Biomedical subjects

D F Teitel

Publications and source records attributed to D F Teitel.

At least 37 records · Page 2Linked to original sources

PubMed1995

Interaction between afterload and contractility in the newborn heart: evidence of homeometric autoregulation in the intact circulation.

OBJECTIVES: We undertook the present study to determine whether afterload and contractility interact in the hearts of newborn lambs. We specifically investigated whether stepwise increases in afterload increase contractility. BACKGROUND: Several studies in the isolated and intact adult dog heart have shown that afterload and contractility are not independent determinants of cardiac performance; rather, they interact. Afterload and contractility are unlikely to interact in the newborn heart because the factors that may mediate the interaction in the adult are missing in the newborn. METHODS: We measured contractility at different steady state levels of afterload in seven newborn lambs under complete anesthesia. Contractility was measured by three different indexes: end-systolic pressure-volume relations (slope and volume position); preload-corrected first derivative of left ventricular pressure (dP/dtmax); and preload-corrected stroke work. Left ventricular pressure and volume were measured with a micromanometer and conductance catheter, respectively. Preload and afterload were manipulated by inflating or deflating a balloon catheter in the inferior vena cava and descending thoracic aorta, respectively. Data are expressed as mean value +/- 1 SD. RESULTS: Stepwise increases in afterload increased contractility, independent of which of the three indexes was used. The slope of the end-systolic pressure-volume relation increased from a mean baseline value of 4.44 +/- 2.43 to 6.69 +/- 2.89 kPa/ml at the highest level of afterload. Concomitantly, volume at 14 kPa of the end-systolic pressure-volume relation decreased from 3.34 +/- 1.52 ml at baseline to 1.12 +/- 0.83 ml at the highest afterload. The other two indexes showed qualitatively similar changes. Beats selected from unloading interventions on the basis of the same end-diastolic volume for each level of afterload showed no difference in stroke volume. CONCLUSIONS: This study in newborn lambs demonstrates that stepwise increases in afterload increase contractility considerably and that this enables the heart to maintain stroke volume at different levels of afterload. This forms direct evidence for the existence of homeometric autoregulation in the intact newborn heart.

Analysis of Variance↗

PubMed1995

Effect of indomethacin on cerebral blood flow and oxygenation in the normal and ventilated fetal lamb.

Indomethacin lowers fetal and neonatal brain blood flow and may reduce the risk of periventricular-intraventricular hemorrhage. However, concerns have been raised that cerebral O2 metabolism may be compromised at lower cerebral perfusion pressures. In 17 near-term lamb fetuses, changes in brain blood flow and cerebral O2 metabolism (CMRO2) were measured at mean carotid arterial pressures (MCBP) ranging from 8 to 70 mm Hg. MCBP was adjusted by inflating balloon occluders around the aortic isthmus and brachiocephalic trunk. This was done before and during intrauterine pulmonary ventilation and oxygenation. Nine fetuses were pretreated with indomethacin (1 mg/kg i.v.); eight served as control. Changes in brain blood flow were assessed from carotid arterial blood flow (Qcar, mL/min) measured with flow transducers. In 15 animals, brain blood flow was also measured intermittently by radionuclide-labeled microspheres (Qbrain). Qcar correlated closely with Qbrain (r = 0.94, p < 0.0001); this relationship was not altered by indomethacin or by ventilation with oxygen. In the nonventilated fetuses, indomethacin decreased Qcar at pressures above the lower limit of cerebral autoregulation (43 mm Hg). However, at MCBP below 44 mm Hg, Qcar with indomethacin was not significantly different from controls. CMRo2 fell when MCBP was decreased below 30 mm Hg (range 8-29 mm Hg), but there was no significant difference between control and indomethacin-pretreated fetuses. In the ventilated fetuses, indomethacin reduced the slope of the pressure-flow relationship above the lower limit of cerebral autoregulation (43 mm Hg), suggesting improved cerebral autoregulation. When MCBP was decreased below 44 mm Hg (range 10-43 mm Hg), indomethacin did not lower Qcar or CMRO2 as compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1995

Effect of drugs on chemoreceptor responsiveness in fetal sheep.

This study was designed to examine the effects of the drugs ketamine, morphine, pentobarbital, and propranolol on fetal chemoreceptor responsiveness. Eleven fetal lambs (gestational age 125-133 d) were chronically instrumented with a catheter in a hindlimb artery and vein and a forelimb artery; a carotid arterial oximeter catheter was placed in six of these fetuses. An inflatable cuff occluder was placed around the maternal hypogastric artery. Acute fetal hypoxemia was induced repeatedly by reducing uterine blood flow. Fetal heart rate, arterial pressure, and carotid arterial oxygen saturation were monitored continuously before and after administering ketamine, morphine, pentobarbital, or propranolol to the fetus. The ratio delta heart rate/delta O2 saturation has been shown previously to be a reproducible index of chemoreflex response. The differences in baseline values and changes with drugs were compared by multiple regression analysis coded by effects. Chemoreflex response was markedly attenuated by ketamine and morphine but not by pentobarbital or propranolol. Because the cardiovascular response to hypoxemia is blunted by some drugs, caution should be exercised in interpreting heart rate responses to hypoxemia in the fetus when these drugs have been administered to the mother.

Acute Disease↗

PubMed1995

Effect of increased intra-abdominal pressure on hepatic extraction and clearance of fentanyl in neonatal lambs.

Fentanyl, an opioid metabolized by hepatic mixed function oxidases, is commonly administered as the primary anesthetic for neonates undergoing surgery. Pharmacokinetic studies have suggested that abdominal surgery in neonates decreases fentanyl clearance, contending that this results from increases in intra-abdominal pressure (IAP) decreasing hepatic blood flow. To examine the effects of IAP on hepatic blood flow and fentanyl clearance, we infused fentanyl to eight neonatal lambs, measured regional blood flows by using the radionuclide-labeled microsphere technique and determined hepatic fentanyl extraction and clearance and hepatic oxygen extraction and consumption at three levels of IAP: 0, 12 and 18 mm Hg. Increased IAP did not affect portal or hepatic blood flow or ductus venosus shunt. Fentanyl extraction was 16.5 +/- 3.0% (mean +/- S.E.) at 0 mm Hg of IAP. Increased IAP decreased hepatic extraction of fentanyl, thereby decreasing fentanyl clearance. Increased IAP did not affect hepatic oxygen extraction or consumption. In two additional animals in which serial measurements of hepatic blood flow were obtained, increased IAP (15 mm Hg) transiently decreased hepatic blood flow with recovery to control values at 2 hr. The authors conclude that fentanyl is poorly extracted by neonatal livers, in contrast to its large extraction ratio in adults. The decrease in fentanyl clearance with increased IAP is consistent with pharmacokinetic studies demonstrating decreased clearance in neonates undergoing abdominal surgery. However, the present study suggests that the mechanism of decreased clearance is decreased hepatic function (decreased fentanyl extraction) rather than decreased hepatic blood flow.

Abdomen↗

PubMed1994

Nonlinearity of the left ventricular end-systolic wall stress-velocity of fiber shortening relation in young pigs: a potential pitfall in its use as a single-beat index of contractility.

OBJECTIVES: We sought to evaluate in the young heart the primary assumptions on which the current use of the mean "velocity of fiber shortening corrected for heart rate" as a noninvasive index of contractility are based. BACKGROUND: End-systolic wall stress-velocity of fiber shortening relation has been applied as a single-beat, load-independent index of contractility in children. This use is based on poorly validated assumptions of linearity, parallel shifts with changing contractile state and inotropic sensitivity of the end-systolic wall stress-velocity of fiber shortening relation. METHODS: In eight anesthetized young piglets, 5F mciromanometric catheters were placed in the ascending aorta and balloon occlusion catheters in the descending aorta. End-systolic wall stress and velocity of fiber shortening were calculated from aortic pressure and M-mode echocardiography under six conditions: in three contractile states 1) baseline, 2) increased contractility during dobutamine infusion (10 micrograms/kg per min), and 3) decreased contractility after propranolol injection (1 mg/kg), each at two afterload states (normal and increased load by partial aortic occlusion). RESULTS: Dobutamine increased and propranolol decreased afterload-matched velocity of fiber shortening corrected for heart rate significantly to 140% and 77% of baseline, respectively. However, the slope of end-systolic wall stress-velocity of fiber shortening relation was much greater (251% of baseline) during dobutamine infusion, which also significantly decreased wall stress, and was much less (27% of baseline) after propranolol injection, which increased wall stress. CONCLUSIONS: The velocity of fiber shortening corrected for heart rate did change predictably with changes in contractility and as such can be used noninvasively in the temporal evaluation of individual patients undergoing therapeutic interventions or to define the natural history of a disease process. However, the relation on which it is based is not defined by parallel straight lines across contractile states, so that abnormal single point measurements may reflect only the nonlinearity of the relation rather than abnormalities in contractility. Thus, we recommend that the end-systolic wall stress-velocity of fiber shortening relation should not be used as a single-beat index of contractility.

Aging↗

PubMed1994

Relationship between brain blood flow and carotid arterial flow in the sheep fetus.

The present study investigates whether changes in total brain blood flow can be reliably estimated by changes in carotid arterial blood flow in fetal and perinatal lambs. We therefore compared carotid arterial blood flow, measured with implanted transit-time ultrasound transducers, with brain blood flow, measured by radioactive microspheres in fetal lambs during normal oxygenation and during pulmonary ventilation with oxygen, with PO2 ranging from levels normal for the healthy fetus to levels normally seen postnatally. Cerebral perfusion pressure was modified over a wide range to alter brain blood flow: it was decreased by balloon occlusion of the brachiocephalic trunk and increased by a balloon occluder around the aortic isthmus. Carotid arterial blood flow and brain blood flow were closely related (r = 0.97, p < 0.0001). The relationship was not altered at different levels of oxygenation. However, measurements during higher cerebral perfusion pressures, obtained during aortic isthmus occlusion, had a negative influence on the agreement between carotid arterial blood flow and brain blood flow. When excluding values obtained by aortic isthmus occlusion, changes of 20% or more in brain blood flow could be predicted with carotid arterial blood flow within a confidence limit of 95%. Blood flow measurements in the carotid artery may be useful to estimate changes in brain perfusion.

Animals↗

PubMed1993

Myocardial perfusion and performance after indomethacin administration in newborn lambs.

Indomethacin is a drug widely used to achieve pharmacologic closure of a patent ductus arteriosus in the premature infant. In several vascular beds (brain, kidney, intestine), indomethacin has been shown to cause vasoconstriction. Possible negative effects on myocardial blood flow and performance could be deleterious in premature infants with limited cardiac reserve. Before, during, and 30 and 60 min after administration of 1 mg.kg-1 of indomethacin in nine newborn lambs, we measured coronary blood flow velocity (Doppler flow probe around the left circumflex coronary artery), left ventricular (LV) pressure (by tip manometer) and volume (by conductance catheter technique), cardiac output, arterial pressure, arterial and venous saturations and calculated systemic and coronary vascular resistance, LV systolic function by the end-systolic pressure-volume relationship, and myocardial oxygen extraction. To investigate the effect of indomethacin on the flow regulation of the coronary vascular bed, we measured coronary flow and LV function under different levels of myocardial demand, achieved by stepwise occluding of the descending aorta. During indomethacin infusion, coronary and systemic vascular resistance increased significantly (by 43 and 76%, respectively), resulting in an increase in arterial pressure from 10.2 to 16.9 kPa, whereas neither coronary flow nor LV systolic function changed despite the increase in afterload. Thirty and 60 min after indomethacin, coronary and systemic vascular resistance had returned to baseline levels and LV systolic function remained unchanged. The relationship between coronary flow and cardiac demand was not different before or after indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Effects of lung distension and spontaneous fetal breathing on hemodynamics in sheep.

In previous studies, we determined that pulmonary ventilation and oxygenation were largely responsible for increasing pulmonary blood flow and for altering central blood flow patterns but could not account for the increase in combined ventricular output (the sum of left and right ventricular outputs) that usually occurs after birth. We had ventilated fetuses with oscillating positive pressures; the possibility that high intrathoracic pressures adversely affected cardiac output could not be ruled out. To determine the effects of negative intrathoracic pressure ventilation, we occluded the umbilical cord of nine long-term instrumented fetal sheep at 135 +/- 1.2 d gestation while introducing humidified oxygen gas intratracheally. This stimulated continuous fetal respiratory activity, which resulted in negative intrathoracic pressures and increased fetal oxygenation. Pulmonary blood flow increased from 121 +/- 60 to 901 +/- 139 mL.min-1.100 g-1 (mean +/- SD) and descending aortic blood pressure increased from 7.0 +/- 1.2 to 9.6 +/- 2.0 kPa. Central blood flow patterns were altered so that right to left shunting of blood through the foramen ovale and ductus arteriosus was abolished and a left to right shunt developed across the ductus arteriosus. However, cardiac output did not increase significantly. This may be related, in part, to the increase in afterload. It is clear that pulmonary ventilation and oxygenation are the major factors responsible for changing pulmonary blood flow and central blood flow patterns at birth. Other birth-related events, such as a decrease in environmental temperature and an increase in metabolic rate, are likely to induce cardiac output to increase.

Animals↗

PubMed1993

Carotid, not aortic, chemoreceptors mediate the fetal cardiovascular response to acute hypoxemia in lambs.

The fetal cardiovascular response to acute hypoxemia consists of a decrease in heart rate, a variable change in mean arterial pressure, and an increase in peripheral vascular resistance. This response is mediated by the arterial chemoreceptors. To determine whether chemoreceptors in the carotid artery or in the aorta mediate the fetal cardiovascular response to acute hypoxemia, we studied the response to acute hypoxemia in fetal lambs at 125 to 130 d of gestation after selective carotid (six fetuses) or aortic (five fetuses) denervation. One to 3 d after insertion of catheters, hypoxemia was induced by inflating a balloon occluder around the ewe's hypogastric artery or by giving the ewe 95% N2 and 5% O2 to breathe. The chemoreflex response was measured as decrease in heart rate per decrease in Hb O2 saturation. To validate our results, we also studied the response to chemical stimulation of the chemoreceptors by injection of sodium cyanide into the inferior vena cava. We found that carotid denervation abolished the heart rate and peripheral vascular resistance responses to hypoxemia but that aortic denervation did not. Responses after injection of sodium cyanide were similar to those seen during acute hypoxemia. We conclude that the carotid chemoreceptors, and not the aortic chemoreceptors, mediate the fetal cardiovascular response to acute hypoxemia.

Animals↗

PubMed1993

The influence of indomethacin on the autoregulatory ability of the cerebral vascular bed in the newborn lamb.

Prevention of hyperperfusion of the brain in the perinatal period has been thought to be an important mechanism by which indomethacin reduces the risk for severe periventricular-intraventricular hemorrhage. The present study investigated whether an indomethacin-induced enhancement of the upper limit of cerebral vascular autoregulatory ability in the neonate contributed to this reduction in cerebral blood flow. In seven anesthetized newborn lambs, we measured temporal blood flow velocity (TMFV) in the carotid artery over a wide range of mean aortic blood pressures (MABP) before and 30 min after an i.v. dose of 1 mg/kg indomethacin. TMFV in the carotid artery was used as an estimate for changes in cerebral blood flow. Stepwise changes in MABP of approximately 10 mm Hg were achieved by progressive balloon occlusion of the thoracic aorta or by progressive bleeding. Multiple linear regression analysis of TMFV versus MABP, indomethacin, and the possible interactive effects confirmed that, at MABP values up to 86 mm Hg, indomethacin lowered TMFV of the carotid artery. Above 86 mm Hg, indomethacin reduced the slope of the TMFV-MABP relationship, indicating an improvement of the autoregulatory ability of the cerebral vascular bed. There was a significant interanimal variability. Thus, indomethacin may reduce the risk for PIVH by limiting cerebral blood flow, especially during increased cerebral perfusion pressures, which often occur after birth asphyxia.

Animals↗

PubMed1993

Heart rate fall during acute hypoxemia: a measure of chemoreceptor response in fetal sheep.

The peripheral arterial chemoreceptor response to hypoxemia in the fetus is predominantly cardiovascular, invoking a fall in heart rate and a variable change in blood pressure. No quantifiable measure of chemoreceptor activity has yet been described in the intact fetus. We described the course, quantified the overall response, and defined the reproducibility of the heart rate response to acute hypoxemia in 22 late-term unanesthetized fetal sheep. Fetuses were chronically instrumented and studied between 1-6 days postoperatively. Acute hypoxemia was induced by occluding a balloon cuff around the common hypogastric artery. We performed 151 occlusions, starting at an initial saturation of 66 +/- 11%, decreasing saturation by 8-50%. Soon after balloon inflation, arterial oxygen saturation fell, followed by a decrease in heart rate. We calculated delta HR/delta sat, the fall in heart rate divided by the fall in saturation. Multiple linear regression analysis showed a sensitive chemoreflex, delta HR/delta sat averaging 2.5 +/- 1.2 bpm.%saturation-1. Initial saturation did not alter the first phase of the response (from the onset of the decrease in oxygen saturation to the onset of the decrease in oxygen saturation to the onset of the decrease in heart rate), but it did increase the overall response (delta HR/delta sat) when saturation was less than 65%. After adjusting in the lower range of initial saturations to that predicted at 65%, delta HR/delta sat was very reproducible within animals, with intra-animal variance being only 7% of inter-animal variance.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1992

Cerebral blood flow velocity: the influence of myocardial contractility on the velocity waveform of brain supplying arteries.

Indices of Doppler-derived velocity waveforms of arteries perfusing the brain are used as relative measures of neonatal brain blood flow. Using a dog model, we investigated the influence of changes in myocardial contractility, induced by dobutamine, on the blood flow velocity waveform of the vertebral artery. The following indices of the velocity waveform were investigated during control states and during 5 or 10 micrograms/kg/min dobutamine infusion: peak systolic flow velocity (PSFV), temporal mean flow velocity (TMFV), end-diastolic flow velocity (EDFV) and acceleration time (ACC-time). PSFV and ACC-time of the vertebral artery showed a strong relationship with myocardial contractile state. These results indicate that PSFV of an artery supplying the brain or indices which combine PSFV with MFV or EDFV should not be used for noninvasive assessment of brain blood flow or cerebral vascular resistance. ACC-time may prove to be very useful in assessing changes in myocardial contractile state.

Animals↗

PubMed1992

Complications of pediatric cardiac catheterization: a 3-year study.

To determine the current risk of pediatric cardiac catheterization, the complications and incidents of all catheterizations performed in a pediatric laboratory between January 1986 and October 1988 were prospectively recorded and compared with results from a 1974 study from the same institution. In the current study 1,037 catheterizations, 885 diagnostic and 152 diagnostic/interventional procedures, were performed in 888 patients (aged 1 day to 27 years, median 15.6 months). There were 15 major complications (1.4%), 70 minor complications (6.8%) and 30 incidents (2.9%). Two patients died as a result of the procedure and two as a result of pericatheterization clinical deterioration caused by the cardiac abnormality. The great majority of complications were successfully treated or were self-limited and the patients had no residua. Of patients with 13 nonfatal major complications and 70 minor complications, residua were evident in 7 patients and 3 without evident residua had the potential for sequelae (0.7% and 0.3% of catheterizations). A comparison of the diagnostic and balloon atrial septostomy cases in the present study with similar cases in the 1974 study shows that the incidence of major complications has decreased from 2.9% to 0.9% (p less than 0.0001); minor complications and incidents have decreased from 11.7% to 7.9% (p less than 0.006) and pericatheterization deaths not attributable to catheterization have decreased from 2.8% to 0.2% (p less than 0.0001). Changes in pericatheterization medical management, patient selection for catheterization and catheterization techniques probably account for these improvements.

Age Factors↗

PubMed1992

The end-systolic pressure-volume relationship in young animals using the conductance technique.

Evaluation of ventricular performance by the end-systolic pressure-volume relationship (ESPVR) has been extensively performed in the adult heart using the conductance technique. We undertook this study to validate the conductance technique and to generate ESPVRs in the small heart. To validate the technique, we simultaneously measured left ventricular volume by the conductance catheter and biplane cineangiography in nine piglets during changes in volume and contractility. Raw conductance volumes correlated highly with cineangiographic volumes (R = 0.97), and the slope was near identity (1.11 +/- 0.04). However, 'alpha Vc-corrected' volumes correlated less well (R = 0.85), probably because of errors induced by the saline technique for alpha Vc. We evaluated the ESPVR in nine lambs by inferior vena cava (IVC) occlusion, aortic occlusion, and volume infusion at rest and during changes in contractility. Reliable and linear ESPVRs were obtained in almost all IVC and aortic occlusions but not in volume infusions. Neither slope (Ees) nor position (V14) significantly changed over time or with dobutamine, but both changed after propranolol, supporting studies showing a limited contractile reserve in the newborn. However, Ees was 25% less steep when generated by IVC occlusion as compared to aortic occlusion. We conclude that the ESPVR can be reliably generated in the small heart using the conductance technique, but that it is sensitive to the loading technique.

Age Factors↗

PubMed1992

The conductance volume catheter technique for measurement of left ventricular volume in young piglets.

The conductance catheter has been used extensively in the adult for instantaneous and continuous measurement of left ventricular volumes, but has not been validated for use in the small heart. To determine the accuracy of this technique, we simultaneously measured left ventricular volume by the conductance catheter and biplane cineangiography in nine piglets (2-5 wk of age) over a wide range of volumes experimentally altered by volume infusion, hemorrhage, inferior vena caval occlusion, or administration of phenylephrine, isoproterenol, or propranolol. We performed 110 comparisons and determined parallel conductance of contiguous structures (alpha Vc) for each comparison using the saline technique. End-systole and end-diastole volumes were estimated by angiography using Simpson's rule. Raw and alpha Vc-corrected conductance volumes were compared to simultaneously obtained angiographic volumes by multiple regression analyses, using dummy variable coding for the effects of the interanimal variability and the phase of the cardiac cycle. Raw conductance volumes correlated highly with the cineangiographic volumes (r = 0.97), and the coefficient of angiographic volumes was near identity (1.11 +/- 0.04). The phase of the cardiac cycle did not have a significant effect. However, alpha Vc-corrected conductance volumes correlated less (well (r = 0.85), probably related to the fact that estimated alpha Vc was found to vary with ventricular volume. Thus, the conductance catheter affords a very accurate technique for measuring instantaneous changes in ventricular volume in the small heart, although correction to absolute volumes using the saline technique for estimation of alpha Vc may induce some inaccuracy.

Animals↗

PubMed1991

In utero ventilation augments the left ventricular response to isoproterenol and volume loading in fetal sheep.

In its normal circulatory environment, the fetal left ventricle can maximally increase output less than 2-fold, in contrast to the nearly 3-fold increase that occurs at birth. Several studies have attributed this finding to fetal myocardial "immaturity," and speculated that there is a rapid maturation of the myocardium in the perinatal period. We investigated the importance of the circulatory environment itself, rather than myocardial immaturity, by measuring left ventricular output (LVO) during in utero oxygen ventilation and isoproterenol infusion. We studied seven near-term fetal sheep greater than or equal to 2 d after placement of intravascular catheters, an endotracheal tube, and an electromagnetic flow transducer around the ascending aorta. We measured hemodynamic variables in the presence and absence of all combinations of oxygen ventilation, isoproterenol infusion, and volume infusion. Baseline LVO was normal (133 +/- 27 mL.kg-1.min-1). Individually, oxygen ventilation (136 +/- 11 mL.kg-1.min-1, p less than 0.001) and isoproterenol (48 +/- 11 mL.kg-1.min-1, p less than 0.05) increased LVO significantly; volume infusion did not. Their cumulative effect increased LVO nearly 3-fold (to 387 +/- 98 mL.kg-1.min-1), similar to levels seen in the newborn lamb. Mean left atrial pressure increased above right during oxygen ventilation (from 0.05 +/- 0.54 kPa to 0.82 +/- 0.39 kPa, p less than or equal to 0.0001). We conclude that the previously observed limitation in maximal LVO in the near-term fetus is primarily caused by its circulatory environment rather than relative myocardial immaturity, and speculate that a prominent Starling response is uncovered by decreases in left ventricular afterload and right ventricular constraint.

Animals↗

PubMed1991

The end-systolic pressure-volume relationship in the newborn lamb: effects of loading and inotropic interventions.

Indices of global systolic performance of the newborn left ventricle exceed those of the adult, despite isolated tissue studies showing immature contractile mechanisms. To evaluate contractility in situ, we investigated the end-systolic pressure-volume relationship (ESPVR) by the conductance technique in nine newborn lambs. After percutaneous placement of catheters, we generated ESPVR by inferior vena cava occlusion, aortic occlusion, and volume infusion in two control states, during three levels of dobutamine infusion, and after propranolol. We performed linear and nonlinear regression analyses of the end-systolic points and derived the slope (Ees) and volume at 14 kPa pressure. We found that reliable ESPVR could be obtained in almost all inferior vena cava and aortic occlusions (50 of 51 in each), but in only 18 of 27 volume infusions. Overall, linear regressions adequately defined the ESPVR (75 of 102 were not statistically different than nonlinear regressions; of those different, the mean linear R2 was 0.934 +/- 0.048). By multiple regression analysis, neither Ees nor volume at 14 kPa significantly changed with dobutamine, but both changed after propranolol (23% less than control and 54% greater, respectively), supporting previous studies showing a limited contractile reserve in the newborn secondary to high resting beta-adrenergic tone. Neither Ees nor volume at 14 kPa was different between control states. However, Ees was 25% less steep when generated by inferior vena cava than by aortic occlusion. We conclude that the ESPVR can be generated reliably and reproducibly in the newborn lamb and is relatively linear and sensitive to changes in contractility, but that it is also sensitive to the technique of load intervention.

Animals↗

PubMed1991

Effect of birth-related events on metabolism in fetal sheep.

At birth, changes in utilization of metabolic substrates occur as the fetus, dependent upon carbohydrates and amino acids available continuously from the placenta, becomes a neonate, dependent primarily upon fat obtained intermittently by suckling. In addition to changes in substrates, at birth, metabolic rate increases dramatically as the activity of several organs and thermoregulatory mechanisms increase. To determine whether metabolic changes are related to certain events that occur at birth, we studied 15 fetal sheep instrumented chronically with vascular catheters and an endotracheal tube at 133 to 137 d gestational age. We measured blood flow with radionuclide-labeled microspheres and arteriovenous concentration differences for oxygen content, blood glucose, and lactate across the placental, cerebral, myocardial, and hindlimb circulations at rest, during in utero ventilation of the fetal lungs with 3% O2, during in utero ventilation with 100% O2, and during ventilation with 100% O2 and umbilical cord occlusion. Ventilation with 3% O2 decreased oxygen uptake by the fetus and by the cerebral circulation but produced no other significant changes. Ventilation with the low and high oxygen gas mixture reduced glucose uptake by the fetus from the placental circulation dramatically to zero. In contrast, blood glucose concentrations increased and glucose uptake by the fetal brain, heart, and hindlimb were not altered significantly. These data indicate that, for a short time at least, complete cessation of glucose supply to the fetus from the placenta is not associated with decreases in blood glucose concentrations or utilization of glucose by a major portion of the fetal body.

Animals↗