Transit-time Ultrasound Flow Probe Research Articles

The role of renal hypoperfusion in development of renal microcirculatory dysfunction in endotoxemic rats

PurposeTo study the role of renal hypoperfusion in development of renal microcirculatory dysfunction in endotoxemic rats.MethodsRats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 6), a group in which LPS administration was followed by immediate fluid resuscitation which prevented the drop of renal blood flow (EARLY group) (n = 6), and a group in which LPS administration was followed by delayed (i.e., a 2-h delay) fluid resuscitation (LATE group) (n = 6). Renal blood flow was measured using a transit-time ultrasound flow probe. Microvascular perfusion and oxygenation distributions in the renal cortex were assessed using laser speckle imaging and phosphorimetry, respectively. Interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α were measured as markers of systemic inflammation. Furthermore, renal tissue samples were stained for leukocyte infiltration and inducible nitric oxide synthase (iNOS) expression in the kidney.ResultsLPS infusion worsened both microvascular perfusion and oxygenation distributions. Fluid resuscitation improved perfusion histograms but not oxygenation histograms. Improvement of microvascular perfusion was more pronounced in the EARLY group compared with the LATE group. Serum cytokine levels decreased in the resuscitated groups, with no difference between the EARLY and LATE groups. However, iNOS expression and leukocyte infiltration in glomeruli were lower in the EARLY group compared with the LATE group.ConclusionsIn our model, prevention of endotoxemia-induced systemic hypotension by immediate fluid resuscitation (EARLY group) did not prevent systemic inflammatory activation (IL-6, IL-10, TNF-α) but did reduce renal inflammation (iNOS expression and glomerular leukocyte infiltration). However, it could not prevent reduced renal microvascular oxygenation.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-011-2267-4) contains supplementary material, which is available to authorized users.

Quantification of coronary microvascular resistance using angiographic images for volumetric blood flow measurement: in vivo validation

Structural coronary microcirculation abnormalities are important prognostic determinants in clinical settings. However, an assessment of microvascular resistance (MR) requires a velocity wire. A first-pass distribution analysis technique to measure volumetric blood flow has been previously validated. The aim of this study was the in vivo validation of the MR measurement technique using first-pass distribution analysis. Twelve anesthetized swine were instrumented with a transit-time ultrasound flow probe on the proximal segment of the left anterior descending coronary artery (LAD). Microspheres were injected into the LAD to create a model of microvascular dysfunction. Adenosine (400 μg·kg(-1)·min(-1)) was used to produce maximum hyperemia. A region of interest in the LAD arterial bed was drawn to generate time-density curves using angiographic images. Volumetric blood flow measurements (Q(a)) were made using a time-density curve and the assumption that blood was momentarily replaced with contrast agent during the injection. Blood flow from the flow probe (Q(p)), coronary pressure (P(a)), and right atrium pressure (P(v)) were continuously recorded. Flow probe-based normalized MR (NMR(p)) and angiography-based normalized MR (NMR(a)) were calculated using Q(p) and Q(a), respectively. In 258 measurements, Q(a) showed a strong correlation with the gold standard Q(p) (Q(a) = 0.90 Q(p) + 6.6 ml/min, r(2) = 0.91, P < 0.0001). NMR(a) correlated linearly with NMR(p) (NMR(a) = 0.90 NMR(p) + 0.02 mmHg·ml(-1)·min(-1), r(2) = 0.91, P < 0.0001). Additionally, the Bland-Altman analysis showed a close agreement between NMR(a) and NMR(p). In conclusion, a technique based on angiographic image data for quantifying NMR was validated using a swine model. This study provides a method to measure NMR without using a velocity wire, which can potentially be used to evaluate microvascular conditions during coronary arteriography.

Urinary flow patterns in infants with distal hypospadias

Objective To investigate preoperative urinary flow patterns in hypospadic infants and compare them to those from normal infant boys. Patients and Methods Twenty-one boys (median age 14.0, range 12.8–21.6 months) referred for distal hypospadias surgery were compared to 19 healthy boys (median age 12.0, 9.2–19.8 months). In both groups a 14-mm transit-time ultrasound flow probe mounted around the base of the penis continuously registered uroflow. Results Median maximum flow rate ( Q max) was significantly lower in hypospadics (2.4 vs 4.4 ml/s, P < 0.01) while there was no difference in the voided volume per micturition (19.0 vs 21.0 ml, P 0.33). Flow curve pattern analysis revealed plateau-shaped curves in 31% of hypospadics compared to none in normal infant boys. Interestingly, dyscoordinated flow curves (interrupted, staccato, spike–dome) were less common in the hypospadics (36% vs 64%, P < 0.01). Meatal size did not correlate to Q max (rho = 0.26, P = 0.26). Conclusions Infants with hypospadias void with a lower Q max and a lesser degree of dyscoordination as compared to normal infant boys. It can be speculated that decreased urethral compliance may contribute to the lower Q max and may act as a silencer for dyscoordination.

Validation of a 1-mm Transit Time Flow Probe and the Potential for Use in Microsurgery

The objective of this study was to validate a prototype transit time ultrasound flow probe (Medi-Stim Butterfly Flowmeter BF 2004) of only 1 mm and to evaluate its potential for use in microsurgery. Knowledge of the ability of this kind of system to measure flow in small vessels and at small flow rates did not previously exist. The experimental design was an in vitro study using the median artery of 15-kg pigs. The vessel was perfused by the pigs' own heparinated blood, at a known flow rate, using a Gemini infusion pump. The infusion rate was increased stepwise, starting at 1 ml/min until 16 ml/min. Transit time flow was measured continuously. The results showed very accurate flow measurements at all flow rates when compared to the known infusion rate of the Gemini pump. However, at flow rates below 4 ml/min, variation became a problem.

Automated Technique for Angiographic Determination of Coronary Blood Flow and Lumen Volume

Visual interpretation of angiographic images has been shown to be inadequate for assessing the severity of intermediate coronary stenoses. An approach for evaluating both the anatomic and functional impact of a stenosis is needed. An automated technique for determining both coronary blood flow and lumen volume based on a first-pass analysis (FPA) of coronary angiograms and a template matching algorithm was evaluated. Coronary angiograms of a swine animal model were obtained during power injections of contrast material into the left coronary ostium. Background anatomy was subtracted with an automated phase matching program. A template matching algorithm and first-pass analysis were then used to quantify coronary blood flow and lumen volume. Coronary blood flow and lumen volume measurements were validated with a transit-time ultrasound flow probe and a polymer cast of the coronary arteries, respectively. In 14 independent comparisons, the mean coronary blood flow measured with FPA showed strong correlation with the mean flow measured with the ultrasound flow probe (Q(FPA) = 0.88Q(probe) - 1.99; r = 0.977; standard error of estimate = 3.23 mL/minute). The lumen volumes determined with FPA and cast measurements demonstrated excellent correlation and can be related to each other by V(FPA) = 0.95V(C) - 0.01 (r = 0.997; standard error of estimate = 0.01 mL). The proposed automated method for accurate determination of coronary blood flow and lumen volume can supplement visual evaluation of coronary anatomy with quantitative physiologic data. This automated technique potentially offers a clinically feasible method of quantifying coronary blood flow and lumen volume in conjunction with routine cardiac catheterization.

Evaluation of a Percutaneously Controlled Hydraulic Occluder in a Rat Model of Gradual Venous Occlusion

To evaluate the efficacy of a percutaneously controlled hydraulic occluder (HO) in a rat model of gradual venous occlusion. Experimental study. Ten male Sprague-Dawley rats. HOs and perivascular transit time ultrasound flow probes were applied to the caudal vena cava (CVC). Occluders in group I rats (n=6) were gradually attenuated over 8 weeks, whereas occluders in group II rats (n=4) were not attenuated. Vena caval blood flow measurements were performed weekly in all rats for 8 weeks. After euthanasia, the CVC was evaluated grossly and by histopathology. Premature occlusion of the vena cava occurred during the 1st week in 3 rats (1 in group I, 2 in group II) because of kinking of the vena cava between the HO and the flow probe. For the remaining rats, mean blood flow in group I decreased significantly from 40.71 mL/min/kg at baseline to 4.68 mL/min/kg at 8 weeks (P=.0094, power=0.91). Group II rats maintained vena caval blood flow at all times during the study. Complete occlusion of the vena cava was confirmed at necropsy in all group I rats. Gradual occlusion of the CVC of rats was achieved with HOs over 8 weeks. This model is limited by the size of the experimental animals and comparatively large implants. HOs may provide a method for gradual occlusion of congenital portosystemic shunts.

Pacing interval optimization using photoplethysmography

Introduction: Optimization of atrioventricular (AV) and interventricular (IV) pacing intervals increases cardiac output acutely. Translating acute benefit into demonstrable clinical improvement may require frequent optimization in order to track changes associated with heart failure progression, fluid status, autonomic tone, and posture. Photoplethysmography (PPG) is an optical technique that senses changes in vascular volume from a location outside the bloodstream. We investigated the ability of a custom, subcutaneously placed PPG sensor to estimate optimum pacing intervals. Such a sensor could be incorporated into pacemakers and ICDs to enable frequent and automatic optimization. Hypothesis: The optimum AV delay (AVD) and IV interval (IVI) estimated by the transient response of subcutaneous PPG are concordant with optima estimated by stroke volume (SV) during steady state pacing. Methods: Data were collected from 6 healthy dogs. Leads were placed endocardially in the RA appendage and RV apex, and epicardially on the left lateral free wall via thoracotomy. A transit-time ultrasound flow probe was placed on the ascending aorta for SV measurements. A custom PPG sensor was placed subcutaneously in the neck. Heart block was induced by AV node/His ablation. AVD optimization was performed during atrial-synchronous RV pacing (VAT) using test AVDs between 30 and 150 ms. IVI optimization was performed during biventricular VAT pacing with LV pace delivered 90 msec after RA depolarization, and RV timing varied between −45 and 60 msec relative to LV pace. Reference method (RM): 3 minutes steady state pacing followed by measurement of SV. Test method (TM): Change in PPG output measured as pacing interval changed from baseline to test AVD or IVI. Third degree polynomials were fit to SV and PPG data with locations of maxima taken as estimated optima. Results: AVD and IVI were optimized 2–4 times in each subject. RM estimates varied by 13–59 and 8–41 msec (AVD, IVI) in each animal. Over all data sets, the average±SD difference between TM and RM estimates were −4.1±28.7 and 7.7±15.3 msec (AVD, IVI). TM estimates differed from RM by less than 25 msec in 10 of the 14 and in 13 of the 15 AVD and IVI data sets. Conclusions: Transient-response PPG and steady-state SV produce concordant estimates of optimum AVD and IVI in healthy dogs with induced heart block. Differences in TM and RM optima were clinically insignificant in a majority of individual trials. Incorporation of PPG sensors into pacemakers and ICDs may enable frequent and automatic optimization of AVD and IVI while eliminating the need for external or intravascular instrumentation.

Regional volumetric coronary blood flow measurement by digital angiography: In vivo validation 1

Rationale and objectives There are well-known limitations to the use of visual estimation to assess the severity of coronary artery disease and luminal stenosis. This is especially true in the case of an intermediate coronary lesion (30%–70% diameter stenosis), where coronary arteriography is very limited in distinguishing ischemia-producing intermediate coronary lesions from non-ischemia-producing ones. For this reason, a functional measure of stenosis severity is desirable. The goal of this study is to validate a video densitometry technique for quantitative assessment of regional volumetric coronary blood flow. Materials and methods Coronary arteriography was performed in eight swine (body weight, 25–50 kg) after power injection of contrast material into the left main coronary artery. Phase-matched subtracted images were used to quantify regional coronary blood flow using a video densitometry technique. The in vivo regional flow measurements were validated using a transit time ultrasound flow probe. Results In 44 measurements, the ultrasound (Q US) and video densitometry (Q VD) regional flow measurements were related by Q VD = 0.98 Q US + 0.11 mL/min ( r = 0.98). The results of mean regional coronary blood flow measurements for repeated coronary arteriograms of the first (Q VD1) and second (Q VD2) measured flows were related by Q VD1 = 1.04 Q VD2 + 0.05 mL/min ( r = 0.97). Conclusions A video densitometry technique for quantification of regional coronary blood flow was validated using a swine animal model. The results demonstrated the feasibility and potential utility of the video densitometry technique for accurate measurement of regional coronary blood flow, in vivo. This study provides an angiographic method that can potentially be used to evaluate intermediate coronary lesions during routine coronary arteriography.

Laser revascularization of ischemic skeletal muscle

Background Clinical trials have shown that transmyocardial laser revascularization is an effective secondary treatment for ischemic heart disease patients. Laser revascularization may also provide an alternative method for treating peripheral vascular disease. Methods The purpose of this study was to investigate the potential for laser revascularization in ischemic skeletal muscle. Eighteen rabbits (3–4 kg) were instrumented chronically with transit time ultrasound flowprobes on both common iliac arteries. All rabbits performed graded exercise tests on a treadmill where maximal blood flow was recorded. Unilateral hindlimb ischemia was produced by ligation of one femoral artery. At week 3 postligation, 10 rabbits received laser therapy and 8 underwent a sham surgery. In each of four muscles (gracilius, medialis, sartorius, and biceps femoris) 5 to 22 laser channels were created (average = 52 channels per leg). Results At week 3 postligation the maximal blood flow of the ischemic limb for the treated group was 64 ± 3 ml/min (mean ± SEM) and at 6 weeks postlaser therapy maximal blood flow increased to 75 ± 5 ml/min. The sham surgery group had a maximal blood flow of 58 ± 4 ml/min at week 3 postligation and 66 ± 3 ml/min at week 6 postsham surgery. Conclusion These results indicate that laser therapy does not induce angiogenesis and vascular remodeling in the ischemic hindlimb of a rabbit which exceeds that seen with a sham surgery.

Portal vein, hepatic vein and circulating plasma amino acids in rats given diets based on lactalbumin, faba bean (Vicia faba) and chickpea (Cicer arietinum)

AbstractThree experiments were carried out to determine plasma amino acids concentrations in circulating, portal and hepatic blood of growing male Wistar rats given diets containing lactalbumin, faba beans or chickpeas as the only protein source. Diets contained the same amount of digestible energy (15·5 kJ/g) and protein (lactalbumin in controls or legume proteins in the experimental diets; 100 g/kg). Appropriate amounts of essential synthetic amino acids were also added to legume-based diets taking into account their amino acid composition to equalize them to control (lactalbumin) diets. Portal blood flow (8·7±0·3 ml/min) was measured by using a transit-time ultrasound flow probe. Higher (P &lt; 001) plasma concentrations of methionine than of controls were determined in hepatic veins of legume-fed rats. In contrast, lower (P &lt; 001) concentrations of threonine, proline, valine, leucine, phenylalanine and lysine than those of controls were found in faba bean- and chickpea-fed rats. The same result as hepatic was obtained for portal and circulating plasma samples except that alanine and histidine values of legume-fed rats were also lower (P &lt; 001) than controls. Calculated net afferent appearance rates of amino acids to the liver were lower (P &lt; 001) than controls in rats given faba bean and chickpea diets for threonine, alanine, proline, valine, leucine, phenylalanine and lysine. This lower contribution of amino acids to the liver mainly via the portal vein in faba bean or chickpea-fed rats might explain previously reported differences in protein utilization and growth in comparison with animals given other protein sources (lactalbumin).

Attenuated vascular responsiveness to noradrenaline release during dynamic exercise in dogs.

During dynamic exercise, there is reduced responsiveness to alpha(1)- and alpha(2)-adrenergic receptor agonists in skeletal muscle vasculature. However, it is desirable to examine the sympathetic responsiveness to endogenous release of neurotransmitter, since exogenous sympathomimetic agents are dependent upon their ability to reach the abluminal receptor. Therefore, to further our understanding of sympathetic control of vasomotor tone during exercise, we employed a technique that would elicit the release of endogenous noradrenaline (norepinephrine) during dynamic exercise. Mongrel dogs (n = 8, 19-24 kg) were instrumented chronically with transit time ultrasound flow probes on both external iliac arteries. A catheter was placed in a side branch of the femoral artery for intra-arterial administration of tyramine, an agent which displaces noradrenaline from the nerve terminal. Doses of 0.5, 1.0 and 3.0 microg ml(-1) min(-1) of iliac blood flow were infused for 1 min at rest and during graded intensities of exercise. Dose-related decreases in iliac vascular conductance were achieved with these concentrations of tyramine. The reductions in iliac vascular conductance (means +/- S.E.M.) were 45 +/- 6 %, 30 +/- 4 %, 26 +/- 3 % and 17 +/- 2 %, for the 1.0 microg ml(-1) min(-1) dose at rest, 3.0 miles h(-1), 6.0 miles h(-1) and 6.0 miles h(-1), 10 % gradient, respectively. At all doses, the magnitude of vasoconstriction caused by administration of tyramine was inversely related to workload. We conclude that there is a reduced vascular responsiveness to sympathoactivation in dynamically exercising skeletal muscle.

Metalloendopeptidases EC 3.4.24.15 and EC 3.4.24.16 and bradykinin B2 receptors do not play important roles in renal wrap hypertension in rabbits.

1. The aim of the present study was to determine the effects of the metalloendopeptidase (EP) 24.15 and 24.16 inhibitor N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Aib-Tyr-p-aminobenzoate (JA-2) on haemodynamics and renal function in conscious rabbits with two-kidney, two-wrapped hypertension. We have also examined the role of endogenous bradykinin in the maintenance phase of this form of renovascular hypertension and whether inhibition of bradykinin degradation contributes to any potential effects of JA-2. 2. In two preliminary operations, rabbits were equipped with transit-time ultrasound flow probes for measuring cardiac output (CO) and renal blood flow (RBF) and had both kidneys wrapped in cellophane. Starting 4 weeks after the last operation, rabbits underwent four studies (3-5 days apart), during which they were treated with combinations of the bradykinin B2 receptor antagonist icatibant or its vehicle (1 mL/kg bodyweight 0.9% w/v NaCl) and JA-2 or its vehicle (1 mL/kg of a 5% w/v 2-hydroxypropyl-beta-cyclodextrin, 2.5% v/v dimethylsulphoxide solution). Renal function was monitored using standard renal clearance methods. 3. Icatibant (10 microg/kg) had no significant effects on systemic haemodynamic variables (mean arterial pressure, heart rate or CO), renal haemodynamic variables (RBF or glomerular filtration rate), urine flow or sodium excretion. At 5 mg/kg plus 3 mg/kg per h, JA-2 also did not affect any of these variables, either after icatibant vehicle treatment or after icatibant treatment. 4. Our data do not support major roles for endogenous bradykinin or bradykinin degradation by EP 24.15/24.16 in the control of systemic and renal haemodynamics or renal excretory function in two-kidney, two-wrapped hypertension in rabbits.

Accuracy and reproducibility of long-term implanted transit-time ultrasound flow probes in dogs

Accuracy and reproducibility of long-term implanted transit-time ultrasound flow probes in dogs

Chronic effects of lovastatin and bezafibrate on cortical and medullary hemodynamics in deoxycorticosterone acetate-salt hypertensive mice.

Cholesterol synthesis inhibitors and fibrates both exercise effects that could influence BP and renal function in hypertension. To test this issue, transit-time ultrasound flow probes, implanted optical fibers, and laser-Doppler flowmetry were used for measurements of total and regional renal blood flows in lovastatin (40 mg/kg body wt) and bezafibrate (50 mg/kg body wt) chronically treated deoxycorticosterone acetate (DOCA)-salt hypertensive mice. Total renal blood flow was well autoregulated between 70 and 150 mmHg (approximately 3.5 ml/min per g kidney weight in DOCA-salt mice). Both lovastatin and bezafibrate increased renal blood flow to a range between 4.7 and 5.5 ml/min per g kidney weight. In the renal perfusion pressure ranges investigated, renal vascular resistance increased in lovastin- and bezafibrate-treated DOCA-salt mice, but not as steeply as in vehicle-treated DOCA-salt mice. During a stepwise increase in renal perfusion pressure in lovastatin-treated DOCA-salt mice, medullary blood flow increased up to 130% of baseline values, which was not seen in vehicle- or bezafibrate-treated mice. After extracellular volume expansion with 1% saline, 1 ml over 1 min, total renal blood flow was also higher in lovastatin- or bezafibrate-treated DOCA-salt mice, whereas medullary blood flow increased more steeply in lovastatin-, compared with bezafibrate- or vehicle-treated mice. Systemic BP was significantly decreased in lovastatin-treated DOCA-salt mice compared with vehicle-treated mice. Lovastatin prevented histologic evidence for hemostasis in the medullary circulation of DOCA-salt mice. The results suggest that both lovastatin and bezafibrate diminished DOCA-salt-induced reductions in total renal blood flow. Lovastatin also abolished the perturbed medullary blood flow reactions to increased perfusion pressure or to volume expansion. Finally, lovastatin decreased systemic BP in DOCA-salt mice. These data suggest that cholesterol synthesis inhibition or fibrate treatment improve disturbed renal function in a mouse model of salt-dependent hypertension.

ATP SENSITIVE POTASSIUM CHANNELS DO NOT MEDIATE THE INITIAL INCREASE IN BLOOD FLOW TO SKELETAL MUSCLE AT THE ONSET OF EXERCISE

1674 At the onset of exercise there is a rapid increase in blood flow to active skeletal muscle. The purpose of this study was to examine the role of ATP sensitive potassium (KATP) channels in skeletal muscle vasodilation at the onset of exercise. Mongrel dogs (n=6) were instrumented with transit time ultrasound flow probes on both external iliac arteries and a catheter in one femoral artery for drug infusion. Blood pressure and blood flow were recorded continuously throughout the experiments. Exercise was performed on a motorized treadmill at 6 miles/hr. The KATP channel blocker, glibenclamide (40 mg/min), or vehicle was infused intraarterially beginning 30 sec before the onset of exercise and continuing for 30 sec into exercise. Each experiment was performed twice in random order and only one experiment was performed per day with each dog. Under both conditions, there was an immediate, rapid increase in iliac blood flow with initiation of treadmill exercise. There were no differences between conditions in blood flow over the first 15 sec of exercise. However, iliac blood flow was lower with glibenclamide infusion at 20, 25 and 30 sec of exercise (501±80 vs 620±86, 447±90 vs 581±67 and 441±98 vs 571±75 ml/min, mean±SE). Neither infusion altered heart rate, blood pressure or blood flow in the contralateral limb. These results do not support the hypothesis that activation of KATP channels is responsible for the initial rapid increase in blood flow to skeletal muscle at the onset of exercise. In contrast, the data indicate that activation of KATP channels plays a role in skeletal muscle vasodilation during steady-state exercise. Supported by NHLBI and VA Medical Research Service

Visceral resorption of intra-abdominal insufflated carbon dioxide in swine

Total intraperitoneal carbon dioxide (CO2) resorption from CO2-pneumoperitoneum increases in relation to intraabdominal pressure (IAP) up to an upper limit of 10 to 15 mmHg. The purpose of this prospective study was to evaluate the visceral fraction of CO2 resorption in comparison to total intraperitoneal CO2 resorption in pigs to address possible reasons for this upper limit. 16 pigs were chronically instrumented. Via midline laparotomy, a transit-time ultrasound flow probe was placed around the portal vein for continuous recording of the portal venous blood flow and a catheter was inserted into the portal vein via lienal vein. After complete recovery (7-10 days), animals were anesthetized with propofol and fentanyl and a pulmonary artery, a hepatic venous, an arterial, and an intraabdominal insufflation catheter were inserted. Mechanical ventilation (O2/air; FiO2 = 0.4) was adjusted to maintain endtidal CO2 at 34 to 36 mmHg using an Engstrøm Elvira ventilator. After an equilibration period of 3h, CO2, (n = 8) or air (n = 8) was insufflated. IAP was increased in steps of 4 mmHg and maintained constant at each respective IAP-level for 20 min. Blood gas analyses were assessed from portal venous, hepatic venous, central venous, and arterial probes at each IAP-level. Total intraperitoneal CO2 resorption was calculated from parameters derived from indirect calorimetry, the portal venous fraction from blood gas values and the portal venous blood flow following Fick's principle. Data were analyzed using Friedman's test. Total CO2 resorption increased continuously with rising IAP. Highest values were measured at IAP = 16 mmHg with 84 (74-93) ml/min. A further increase of IAP resulted in a significant decrease of total CO2 resorption. The visceral fraction of intraperitoneal CO2 resorption increased up to 28 (17-36) ml/min at IAP = 12 mmHg. Portal venous blood flow was also elevated or unchanged up to this IAP. At IAP = 20 mmHg or IAP = 24 mmHg portal venous blood flow decreased (79% of baseline) and in consequence portal venous calculated fraction of intraperitoneal carbon dioxide resorption decreased to 14 (8-20) ml/min. 20 min after desufflation, intraabdominal CO2 resorption was completed. With air insufflation, all parameters of CO2 balance were unchanged. The IAP dependent increase in CO2 resorption is limited due to an IAP related occlusion of the peritoneal capillaries and the limited expansion of peritoneal diffusion area. In this model, it was possible to show that visceral fraction is about one third of the total intraperitoneal carbon dioxide resorption and that this fraction depends on portal venous blood flow. Thus, a decrease in total CO2 resorption may indicate a reduction in portal venous blood flow.

Cortical and medullary hemodynamics in deoxycorticosterone acetate-salt hypertensive mice.

The effect of acutely increasing renal perfusion pressure or extracellular fluid volume on renal medullary and cortical blood flow was examined in the low-renin deoxycorticosterone acetate (DOCA)-salt hypertension model in mice. A 50-mg DOCA tablet was implanted, and 1% saline was given as drinking water for 3 wk. Medullary and cortical blood flow were determined with laser-Doppler flowmetry, and whole-kidney blood flow was measured with a transit-time ultrasound flowprobe around the renal artery. In control mice, total renal blood flow ranged from 6.3 and 7.6 ml/min per g kidney weight and in DOCA-salt mice from 4.3 and 4.7 ml/min per g kidney weight, respectively, and was minimally affected as renal perfusion pressure was increased. Renal vascular resistance increased correspondingly. During stepwise increases in renal artery pressure from 90 to 140 mmHg, medullary blood flow progressively increased in control mice to 125% of baseline values, whereas cortical blood flow did not change. In DOCA-salt mice, increasing BP from 100 to 154 mmHg had no effect on either cortical or medullary blood flow. Urine flow and sodium excretion were lower in DOCA-salt mice than in controls and increased nearly to the same extent in both groups after volume expansion with isotonic saline. Total renal blood flow increased after saline loading, more in controls than in DOCA-salt mice. Increases in medullary blood flow after saline loading were up to 122% of baseline values in controls and demonstrated a significantly steeper slope than the 110% of baseline increases in DOCA-salt mice. Cortical blood flow, however, was not different between the groups. Thus, medullary blood flow is not as tightly autoregulated as cortical blood flow in normal mice. Natriuresis with acute volume loading is facilitated by increased medullary blood flow. In DOCA-salt mice, the medullary blood flow reaction to renal perfusion pressure increases is abolished, whereas flow increases with extracellular volume expansion are diminished. These results suggest that diminished pressure-natriuresis responses in DOCA-salt mice are related to perturbed medullary blood flow.

Mixed venous oxygen saturation and biochemical parameters of hypoxia during progressive hypoxemia in 10- to 14-day-old piglets.

In this study we wanted to assess the relationship between mixed venous oxygen saturation (SVO2) and tissue oxygenation. For that, we compared the values of SVO2 with oxygen delivery (DO2), oxygen consumption (VO2), and markers of tissue hypoxia such as lactate and pyruvate during progressive hypoxemia. Eight 10-14-d-old piglets were anesthetized, tracheotomized, intubated, and ventilated. A fiberoptic catheter was placed in the carotid artery to monitor arterial oxygen saturation (SaO2). A thoracotomy was performed, and a fiberoptic catheter was placed in the pulmonary artery to monitor SVO2. A transit time ultrasound flow probe was positioned around the ascending aorta to measure aorta flow. Progressive graded hypoxemia was induced by decreasing fractional inspiratory oxygen concentration (FIO2) from 1.0 to 0.30, 0.21, 0.15, and 0.10. After each FIO2 interval blood samples were taken for blood gases, lactate, and pyruvate. DO2 and VO2 were calculated. SVO2 decreased similarly to SaO2. A value of SVO2 of more than 40% excluded oxygen restricted metabolism. When DO2 decreased below a critical range (8.4-12.8 mL/kg x min), SVO2 decreased below 15%, and lactate and the lactate/pyruvate ratio increased. We conclude 1) that baseline SVO2 values excluded oxygen-restricted metabolism, 2) that SVO2 values between 15 and 40% were not a marker for oxygen-restricted metabolism, and 3) that SVO2 values below 15% were associated with oxygen-restricted metabolism. Reduced SVO2 values must be interpreted as a change of the factors that determine the balance between DO2 and VO2 and as a warning that, with further reduction of SVO2, oxygen restricted metabolism can develop.

Noninvasive analysis of renal artery blood flow dynamics with MR cine phase-contrast flow measurements.

It was the aim of this study to quantify the measurement of pulsatile flow in the renal artery with the noninvasive magnetic resonance cine phase-contrast (MRCPC) method and combine it with the simultaneous assessment of pulsatile flow with a transit-time ultrasound (TTUS) flowmeter. In seven foxhounds with a chronically implanted precalibrated TTUS flow probe, MRCPC flow measurements were made in the renal artery with a temporal resolution of 32 ms. Mean and pulsatile flow signal were compared by the simultaneous ipsi- or contralateral measurement of the renal blood flow signal by both methods (TTUS and MRCPC). In addition, comparative MRCPC and TTUS flow measurements were made with artificial renal artery stenosis and after the administration of angiotensin II. The mean flow data assessed by the noninvasive MRCPC flow measurements showed an excellent correlation with corresponding TTUS recording (r = 0.99). The MRCPC flow signal displayed a waveform of the renal artery flow profile that was very similar to the TTUS flow pulse. The hemodynamic changes induced by angiotensin II or due to renal artery stenosis were also reliably detected by MRCPC. MRCPC provides a reliable noninvasive method for the quantification of mean blood flow and the assessment of the pulsatile flow signal in the renal artery and proves to be sensitive to hemodynamic changes of pathophysiological importance. Alternatively, the method may be used for studies in physiology that demand a noninvasive approach.

Changes in adrenocorticotropin and cortisol responsiveness after repeated partial umbilical cord occlusions in the late gestation ovine fetus.

Despite many studies reporting fetal ACTH and cortisol (F) responses to acute fetal hypoxemia induced by several methods, effects of repeated short-term fetal hypoxia produced by umbilical cord occlusion (UCO) on ACTH and F are unknown. We examined fetal ACTH and F responses to repeated, controlled, 50% reductions in common umbilical arterial blood flow (CUBF) produced by an inflatable cord occluder. Ten sheep fetuses were instrumented at 123-128 days gestation (dGA) with arterial, venous, and amniotic catheters. A common umbilical artery transit-time ultrasound flow probe was implanted to measure CUBF. An inflatable occluder was placed around the proximal portion of the umbilicus. In five fetuses (group I) at 131 +/- 1 dGA (mean +/- SEM), 12 UCOs (CUBF reduced by 50%), each lasting 5 min separated by 15 min recovery, were performed. Changes in fetal arterial blood gases, pH and plasma ACTH, and F concentrations were determined before, during, and after the 1st, 6th, and 12th UCOs. Sham experiments were conducted on the other five fetuses at 130 +/- 1 dGA (group II). In group I, CUBF decreased to 49 +/- 1% (mean +/- SEM of 12 UCOs). After each UCO, CUBF returned to baseline within 5 min. A modest fall in fetal arterial PO2 and arterial pH (21.2 +/- 0.2 to 16.8 +/- 0.2 mmHg and 7.33 +/- 0 to 7.29 +/- 0, respectively) and a mild increase in fetal PaCO2 (49.9 +/- 0.5 to 54.9 +/- 0.4 mmHg; mean +/- SEM of 12 UCOs) occurred with each UCO. Whereas preocclusion fetal ACTH concentrations increased by the 12th UCO, F remained unchanged. Fetal ACTH increased after the 1st, 6th, and 12th UCOs. Fetal F increased after the 1st and 6th UCOs but not after the 12th UCO. Fetal plasma ACTH and F remained unchanged throughout the experiments in group II fetuses. We conclude that: 1) partial reductions in CUBF induce significant activation of the fetal anterior pituitary-adrenocortical axis in late-gestation fetal sheep; 2) after repeated UCOs, fetal ACTH responsiveness is maintained, but fetal F responses become attenuated.