The 400 microsphere per piece “rule” does not apply to all blood flow studies

2000 ◽  
Vol 278 (1) ◽  
pp. H16-H25 ◽  
Author(s):  
Nayak L. Polissar ◽  
Derek C. Stanford ◽  
Robb W. Glenny

Microsphere experiments are useful in measuring regional organ perfusion as well as heterogeneity of blood flow within organs and correlation of perfusion between organ pieces at different time points. A 400 microspheres/piece “rule” is often used in planning experiments or to determine whether experiments are valid. This rule is based on the statement that 400 microspheres must lodge in a region for 95% confidence that the observed flow in the region is within 10% of the true flow. The 400 microspheres precision rule, however, only applies to measurements of perfusion to a single region or organ piece. Examples, simulations, and an animal experiment were carried out to show that good precision for measurements of heterogeneity and correlation can be obtained from many experiments with <400 microspheres/piece. Furthermore, methods were developed and tested for correcting the observed heterogeneity and correlation to remove the Poisson “noise” due to discrete microsphere measurements. The animal experiment shows adjusted values of heterogeneity and correlation that are in close agreement for measurements made with many or few microspheres/piece. Simulations demonstrate that the adjusted values are accurate for a variety of experiments with far fewer than 400 microspheres/piece. Thus the 400 microspheres rule does not apply to many experiments. A “rule of thumb” is that experiments with a total of at least 15,000 microspheres, for all pieces combined, are very likely to yield accurate estimates of heterogeneity. Experiments with a total of at least 25,000 microspheres are very likely to yield accurate estimates of correlation coefficients.

2001 ◽  
Vol 280 (6) ◽  
pp. R1601-R1605 ◽  
Author(s):  
M. Iwase ◽  
K. Tashiro ◽  
Y. Uchizono ◽  
D. Goto ◽  
M. Yoshinari

Anesthesia affects general hemodynamics and regulation of organ perfusion. We used colored microspheres to measure pancreatic islet blood flow in conscious rats at two time points, during either hyperglycemia or hypoglycemia. This method, using black and green microspheres, was validated by comparison with previous microsphere experiments and by lack of effect of a nonmetabolizable glucose analog, 3- O-methylglucose, on islet perfusion. Basal and glucose-stimulated islet blood flow levels were similar in pentobarbital sodium-anesthetized and conscious rats. However, the basal distribution of pancreatic blood flow was altered by anesthesia (fractional islet blood flow 5.8 ± 0.4% in conscious rats, 7.9 ± 0.8% in pentobarbital-anesthetized rats, P < 0.05). Insulin-induced hypoglycemia significantly increased whole pancreatic blood flow in conscious rats, whereas islet blood flow remained unchanged and fractional islet blood flow was decreased (5.8 ± 0.5% in the basal state, 4.2 ± 0.4% during hypoglycemia, P < 0.001). Methylatropine pretreatment significantly increased islet blood flow during hypoglycemia by 181%. This result suggests that prevention of hypoglycemia-induced increase in islet perfusion may be mediated, at least in part, by a cholinergic, vagal muscarinic mechanism.


1998 ◽  
Vol 275 (6) ◽  
pp. E974-E979 ◽  
Author(s):  
G. R. Steenge ◽  
J. Lambourne ◽  
A. Casey ◽  
I. A. Macdonald ◽  
P. L. Greenhaff

This study investigated the effect of insulin on plasma and muscle creatine accumulation and limb blood flow in humans after creatine administration. Seven men underwent a 300-min euglycemic insulin clamp combined with creatine administration on four separate occasions. Insulin was infused at rates of 5, 30, 55, or 105 mU ⋅ m−2 ⋅ min−1, and on each occasion 12.4 g creatine was administered. During infusion of insulin at rates of 55 and 105 mU ⋅ m−2 ⋅ min−1, muscle total creatine concentration increased by 4.5 ± 1.4 ( P < 0.05) and 8.3 ± 1.0 mmol/kg dry mass ( P < 0.05), and plasma creatine concentrations were lower at specific time points compared with the 5 mU ⋅ m−2 ⋅ min−1infusion rate. The magnitude of increase in calf blood flow (plethysmography) was the same irrespective of the rate of insulin infusion, and forearm blood flow increased to the same extent as the three highest infusion rates. These findings demonstrate that insulin can enhance muscle creatine accumulation in humans but only when present at physiologically high or supraphysiological concentrations. This response is likely to be the result of an insulin-mediated increase in muscle creatine transport rather than creatine delivery.


1990 ◽  
Vol 259 (1) ◽  
pp. R119-R125 ◽  
Author(s):  
J. L. Sondeen ◽  
G. A. Gonzaludo ◽  
J. A. Loveday ◽  
G. E. Deshon ◽  
C. B. Clifford ◽  
...  

We developed a conscious pig model with a chronically instrumented kidney to measure renal blood flow (RBF), glomerular filtration rate (GFR), and excretory functions during hemorrhage. Seven to 10 days before experimentation, pigs were splenectomized, arterial and venous catheters were implanted, an ultrasonic flow probe was placed on the renal artery, and a pyelostomy was performed for nonocclusively placing a ureteral catheter. Measurements were taken before hemorrhage, and at hemorrhage volumes of 7, 14, 21, and 28 ml/kg (equivalent to 10.5, 21, 31, and 42% of the estimated blood volume), or at corresponding time points for controls. RBF was decreased by 30% when 21% of the blood (14 mg/kg) was removed, before arterial pressure, GFR, or urine flow or excretion was changed. At volumes of hemorrhage greater than 14 ml/kg, there were progressive decreases in RBF, GFR, urine flow rate, osmotic and electrolyte excretion, and arterial pressure. Thus pigs, like humans, respond to hypovolemia with an early redistribution of blood flow away from the kidney.


1994 ◽  
Vol 266 (4) ◽  
pp. H1558-H1564 ◽  
Author(s):  
M. F. Mulder ◽  
A. A. van Lambalgen ◽  
E. Huisman ◽  
J. J. Visser ◽  
G. C. van den Bos ◽  
...  

The role of NO during the first hour of endotoxemia is still controversial. To evaluate whether NO is protective or detrimental to the regulation of systemic blood pressure, cardiac output (CO), and organ perfusion in rats during acute endotoxemia, we have studied the effects of inhibition of NO synthesis. Thirty minutes after 0.1 mg NG-nitro-L-arginine (L-NNA; group L, n = 7, partial inhibition), 1 mg L-NNA (group H, n = 6, complete inhibition), or saline (group E, n = 7) intravenous infusion, anesthetized volume-loaded rats were infused with endotoxin Escherichia coli O127:B8 (8 mg.kg-1 x h-1) from time (t) = 0 to 60 min. Organ blood flow was measured with radioactive microspheres. In group H, at time 0, CO was lower than in group E (by -29%; P < 0.05), and systemic vascular resistance (SVR) was higher than in groups E and L (by 72 and 51%, respectively; P < 0.05). Perfusion of the pancreas, stomach, intestines, and kidney was lower (P < 0.05) and corresponding organ vascular resistance (OVR) higher (P < 0.05) in group H than in groups E and L (except kidney in group L). At t = 60 min, in groups H and L, CO was lower (by -45 and -26%, respectively; P < 0.05) and SVR was higher (by 112 and 54%, respectively; P < 0.05) than in group E. In group L only blood flow to the heart, pancreas, intestines, and kidney was significantly lower than in group E, and corresponding OVR was higher.(ABSTRACT TRUNCATED AT 250 WORDS)


2001 ◽  
Vol 281 (3) ◽  
pp. H1148-H1155 ◽  
Author(s):  
C. Cerutti ◽  
M. P. Gustin ◽  
P. Molino ◽  
C. Z. Paultre

Several methods for estimating stroke volume (SV) were tested in conscious, freely moving rats in which ascending aortic pressure and cardiac flow were simultaneously (beat-to-beat) recorded. We compared two pulse-contour models to two new statistical models including eight parameters extracted from the pressure waveform in a multiple linear regression. Global as well as individual statistical models gave higher correlation coefficients between estimated and measured SV ( model 1, r = 0.97; model 2, r= 0.96) than pulse-contour models ( model 1, r = 0.83; model 2, r = 0.91). The latter models as well as statistical model 1 used the pulsatile systolic area and thus could be applied to only 47 ± 17% of the cardiac beats. In contrast, statistical model 2 used the pressure-increase characteristics and was therefore established for all of the cardiac beats. The global statistical model 2 applied to data sets independent of those used to establish the model gave reliable SV estimates: r= 0.54 ± 0.07, a small bias between −8% to +10%, and a mean precision of 7%. This work demonstrated the limits of pulse-contour models to estimate SV in conscious, unrestrained rats. A multivariate statistical model using eight parameters easily extracted from the aortic waveform could be applied to all cardiac beats with good precision.


1996 ◽  
Vol 81 (3) ◽  
pp. 1051-1061 ◽  
Author(s):  
M. P. Hlastala ◽  
S. L. Bernard ◽  
H. H. Erickson ◽  
M. R. Fedde ◽  
E. M. Gaughan ◽  
...  

Recent studies using microspheres in dogs, pigs and goats have demonstrated considerable heterogeneity of pulmonary perfusion within isogravitational planes. These studies demonstrate a minimal role of gravity in determining pulmonary blood flow distribution. To test whether a gravitational gradient would be more apparent in an animal with large vertical lung height, we measured perfusion heterogeneity in horses (vertical lung height = approximately 55 cm). Four unanesthetized Thoroughbred geldings (422-500 kg) were studied awake in the standing position with fluorescent microspheres injected into a central vein. Between 1,621 and 2,503 pieces (1.3 cm3 in volume) were obtained from the lungs of each horse with spatial coordinates, and blood flow was determined for each piece. The coefficient of variation of blood flow throughout the lungs ranged between 22 and 57% among the horses. Considerable heterogeneity was seen in each isogravitational plane. The relationship between blood flow and vertical height up the lung was characterized by the slope and correlation coefficient of a least squares regression analysis. The slopes within each horse ranged from -0.052 to +0.021 relative flow units/cm height up the lung, and the correlation coefficients varied from 0.12 to 0.75. A positive slope, indicating that flow increased with vertical distance up the lung (opposite to gravity), was observed in three of the four horses. In addition, blood flow was uniformly low in three of the four horses in the most cranial portions of the lungs. We conclude that in lungs of resting unanesthetized horses, animals with a large lung height, there is no consistent vertical gradient to pulmonary blood flow and there is a considerable degree of perfusion heterogeneity, indicating that gravity alone does not play the major role in determining blood flow distribution.


2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Yousef Arar ◽  
Tarique Hussain ◽  
Riad Abou Zahr ◽  
Vasu Gooty ◽  
Joshua S. Greer ◽  
...  

Abstract Background Cardiac catheterization and cardiovascular magnetic resonance (CMR) imaging have distinct diagnostic roles in the congenital heart disease (CHD) population. Invasive CMR (iCMR) allows for a more thorough assessment of cardiac hemodynamics at the same time under the same conditions. It is assumed but not proven that iCMR gives an incremental value by providing more accurate flow quantification. Methods Subjects with CHD underwent real-time 1.5 T iCMR using a passive catheter tracking technique with partial saturation pulse of 40° to visualize the gadolinium-filled balloon, CMR-conditional guidewire, and cardiac structures simultaneously to aid in completion of right (RHC) and left heart catheterization (LHC). Repeat iCMR and catheterization measurements were performed to compare reliability by the Pearson (PCC) and concordance correlation coefficients (CCC). Results Thirty CHD (20 single ventricle and 10 bi-ventricular) subjects with a median age and weight of 8.3 years (2–33) and 27.7 kg (9.2–80), respectively,  successfully underwent iCMR RHC and LHC. No catheter related complications were encountered. Time taken for first pass RHC and LHC/aortic pull back was 5.1, and 2.9 min, respectively. Total success rate to obtain required data points to complete Fick principle calculations for all patients was 321/328 (98%). One patient with multiple shunts was an outlier and excluded from further analysis. The PCC for catheter-derived pulmonary blood flow (Qp) (0.89, p < 0.001) is slightly lower than iCMR-derived Qp (0.96, p < 0.001), whereas catheter-derived systemic blood flow (Qs) (0.62, p = < 0.001) was considerably lower than iCMR-derived Qs (0.94, p < 0.001). CCC agreement for Qp at baseline (C1-CCC = 0.65, 95% CI 0.41–0.81) and retested conditions (C2-CCC = 0.78, 95% CI 0.58–0.89) were better than for Qs at baseline (C1-CCC = 0.22, 95% CI − 0.15–0.53) and retested conditions (C2-CCC = 0.52, 95% CI 0.17–0.76). Conclusion This study further validates hemodynamic measurements obtained via iCMR. iCMR-derived flows have considerably higher test–retest reliability for Qs. iCMR evaluations allow for more reproducible hemodynamic assessments in the CHD population.


2013 ◽  
Vol 109 (06) ◽  
pp. 1158-1169 ◽  
Author(s):  
Christine M. Alvarado ◽  
Shirley K. Wrobleski ◽  
Dallas W. Slack ◽  
Angela E. Hawley ◽  
Diana M. Farris ◽  
...  

SummaryPreviously, we presented the electrolytic inferior vena cava (IVC) model (EIM) during acute venous thrombosis (VT). Here, we present our evaluation of the EIM for chronic VT time points in order to determine whether this model allows for the study of thrombus resolution. C57BL/6 mice (n=191) were utilised. In this model a copper-wire, inserted into a 25-gauge needle, is placed in the distal IVC and another subcutaneously. An electrical current (250 Amp/15 minutes) activates the endothelial cells, inducing thrombogenesis. Ultrasound, thrombus weight (TW), vein wall leukocyte counts, vein wall thickness/ fibrosis scoring, thrombus area and soluble P-selectin (sP-sel) were performed at baseline, days 1, 2, 4, 6, 9, 11 and 14, post EIM. A correlation between TW and sP-sel was also determined. A thrombus formed in each mouse undergoing EIM. Blood flow was documented by ultrasound at all time points. IVC thrombus size increased up to day 2 and then decreased over time, as shown by ultrasound, TW, and sP-sel levels. TW and sP-sel showed a strong positive correlation (r=0.48, p<0.0002). Vein wall neutrophils were the most common cell type present in acute VT (up to day 2) with monocytes becoming the most prevalent in chronic VT (from day 6 to day 14). Thrombus resolution was demonstrated by ultrasound, TW and thrombus area. In conclusion, the EIM produces a non-occlusive and consistent IVC thrombus, in the presence of constant blood flow, allowing for the study of VT at both acute and chronic time points. Thrombus resolution was demonstrated by all modalities utilised in this study.Note: Results were presented, in part, at the 24th American Venous Forum Annual Meeting 2012 in Orlando, FL, USA.


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