Determination Of Regional Blood Flow Research Articles

Quantification of fluorescent dyes in organ tissue samples via HPLC analysis.

The determination of regional blood flow via the accumulation of fluorescent microspheres is a concept regularly used in medical research. Typically, the microbeads get extracted from the tissue of interest and are then quantified by measuring the absorption or fluorescence of the incorporated dyes without further separation from the medium. However, in that case the absorption spectra of different dyes can overlap when used simultaneously, leading to an overestimation of the concentration. Additionally, background absorption from the medium can be problematic. Therefore, a high performance liquid chromatography method for the simultaneous detection of four dyes (orange, crimson, yellow-green and red) incorporated in different microbeads in samples from biological media such as organ tissue (brain, heart and kidneys) was developed. Since for biological samples often a large sample size is required for sufficient statistics, the method was optimized to yield very short run times. With this method it was possible to detect very low concentrations of only one microsphere per gram of organ tissue. By applying this sensitive quantification technique, it was demonstrated that the application of microbeads for perfusion measurements might not be reliable due to different organ distributions in each animal.

Multiple versus single injections of fluorescent microspheres for the determination of regional organ blood flow in septic sheep

Determination of regional blood flow by the injection of microspheres in sepsis models is crucial for the experimental evaluation of the influence of experimental treatment strategies on organ perfusion. However, multiple injections may critically increase the total quantity of microspheres, thereby restricting regional microcirculation and altering the results of blood flow measurements. This study was designed to compare the results of multiple versus single injections of microspheres in an established ovine sepsis model. Injury was induced by smoke inhalation and instillation of Pseudomonas aeruginosa into the lungs. Twenty sheep were studied for 4, 8, 12, 18, or 24 h, respectively. Microspheres were injected at the end of the study period and the animals were euthanized and organ tissues were harvested. Another four sheep were studied for 24 h and multiple microsphere injections were performed at the above indicated time points in the same animals. Tracheal blood flow significantly increased and blood flow to the pancreas and ileum significantly decreased versus baseline in both groups (P < 0.05 each). Blood flow to the ileum, renal cortex and skin did not significantly change versus baseline in both groups (P > 0.05). Blood flow was higher to the trachea in the multiple injection group at 18 h (P = 0.048) and to the ileum at 12 h (P = 0.049), and lower to the skin at 18 h (P = 0.015). In conclusion, the results indicate that multiple versus single microsphere injections induced no or negligible alterations during ovine sepsis. This finding may help reduce the quantity of animals needed in future experiments.

Determination of Regional Bone Blood Flow by Means of Fluorescent Microspheres Using an Automated Sample-Processing Procedure

The determination of regional blood flow utilizing fluorescent microspheres (FMs) is an established method for numerous organs. Recent progress, in particular the automation of sample processing, has further improved this method. However, the FM method (reference sample technique), which allows repetitive measurement of regional organ blood flow, has so far not been used for the determination of blood flow in bone. The aim of the present study was to establish FM for the quantification of regional bone blood flow (RBBF). Female, anesthetized New Zealand rabbits (n = 6) received left ventricular injections of different amounts of FM at six subsequent time points. In order to examine the precision of RBBF determination, two different FM species were injected simultaneously at the sixth injection. At the end of the experiments the femoral and tibial condyles of each hind limb were removed and the fluorescence intensity in the tissue samples was measured by an automated procedure. In an in vitro study we have shown that acid digestion of the crystalline matrix has no effect on the fluorescence characteristics of FM. The determination of the number of spheres per tissue sample revealed that depending on the tissue sample size up to 3 × 10⁶ spheres/injection were necessary to obtain about 400 microspheres in the individual bone samples. RBBF values of the tibial and femoral condyles did not differ at various injection intervals. The tibial blood flow values varied between 6.6 ± 1.1 and 8.5 ± 1.4 ml/min/100 g and were significantly higher than those of the femur (4.3 ± 1.1 to 6.0 ± 1.8 ml/min/100 g). The bone blood flow values obtained by simultaneous injection of two FM species correlated significantly (r = 0.96, slope = 1.06, intercept = 0.05), the mean difference was 0.39 ± 1.11 ml/min/100 g. Our data demonstrate that the measurement of RBBF by means of FM allows a valid determination of RBBF.

Cardiopulmonary effects of HI-6 treatment in soman intoxication.

The cardiopulmonary effects of HI-6, together with atropine and soman, were studied in the rat. HI-6 is an effective antidote in acute poisoning with the nerve agent soman. The therapeutic efficiency of HI-6 is still unclear and cannot be explained entirely by the HI-6 reactivating ability of acetylcholinesterase (AChE). Other non-cholinergic factors must be involved. One possible detoxifying process might be an effect of HI-6 on the blood flow to sensitive organs. The purpose of the present study was to investigate 1) whether soman per se induces changes in regional blood flow and 2) whether the blood flow to different organs is affected when HI-6 (50 mg x kg(-1) i.m.) and atropine (10 mg x kg(-1) i.m.) are given either before or immediately after soman intoxication (90 microg x kg(-1) s.c.). For regional blood flow determinations the microsphere method was used with male Wistar rats weighing 300-400 g. The rats were anaesthetised and breathed spontaneously during the experiment. Three different blood flow measurements were made in the same animal and concomitant physiological parameters such as mean arterial blood pressure and respiratory rate were recorded. The blood AChE activity was followed throughout the experiment. Our results show that when HI-6 is given after intoxication with soman, dramatic changes in blood flow occur with a significant decrease in both respiratory rate and blood AChE activity. If HI-6 is given prior to the intoxication, however, all rats are unaffected and none of the parameters measured are changed.

Distribution and hierarchy of regional blood flow during hypothermic cardiopulmonary bypass

Background. Cardiopulmonary bypass (CPB) may decrease oxygen delivery relative to the nonbypass state. We predicted that a hierarchy of regional blood flow could be characterized under hypothermic (27°C) CPB. Methods. Ten pigs underwent bypass at 27°C. Fluorescent microspheres were administered before and during CPB at four randomized flows: 1.9, 1.6, 1.3, and 1.0 L · min −1 · m −2. At completion, tissue samples were obtained from brain, renal cortex and medulla, pancreas, small bowel, and limb muscle for regional blood flow determination. Results. Cerebral blood flow remained unchanged between CPB flows of 1.9 and 1.3 L · min −1 · m −2. Renal perfusion was stable between flows of 1.9 and 1.6 L · min −1 · m −2, whereas perfusion of small bowel decreased linearly with pump flow. Pancreatic perfusion was unchanged over the range of flows studied; muscle blood flow was profoundly reduced at the highest CPB flow and further decreased if pump flow was reduced below 1.6 L · min −1 · m −2. Conclusions. This study characterizes the organ-specific hierarchy of blood flow and oxygen distribution during hypothermic CPB. These dynamics are relevant to clinical decisions for perfusion management.

Hierarchy of regional oxygen delivery during cardiopulmonary bypass

Background. Relative to the nonbypass state, cardiopulmonary bypass may decrease whole-body oxygen (O 2) delivery. We predicted that during cardiopulmonary bypass, a hierarchy of regional blood flow and O 2 delivery could be characterized. Methods. In 8 46.5 ± 1.2-kg pigs, fluorescent microspheres were used to determine blood flow and O 2 delivery to five organ beds before and during 37°C cardiopulmonary bypass at four randomized bypass flows (1.4, 1.7, 2.0, and 2.3 L/min/m 2). At completion, 18 tissue samples were obtained from the cerebral cortex (n = 4), renal cortex (n = 2), renal medulla (n = 2), pancreas (n = 3), small bowel (n = 3), and limb muscle (n = 4) for regional blood flow determination. Results. At conventional cardiopulmonary bypass flow (2.3 L/min/m 2), whole-body O 2 delivery was reduced by 44 ± 6% relative to the pre-cardiopulmonary bypass state ( p < 0.05). Over a range of cardiopulmonary bypass flows (2.3 to 1.7 L/min/m 2), brain and kidney maintained their perfusion. Blood flow and O 2 delivery to both regions were reduced when the cardiopulmonary bypass flow was reduced to 1.4 L/min/m 2. However, perfusion and O 2 delivery to other visceral organs (pancreas, small bowel) and skeletal muscle showed pump flow dependency over the range of flows tested. Conclusions. This study characterizes the organ-specific hierarchy of blood flow and O 2 distribution during cardiopulmonary bypass. These dynamics are relevant to clinical decisions for perfusion management.

Effect of prolonged asphyxia on skin blood flow in fetal lambs

Objective: To determine the effect of a prolonged period of asphyxia on skin blood flow, a potential indicator of fetal cardiovascular responses to asphyxia, in the chronically catheterized fetal lamb. Methods: Eight chronically instrumented pregnant ewes were studied at 118 ± 1 days’ gestation. After a control period, fetal acid-base status was assessed and regional blood flows were determined with dye-labeled microspheres. Fetal asphyxia was then induced by partial umbilical cord occlusion, decreasing fetal arterial oxygen pressure to 15 torr while maintaining pH above 7.28. Fetal cardiovascular status was monitored continuously. Fetal acid base status was evaluated every 10–15 minutes during cord occlusion. Regional blood flow determinations were repeated after 90 minutes of stable asphyxia. Results are expressed as the mean ± standard error. Student t test for paired data was used to compare hemodynamic, acid-base, and regional blood flow determinations before cord occlusion and after 90 minutes of asphyxia. Results: There was a significant increase in blood flow to the fetal scalp from a control value of 52 ± 8 mL per minutes per 100 g to 175 ± 30 mL per minute per 100 g at 90 minutes of asphyxia ( P = .01). Similarly, there was an increase in blood flow to the skin overlying the fetal hindquarter from 39 ± 12 mL per minute per 100 g during control to 153 ± 47 mL per minute per 100 g at asphyxia ( P = .038). Conclusion: In the chronically instrumented fetal lamb, a 90-minute period of asphyxia produced by partial cord occlusion resulted in a significant increase in blood flow to the fetal skin.

Development of the Fluorescent Microsphere Technique for Quantifying Regional Blood Flow in Small Mammals

We have demonstrated that the fluorescent microsphere technique can be used in small mammals for accurate determination of regional blood flows. In particular we have shown that 100% recovery of trapped microspheres is possible, that tissue digestion can be completed in a shorter time than previously reported, and the error-prone filtration method can be replaced with one of sedimentation. The method gave very good agreement among different fluorescent labels (r2 > 0.99) and low variability among tissues (mean coefficient of variation = 0.06). Simultaneous injection of radiolabelled and fluorescent microspheres established comparability between these methods (r2 = 0.96) for blood flows measured at rest, during vasodilator-induced hypotension, and in muscle hyperaemia during indirect electrical stimulation. Fluorescent microspheres can therefore replace radioactive microspheres for the determination of blood flow with advantages in both safety and cost, without loss of sensitivity.

The age-related effects of epidural lidocaine, with and without epinephrine, on spinal cord blood flow in anesthetized rabbits.

The effect of epidural or spinal epinephrine when added to local anesthetics on spinal cord blood flow (SCBF)are controversial. We evaluated the effects of epidural lidocaine, with or without epinephrine, on spinal cord blood flow in young and adult rabbits receiving 2% plain lidocaine, 2% lidocaine with epinephrine (1:200,000), or saline epidurally. Colored microspheres were injected through the left ventricle 10 min before and 7.5 and 30 min after epidural injection. The organs (brain, heart, kidneys, and the L6-7 segment of the spinal cord) were analyzed for regional blood flow determination. A significant decrease in mean arterial pressure was observed after the administration of lidocaine, with or without epinephrine, in both adult and young animals compared with saline. SCBF did not change over time in adult rabbits. Conversely, a significant decrease in SCBF was observed in the two groups of young rabbits receiving lidocaine. This decrease correlated with the decrease in mean arterial pressure but did not correlate with the use of epinephrine. We conclude that any reduction in blood pressure occurring in pediatric patients receiving a combined epidural-general anesthetic may result in decreased SCBF. In young rabbits, any decrease in blood pressure was followed by a decrease in spinal cord blood flow, a decrease that did not correlate to the use of epinephrine and was not observed in adult animals. These data suggest that blood pressure should be monitored closely to promptly treat any decrease in blood pressure when combined epidural-general anesthesia is used in children.

Application of HPLC to counting of colored microspheres in determination of regional blood flow.

Colored microspheres have become popular compared with radioactive microspheres because they do not use radioactivity. However, they suffer from a much greater variability in their determination. We have developed a new method for assaying the dye using high-performance liquid chromatography (HPLC) with internal standard. This technique permits accurate determination of < or = 400 spheres in rat blood, heart, kidney, liver, and brain with a relative error [coefficient of variation (CV)] < 10%. To date, only three colors (white, yellow, and red) may be used because, of the five colors tested, one (violet) served as internal standard and another (blue) exhibited marked degradation during extraction. Compared with the classical spectrophotometric technique, HPLC allows a three to five times improvement in reproducibility with a relative error significantly lower (P < 0.01) than with direct spectrophotometry. Although this new technique appears to be more time consuming than the classical method, its use seems to be preferable because of the improvement in measurement sensitivity.

Estimation of splanchnic blood flow by the Fick principle in man and problems in the use of indocyanine green

Measurement of splanchnic blood flow is necessary to evaluate the effect of therapeutic interventions on splanchnic tissue perfusion. Systemic indocyanine green (ICG) clearance has been used to estimate splanchnic blood flow, but the results may be compromised by altered hepatic dye extraction. We evaluated the applicability of simultaneous estimation of splanchnic and femoral blood flow by dye dilution and regional blood sampling in intensive care patients. 240 simultaneous determinations of regional blood flow were conducted in different patient groups (cardiac surgery, ARDS, pancreatitis, septic shock, preoperative controls). The measurement protocol consists of catheterizations of hepatic vein, femoral artery and vein and primed constant infusion of two different ICG preparations. The method was used successfully in a wide variety of patients. Steady-state dye concentration and sufficient dye extraction was achieved in each group of patients. The coefficient of variation of splanchnic blood flow estimation was 7 +/- 1% and of femoral blood flow estimation 6 +/- 0%. There was a great intra- and interindividual variation of ICG extraction. Use of dobutamine modified the extraction in most patients but did not lessen the performance of the method. ICG extraction was markedly lower and the coefficient of variation of both femoral and splanchnic blood flow markedly higher with propylene glycol-dissolved ICG preparation as compared with the freeze-dried. The prerequisites for the method of primed, constant infusion of indocyanine green with hepatic vein catheterization are achieved in intensive care patients. The results of splanchnic blood flow estimations based on techniques with peripheral blood sampling should be interpreted with caution, and the use of ICG clearance as a flow-related indicator without the measurement of ICG extraction cannot be justified because of the great variability of dye extraction. Certain indocyanine green preparations may greatly modify the results of the regional blood flow determinations.

Effect of prostaglandin E 1 on experimental acute hepatic failure in rabbits: prostaglandin E 1 prevents the development of multiple-organ failure

Acute hepatic failure was induced in 50 male rabbits by D-galactosamine HCl (1 g per kg bw), and the effects of prostaglandin E1 on this model were investigated. Twelve hours after the administration of D-galactosamine HCl, a continuous infusion of prostaglandin E1 (2 micrograms.kg-1.h-1 or 20 micrograms.kg-1.h-1) was started. Ten animals in each group were observed until the time of death and mean survival times were compared between the groups. Five animals in each group were used for the determination of regional blood flows and brain water content. After the injections of D-galactosamine HCl, serum aspartate transaminase and alanine transaminase activity rose markedly and prothrombin time was prolonged. The administration of prostaglandin E1 did not affect these levels. However, the survival time in the prostaglandin E1 20 micrograms.kg-1.h-1 group (48.2 +/- 10.4 h) was significantly longer (p < 0.005, p < 0.01) than those in the untreated group (24.9 +/- 5.0 h) and the prostaglandin E1 2 micrograms.kg-1.h-1 group (28.1 +/- 5.8 h). Prostaglandin E1 20 micrograms.kg-1.h-1 inhibited elevations of blood urea nitrogen and creatinine and significantly inhibited the decrease of urine volume and urinary sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Is the high lactate release during arm exercise due to a low training status?

To determine whether arm lactate release during arm exercise is related to the training status of the arms, seven arm-trained athletes were studied during 30 min of continuous arm exercise (AE) or leg exercise (LE) of increasing intensities corresponding to 30%, 50%, and 80% of peak VO2 during AE and LE respectively. Blood vessels were catheterized for determination of regional blood flows and substrate exchanges. The respiratory exchange ratio was higher during AE than LE (P less than 0.01). The arteriovenous oxygen difference, [(A-V)O2], for the leg during LE was 11-19% higher than the (A-V)O2 for the arm during AE (P less than 0.01). At the highest intensity the (A-V)O2 was 170 +/- 6 ml O2l-1 during LE, vs. 143 +/- 9 during AE (P less than 0.01). Arm blood flow in relation to limb volume was 56-95% higher during AE (P less than 0.05). Arterial lactate concentrations were 27-60% higher during AE (P less than 0.01) and lactate release from the exercising limb was 2-4 times higher (P less than 0.05) during AE compared to LE. Adrenaline and noradrenaline rose 6- and 21-fold, respectively, during AE and did not differ from corresponding LE values. During AE the (A-V)O2 difference across the arm, arterial lactate concentration, and arm lactate release were of the same magnitude in arm-trained and relatively less arm-trained subjects. Lactate release in relation to O2 uptake by the exercising limb was 7-37% lower during AE in arm-trained subjects compared to AE in arm-untrained subjects but was 3-6 times higher than the corresponding relation during LE (P less than 0.01). We conclude that AE is associated with a larger lactate release compared to LE. This difference is only to a minor extent influenced by intense training of the arms. The high arm vs. leg lactate release appears to be associated with differences in regional circulatory adaptation by the exercising limb.

The DDT method: An alternative to the use of radiolabelled microspheres for the determination of regional blood flows in the rat

Intravenous administration of the 14C-radiolabelled insecticide DDT — 1,1,1-trichloro-2,2-bis-( p-chlorophenyl)ethane — can be used for the estimation of regional blood flows in small rodents. A mathematical model is presented which enables the conversion of relative into absolute blood flows.

The Effects of Methoxamine and Epinephrine on Survival and Regional Distribution of Cardiac Output in Dogs with Prolonged Ventricular Fibrillation

This study compares the effects of methoxamine, a pure alpha 1-agonist, and epinephrine on cerebral and myocardial blood flow, central hemodynamics, and survival in a randomized placebo-controlled fashion during prolonged ventricular fibrillation (VF) in a canine model. Twenty-four anesthetized and ventilated adult mongrel dogs were instrumented for regional blood flow determinations using radio-labeled microspheres. The dogs were randomized to receive either 20 mg of methoxamine as a single intravenous bolus or repeated boluses of 0.02 mg/kg of epinephrine, 0.2 mg/kg of epinephrine, or normal saline solution placebo beginning at three minutes following induction of VF and initiation of closed chest cardiac massage (CCCM). Organ blood flow measurements were determined during normal sinus rhythm and after five and 20 minutes of VF. All six dogs receiving methoxamine were successfully resuscitated in contrast to only one in each of the epinephrine-treated groups and none of the dogs receiving placebo (p less than .01). Although epinephrine was associated with significantly higher blood pressures than placebo during cardiopulmonary resuscitation (CPR), blood pressures achieved with methoxamine were significantly higher than those observed in the other three treatment groups (p less than .001). Cerebral blood flow was significantly higher with both methoxamine and high-dose epinephrine (p less than .05). Mean left and right ventricular myocardial flows were highest with methoxamine but this did not achieve statistical significance. In contrast, organ flows measured in the animals receiving the lowest dose of epinephrine were not significantly higher than those associated with placebo. Cardiac output after 20 minutes of CPR was significantly lower with high-dose epinephrine than with methoxamine or placebo (p less than .05). Our results suggest that methoxamine significantly improves regional cerebral blood flow and survival during CPR and although high-dose epinephrine is associated with comparable improvements in regional cerebral blood flow, this treatment is associated with deterioration in central hemodynamics during prolonged VF and does not enhance survival.

A comparison of the cerebral pressure-flow relationship for halothane and isoflurane at haemodynamically equivalent end-tidal concentrations in the rabbit

The cerebral pressure-flow relationship for halothane and isoflurance was studied at end-tidal concentrations which resulted in similar baseline mean arterial pressure (MAP). Two groups of New Zealand white rabbits (n = 8; each group) were studied with five regional blood flow determinations in each animal. Blood flow was determined by injecting radioactive microspheres during the following conditions: injection 1: after stable 2.05 per cent end-tidal isoflurane (1.0 MAC) Group I; or after stable 0.74 +/- 0.04 per cent end-tidal halothane (0.53 MAC) Group H. Injections 2-5: after MAP was increased 20, 40, 60, and 80 per cent respectively above baseline MAP by phenylephrine infusion. Baseline MAP was the same for both groups (64.3 +/- 3.1 vs 67.2 +/- 2.0 mmHg; mean +/- SEM; Group I and H respectively). Baseline total CBF (tCBF; 0.68 +/- 0.03 vs 0.86 +/- 0.05) and hemispheric CBF (hCBF; 0.64 +/- 0.03 vs 0.96 +/- 0.06) were significantly greater in Group H; no significant difference between groups was seen for baseline posterior fossa CBF (pCBF; 0.79 +/- 0.06 vs 0.75 +/- 0.04). For each experiment a pressure-flow curve was generated by curvilinear regression analysis. Significantly greater phenylephrine concentrations were required for injections 2-5 in Group H. Mean slopes and intercepts were derived for each group. Within each group comparison of the pressure-flow curves for hCBF vs MAP and pCBF vs MAP showed autoregulation was less impaired in posterior fossa structures (cerebellum and brain stem) for both anaesthetic agents (P less than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of regional blood flow in abdominal organs and other structures in normal female rats and in rats with TAA-induced chronic liver injury using 99mTc labelled HSA-microsphere technique

A method for simultaneous determination of cardiac output and regional blood flow distribution in a chronically instrumented, unrestrained rat preparation for different experimental conditions (i.e. conscious, free movement; general anesthesia) and in an experimental chronic liver injury model is described. The use of a modified radioactive microsphere reference sample method using 99mTc labelled HSA-microspheres provides valid measurements of cardiac output [255 +/- 21.6 ml/(min.kg b.wt.)] and of the determined blood flow rates of abdominal organs (with separate determination of arterial and portal-venous hepatic blood flow rates; the latter by means of arterial blood flow measurement of the gastrointestinal tract and the spleen), the myocard, the adrenals, the kidneys, and various brain regions. Furthermore, it is demonstrated that this measuring approach with chronical preparation can also advantageously be used in pharmacological or pathogenetical studies, especially because of the simple measuring equipment and the comparatively low costs that offer a broader application.

Renal and hormonal effects of phosphodiesterase III inhibition in congestive heart failure

Evaluation of the impact of therapeutic interventions in congestive heart failure (CHF) with compounds such as the phosphodiesterase (PDE) III inhibitors must include the determination of regional blood flow and functional changes. Thus, whereas PDE III inhibitors produce a significant increase in cardiac output and reduction of systemic vascular resistance, it is necessary to understand their effects on the kidney and neurohormonal parameters. The evaluation of these effects must take into consideration both the baseline renal and neurohormonal abnormalities in CHF, and the cellular actions of PDE III inhibition, which include an increase in cyclic adenosine monophosphate and cytosolic calcium. In a group of 13 patients with CHF, milrinone therapy for 1 month did not increase renal blood flow or glomerular filtration rate, or favorably affect neurohormonal parameters. However, forearm blood flow increased proportionately with cardiac output. Therefore PDE III inhibition produces a preferential increase in skeletal muscle blood flow, which may be a relative shunting of blood from the kidney. Alternatively, PDE III inhibition may activate renal cellular mechanisms that offset the anticipated favorable response to the increase of cardiac output produced by milrinone.

Cardiocirculatory dynamics during heart failure in the rat: Effects of prototypic drugs

AbstractThe goal of these studies was to evaluate the effects of congestive heart failure on the peripheral circulations, looking specifically for the regions responsible for the rise in peripheral resistance observed in patients with this disease condition. During the course of these experiments, we evaluated the effects of different modes of exercise on cardiocirculatory dynamics and cardiac output distribution in normal animals in order to determine the most appropriate mode to induce an adequate exercise stess. Based on these studies, we chose treadmill exercise for use in animal models of heart failure. The animal species chosen for these studies was the rat. This choice was based on the availability of novel techniques which allowed for repetitive and accurate hemodynamic and regional blood flow determinations in rodents which provided a cost‐effective approach to the study of heart disease. Once appropriate models for congestive failure and for exercise were adequately characterized and studied, additional experiments designed to evaluate the acute effects of appropriate therapeutic agents such as calcium blockers, nitro‐vasodilators, and angiotensinconverting enzyme inhibitors were conducted. In order to determine the scope of the therapeutic efficacy of some of these compounds, studies were also conducted on models of hypertensive disease.

Dose-response curves of the uterine and placental vascular beds to prostaglandin I2

Local infusion of prostaglandin I2 (PGI2) has been reported to dilate the uteroplacental vasculature in a dose-dependent manner. In this experiment we attempted to distinguish the placental and nonplacental (uterine) components of this response over four concentrations of PGI2. Eleven near-term sheep were chronically instrumented for determination of regional blood flows by the use of radioactive microspheres. PGI2 was administered in a retrograde manner via a branch of the middle uterine artery at 1, 3, 10, and 20 μg/min. Flows were measured before (control) and after 5-minute infusions at each of the four concentrations (test). The uterine vasculature vasodilated in response to local PGI2 infusion. The 10 μg/min dose, for example, produced a mean (±SEM) flow of 0.70 ± 0.07 ml/min/gm; the control value was 0.41 ± 0.03 ml/min/gm (p < 0.001). At 20 μg/min the test and control flows were 0.75 ± 0.16 and 0.36 ± 0.06 ml/min/gm (p < 0.05), respectively. Uterine vascular resistance fell in a dose-dependent manner as well. There was no evidence of placental vasodilation at any of the doses tested. Renal vasodilation and decreased systemic arterial pressure at higher PGI2 doses suggest a recirculation effect. We conclude that PGI2 does not dilate the placental vasculature over the dose range of 1 to 20 μg/min and that the reported vasodilation of the uteroplacental vasculature is a result of decreased resistance in the uterine vasculature alone.