Absolute Perfusion Research Articles

Continuous positive pressure ventilation during epidural blockade--effects on cardiac output distribution.

It has been shown that when cardiac output (CO) decreases during continuous positive pressure ventilation (CPPV), its regional distribution adapts with a favouring of vital organs. Does epidural blockade modify this adaptation? Regional blood flows were assessed by the microsphere technique (15 microm) in 17 anaesthetised pigs during spontaneous breathing and CPPV with 8 cm H2O end-expiratory pressure (CPPV8) before and after epidural blockade. The block was induced at either the Th6-7 (Thep) or the L6-S1 (Lep) level with 1 ml of lidocaine 40 mg x ml(-1). When Lep was combined with CPPV8, mean arterial pressure and CO decreased significantly, and they decreased even more when combined with Thep. In contrast, the relative perfusion of the central nervous system, heart and kidneys remained stable during the four conditions studied. The adrenal perfusion during CPPV8 was obviated by epidural blockade. The absolute and relative perfusion of the skeletal muscle decreased during epidural blockade. The administered doses of epidural lidocaine did not affect blood flow in the spinal cord. The locally mediated nutritive vasoregulation of vital organs outweighed the sympathetic blockade induced by epidural blockade. During Thep blockade the animals were less capable of responding to the haemodynamic changes induced by CPPV8, probably due to the blockade of the cardiac part of the sympathetic nervous system.

Absolute renal blood flow quantification by dynamic MRI and Gd-DTPA.

The aim of this study was to demonstrate the feasibility of the absolute renal blood flow quantification using MRI and injection of contrast media. Using a T1-weighted fast gradient sequence following an intravenous bolus injection of Gd-DTPA, dynamic images of the kidney were obtained in patients with well-functioning native kidneys (n = 7) or transplant (n = 9), with significant renal artery stenosis (n = 4) and with renal failure (n = 7). After signal intensity calibration, the absolute renal perfusion was equal to the wash-in slope of the renal transit curve divided by the contrast medium concentration at the peak of the bolus in the aorta. The cortical blood flow was 2.54+/-1.16 ml/min per gram in well-functioning kidneys decreasing to 1.09+/-0.75 ml/min per gram in case of renal artery stenosis (p = 0.04) and to 0.51+/-0.34 ml/min per gram in case of renal failure (P<0.001). These measurements were in agreement with previous results obtained by other methods. A standard MRI imaging sequence and a simple model can provide realistic quantitative data on renal perfusion. This work justifies further studies to compare this model with a gold standard for renal blood flow measurements.

Validation of real-time continuous perfusion measurement

Perfusion, the rate at which blood in tissue is replenished at the capillary level, is a primary factor in the transport of heat, drugs, oxygen and nutrients. While there have been many measurement techniques proposed, most do not lend themselves to routine, continuous and real-time use. A minimally invasive probe, called the thermal diffusion probe (TDP), which uses a self-heated thermistor to measure absolute perfusion continuously and in real time, was validated at low flows with the microsphere technique. In 27 rabbits, simultaneous TDP measurements were made in liver from 0 to 60 ml min-1 100 g-1. The TDP perfusion correlated well with the microspheres (R2 = 0.898) and the agreement between techniques is very good with a slope close to unity (0.921) and an intercept close to zero (0.566 ml min-1 100 g-1). Variability between the two techniques was primarily due to the sampling error from the microsphere 'snap shot' of periodic blood flow when compared with the continuous TDP perfusion measurement. The ability to quantify local perfusion continuously and in real time may have a profound impact on patient management in a number of clinical areas such as organ transplantation, neurosurgery, oncology and others, in which quantitative knowledge of perfusion is of value.

MR perfusion imaging: correlation with PET and quantitative angiography

The presented MR approach reliably identifies patients with anatomically and hemodynamically signiticant coronary artery stenoses. This is due to the fact, that the pulse sequence used produces a substantial change in signal intensity in the perfused versus poorly perfused myocardial regions. Analysis of upslope in this setting rather than of other parameters provides a very sensitive and specific measure of myocardial ischemia. As upslope is a semiquantitative measure of absolute perfusion, even patients with triple vessel disease may be evaluated using this method. This is not the case when using conventional nuclear techniques. Furthermore, the spatial resolution of the MR images permits one to resolve the subendocardial layers of the myocardium, which thus can be evaluated separately from the entire wall. Again, this is not possible using nuclear cardiology perfusion imaging. The robustness of this MR perfusion imaging approach and the fact, that most of the heart can be covered may qualify for its clinical application in the management of coronary artery disease.

Quantitative assessment of pulmonary perfusion with dynamic contrast-enhanced MRI.

The feasibility of qualitative assessment of pulmonary perfusion using dynamic contrast enhanced MRI with ultra-short TE has recently been demonstrated. In the current study, quantitative analysis was attempted based on the indicator dilution principle using a pig model of pulmonary embolism. The results were compared with the absolute pulmonary perfusion obtained with colored microspheres. The inverse of apparent mean transit time (1/tau(app)), distribution volume (V), and V/tau(app) were correlated well with the absolute lung perfusion. This study demonstrates that MR has the potential to evaluate pulmonary perfusion quantitatively. Magn Reson Med 42:1033-1038, 1999.

Magnetic resonance first-pass myocardial perfusion imaging: clinical validation and future applications.

Clinical studies suggest that magnetic resonance first-pass (MRFP) perfusion imaging is comparable to current diagnostic tests that are used clinically for the assessment of myocardial perfusion. In addition, magnetic resonance imaging (MRI) perfusion imaging is a noninvasive method for determining myocardial blood flow. The spatial resolution (in-plane spatial resolution < 3 mm) is sufficient to differentiate between subendocardial perfusion and subepicardial perfusion. The measurement can be repeated regularly without any adverse effects for the patient. MRI perfusion measurements can be combined with the evaluation of global function and regional wall thickening. Currently, there is no other imaging technique that offers similar advantages. The MRI perfusion measurements can be carried out during baseline conditions and during maximal hyperemia induced with either adenosine or dipyridamole. The ratio of the measured myocardial blood flows provides an estimate of the absolute and relative myocardial perfusion reserve. The perfusion reserve determined with MRFP imaging is a quantitative measure for the assessment of the collateral-dependent myocardial flow. Based on the available data using MRFP perfusion imaging, the current clinical first-line perfusion imaging tests are going to be challenged in the near future. J. Magn. Reson. Imaging 1999;10:676-685.

Magnetic resonance first‐pass myocardial perfusion imaging: Clinical validation and future applications

Clinical studies suggest that magnetic resonance first-pass (MRFP) perfusion imaging is comparable to current diagnostic tests that are used clinically for the assessment of myocardial perfusion. In addition, magnetic resonance imaging (MRI) perfusion imaging is a noninvasive method for determining myocardial blood flow. The spatial resolution (in-plane spatial resolution < 3 mm) is sufficient to differentiate between subendocardial perfusion and subepicardial perfusion. The measurement can be repeated regularly without any adverse effects for the patient. MRI perfusion measurements can be combined with the evaluation of global function and regional wall thickening. Currently, there is no other imaging technique that offers similar advantages. The MRI perfusion measurements can be carried out during baseline conditions and during maximal hyperemia induced with either adenosine or dipyridamole. The ratio of the measured myocardial blood flows provides an estimate of the absolute and relative myocardial perfusion reserve. The perfusion reserve determined with MRFP imaging is a quantitative measure for the assessment of the collateral-dependent myocardial flow. Based on the available data using MRFP perfusion imaging, the current clinical first-line perfusion imaging tests are going to be challenged in the near future. J. Magn. Reson. Imaging 1999;10:676–685. © 1999 Wiley-Liss, Inc.

RES1/384: Spreading the Use of Kinetic Modeling Techniques by JAVA Analysis Software

IntroductionKinetic modeling is the method of choice for assessing the behaviour of new PET (Positron Emission Tomography) tracers. For suitable tracers, kinetic models allow to derive unique functional information from the acquired PET data, for instance the absolute perfusion or the density of specific receptors in brain tissue. However, the processing steps required are sophisticated. As there has no comprehensive modeling software been available in the past, kinetic models could only be developed and applied by a limited number of sites. This paper presents such a software package called PMOD. Being developed with Internet technologies it can easily be distributed and may thus help consolidate more widespread use of kinetic modeling.MethodsAiming at maximal portability, the entire software was programmed in Java 2. An interface was defined such that new models can easily and seamlessly be added by a sort of plug-in programming. It is general enough to cope with virtually all models published so far. Innovative models may therefore directly be implemented in PMOD, or they may easily be incorporated even by external researchers. The supported features include weighted least squares fitting, parameter coupling among models, Monte Carlo simulations for assessing parameter identifiability, and batch processing for scheduling a sequence of time-consuming trials. The software can be configured as a local JAVA application, but can also be installed on an Internet server and be run from any Java2-enabled WWW-browser.ResultsThe modeling software currently supports 19 different models ranging from simple tissue ratio methods to complex multi-injection protocols with two input curves plus metabolite correction. It has been tested on different platforms such as HP-UX, Sun Solaris, Linux, and Windows. At present it has been adopted by 7 sites which run the software on PC/NT. Experiences on this platform demonstrate:The Java Virtual Machine runs with high reliability.Despite just-in-time compilation there still exists a significant performance penalty for Java applications, especially with respect to memory management.The kinetic modeling environment in its present form is used on a daily basis at several sites for scientific studies and even for some types of clinical studies.DiscussionEarlier kinetic modeling programs were typically based on high-level languages such as Matlab or IDL and tailored to the need of individual sites. Every attempt to port them to a different environment was a major undertaking. This is in contrast to the present modeling software which runs on any platform as an application and supports easy data input.Acknowledgement:This work was supported by the Swiss National Science Foundation, Project 7PLPJ048289.

Changes in myocardial oxygenation and perfusion under pharmacological stress with dipyridamole: assessment using T*2 and T1 measurements.

The aim of this pilot-study was to evaluate changes in myocardial oxygenation and perfusion under pharmacological stress with dipyridamole (DIP) by means of MRI. Twenty healthy volunteers were examined using a multi-echo gradient-echo sequence. The differential myocardial signal response due to the blood oxygen level dependent (BOLD) effect was studied under variable conditions of myocardial oxygen supply caused by the vasodilator DIP. Unlike contrast agents (CA) methods, which require at least two injections of CA and DIP, the presented methods require only a single infusion of DIP. To assess changes in myocardial perfusion, a saturation recovery TurboFLASH (SRTFL) sequence with centric reordering for T1 measurements was used with global and slice-selective spin-preparation (five volunteers). The signal response was measured at baseline conditions and when myocardial blood flow was increased during pharmacological stress with DIP. Administration of DIP induced a 17 +/- 9% increase in T2*. Enhanced perfusion resulted in a 15 +/- 5% decrease of T1 after slice-selective spin preparation and a calculated increase in absolute perfusion of about 5.1 ml/(g x min), which reflects coronary reserve. The study shows that DIP-induced alterations in the relationship between myocardial oxygen supply and demand are detectable in healthy volunteers using T2* and T1 measurements. A combination of T2* and T1 examinations could become a useful diagnostic tool for the non-invasive assessment of myocardial oxygenation and perfusion in patients with coronary artery disease (CAD).

CBF and CBV measurements by USPIO bolus tracking: Reproducibility and comparison with Gd‐based values

The authors measured cerebral blood flow (CBF) and cerebral blood volume (CBV) by bolus tracking of a novel ultrasmall superparamagnetic iron oxide (USPIO) contrast agent (NC100150) and compared absolute and relative perfusion measurements with those obtained by a standard gadolinium-based contrast agent. They found a linear correlation between the two methods. A dose of 0.4 mg Fe/kg body weight was found to produce a signal drop similar to that of a standard 0.2 mmol/kg gadodiamide injection using spin-echo echoplanar imaging (SE-EPI) at 1.0 T. The measurements showed a high degree of reproducibility of repeated absolute as well as relative CBF and CBV values, lending further hope to the possibility of using magnetic resonance bolus tracking for routine CBF and CBV measurements. Finally, the authors present their initial experience with high-resolution, non-EPI CBV maps obtained from steady-state levels of an intravascular superparamagnetic contrast agent.J. Magn. Reson. Imaging 1999;9:342–347. © 1999 Wiley-Liss, Inc.

The portal component of hepatic perfusion measured by dynamic CT: an indicator of hepatic parenchymal damage.

CT can measure absolute hepatic arterial and portal venous perfusion; pilot data suggests these are raised and lowered, respectively, in cirrhosis. This study examined the value of functional CT in assessing cirrhosis, using the prothrombin ratio (PTR) as a marker for hepatic parenchymal damage. Twenty subjects with viral-induced cirrhosis (11 men and 9 women; 55.41 +/- 7.86 years) and 14 controls (8 men and 6 women; 48.36 +/- 17.67 years) were studied. A single section through the liver was scanned after bolus intravenous injection of 40 ml ioversol 320 mgI/ml. Hepatic arterial and portal perfusion was measured using a previously described technique. Hepatic portal perfusion was decreased in patients (0.66 +/- 0.21 ml/min/ml) compared with controls (1.11 +/- 0.23 ml/min/ml; P < 0.0001). A strong correlation was seen between PTR and portal perfusion (r = 0.662, P = 0.0038) in cirrhotics. Hepatic arterial perfusion did not differ between patients (0.088 +/- 0.082 ml/min/ml) and controls (0.091 +/- 0.067), and did not correlate with PTR. In conclusion, portal perfusion is reduced in cirrhosis, and this reduction correlates with PTR. It could thus be used as a marker of hepatic parenchymal damage. This technique may be useful in the follow-up of chronic liver disease, potentially reducing the need for serial liver biopsy.

Regional cerebral blood flow in peritumoral brain edema during dexamethasone treatment: a xenon-enhanced computed tomographic study.

Regional cerebral flood flow (rCBF) in peritumoral brain edema is assumed to be decreased because of increased interstitial pressure. Impaired blood flow might lead to local hypoxia, altered metabolism, and disturbed ion homeostasis, thus causing neurological sequelae. Steroid treatment is thought to positively influence the sequelae of brain edema. We aimed to determine the rCBF in peritumoral edema in humans receiving dexamethasone treatment and the relationship of rCBF to global CBF. We measured rCBF in 11 patients with untreated anaplastic gliomas or glioblastomas that were World Health Organization Grade III or IV restricted to one hemisphere with significant peritumoral edema who were receiving a standard dose of dexamethasone. rCBF was determined using stable xenon-enhanced computed tomography in a stereotactic frame. Edema was defined both by means of actual histology (stereotactic biopsies) and by imaging criteria. rCBF in peritumoral edema was decreased by 32% as compared with contralateral normal white matter. In each patient, this reduction was linearly related to blood flow in nonaffected white matter and cortex. The flow ratio in the different compartments was 1 (edema):1.5 (contralateral white matter):2.7 (contralateral cortex). Absolute perfusion values in contralateral cortex (means +/- standard deviations) (29.9+/-7.1 ml/100 g/min) and contralateral white matter (16.1+/-3.7 ml/100 g/min) were significantly decreased as well. Our study demonstrated that rCBF in peritumoral brain edema during steroid treatment is still decreased and is in a range in which it may cause neurological sequelae. Also, global CBF was decreased in all patients.

BASE imaging: a new spin labeling technique for measuring absolute perfusion changes.

A new technique for magnetic resonance imaging of absolute perfusion changes that uses magnetically labeled tissue water proton spins as a freely diffusible tracer is described. It consists of unprepared basis (BA) images that serve as a reference and selective (SE) inversion prepared images that are sensitive to perfusion changes. In the present study, the BASE technique was applied to functional neuroimaging. BA and SE images were alternatingly and repeatedly acquired during periods of visual stimulation and control. Visual stimulation was achieved with an alternating black/white checkerboard operating at a frequency of 8 Hz. Maps of the absolute cerebral blood flow changes (deltaCBF) were calculated from the image intensities of the corresponding BA and SE images. The individual mean values of deltaCBF measured in five healthy volunteers ranged from 69 +/- 18 to 99 +/- 26 ml/min/100 g. Since the BASE technique does not require nonselective spin inversion, it can be used with small transmit/receive head coils (e.g., surface coils). In addition, the BASE technique is robust against a mismatch of the inversion and detection slice profiles.

Quantitative evaluation of regional myocardial perfusion using fast X-ray computed tomography.

Clinical quantitation of regional myocardial perfusion using a minimally invasive and easily applied technique could allow for ready quantitation of the functional significance of coronary disease, allow for further understanding of flow reserve in various cardiomyopathic and hemodynamic overload (pressure versus volume) conditions, and possibly provide basic information needed regarding the development and clinical significance of coronary collateral vessels and diseases of the myocardial microcirculation. Electron beam CT (EBCT) is a unique cardiac imaging modality that allows for rapid acquisition tomographic slices of the heart with excellent spatial resolution. It has been demonstrated to provide accurate measurements of cardiac anatomy, biventricular function, myocardial mass, and estimates of mural atherosclerotic plaque burden via quantification of coronary calcium. The application of classical indicator techniques for use by fast x-ray computed tomography techniques such as electron beam CT has been shown to allow quantitative analysis of regional myocardial perfusion throughout the myocardium. Initial studies using central intravenous contrast injection in experimental animals showed a close correlation of regional myocardial perfusion as quantitated by electron beam CT with measurements using radiolabeled microspheres at resting and moderately increased flow states. At high flow states, however, electron beam CT significantly underestimated absolute myocardial perfusion and thus myocardial flow reserve. Using another fast CT device, the Dynamic Spatial Reconstructor (DSR), concepts of intramyocardial vascular blood volume and its relation to myocardial flow have been established. By adapting these concepts to electron beam CT scanning and accounting for the increase in intramyocardial vascular blood volume at vasodilatation, the ability to correctly quantitate perfusion states up to approximately 400 mL.min-1. 100 g-1 using central intravenous contrast administration was demonstrated. This implies that studies can be done with intravenous injection methods for characterization of regional myocardial perfusion up to the normal flow reserve of approximately 4:1. Important physiologic and clinical abnormalities in flow reserve generally result in a ratio < 3:1. Electron beam CT offers the capability to quantitate regional myocardial perfusion in both the clinical and research setting. Of particular interest is the ability to provide quantitative regional myocardial perfusion which can be coupled to the evaluation of cardiac anatomy and function as well as mural coronary atherosclerotic calcium burden during the same scanning session. Thus, electron beam CT has the potential to become a valuable, minimally invasive clinical tool for comprehensive analysis of cardiac function and coronary status.

Diet-induced obesity and pancreatic islet blood flow in the rat: a preferential increase in islet blood perfusion persists after withdrawal of the diet and normalization of body weight.

The aim of the present study was to evaluate the effects of diet-induced obesity on pancreatic islet blood perfusion in normal Wistar rats. Furthermore, we investigated to what extent any obesity-associated changes in islet blood flow could be reversed after reversion to a normal diet with normalization of body weight. Young adult female Wistar rats were offered a palatable mixed high-caloric diet (cafeteria diet) in addition to standard pelleted chow. Age-matched control rats received standard pelleted chow only. After 4 weeks the diet-treated rats had a body weight of approximately 15% more than that of the controls. All diet-treated rats had decreased glucose tolerance and increased serum insulin concentrations, but basal blood glucose concentrations were similar in anesthetized diet-treated and control rats. Whole pancreatic and islet blood flow rates were measured with a microsphere technique. The islet blood flow as well as fractional islet blood flow were increased (P < 0.01) in rats fed the cafeteria diet, while blood perfusion of the whole pancreas was similar to that of the control rats. In a second experiment, rats received the cafeteria diet for 4 weeks and were then fed standard pelleted food alone for another 3 weeks, while controls received standard diet for 7 weeks. After this period total body weight, retroperitoneal fat pad weight and glucose tolerance were similar to those of the controls. Whole pancreatic blood flow was unchanged as compared with that of control rats. However, both islet blood flow (P < 0.01) and fractional blood flow (P < 0.01) were increased. We conclude that diet-induced obesity in rats is associated with decreased glucose tolerance, hyperinsulinemia and a specific increase in absolute and fractional islet blood perfusion. This increase persists for at least 3 weeks after the diet is withdrawn despite normalization of body weight and glucose tolerance.

Effects of permanent dual chamber pacing on myocardial perfusion in symptomatic hypertrophic cardiomyopathy.

Angina and the presence of myocardial ischaemia are common in hypertrophic cardiomyopathy. Dual chamber pacing results in clinical improvement in these patients. This study evaluates the effects of permanent dual chamber pacing on absolute regional myocardial perfusion and perfusion reserve. University hospital. Six patients with hypertrophic cardiomyopathy and severe symptoms of angina received a dual chamber pacemaker. Absolute myocardial regional perfusion and perfusion reserve (dipyridamole 0.56 mg/kg) were measured by dynamic positron emission tomography with 13N-ammonia both during sinus rhythm and 3 months after pacemaker insertion. Results were compared with those from 28 healthy volunteers. Pacing resulted in a reduction of anginal complaints and a reduction in intraventricular pressure gradient from 65 (SD 30) mm Hg to 19 (10) mm Hg. During sinus rhythm, baseline perfusion was higher in patients with hypertrophic cardiomyopathy than controls (184 (31) v 106 (26) ml/min/100 g, P < 0.01), and perfusion reserve was lower (1.6 (0.4) v 2.8 (1.0), P < 0.05). During pacing myocardial perfusion decreased to 130 (27) ml/min/100 g (P < 0.05), with variable responses in terms of perfusion reserve. Pacing caused a redistribution of myocardial stress perfusion and perfusion reserve. The coefficient of regional variation of myocardial stress perfusion decreased from 19.7 (7.0)% to 14.6 (3.9)% during pacing (12.9 (3.8)% in controls, P < 0.01). The coefficient of regional variation of perfusion reserve decreased from 16.7 (6.6)% to 11.4 (2.6)% during pacing (9.8 (4.1)% in controls, P < 0.01). Pacing caused a decrease of resting left ventricular myocardial blood flow and blood flow during pharmacologically induced coronary vasodilatation. Although global perfusion reserve remained unchanged, myocardial perfusion reserve became more homogeneously distributed.

Chronic sodium-potassium-ATPase inhibition with ouabain impairs renal haemodynamics and pressure natriuresis in the rat.

1. Chronic Na+, K(+)-ATPase inhibition with ouabain induces hypertension in the rat. To examine the role of the kidney in this process, the effect of changes in renal perfusion pressure on glomerular filtration rate, renal blood flow and urinary sodium excretion were determined in rats treated intraperitoneally with ouabain (27.8 micrograms day-1 kg-1 body weight) or vehicle for 6 weeks. 2. After ouabain administration, baseline mean arterial pressure was significantly higher (P < 0.05) in ouabain-treated rats (151 +/- 2 mmHg; n = 9) than in control rats (116 +/- 4 mmHg; n = 8). 3. At equivalent renal perfusion pressures, glomerular filtration rate was significantly lower (P < 0.05) in ouabain-treated rats compared with control rats. Glomerular filtration rate was 721 +/- 73 microliters/min at 150 mmHg, and fell significantly to 322 +/- 64 microliters/min at 100 mmHg. In the control group, glomerular filtration rate was well autoregulated. The glomerular filtration rate autoregulatory index was calculated to determine the ability to maintain glomerular filtration rate during changes in renal perfusion pressure (0 reflects perfect autoregulation; > 1 reflects the absence of autoregulation). This index was greater in the ouabain group than in the control group (1.54 +/- 0.2 compared with 0.29 +/- 0.2; P < 0.05). Renal blood flow showed a similar pattern. 4. Absolute urinary sodium excretion rate was less in ouabain-treated rats than in control rats at equivalent renal perfusion pressures. The slope of the relationship between absolute urinary sodium excretion rate and renal perfusion pressure was greater (P < 0.05) in the control group than in the ouabain group (309.1 +/- 57.1 compared with 82.1 +/- 14.8 mumol min-1 mmHg-1). 5. Thus, chronic inhibition of Na+,K(+)-ATPase induces less efficient autoregulation of glomerular filtration rate and renal blood flow as well as a rightward shift in the pressure natriuresis relationship, such that a 25-30 mmHg higher renal perfusion pressure is necessary to excrete any given sodium load. These abnormalities may contribute to the development and maintenance of hypertension in this model.

The Influence of Flow and Hematocrit on the Laser Doppler Flux Signal from the Surface of the Perfused Pig Liver

We tested the hypothesis that the measurement volume of the laser Doppler flowmeter (LDF) is too small to provide reliable quantitative estimates of total liver blood flow of large mammals, such as the pig. In a perfused pig liver, the influence of changing (i) hepatic arterial (HA) and portal venous flows individually (n = 9), (ii) HA flow at fixed portal venous flow (50%, 70%, and 100% expected total liver blood flow), and (iii) hematocrit (0-30%) at fixed total liver blood flow on LDF flux was tested (n = 8). Linearity of LDF with hepatic arterial flow and portal venous flow was confirmed; however, the slope of the regression lines was higher for hepatic artery [1.92 +/- 0.60 (SD)] than portal vein perfused livers (0.66 +/- 0.34; P < 0.001). With portal venous flow at 50% and 70% total liver blood flow, changing hepatic arterial flow produced linear LDF versus flow responses, but at 100% total liver blood flow, linearity was achieved in only 6/9 livers. The coefficient of variation for the slopes of regression lines was always > 30%. At constant total liver blood flow (100 ml/min per 100 g), LDF response decreased linearly by a factor of about 2 on changing the hematocrit from 30% to 5% and markedly fell as the hematocrit was further decreased to zero. These results suggest that (i) the LDF flux signal from the liver surface provides a poor measure of hepatic microcirculatory blood flow during changes in total liver blood flow as the LDF responds with about three times greater sensitivity to changes in hepatic arterial than in portal venous flow, and (ii) when hematocrit is falling, LDF may underestimate hepatic perfusion to a significant extent. In addition, due to high measurement variability, the LDF flux signal cannot be quantified in absolute perfusion units.

The effect of labetalol on maternal haemodynamics and placental perfusion in awake near term guinea pigs.

The effect of labetalol (20 micrograms/kg/min) on maternal haemodynamics in general, and absolute placental perfusion in particular, was studied in eight chronically instrumented hypertensive guinea pigs near term. One day before drug testing, all experimental animals were subjected to haemoconcentration (haematocrit was gradually raised from 35.9 +/- 2.9 to 49.4 +/- 5.6 vol%, mean +/- S.D.) to establish a prolonged and stable state of hypertension. This procedure increased mean arterial pressure from 59.7 +/- 7.2 to 70.3 +/- 8.6 mmHg, and was paralleled by mild foreseeable systemic haemodynamic effects (redistribution of cardiac output away from intestines and brain), without consistent changes in the maternal placental blood flow. The hypotensive effect of labetalol was paralleled by a selective reduction in placental perfusion as reflected by a consistent fall in weight-specific cardiac output fraction (from 55.5 +/- 26.6 to 40.9 +/- 12.5%/100 g, P < 0.05) and blood flow (from 155 +/- 76 to 112 +/- 44 ml/min/100 g, P < 0.05) to the placentas. The concomitant placental resistance had increased consistently from 0.55 +/- 0.26 to 0.62 +/- 0.32 mmHg.min.100 g/ml, P < 0.05. We conclude that in awake late-pregnant hypertensive guinea pigs, labetalol reduces uteroplacental blood flow selectively. We speculate that the latter selective effect is secondary to the fall in blood pressure.

The effect of labetalol on maternal haemodynamics and placental perfusion in awake near term guinea pigs

The effect of labetalol (20 micrograms/kg/min) on maternal haemodynamics in general, and absolute placental perfusion in particular, was studied in eight chronically instrumented hypertensive guinea pigs near term. One day before drug testing, all experimental animals were subjected to haemoconcentration (haematocrit was gradually raised from 35.9 +/- 2.9 to 49.4 +/- 5.6 vol%, mean +/- S.D.) to establish a prolonged and stable state of hypertension. This procedure increased mean arterial pressure from 59.7 +/- 7.2 to 70.3 +/- 8.6 mmHg, and was paralleled by mild foreseeable systemic haemodynamic effects (redistribution of cardiac output away from intestines and brain), without consistent changes in the maternal placental blood flow. The hypotensive effect of labetalol was paralleled by a selective reduction in placental perfusion as reflected by a consistent fall in weight-specific cardiac output fraction (from 55.5 +/- 26.6 to 40.9 +/- 12.5%/100 g, P < 0.05) and blood flow (from 155 +/- 76 to 112 +/- 44 ml/min/100 g, P < 0.05) to the placentas. The concomitant placental resistance had increased consistently from 0.55 +/- 0.26 to 0.62 +/- 0.32 mmHg.min.100 g/ml, P < 0.05. We conclude that in awake late-pregnant hypertensive guinea pigs, labetalol reduces uteroplacental blood flow selectively. We speculate that the latter selective effect is secondary to the fall in blood pressure.