Blood pressure and heart rate in the ovine fetus: ontogenic changes and effects of fetal adrenalectomy.

Ontogenic changes in baseline and 24-h rhythms of fetal arterial blood pressure (FABP) and heart rate (FHR) and their regulation by the fetal adrenal were studied in 18 fetal sheep chronically instrumented at 109-114 days gestation (GA). In the long-term study, FABP and FHR were continuously recorded from 120 days GA to spontaneous term labor (>145 days GA) in five animals. Peak times (PT) and amplitudes (Amp) of cosinor analysis were compared at 120-126, 127-133, and 134-140 days GA. Consistent, significant linear increases in FABP and linear decreases in FHR were observed in all fetuses. Significant 24-h rhythms in FABP and FHR were observed during all the time windows. In the adrenalectomy study, to test the hypothesis that fetal cortisol plays a key role in cardiovascular maturation, fetal adrenals were removed in eight animals (ADX); sham fetal adrenalectomy was performed on five animals (Con). Cortisol (4 microgram/min) was infused intravenously in four ADX fetuses from day 7 postsurgery for 7 days (ADX+F). No significant changes in PT and Amp in FABP and FHR were observed. Plasma cortisol levels remained low in Con and ADX fetuses (<4.9 ng/ml). Cortisol infusion increased fetal plasma cortisol to 22.3 +/- 3.2 ng/ml (mean +/- SE) on day 13 in ADX+F fetuses. FABP increased in control and ADX+F but not ADX fetuses; FHR decreased in control and ADX but rose in ADX+F fetuses. These results suggest that, in chronically instrumented fetal sheep at late gestation, 1) increases in FABP and decreases in FHR are maintained consistently from 120 to 140 days GA, with distinct 24-h rhythms, the PT and Amp of which remain unchanged, and 2) the physiological increase in FABP is dependent on the fetal adrenal; bilateral removal of the fetal adrenals does not prevent the ability of cortisol to produce a sustained increase in FABP.

Parathyroid hormone-related peptide (1 to 34) inhibits in vitro oxytocin-stimulated activity of pregnant baboon myometrium.

OBJECTIVES: We sought to determine the in vitro effect of parathyroid hormone-related protein fragment 1 to 34 on oxytocin precontracted myometrium from baboons in late gestation and to explore possible regional uterine differences in responsiveness comparing muscle strips from the lower uterine segment, posterior and anterior corpus, and fundus. STUDY DESIGN: We used cumulative concentration response (1 to 100 nmol/L) curves to parathyroid hormone-related protein (1 to 34) in isolated strips of baboon myometrium obtained at cesarean hysterectomy of 6 pregnant baboons in the last third of pregnancy. RESULTS: Parathyroid hormone-related protein (100 nmol/L) decreased both amplitude and frequency of contraction. The maximum effect of parathyroid hormone-related protein on the amplitude of contractions was greater than saline solution (2-way analysis of variance, F ratio 424.0, P < .001), but there was no difference comparing the four regions of the uterus (F ratio 1.342, P = .286). The maximum effect of parathyroid hormone-related protein on the frequency of contractions was greater than saline solution (2-way analysis of variance, F ratio 162.5, P < .0001), but no difference in response was noted in the 4 regions of the uterus (F ratio = 0.682, P = .572). CONCLUSION: Parathyroid hormone-related protein completely inhibited the contractile effect of high doses of oxytocin in the lower segment, corpus, and fundus of the baboon uterus. No difference in response of myometrium was obtained from different regions of the uterus.

Differences in the in vitro sensitivity of ovine myometrium and mesometrium to oxytocin and prostaglandins E2 and F2alpha.

We compared the in vitro response to oxytocin, prostaglandin (PG)E2, and PGF2alpha of myometrium and mesometrium from six ovariectomized ewes and 53 ewes at 106-145 days gestational age (dGA), including 14 ewes in spontaneous or betamethasone-induced labor. Myometrial baseline activity increased from 217+/-27 mN/cm2 of cross-sectional area (mean +/-SEM) in ovariectomized ewes to a plateau of 696+/-39 mN/cm2 at 126-135 dGA. No gestation-related changes were observed in mesometrial baseline activity. Myometrial, but not mesometrial, maximum tension in response to agonists increased with gestation to a plateau at 126-135 dGA. The pD2 (negative logarithm of the EC50) values for oxytocin were similar in both tissues and did not change with gestation. During pregnancy, the myometrial pD2 of both PGs was one order of magnitude higher than the mesometrial pD2. The results indicate an increase in myometrial uterotonic receptor-mediated activity that precedes labor with no increase at labor, suggesting that in sheep, activation of the basic mechanisms responsible for strength of myometrial activity at labor occurs by 135 dGA. The greater sensitivity of the myometrium than the mesometrium to PGs supports a major role for intrauterine paracrine factors in regulating myometrial contractility.

Dynamics of cardiovascular responses to repeated partial umbilical cord compression in late-gestation sheep fetus.

We characterized the detailed hemodynamics of fetal blood pressure, heart rate, common umbilical blood flow, and femoral blood flow responses to partial compression of the umbilical cord and tested the hypothesis that repeated cord compression modulates fetal cardiovascular responses in 10 chronically instrumented fetal sheep at approximately 130 days of gestation. In five fetuses (group I), partial compression of the umbilical cord was induced 12 times, each for 5 min at 15-min intervals. Each cord compression reduced common umbilical blood flow by 50% and produced modest falls in fetal pH (7.33 +/- 0 to 7.29 +/- 0) and arterial PO2 (21.1 +/- 0.2 to 16.8 +/- 0.2 mmHg) and a mild increase in arterial PCO2 (49.9 +/- 0.5 to 54.9 +/- 0.4 mmHg). Sham experiments were performed in five other fetuses (group II). Second-by-second analysis of group I fetal cardiovascular data revealed a clear biphasic response to partial cord compression. Phase I (1st min of cord compression) was characterized by a rapid bradycardia and a rapid femoral vasoconstriction (primary response); phase II (minutes 2-5 of cord compression) was characterized by a delayed bradycardia and a return of femoral vascular resistance toward baseline (secondary response). Repeated cord compression abolished the primary, but not the secondary, cardiovascular responses. These results demonstrate that fetal cardiovascular responses to stress may be modified by preexposure to repeated intrauterine challenges.

Effect of in vivo estradiol administration to bilaterally ovariectomized rats on in vitro myometrial responsiveness to prostaglandin F2alpha and oxytocin.

Bilaterally ovariectomized, nonpregnant female CD rats were studied to investigate the effect of estradiol treatment on in vitro myometrial responsiveness to oxytocin and prostaglandin F2alpha. The first study investigated dose-dependent effects. Seven days after ovariectomy rats were given a single s.c. dose of corn oil (n = 4) or estradiol (5 microg, n = 5; 15 microg, n = 5; 50 microg, n = 4). A second identical injection of corn oil or estradiol was administered 24 h after the initial injection. Rats were killed 48 h after the first injection. A second study investigated time-dependent effects of estradiol treatment. A second group of ovariectomized rats received s.c. estradiol (50 microg) seven days after ovariectomy. These rats were killed either 12 h (n = 5) or 24 h (n = 4) after injection. Full-thickness cross-sections of uteri were suspended in vitro in the longitudinal direction in a superfusion system. Cumulative concentration-response curves were constructed to oxytocin and prostaglandin F2alpha. Both the duration and dose of estradiol treatment significantly (p < 0.05) attenuated baseline contractile activity, and the maximum myometrial response to oxytocin and prostaglandin F2alpha. Estradiol, in a dose-dependent manner, significantly reduced myometrial sensitivity (p < 0.05) for oxytocin and prostaglandin F2alpha.

Timing of the switch from myometrial contractures to contractions in late-gestation pregnant rhesus monkeys as recorded by myometrial electromyogram during spontaneous term and androstenedione-induced labor.

Pregnant rhesus monkeys were studied to determine the precise time in relation to photoperiod of the onset, and the nature, of the switch in myometrial activity patterns from contractures to contractions. We investigated both spontaneous term labor and androstenedione-induced preterm labor. Under general anesthesia at 127 +/- 2 days gestation (dGA) (mean +/- SEM), 16 pregnant rhesus monkeys were instrumented with maternal femoral arterial and venous catheters and myometrial electromyogram electrodes. Eight animals (group I) received continuous i.v. infusion of intralipid (n = 7) or saline (n = 1) that was started at 143.3 +/- 2 dGA and maintained until the spontaneous onset of term labor. Nine animals (group II) received continuous i.v. infusion of androstenedione that was started at 139 +/- 0.4 dGA and maintained until the onset of prematurely induced labor. Myometrial activity was recorded continuously. All monkeys in both groups demonstrated nocturnal switches in myometrial activity from contractures to contractions. The mean time of onset of the switch in group I and group II monkeys was similar, occurring at 0.7 +/- 0.4 h or 0.8 +/- 0.5 h, respectively, after the onset of darkness. Group II monkeys demonstrated greater regularity in both the time of onset and the repetitive occurrence each night once the switch occurred, as well as greater consistency in duration in their switch patterns, than did group I monkeys.

A comparative study of cardiovascular, endocrine and behavioural effects of betamethasone and dexamethasone administration to fetal sheep.

1. Chronically instrumented, late-gestation fetal sheep were prepared to: (1) characterize cardiovascular, endocrine and behavioural effects of fetal treatment with clinical doses of betamethasone and dexamethasone; (2) define specific differences, if any, in the actions of betamethasone and dexamethasone of measured fetal responses; and (3) assess the contribution of changes in peripheral vascular resistance to the glucocorticoid-induced hypertension. 2. Following baseline, either saline (n = 9), betamethasone (n = 9), or dexamethasone (n = 6) was infused for 48 h in fetal sheep commencing at 125 days of gestation. A pronounced increase in fetal blood pressure occurred following both betamethasone and dexamethasone treatment. The nature and magnitude of this increase was similar following treatment with either glucocorticoid. 3. To address possible mechanisms contributing to the glucocorticoid-induced fetal hypertension, fetal plasma catecholamine levels and changes in fetal femoral haemodynamics were assessed following fetal glucocorticoid treatment. A fall in fetal plasma noradrenaline and adrenaline concentrations occurred during betamethasone and dexamethasone treatment. In contrast, a progressive femoral vasoconstriction occurred during betamethasone treatment. 4. A modest fall in the incidence of fetal breathing movements occurred during fetal treatment with either betamethasone or dexamethasone. The magnitude of this reduction was similar with treatment of either glucocorticoid. The fall in fetal breathing during betamethasone and dexamethasone treatment was not associated with a fall in the incidence of fetal low voltage electrocortical activity. 5. Our results indicate that prenatal betamethasone and dexamethasone treatment of late-gestation fetal sheep, in doses similar to those employed clinically, is associated with fetal cardiovascular, endocrine and behavioural effects. Both betamethasone and dexamethasone induce similar increases in fetal blood pressure and similar falls in the incidence of fetal breathing movements. The pronounced betamethasone-induced fetal hypertension is associated with an increase in fetal femoral vascular resistance.

Evidence for the presence of AH 13205-sensitive EP2-prostanoid receptors in the pregnant baboon but not in the pregnant sheep myometrium near term.

OBJECTIVE: Our purposes were to assess the effects of prostaglandin (PG) E2 and PGF2 alpha on myometrial contractility in pregnant sheep and baboons in an in vitro superfusion study, and to characterize further the PGE-sensitive (EP) receptor subtype involved in the myometrial response to PGE2 by using the selective prostanoid EP2 agonist AH 13205. METHODS: Strip preparations of uterine muscle from 15 sheep (107-145 days' gestational age) and ten baboons (158-185 days' gestation) were studied. Cumulative concentration-response curves (CRC) were constructed to oxytocin (4.2 pmol/L to 0.42 mumol/L, PGE2 (0.1 nmol/L to 1 mumol/L), and PGF2 alpha (1 nmol/L to 100 mumol/L), and 50% effective concentration (EC50) values (mean and 95% confidence interval) were calculated. We also tested the hypothesis that PGE2-induced myometrial relaxation in pregnant baboons could be mediated by EP2-prostanoid receptors. Myometrial strips were stimulated by oxytocin (0.42 nmol/L), and CRCs to the EP2-agonist AH 13205 (0.1 nmol/L to 10 mumol/L) were constructed. RESULTS: Prostaglandin F2 alpha stimulated myometrial activity in a concentration-related fashion in all preparations from both sheep and baboons. The EC50 in the sheep myometrium for PGF2 alpha (52 nmol/L, 95% confidence interval [CI] 25-110) was significantly (P < .05) lower than that in baboon myometrium (183 nmol/L, 95% CI 93-355). Oxytocin stimulated myometrial activity in preparations of both sheep (EC50 = 0.29 nmol/L, 95% CI 0.11-0.71) and baboon (EC50 = 0.31 nmol/L, 95% CI 0.18-0.52). In contrast, responses to PGE2 were species-related: PGE2 caused concentration-related stimulation of myometrial activity in sheep tissue (EC50 = 3.2 nmol/L, 95% CI 2.0-5.0), but induced concentration-related inhibition of activity in baboon myometrium (50% inhibitory concentration [IC50] = 21 nmol/L, 95% CI 2.2-203). A concentration-related inhibitory response to AH 13205 (IC50 = 3.56 nmol/L, 95% CI 1.28-5.99) was obtained in the baboon. In contrast, AH 13205 failed to inhibit comparable myometrial strip preparations from pregnant sheep. CONCLUSIONS: The present studies suggest that both sheep and baboon myometrium contain prostanoid receptors that mediate stimulation. In addition, baboon myometrium, like that from the human, contains AH 13205-sensitive EP receptors (EP2 receptors), which mediate inhibition. The pregnant baboon may therefore represent a suitable animal model for investigations into the use of EP2 agonists for the prevention of premature labor in humans.

Intravenous administration of cocaine stimulates gravid baboon myometrium in the last third of gestation.

OBJECTIVE: The hypothesis for this investigation was that intravenous cocaine results in a dose-dependent increase in myometrial activity of the unanesthetized, chronically instrumented gravid nonhuman primate. STUDY DESIGN: Seven chronically instrumented gravid baboons were individually caged in an environment of 14 hours of light and 10 hours of darkness. Maternal femoral artery and vein catheters and three pairs of myometrial electromyographic wires were surgically placed at 90 to 121 days' gestation (term 180 days). At least 5 days after surgery, bolus intravenous cocaine hydrochloride doses of 0.05, 0.1, 0.3, 0.5, and 1.0 mg/kg maternal body weight were administered according to various schedules. Myometrial activity was analyzed by quantifying the myometrial electromyographic envelope data as the power spectral density window of contraction activity and as the total area under the rectified electromyographic voltage signal (i.e., total electromyographic activity) before and during the experimental period. RESULTS: Myometrial contraction activity increased after the 0.3 mg/kg dose (p < 0.01), the 0.5 mg/kg dose (p < 0.005), and the 1.0 mg/kg dose (p = 0.07) compared with baseline. The total myometrial electromyographic activity also increased as the cocaine dose increased. CONCLUSION: Intravenous cocaine results in increased myometrial contractions in the gravid baboon during the latter third of pregnancy.

Different patterns of myometrial activity and 24-h rhythms in myometrial contractility in the gravid baboon during the second half of pregnancy.

Two clearly distinct epochs of myometrial contractility were observed in 13 pregnant baboons when recorded either as intraamniotic pressure (IAP) or myometrial electromyogram (EMG). Contractures, epochs lasting longer than 3 min, were the characteristic form of myometrial activity throughout pregnancy. Contractures generated only small increases in IAP. Short-lived contractions, generating larger increases in IAP, were characteristic of labor and delivery. Power spectral analysis of IAP and myometrial EMG activity proved to be an effective means whereby periods when the myometrium was in the contractures or contractions mode could be easily distinguished. Concomitantly recorded maternal intraabdominal temperature showed significant 24-h variations. When myometrial activity switched from low-amplitude, long-lasting regular contractures of pregnancy to contractions, the switch always occurred around the onset of darkness. Five baboons went into spontaneous labor, 3 prematurely and 2 at term. In these animals the switch from contractures to contractions occurred for several nights before delivery. The recurrence and timing of the switch from contractures to contractions for several nights before delivery were similar to the pattern we and others have observed in the pregnant rhesus monkey. The presence of 24-h periodicity in the patterns of specific types of myometrial activity in another nonhuman primate lends support to the view that similar 24-h patterns of myometrial activity may occur in pregnant women.

Temporal structuring of delivery in the absence of a photoperiod: preparturient myometrial activity of the rhesus monkey is related to maternal body temperature and depends on the maternal circadian system.

No convincing evidence exists that the shift from myometrial contractures to contractions, which determines the synchronized 24-h rhythm in the dynamics of the primate uterus, may be attributed to an endogenous circadian rhythm. We therefore wished to ascertain whether a 24-h periodic shift would also occur in the myometrial activity of animals kept under constant conditions. We studied five pregnant rhesus monkeys, kept in continuous darkness from 56-77 days gestational age until delivery at 117-167 days gestational age. During the last week before delivery we determined the individual phase, level, and amplitude of circadian changes in maternal body temperature and 24-h myometrial activity patterns in the form of contractions. In all five monkeys, a rhythm with a period of 24-h characterized the temporal incidence of preparturient contraction activity. A consistent phase lag of 6-7 h from the temperature crest was observed in four out of the five animals. The circadian phase of all individual rhythms was idiosyncratic among animals. We conclude that endogenous rhythms in body temperature and preparturient myometrial activity are truly circadian. In addition, these rhythms are either interdependent or subject to the same maternal timekeeping mechanism, supporting the hypothesis that the exact time of the day at which birth occurs in the rhesus monkey depends on the maternal circadian system.

Effect of intravenous cocaine on uterine blood flow in the gravid baboon.

Cocaine abuse during pregnancy is associated with adverse perinatal outcome, believed to be a result of potent vasoconstrictive effects that cocaine has on the maternal cardiovascular system. The direct effect of cocaine on the pregnant, nonhuman primates' uterine vasculature in vivo has not been examined. We investigated the effects of intravenous cocaine on maternal arterial blood pressure, uterine blood flow, and uterine vascular resistance in four unanesthetized, chronically instrumented pregnant baboons. Baboons were instrumented during the latter half of pregnancy, placing an ultrasonic flow probe around one uterine artery and catheters in the maternal inferior vena cava and aorta. Bolus intravenous cocaine hydrochloride doses of 0.05 mg/kg, 0.1 mg/kg, and 0.3 mg/kg by maternal weight were infused 30 minutes apart at least 5 days after surgical instrumentation. The maternal blood pressure rose 7.3% and 12.0% after the 0.1 mg/kg and 0.3 mg/kg cocaine infusions, respectively, and the uterine blood flow fell in a dose-dependent fashion 13.1% and 22.7%. Plasma norepinephrine levels rose in response to the 0.3 mg/kg cocaine infusion. These studies show that low doses of cocaine significantly reduce uterine blood flow in the pregnant baboon in a dose-dependent manner by increasing uterine vascular resistance.

Intrauterine asphyxia and the breakdown of physiologic circulatory compensation in fetal sheep.

In response to acute hypoxemia, the fetus invokes physiologic compensatory mechanisms that cause a preferential redistribution of the circulation to sustain the brain, heart, and adrenal gland and maintain blood flow to the placenta. These mechanisms are available for a limited time and eventually the fetus is no longer able to maintain preferential perfusion and decompensation occurs. To identify the relationship between hypoxemia with severe acidemia and the breakdown of circulatory compensation, we decreased uterine blood flow in 10 chronically instrumented pregnant sheep. We measured fetal blood gases and pH, arterial and central venous pressures, heart rate, combined ventricular output, and regional blood flow distribution during hypoxemia with severe acidemia and when a fixed-baseline sustained bradycardia (agonal) heart rate pattern developed. Hypoxemia with severe acidemia was characterized by markedly decreased blood flow to most organs; however, the preferential perfusion of the brain, heart, adrenal gland, and placenta was still present. An agonal heart rate pattern was characterized by complete cardiovascular collapse. This study demonstrates that circulatory compensation is present in fetal sheep affected by deficiency of oxygen delivery despite hypoxemia with severe acidemia.

Regional blood flow distribution in fetal sheep with intrauterine growth retardation produced by decreased umbilical placental perfusion.

To determine the capacity of the fetus to adapt to chronic O2 deficiency produced by decreased placental perfusion in the early development of growth retardation, we embolized the umbilical placental vascular bed of fetal sheep for a period of 9 days. Fetal umbilical placental embolization decreased arterial O2 content by 39%, decreased total placental blood flow by 33%, and produced a 20% reduction in mean fetal body weight. Neither the combined ventricular output nor the regional blood flow distribution was significantly different between the 8 growth-retarded and 7 normally grown fetuses despite the 39% decrease in fetal arterial O2 content. Thus a 33% reduction in total placental blood flow restricts normal fetal growth, but does not exceed the placental circulatory reserve capacity necessary to maintain normal basal metabolic oxygenation. Because the proportion of combined ventricular output to the placenta at rest is decreased in late IUGR fetuses but not in early IUGR fetuses, despite chronic oxygen deficiency, we conclude that the growth retarded fetus maintains a normal regional blood flow distribution until the placental circulatory reserve capacity is depleted.

Intrauterine growth retardation and the circulatory responses to acute hypoxemia in fetal sheep.

Intrauterine growth retardation has been produced experimentally by umbilical placental embolization for 9 days (early intrauterine growth retardation) in pregnant sheep. Fetuses with early intrauterine growth retardation had a 20% decrease in mean body weight and 33% decrease in placental blood flow. However, the regional blood flow distribution was not significantly different at rest between the embolized and normally grown fetuses despite the 39% decrease in fetal arterial oxygen content. The purpose of this study was to determine the circulatory responses to acute hypoxemic stress in the early development of intrauterine growth retardation. We found that the regional blood flow distribution was not significantly different during imposed acute hypoxemia between the seven fetuses with early intrauterine growth retardation and seven nonembolized normally grown fetuses. We conclude that growth-retarded fetuses are able to meet basal metabolic oxygen requirements and to respond normally to imposed acute hypoxemia until the placental circulatory reserve capacity is depleted.

Use of nonabsorbable markers for gastrointestinal contents in in vivo measurement of magnesium bioavailability.

Magnesium absorption from five leafy vegetables was measured in rats using 28Mg as an extrinsic label and polyethylene glycol (PEG) and chromium-mordanted vegetable fibers (cr-mordants) as unabsorbable markers of soluble and particulate gut and fecal contents, respectively. The test meals used in this investigation were identical to those used in a previous test in which we found: a) that stable 26Mg biologically incorporated into the vegetables was freely exchangeable with an extrinsic 28Mg tracer; b) PEG consistently preceded Cr-mordants in transit through the gut; and c) fecal Mg isotope excretion 12 hours after the test meal was inadequate for measurement of Mg absorption. Accordingly, in the present investigation, all measurements in feces and gut contents were made 24 hours after the test meal. By that time an average of greater than 60% of the ingested PEG had been excreted. Magnesium-28 excretions, estimated under these conditions, were 4-5% less than they would have been had fecal PEG excretion been 100%. The discrepancy was due to partial separation of PEG and Mg in the lower gastrointestinal tract (GIT), possibly due to sequestration of Mg by microorganisms. That Mg must have entered an insoluble phase in the lower GIT was born out by the observation that little or no Mg absorption occurred in the cecum or colon. As before, Cr-modants lagged behind PEG and unabsorbed 28Mg, and thus do not seem suitable to monitoring intestinal transit of Mg.

Magnesium absorption from leafy vegetables intrinsically labeled with the stable isotope 26Mg.

Five leafy vegetables were grown in nutrient solutions in which the natural magnesium was replaced by the stable isotope, 26Mg. They were fed to rats in a test meal together with the extrinsic tracer 28Mg: a) to determine to what extent the instrinsic tracer (26Mg) was exchangeable with extrinsic 28Mg during the digestion and absorption processes, and b) measure the relative Mg availability from the different vegetables. The two tracers, 26Mg and 28Mg, were close to 100% exchangeable, as judged by the ratio of 26Mg/28Mg in the livers. Mean relative Mg absorption from the various vegetables ranged from 108 to 118% of the Mg absorbed from a standard test meal containing MgSO4. There were no statistically significant differences between the rates of Mg absorption from the five vegetables although two of the vegetables tested contained oxalate. The usefulness of stable 26Mg as a tracer in Mg bioavailability tests is discussed.

The renal excretion of iodine following oral administration of Gastrografin to domestic cats.

Serum and urinary levels of iodine were determined in six cats before and after oral administration of Gastrografin. Iodine was identified by gamma spectrometry after the specimens had been subjected to neutron activation. Peak serum iodine levels, compared to undetectable preadministration levels in five of the six cats, ranged from 8.0 to 50.7 micrograms/ml 1 to 2 hours after Gastrografin administration. Twenty-four hour cumulative urinary excretion of iodine represented 0.9 to 4.08% of this element calculated to be in Gastrografin. Pharmacokinetic analysis of the serum concentrations using the one-compartment open model resulted in an estimate of ka, the fraction of Gastrografin dose absorbed per unit time, of 2.24 hr-1 (95% CL = -5.4, 7.7) and an estimate of ke, the fraction of the dose eliminated per unit time, of 0.10 hr-1 (95 % CL = -0.01, 0.21). Analysis of urinary elimination rates also yielded ke = 0.10 hr-1 (95% CL = 0.01, 0.18). At necropsy the gastrointestinal tract of each cat was normal.