Low Blood Flow Rates Research Articles

Reassessing the Need for Ventilation During CPR

In the United States debate continues about the necessity of ventilation during CPR because of fear of contracting infectious diseases. Three questions will be considered in this article. First, is ventilation necessary for the treatment of cardiac arrest? Second, is mouth-to-mouth ventilation any better than no ventilation at all? Third, are other techniques of ventilation as effective or more effective than mouth-to-mouth ventilation during basic life support CPR? Although research is still inconclusive with regard to the need for ventilation during CPR, recent findings have clarified the effect of ventilation during low blood flow states and how ventilation influences resuscitation. Ventilation affects oxygenation, carbon dioxide elimination, and pH during times of low rates of blood flow. Ventilation may be unnecessary during the first few minutes of CPR. Under conditions of prolonged, untreated cardiac arrest, ventilation during CPR affects return of spontaneous circulation. Isolated hypoxemia and hypercarbia independently have adverse effects on survival of cardiac arrest. Because ventilation with exhaled gas contains as much as 4% CO 2 and less oxygen than air, it may have adverse effects during CPR. Spontaneous gasping may provide sufficient ventilation during CPR. Chest compression alone provides some pulmonary ventilation and gas exchange. Active chest compression-decompression may improve gas exchange better than does standard chest compression. Other forms of manual ventilation may also have a role in CPR. [Idris AH: Reassessing the need for ventilation during CPR. Ann Emerg Med May 1996;27:569-575.]

Cerebral blood flow and carbon dioxide reactivity in neonates during venoarterial extracorporeal life support.

a) To determine if cerebral blood flow is symmetric after internal carotid artery and ipsilateral internal jugular vein ligation in infants during venoarterial extracorporeal life support. b) To determine the cerebral CO2 reactivity (delta cerebral blood flow/delta torr CO2) of neonates during venoarterial extracorporeal life support and its correlation to neurodevelopmental outcome. Prospective, clinical study. University hospital pediatric intensive care unit. Fourteen neonates with respiratory failure who were receiving venoarterial extracorporeal life support. PaCO2 was altered by adjusting the CO2 gas flow through the membrane oxygenator. Cerebral blood flow was measured over both parietal-temporal regions at three PaCO2 values using xenon-133 clearance methodology. Cerebral blood flow measurements were made early (< or = 12 hrs of extracorporeal life support, n = 10) or late (> or = 48 hrs of extracorporeal life support, n = 10). In six of 14 infants, both early and late cerebral blood flow rates were measured. PaO2, mean arterial pressure, pump flow rate, and temperature were stable during each study period. Neurodevelopmental outcome was assessed in the neonatal follow-up clinic. Right and left hemispheric cerebral blood flow rates were significantly correlated with each other during early and late extracorporeal life support (p = .0001; r2 = .91). Overall, hemispheric cerebral blood flow was statistically symmetric. There was no association of CO2 reactivity (delta cerebral blood flow/delta torr PCO2, range 0.04 to 1.36 mL/min/100 g/torr) with short-term neurodevelopmental outcome. Infants with normal neurodevelopmental outcome had variable CO2 reactivity (range 0.04 to 0.67 mL/min/100 g/torr). Normal short-term neurodevelopmental outcome was observed in two infants with cerebral blood flow of < 10 mL/min/100 g. Hemispheric cerebral blood flow was symmetric in infants during early and late venoarterial extracorporeal life support. Some subgroups showed a trend toward decreased right hemispheric cerebral blood flow, but the small number of patients limited interpretation of this finding. CO2 reactivity and cerebral blood flow were highly variable in this population, and were not predictive of short-term neurodevelopmental outcome. Stressed neonates with extremely low cerebral blood flow rates may have relatively normal short-term neurodevelopmental outcome after venoarterial extracorporeal life support.

The significance of high umbilical venous blood flow measurements in a high-risk population.

We report a statistical analysis of 893 high-risk patients who underwent Doppler sonographic estimation of umbilical venous blood flow within 2 weeks of delivery. Patients with red cell isoimmunization were excluded. In a total of 84 patients, the umbilical venous flow rate was above the 95th centile for normal pregnancy. This finding was associated significantly with an increased prevalence of maternal diabetes mellitus, polyhydramnios, fetal abnormalities, premature delivery, low 5 min Apgar scores, and neonatal death. Umbilical venous flow rates per kilogram of fetal weight above the 95th centile were recorded in 93 patients. This finding was associated significantly with an increased rate of antepartum hemorrhage, premature delivery, low 5 min Apgar scores, longer stays in intensive care nursery, and neonatal death. Low umbilical venous blood flow rates have been investigated extensively and associated with impaired perinatal outcome. The work reported in this paper indicates that a percentage of fetuses will have abnormally high umbilical venous flow rates and that this is also indicative of increased risk.

Correlation of venography, venous pressure, and hemoaccess function

We analyzed the anatomic features of both grafts and fistulas and correlated these features with access function. We also attempted to determine venous pressures predicting access dysfunction (critical venous pressures) at various blood flow rates (BFRs). Therefore, accesses of 46 chronic hemodialysis patients were studied by venography in a prospective fashion. We defined the incidences of various lesions and the effects of venous collaterals on graft function, and determined critical venous pressures at various BFRs. Eighty-three percent of the accesses had outflow obstruction. Five types of anatomic lesions were identified. The incidences were venous stenosis of the draining vein immediately proximal to the venous anastomosis, 38.4%; central vein, 23.6%; venous anastomosis, 25.5%; arterial anastomosis, 10.9%; and intragraft hyperplasia, 3.6%. Twelve patients had multiple lesions. When the homogenous polytetrafluoroethylene arm graft population was studied for the effect of venous collaterals, we found that venous collaterals conferred protection but did not prevent graft failure. Venous pressure measurements were good predictors of access failure at the lower BFRs. Venous pressures increased with increasing BFRs. A critical venous pressure of 145 mm Hg was found for a BFR of 250 mL/min. At a BFR of 300 mL/min, the critical venous pressure was 170 mm Hg. A critical venous pressure could not be found for a BFR of 400 mL/min.

Effect of ventilation on acid-base balance and oxygenation in low blood-flow states

To investigate how minute ventilation affects the partial pressure of end-tidal CO2 and arterial and mixed venous pH, PCO2, PO2, and the concentration of bicarbonate during low blood-flow states. We tested the null hypothesis that acid-base conditions during low rates of blood flow are not significantly different when minute ventilation is doubled or halved.Prospective, experimental, animal study.University hospital laboratory.Domestic swine.We studied ten anesthetized and mechanically ventilated swine (weight, 43 to 102 kg) in a new model of controlled systemic and pulmonary blood flow in which each animal was maintained on ventricular assist devices. After electrical induction of ventricular fibrillation, ventricular assist device blood flow was decreased in steps. At each decrease, control minute ventilation, two times the control minute ventilation (hyperventilation), and one-half the control minute ventilation (hypoventilation) were administered; each ventilatory change was maintained for 6 mins.Aortic, pulmonary arterial and central venous pressures, ventricular assist device blood flow, and end-tidal CO2 were recorded continuously. Acid-base conditions were studied at three different mean blood flow rates: 49%, 30%, and 12% of baseline prearrest cardiac index. Arterial pH and PaO2 and mixed venous pH varied directly (p < .003) with minute ventilation, while PaCO2 and mixed venous PCO2, and end-tidal CO2 varied inversely (p < .0001) with minute ventilation. Mixed venous PO2 was not significantly related to minute ventilation (p = .6). PaCO2 and arterial bicarbonate; mixed venous pH, mixed venous PO2, and mixed venous bicarbonate, and end-tidal CO2 varied directly (p < .001) with blood flow, while mixed venous PCO2 varied inversely with blood flow (p < .05). Arterial pH was not significantly related to blood flow (p = .3). When minute ventilation changed from hyperventilation to hypoventilation at a mean blood flow rate of 49%, mean arterial pH decreased 0.22 +/- 0.06 (p < .05), mean PaCO2 increased 28 +/- 6 torr (3.7 +/- 0.8 kPa) (p < .05), and mean PaO2 decreased 99 +/- 77 torr (13.2 +/- 10 kPa); mean mixed venous pH decreased 0.11 +/- 0.02, mean mixed venous PCO2 increased 16 +/- 2.2 torr (2.1 +/- 0.3 kPa) (p < .05), and mean mixed venous PO2 did not change; mean end-tidal CO2 increased 18 +/- 2 torr (2.4 +/- 0.3 kPa) (p < .05). The effect of changes in minute ventilation on blood gases and end-tidal CO2 was similar for mean blood flow rates of 30% and 12% of baseline cardiac index.During low rates of blood flow similar to those rates found in shock and cardiopulmonary resuscitation, alterations in minute ventilation significantly influenced end-tidal CO2 and both arterial and mixed venous pH and PCO2. These findings may have clinical importance in improving the treatment of shock and cardiac arrest.

Effect of ventilation on acid-base balance and oxygenation in low blood-flow states

To investigate how minute ventilation affects the partial pressure of end-tidal CO2 and arterial and mixed venous pH, PCO2, PO2, and the concentration of bicarbonate during low blood-flow states. We tested the null hypothesis that acid-base conditions during low rates of blood flow are not significantly different when minute ventilation is doubled or halved. Prospective, experimental, animal study. University hospital laboratory. Domestic swine. We studied ten anesthetized and mechanically ventilated swine (weight, 43 to 102 kg) in a new model of controlled systemic and pulmonary blood flow in which each animal was maintained on ventricular assist devices. After electrical induction of ventricular fibrillation, ventricular assist device blood flow was decreased in steps. At each decrease, control minute ventilation, two times the control minute ventilation (hyperventilation), and one-half the control minute ventilation (hypoventilation) were administered; each ventilatory change was maintained for 6 mins. Aortic, pulmonary arterial and central venous pressures, ventricular assist device blood flow, and end-tidal CO2 were recorded continuously. Acid-base conditions were studied at three different mean blood flow rates: 49%, 30%, and 12% of baseline prearrest cardiac index. Arterial pH and PaO2 and mixed venous pH varied directly (p < .003) with minute ventilation, while PaCO2 and mixed venous PCO2, and end-tidal CO2 varied inversely (p < .0001) with minute ventilation. Mixed venous PO2 was not significantly related to minute ventilation (p = .6). PaCO2 and arterial bicarbonate; mixed venous pH, mixed venous PO2, and mixed venous bicarbonate, and end-tidal CO2 varied directly (p < .001) with blood flow, while mixed venous PCO2 varied inversely with blood flow (p < .05). Arterial pH was not significantly related to blood flow (p = .3). When minute ventilation changed from hyperventilation to hypoventilation at a mean blood flow rate of 49%, mean arterial pH decreased 0.22 +/- 0.06 (p < .05), mean PaCO2 increased 28 +/- 6 torr (3.7 +/- 0.8 kPa) (p < .05), and mean PaO2 decreased 99 +/- 77 torr (13.2 +/- 10 kPa); mean mixed venous pH decreased 0.11 +/- 0.02, mean mixed venous PCO2 increased 16 +/- 2.2 torr (2.1 +/- 0.3 kPa) (p < .05), and mean mixed venous PO2 did not change; mean end-tidal CO2 increased 18 +/- 2 torr (2.4 +/- 0.3 kPa) (p < .05). The effect of changes in minute ventilation on blood gases and end-tidal CO2 was similar for mean blood flow rates of 30% and 12% of baseline cardiac index. During low rates of blood flow similar to those rates found in shock and cardiopulmonary resuscitation, alterations in minute ventilation significantly influenced end-tidal CO2 and both arterial and mixed venous pH and PCO2. These findings may have clinical importance in improving the treatment of shock and cardiac arrest.

End-tidal carbon dioxide during extremely low cardiac output

A number of studies have shown that expired CO2 concentration is closely related to cardiac output, but that cardiac output was not controlled as an independent variable. In addition, the partial pressure of end-tidal CO2 (PETCO2) during extremely low cardiac output has not been reported. The objective of the present study was to measure PETCO2 during well-controlled, very low blood flow rates under conditions of constant minute ventilation. Ten anesthetized, intubated, and mechanically ventilated swine (weight, 43 to 102 kg) were placed on two ventricular assist devices in order to control cardiac output. Minute ventilation was measured and kept constant. Ventricular assist device output (measured with an ultrasonic flow probe); PETCO2; and aortic, pulmonary artery, and central venous pressures were recorded continuously. After electrical induction of ventricular fibrillation, pump output was decreased in steps. Cardiac index ranged from 0 to 5,371 mL/min/m2; 59% of PETCO2 measurements were made at cardiac indexes of less than 1,313 mL/min/m2 (30 mL/min/kg). The relationship of PETCO2 levels to cardiac index was determined with linear regression analysis; P < .05 was statistically significant. PETCO2 correlated significantly with cardiac index (P < .0001). The best-fit line by least-squares analysis produced the equation: PETCO2 = 4.98 + 0.012 [cardiac index] (r2 = .82). Under conditions of constant minute ventilation, PETCO2 correlated closely with cardiac index over a large range of blood flow rates, including extremely low rates.

Where Should the Hemofiltration Circuit be Placed in Relation to the Extracorporeal Membrane Oxygenation Circuit?

Patients requiring extracorporeal membrane oxygenation (ECMO) frequently experience hypervolemia and metabolic abnormalities that can be effectively managed by hemofiltration. Although several options for hemofiltration circuit placement exist, some may have the disadvantage of recirculation or shunting of poorly oxygenated blood to the patient. Attachment of the entire hemofiltration circuit to the pre-ECMO pump region is described. Despite the absence of pump generated pressure and a low blood flow rate, effective hemofiltration and diafiltration were achieved. This article examines whether placement of the hemofiltration circuit proximal to the ECMO pump has advantages over other hemofiltration circuit placements.

Continuous arteriovenous hemodialysis: Effect of dialyzer geometry

Continuous arterio-venous hemodialysis (CAVHD) is an alternative to conventional hemodialysis for treating acute renal failure in critically ill patients [1, 2]. With this technique, a high flux dialyzer is connected to the arterial and venous blood circuit and dialysate is administered counter-current to the direction of blood flow [1, 2]. In this configuration, both diffusive clearance and ultrafiltration occur continuously but at relatively low blood and dialysate flow rates. Since CAVHD uses the patients' arterial blood pressure to circulate blood through the extracorporeal circuit, it is often better tolerated than standard hemodialysis in hemodynamically unstable patients [1]. Moreover, the large ultrafiltration capacity and diffusive clearances of CAVHD devices potentially permits control of fluid balance and biochemical manifestations of uremia [2]. A variety of high flux membranes of different composition are available in both parallel plate and hollow fiber configurations for use in CAVHD. Whereas the performance of parallel plates and hollow fiber dialyzers are roughly equivalent when used in high flow rate hemodialysis [3], dialyzer configuration may influence clearance during CAVHD. In particular, clearances could be limited in hollow fiber dialyzers, which have high flow resistance and consequently, a greater tendency for unstirred layers and/or flow mismatches between dialysate and blood at low flow rates [3]. Whether important differences exist between parallel plates and hollow fiber dialyzers with regard to performance in CAVHD is unknown. Thus, to evaluate the role of dialysis configuration in CAVHD, we performed a crossover study that sequentially used parallel plates and hollow fiber artificial kidneys in acute renal failure patients treated with CAVHD.

Femoral arteriovenous extracorporeal carbon dioxide elimination using low blood flow.

Conventional extracorporeal CO2 removal systems require blood flow rates of 1 to 2.5 L/min in the extracorporeal circuit. We hypothesized that standard hemofiltration equipment can be combined with a high-performance extracorporeal lung to achieve high rates of CO2 removal at lower blood flow rates. To test this hypothesis, we performed experiments on nine sheep to examine the extent to which CO2 elimination can be achieved at blood flow rates less than 600 mL/min using a 5-m2 hollow fiber membrane lung with countercurrent gas flow, combined with a hemofiltration blood pump, and connected to femoral arterial and venous hemodialysis catheters. CO2 eliminations of 130 to 180 mL/min at standard temperature and pressure were achieved with blood flow rates in the range 470 to 600 mL/min. With a pumpless artery-to-vein shunt, up to 90 mL/min of CO2 at standard temperature and pressure was eliminated. However, in this mode, the resistance of the access catheters and tubing was the main factor limiting CO2 elimination. Standard hemofiltration equipment may be combined with a hollow fiber membrane lung to remove the equivalent of a high proportion of the basal metabolic CO2 production of an adult human at low blood flow rates. Use of this technology would bring extracorporeal CO2 removal within the budget and capability of more ICUs.

Morphology and physiology of capillary systems in subregions of the subfornical organ and area postrema

From recent morphological and physiological studies of capillaries, I shall review four new or revised concepts about blood-tissue communication in the subfornical organ (SFO) and area postrema (AP). First, the capillary systems of SFO and AP exhibit subregional differentiation correlated topographically with cytoarchitecture, densities of immunoreactivity for several peptides and amines, cellular sensitivity to neuroactive substances, afferent neural terminations, and tissue metabolic activity. Thus, contrary to frequent citations, the angioarchitecture and microcirculatory physiology of these small sensory nuclei are not homogeneous. Second, electron microscopic, morphometric, and topographical studies reveal that SFO contains three different types of capillary and AP has two. The differentiated capillary morphology appears to be well organized for specialized functions particularly in SFO subregions. No other body organ or small tissue region is known to have such capillary diversity, further highlighting the complex functions served by SFO. Third, pools of interstitial fluid (Virchow-Robin spaces) surrounding type I and III capillaries in SFO and AP may participate in the receptive properties of these organs as low-resistance pathways for rapid dispersion of blood-borne hormones inside their organ boundaries. The parenchymal walls of Virchow-Robin spaces appear to harbour metabolic mechanisms for hormones such as angiotensin II, and thus could vastly extend the effective blood-brain surface area of permeable capillaries in SFO and AP. Fourth, SFO and AP bear similar physiological characteristics of high blood volume, yet relatively low rates of blood flow. Accordingly, intracapillary blood velocity must be quite slow in these organs, and the duration of transit by blood and circulating messengers rather protracted. This feature of slow blood transit time likely compounds the sensory capability of SFO and AP, rendering increased contact time for blood-borne hormones to penetrate the permeable capillaries of these structures and interact with their known dense populations of receptors for several homeostatic substances involved in regulation of blood pressure and body fluids.

Derecruitment of filtration surface area in paraquat-injured isolated dog lungs

The capillary filtration coefficient (Kf,c) is a sensitive and specific index of vascular permeability if surface area remains constant, but derecruitment might affect Kf,c in severely damaged lungs with high vascular resistance. We studied the effect of high and low blood flow rates on Kf,c in papaverine-pretreated blood-perfused isolated dog lungs perfused under zone 3 conditions with and without paraquat (PQ, 10(-2) M). Three Kf,cs were measured successively at hourly intervals for 5 h. These progressed sequentially from isogravimetric blood flow with low vascular pressure (I/L) to high flow with low vascular pressure (H/L) to high flow with high vascular pressure (H/H). The blood flows of H/L and H/H were greater than or equal to 1.5 times that of I/L. There were no significant changes in Kf,c in lungs without paraquat over a 50-fold range of blood flow rates. At 3 h after PQ, I/L-Kf,c was significantly increased and both isogravimetric capillary pressure and total protein reflection coefficient were decreased from base line. At 4 and 5 h, H/L-Kf,c was significantly greater than the corresponding I/L-Kf,c (1.01 +/- 0.22 vs. 0.69 +/- 0.09 and 1.26 +/- 0.19 vs. 0.79 +/- 0.10 ml.min-1.cmH2O-1.100 g-1, respectively) and isogravimetric blood flow decreased to 32.0 and 12.0% of base line, respectively. Pulmonary vascular resistance increased to 12 times base line at 5 h after PQ. We conclude that Kf,c is independent of blood flow in uninjured lungs. However, Kf,c measured at isogravimetric blood flow underestimated the degree of increase in Kf,c in severely damaged and edematous lungs because of a high vascular resistance and derecruitment of filtering surface area.

Membrane oxygenators: current developments in design and application

Cardiopulmonary bypass (CPB) procedures require a blood-gas exchanger (oxygenator) to temporarily replace the respiratory function of the lungs. In the past the majority of CPB procedures have been carried out with bubble oxygenators which effect gas exchange by dispersion of bubbles into the blood. Membrane oxygenators, on the other hand, utilize a hydrophobic gas permeable membrane between the blood and gas phases. Bubble oxygenators are being superseded by membrane types for CPB due to improvements in membrane technology and mass transfer efficiency. These advances are reviewed in this paper and are illustrated by reference to the gas exchange and operating characteristics of a number of clinical oxygenators designed for adult CPB. Membrane oxygenatorsare also being used for long-term support in the treatment of acute respiratory failure. Operated in a partial bypass circuit, the oxygenator may have to function for several days or weeks. In one particular treatment method, the rate of spontaneous breathing is controlled by the partial or total removal of the metabolic CO 2 production by the membrane oxygenator. For this method, known as extracorporeal CO 2 removal (ECCO 2R), the oxygenator must be optimized for CO 2 transfer at low blood flow rates. The suitability of clinical oxygenators for ECCO 2R is discussed in terms of gas exchange and functionality over a prolonged operation.

7 BICARBONATE REMOVAL DURING ACETATE HEMODIALYSIS AND ITS POSSIBLE USE IN RESPIRATORY FAILURE OF THE NEWBORN: ANIMAL STUDIES ON EXTRACORPOREAL BICARBONATE/C02-REMOVAL (ecBICC02R) AND APNEIC OXYGENATION

Extracorporeal techniques for respiratory support in the newborn are feasible and established as neonatal extracorporeal membrane oxygenation (ECMO). It has been shown however, that even in severly damaged lungs, sufficient oxygenation (apneic oxygenation) can be maintained by only removing CO2 with an artificial lung, a technique called extracorporeal CO2-removal (ECCO2R). During routine acetate hemodialysis in 22 patients with end stage renal disease an overall CO2-removal of 79.1 +/- 15.1 ml was measured, at least one third of the entire metabolic CO2-production. For total metabolic CO2-removal, acetate dialysate (22mmol/l) was modified with phosphate buffer (2mmol/l), lactate (5mmol/l) and sodium hydroxide (7mmol/l) to compensate for the bicarbonate loss. In 6 sheep, apneic oxygenation could be achieved with blood flow rates as low as 10-15 ml/kg/min for 4-6 hours. These data suggest that a hemodialysis procedure for bicarbonate and CO2elimination (ecBICCO2R) is an efficient method for CO2-removal necessitating much lower blood flow rates than other techniques presently used. An other advantage of this technique is the maintainence of acid-base, electrolyte and fluid balance as well as renal replacement in multiple organ failure.

Basal rate subcutaneous insulin infusion: absorption kinetics and relation to local blood flow.

Twenty diabetic patients received a constant subcutaneous infusion of 125I-labelled short-acting insulin (1.12 U/h) into the anterior abdominal wall. Measurement of the size of the insulin depot at the infusion site was performed by measuring the radioactivity and by using a calibration bolus to transform count rate to units of insulin in the depot. By the 133Xenon technique, local subcutaneous blood flow rate was measured on the contralateral side of the anterior abdominal wall. From the start of the infusion the SC depot built up slowly, but did not reach steady-state by 6 h. After 24 h of infusion, the size of the depot ranged between 2.7 and 10.9 U (5.2 +/- 0.5 U, mean +/- SE). The size of this steady-state depot was inversely correlated with SC blood flow. After stopping the infusion, insulin disappeared according to first order kinetics without any lag period. The insulin disappearance rate from the depot was positively correlated with the blood flow in a curvilinear fashion. The results suggest that the relationship between blood flow and the size of the insulin depot is best explained by a predominantly blood flow limited removal of insulin at low rates of blood flow, with increasing limitation by diffusion at higher rates.

Continuous arteriovenous hemofiltration: An in vitro simulation and mathematical model

In vitro and mathematical models of continuous arteriovenous hemofiltration (CAVH) have been developed. Human erythrocytes resuspended in normal saline containing 5% bovine albumin were used to perfuse the circuit from a gravity driven pressure source. Membrane hydraulic permeability was observed to decline from 31.2 x 10(-5) +/- 11.9 x 10(-5) cm/(min.mm Hg) before use to 12.3 x 10(-5) +/- 3.3 x 10(-5) (mean +/- SD) after use. This fall occurred during the first one to two hours whether perfused with blood or 5% albumin alone. Pressure-flow relationships of each circuit component, measured with 40% sucrose as a calibration medium, conformed to Poiseuille's equation. Use of high resistance blood access on the venous end of the circuit resulted in a low blood flow rate and high filtration fraction. The same access, when placed on the arterial end, produced both low blood flow rate and low filtration fraction. These results were a consequence of pressure distribution within the circuit as demonstrated by measurements of perfusion, prefilter, and postfilter pressures. The importance of negative pressure applied to the filter chamber in order to maintain favorable Starling forces, when the system was operated with a small bore arterial access, was demonstrated by similar methods. Enhancement of urea clearance by predilution was verified. Model simulations suggest that predilution will be of less benefit or even detrimental for other solutes which fail to distribute across the erythrocyte membrane. Comparison of results with predictions of a mathematical model demonstrated good agreement, but with some tendency to overestimate filtrate production. The latter was attributed to neglect of concentration polarization of plasma proteins in model development.

Hemodynamics of the Recently Opened Glomeruli

In 22- to 26-day-old beagle puppies, just after superficial nephrons have begun to function, the single nephron glomerular filtration rate is extremely low (6.7nl·min&lt;sup&gt;-1&lt;/sup&gt;) approximating a tenth of the adult value (5 7 nl min-&lt;sup&gt;1&lt;/sup&gt;) even though blood pressure is as high as 90 mm Hg. Glomerular vascular resistance is almost six times the value found in the adult dog (1.8 vs. 0.32 mm Hg· ml&lt;sup&gt;-1&lt;/sup&gt; min), this increase being mainly due to a rise in afferent (80%) rather than in efferent (20%) resistance. The glomerulus, having only recently started to function, is characterized by filtration pressure equilibrium, a phenomenon atypical of superficial glomeruli in the adult dog. These findings favor the concept that a low glomerular blood flow rate might be the main cause of the very low SNGFR in the new glomeruli, although some contribution of an altered ultrafiltration coefficient cannot be excluded.

Arterial blood-flow waveform measurement in intact animals: new digital radiographic technique.

With a new radiographic method to determine the pulsatile flow pattern in an imaged artery, flow velocity is determined by tracking the movement of contrast material along the artery over time. Flow velocity is multiplied by an automatically determined cross-sectional area of the artery to determine blood flow. Pulsatile blood-flow waveforms were determined by radiographic and electromagnetic techniques in each femoral artery of four dogs while flow conditions were varied. Peak and average blood flows measured by the two techniques were highly correlated (r = .97 and .95, respectively). The closest agreement between the flow waveforms measured by the electromagnetic and radiographic techniques was found under normal flow conditions. The radiographically derived flow waveforms tended to be noisy at low blood-flow rates, and instantaneous blood-flow rates exceeding 700 ml/min were underestimated.

Measurement of peripheral blood flow by thermodilution techniques.

Recent advances in the diagnosis and treatment of cardiovascular pathology, including balloon angioplasty of atherosclerotic lesions in peripheral vascular disease, have led to an increased need for in vivo quantitation of blood flow. This study has three purposes: (1) to validate thermodilution techniques as a viable method for measuring low blood flow rates, (2) to calibrate accurately thermodilution catheters at these low flows, and (3) to develop an animal model that can be used to quantitate and compare many different flow measuring techniques. Modified commercially available 6F thermodilution catheters were used with a standard cardiac output computer to measure flows between 200 and 700 ml/minute. Eight anesthetized dogs were surgically interfaced with a variable flow, pressure, and compliance carotid-carotid/jugular bypass perfusion system. Three milliliters of normal saline at room temperature were injected through the catheters intra-arterially to measure different flows below, at, and above physiologic pressures and compliances. Results of this study indicate that with proper calibration, thermodilution techniques of measuring arterial and venous flows between 200 and 700 ml/minute are simple, accurate, and reliable. Using the designed system to generate known flows in vivo at various physiologic conditions allowed easy calibration of catheters and should facilitate calibration and comparison of other measurement techniques.

Current models of hepatic pharmacokinetics: Flow effects on kinetic constants of ethanol elimination in perfused rat liver

At present two different pharmacokinetic models of the enzymic elimination of substances from the blood flowing through the liver are used: the sinusoidal perfusion model assuming the elimination to take place at the local sinusoidal blood substrate concentration, falling continuously from the inlet to the outlet of the sinusoid, and the venous equilibration model assuming elimination at the hepatic outlet concentration. It is an ultimate requirement of such models that the estimates of the enzymic parameters V max and K m be independent of variations in hepatic blood flow rate. This was used to compare the two models experimentally. Ethanol was given at two successive constant infusion rates (7 and 10 μmol/min) to 11 livers from rats (200 g) perfused by a recirculating medium. In each of the infusion periods the hepatic blood flow rate was varied experimentally (10 and 17 ml/min, respectively). From the measured steady-state ethanol concentrations in the hepatic inlet and outlet, K m and V max were calculated from both models at both low and high blood flow rates. The K m calculated according to the venous equilibration model was significantly lower in the low-flow than in the high-flow periods (P < 0.05); this model is thus not consistent with data. V max values were not influenced by hepatic blood flow. The K m calculated according to the sinusoidal perfusion model were not influenced by flow (P < 0.5) and V max was also unchanged. The sinusoidal perfusion model is thus not inconsistent with data.