comparable to thermodilution measurements (r = 1.00, m = 1.03 and SEE = 0.02). In patients undergoing cardiac catheterization, Doppler catheter-determined cardiac output appeared to modestly underestimate Fick cardiac output (r = 0.82, m = 0.80 and SEE = 0.09; mean error +/- SEM = -0.26 +/- 0.14 liters/min). However, predictive accuracy was comparable to simultaneously obtained thermodilution measurements (r = 0.85, m = 1.07 and SEE = 0.10; mean error +/- SEM = 0.61 +/- 0.16 liters/min). This new Doppler catheter system utilizes multiple ultrasound transducers to provide angle-independent measurements of vessel diameter and instantaneous velocity within the main pulmonary artery, resulting in a more accurate assessment of Doppler-derived cardiac output. In addition, useful information concerning hemodynamic variables such as peak flow, acceleration, deceleration, stroke work and pulmonary impedance may be derived.

Adult↗

Transoesophageal pulsed wave Doppler measurement of cardiac output during major vascular surgery: comparison with the thermodilution technique.

We measured cardiac output in 12 patients undergoing elective abdominal vascular surgery at specific times during the procedure with simultaneous thermodilution and transoesophageal pulsed Doppler echocardiographic techniques. No patient had clinical evidence of valvular heart disease before surgery. Five patients had echocardiographic evidence of mitral regurgitation on colour-coded Doppler. Using Bland and Altman analysis to compare the cardiac output measurement by the two techniques, the Doppler method overestimated the cardiac output (bias = 0.86 litre min-1) compared with the thermodilution technique and there were wide limits of agreement between the two techniques (+2.4 to -4.1 litre min-1). However, in the seven patients with no evidence of mitral regurgitation, closer agreement (bias 0.14 litre min-1) and narrower limits (+1.6 to -1.3 litre min-1) were observed. We conclude that, in patients with competent mitral valves, transoesophageal echocardiograph may provide accurate determination of cardiac output.

Aorta↗

Relationship between cardiac output and cerebral blood flow in patients with intact and with impaired autoregulation.

Intravascular volume expansion has been successfully employed to promote blood flow in ischemic brain regions. This effect has been attributed to both decreased blood viscosity and increased cardiac output resulting from volume expansion. The physiological mechanism by which changes in cardiac output would affect cerebral blood flow (CBF), independent of blood pressure variations, is unclear, but impaired cerebral autoregulation is believed to play a role. In order to evaluate the relationship between cardiac output and CBF when autoregulation is either intact or defective, 135 simultaneous measurements of cardiac output (thermodilution method) and CBF (by the 133Xe inhalation or intravenous injection method) were performed in 35 severely head-injured patients. In 81 instances, these measurements were performed after manipulation of blood pressure with phenylephrine or Arfonad (trimethaphan camsylate), or manipulation of blood viscosity with mannitol. Autoregulation was found to be intact in 55 of these cases and defective in 26. A wide range of changes in cardiac output occurred after administration of each drug. No correlation existed between the changes in cardiac output and the changes in CBF, regardless of the status of blood pressure autoregulation. A significant (40%) increase in CBF was found after administration of mannitol when autoregulation was defective. These data support the hypothesis that, within broad limits, CBF is not related to cardiac output, even when autoregulation is impaired. Thus, the effect of intravascular volume expansion appears to be mediated by decreased blood viscosity rather than cardiac output augmentation.

Brain Ischemia↗

Effect of ventilatory strategy on cardiac output during high frequency jet ventilation.

STUDY OBJECTIVE: The aim was to study the effects of changes in ventilation variables on cardiac function during high frequency jet ventilation. DESIGN: Controlled changes in mean airway pressure (2-10 cm H2O), tidal volume (4 and 8 ml), and frequency (4-8 Hz) were used to assess the effects of ventilatory variables on cardiac output in cats with normal and reduced lung compliance during high frequency jet ventilation. Cardiac output was continuously measured with an electromagnetic flow probe placed around the aorta. Respiratory compliance was reduced by lung lavage. EXPERIMENTAL MATERIAL: Seven anaesthetised adults cats, weight 3.0(SEM 0.2) kg, were used in the study. MEASUREMENTS AND MAIN RESULTS: Cardiac output fell as mean airway pressure was raised from 2 to 10 cm H2O at all frequencies and tidal volumes. At identical levels of minute ventilation and mean airway pressure, cardiac output was improved with combinations of smaller tidal volumes and higher frequencies. Reducing respiratory compliance by lung lavage dampened the effect of mean airway pressure on cardiac output, but maintained the relationship between ventilatory variables observed before lavage. CONCLUSION: At identical settings of minute ventilation and mean airway pressure, cardiac output may be improved with smaller tidal volumes during high frequency jet ventilation.

Airway Resistance↗

Measurement of cardiac output by impedance cardiography in patients with myocardial infarction. Comparative evaluation of impedance and dye dilution methods.

The cardiac output was measured simultaneously by the impedance cardiography and dye dilution methods in 10 patients with acute myocardial infarction 2-3 weeks after admission to the Coronary Care Unit. The impedance cardiac output was on the average 9.7% higher than the dye dilution cardiac output. The reproducibility of impedance cardiac output 4.1%, compared with 5.1% for the dye dilution method. The study showed a satisfactory reliability of impedance in predicting the relative changed of cardiac output in response to tilting from the supine to the 30 degrees head-up position, to a 10 degrees head-down position, and to the intravenous administration of propranolol.

Acute Disease↗

Noninvasive measurement of cardiac output by an acetylene uptake technique and simultaneous comparison with thermodilution in ICU patients.

A simple, accurate, and noninvasive method of cardiac output measurement can be an extremely useful tool for the clinician and researcher. This study used the acetylene gas uptake technique to measure the absorption of acetylene into the pulmonary circulation during a constant exhalation, which is proportional to the pulmonary capillary blood flow and to the cardiac output, assuming no anatomic shunts. We compared cardiac output measured simultaneously by this and by the standard thermodilution (TD) technique in 21 patients in the ICU with a variety of medical and surgical conditions and a wide range of cardiac outputs. We also compared the two techniques in 19 ambulatory patients with a 2-h interval between the invasive and noninvasive test to assess variability over time. The two tests had an excellent correlation when done simultaneously with a correlation coefficient of 0.89 (p < 0.001). With a 2-h interval between the two tests, the correlation coefficient was 0.66 (p = 0.0018). Nine patients in the simultaneous group had cardiomyopathy. When they were excluded, the correlation coefficient increased to 0.96. Most of these patients had documented tricuspid regurgitation (TR), which may underlie the greater difference between acetylene uptake and TD values, with consistently higher TD values in these patients. This study confirms the correlation between the acetylene uptake and the standard invasive TD techniques in sick patients with various medical and surgical conditions and a wide range of cardiac outputs. Furthermore, we believe this would be a more accurate method for measuring cardiac output in patients with cardiomyopathy and TR because it is based only on pulmonary capillary blood flow.

Absorption↗

Reduction in arterial compliance alters carotid baroreflex control of cardiac output in a model of hypertension.

Baroreflex regulation of cardiac output is determined by the performance of the heart as well as the available blood flow returning to the heart (i.e., venous return). We hypothesized that a decrease in arterial compliance (C(a)) would affect carotid baroreflex control of cardiac output by altering the slope of the venous return curve (VR curve). Baroreflex control of systemic arterial pressure (Pa), central venous pressure (Pv), heart rate, cardiac output (CO), and peripheral vascular resistance (R) were determined during bilateral carotid occlusion (BCO) in spontaneously hypertensive (hypertensive, HT) and Sprague-Dawley (normotensive, NT) rats. C(a) was determined from the rate of arterial pressure decay when CO was transiently stopped, and the VR curve was obtained during graded inflation of a vascular balloon positioned in the right atrium. The inverse slope of the VR curve was used as an index of the resistance to venous return (RVR). The baseline slope of the VR curve was -50.5 +/- 3.3 vs. -35.5 +/- 2.6 ml.kg-1.min-1.mmHg-1 in NT vs. HT, respectively (P < 0.05). Control values of Pa (96 +/- 5 vs. 124 +/- 8 mmHg) and R [0.43 +/- 0.04 vs. 0.80 +/- 0.07 peripheral resistance units (PRU)] were reduced in NT, whereas Ca (0.062 +/- 0010 vs. 0.036 +/- 0.003 ml.kg-1.mmHg-1) was elevated in NT vs. HT, respectively (P < 0.05). Analysis of the pressure dependence of C(a) demonstrated that C(a) was a nonlinear function of Pa, and the exponential decay constant for the C(a)-Pa relationship was reduced in HT (0.0055 +/- 0.0012 vs. 0.0012 +/- 0.0002 min, NT vs. HT, P < 0.05). Baroreflex activation by BCO significantly increased Pa (delta Pa, 20 +/- 4 vs. 28 +/- 3 mmHg) and R (delta R, 0.16 +/- 0.04 vs. 0.24 +/- 0.06 PRU) in NT vs. HT, respectively. However, BCO significantly decreased CO in NT but not HT (delta CO, -24 +/- 5 vs. -4 +/- 6 ml.kg-1.min-1, P < 0.05). In NT, RVR was increased 39 +/- 9% during BCO (P < 0.05), whereas RVR increased 8 +/- 3% in HT (P = NS). From these findings, we conclude that the difference in baroreflex control of CO is mediated, in part, by the reduction in C(a), which minimized the baroreflex-evoked increase in RVR.

Animals↗

Feasibility and variability of six methods for the echocardiographic and Doppler determination of cardiac output.

The feasibility and the intrinsic variability of six different methods of echocardiographic and Doppler flow determination of cardiac output were analysed in 34 healthy volunteers. Four were excluded because of poor quality echocardiograms. The mean (range) age of the remaining 30 (12 women, 18 men) was 21 years (13-36 years). Cardiac output was calculated by six methods as a product of echocardiographically determined cross sectional area of the aorta (apical and suprasternal views), pulmonary trunk, tricuspid annulus, and mitral annulus (circular and corrected for diastolic variations), and the flow velocity integral measured by Doppler. Cardiac output ranged from 2.79 to 6.56 1/min (4.45 (1.29) 1/min) (mean (SD)). The feasibility of the methods ranged from 87% (26 patients) for the aorta from the suprasternal notch to 100% (30 patients) for the mitral orifice corrected for diastolic variations and for the tricuspid valve. The corresponding results for all 34 individuals were 76% and 88% respectively. Three way analysis of variance was performed in the 23 healthy volunteers in whom all six methods were feasible. Interobserver and intraobserver interpretative variabilities were 6.8% and 5.9% respectively. The intrinsic variability of each single measurement of cardiac output, independently of the observer and the method used, was 25%. Provided the image was suitable for analysis echocardiographic and Doppler flow determination of cardiac output was feasible in most healthy volunteers. But there was significant intrinsic variability for each of different methods. A single value of cardiac output in an individual should be interpreted with caution.

Adolescent↗

Immediate effect on cardiac output of reversion to sinus rhythm from rapid arrhythmias.

Cardiac output was estimated immediately before and after conversion to sinus rhythm in nine patients with rapid arrhythmias. Conversion was by synchronized direct-current shock in eight patients, and by direct atrial wall stimulation in the other. In seven patients there was an immediate increase in cardiac output after restoration of sinus rhythm. The percentage increase in output was directly proportional to the rate of the arrhythmia immediately before conversion (r=0.91, P<0.01). The critical heart rate, above which an immediate increase in cardiac output might be expected on conversion to sinus rhythm, appeared in these patients to be about 160 beats per minute.

Adolescent↗

[Heart size and left ventricular function in coronary artery disease: I. Heart size, exercise tolerance, cardiac output and filling pressures (author's transl)].

The possible relationship between the cardiac volume, as determined radiologically in the supine position in 119 patients with angiographically proven coronary artery disease, and the results of ergometry and balloon catheterization was investigated. There was no relationship between the heart size on the one side and the maximum exercise tolerance and the maximum cardiac output on the other, except for the fact, that these parameters tended to decrease with increasing heart size. This was especially true in patients with angina. The maximum cardiac output of patients with angina was always below the value of patients without angina but comparable heart size. Reduced cardiac output under exercise (exertional cardiac insufficiency) was present in 50% of patients with enlarged hearts but already in 22% of patients with heart volumes in the lower range of normal. The diastolic pulmonary artery pressure, determined under exercise, was the only parameter with a significant relationship to the heart size: The larger the heart size, the higher the diastolic pulmonary artery pressure. On the other hand: the diastolic pulmonary artery pressure at rest was abnormal with significant frequency only, when the heart was enlarged. Our data suggest, that the hemodynamics are determined by 2 factors: Myocardial scarring secondary to infarction and coronary insufficiency (ischemia). Of these two factors only the former influences cardiac size. Therefore, determination of the heart volume helps evaluating the respective role of these two factors in individual cases.

Adult↗

Alveolar dead space does not affect indirect Fick cardiac output determinations.

We examined the influence of three variables (different breathing circuits, breath selected for analysis, and alveolar dead space ventilation) on the accuracy of noninvasive cardiac output determinations with the Fick CO2 (indirect) equation. We compared noninvasive determinations with invasive thermodilution measurements over a wide range of cardiac outputs in 17 2-mo-old pigs anesthetized with halothane and nitrous oxide and paralyzed with either pancuronium or d-tubocurare. We found that rebreathing and nonrebreathing circuits provide accurate cardiac output determinations and that the optimal breath for analysis with either the rebreathing or nonrebreathing technique appears to depend on the cardiac output. When alveolar dead space was increased by using positional changes and the intracardiac administration of glass beads, there was still a good correlation between noninvasive and invasive cardiac output determinations. We conclude that both rebreathing and nonrebreathing techniques of indirect Fick cardiac output determinations correlate well with thermodilution measures over a wide range of cardiac outputs and alveolar dead space/tidal volume fractions.

Animals↗

Room-temperature thermodilution cardiac output: proximal injectate lumen vs proximal infusion lumen.

OBJECTIVE: To assess the accuracy of room-temperature thermodilution cardiac output measurements from the venous infusion port. DESIGN: Central venous port cardiac output measurements were compared with venous infusion port measurements in 48 right-heart catheters. INTERVENTION: Three 10-mL injections of 5% dextrose in water were made through each port. The order of port injection was random. RESULTS: The cardiac outputs were 5.8 +/- 1.8 L/min from both ports, with no difference between ports (paired t test). CONCLUSION: Room-temperature thermodilution cardiac output determinations from the venous infusion port can be used in place of central venous port cardiac outputs if the central venous port becomes nonfunctional.

Adult↗