Biomedical subjects

C Roman

Publications and source records attributed to C Roman.

At least 55 records · Page 3Linked to original sources

PubMed1991

A dominant negative form of transcription activator mTFE3 created by differential splicing.

Transcription factor E3 (mTFE3) is a murine transcription activator that binds to the intronic enhancer of the immunoglobulin heavy chain gene. A naturally occurring splice product of mTFE3 messenger RNA (mRNA) lacked 105 nucleotides that encode an activation domain; both absolute and relative amounts of long and truncated mRNAs varied in different tissues. Cells were cotransfected with complementary DNAs that encoded the two mRNA forms in amounts that corresponded to the amounts of each mRNA found in different cells. Small changes in substoichiometric amounts of the truncated form of mRNA effected trans-dominant negative modulation of mTFE3 activity. These findings identify a function for differential splicing in the regulation of transcription factor activity.

Amino Acid Sequence↗

PubMed1991

Catheter ablation of atrioventricular junction using radiofrequency current in 17 patients. Comparison of standard and large-tip catheter electrodes.

BACKGROUND: Two catheter electrode systems were compared for delivering radiofrequency current for ablation of the atrioventricular junction. Seventeen patients with drug-resistant supraventricular tachyarrhythmias were studied. METHODS AND RESULTS: A 6F or 7F catheter with six or eight standard electrodes (1.25 mm wide, 2.5-mm spacing) was used in the first seven patients (group 1). A 7F quadripolar catheter with a large-tip electrode (4 mm long; surface area, 27 mm2) was used in the final 10 patients (group 2). Both ablation catheters were positioned to record a large atrial potential and a small but sharp His bundle potential from the distal bipolar electrode pair. Radiofrequency current was applied between a large skin electrode on the left posterior chest and either 1) each individual electrode on the standard-tip electrode catheter at 40 V (group 1) or 2) the large-tip electrode at 50-60 V (group 2). Radiofrequency current was limited to 40 V in group patients because of the strong potential for an early impedance rise when higher voltage is applied through standard electrodes. Complete atrioventricular block was achieved in six of seven group 1 patients and all 10 group 2 patients. A junctional escape rhythm followed ablation in five or six group 1 patients (mean cycle length, 1,066 +/- 162 msec) and eight of 10 group 2 patients (mean cycle length, 1,281 +/- 231 msec). Atrioventricular block was produced in a mean of 4.7 +/- 4.6 radiofrequency current applications delivered over a period of 42 +/- 45 minutes using the large-tip electrode (group 2) compared with 46 +/- 22 applications using standard electrodes (15.9 +/- 10.2 applications delivered through the standard-tip electrode) over a period of 147 +/- 59 minutes (group 1). For the application producing atrioventricular block, the large-tip electrode used higher voltage (58 +/- 17 versus 38 +/- 5 V, p less than 0.03) and had lower impedance (103 +/- 22 versus 148 +/- 40 omega, p less than 0.01), resulting in greater power (33.0 +/- 13.0 versus 10.2 +/- 0.6 W, p less than 0.003) and shorter time to block (8 +/- 3 versus 22 +/- 3 seconds, p less than 0.001). Current delivery through standard electrodes was limited by an impedance rise occurring 7 +/- 7 seconds after the onset of one or more radiofrequency current applications at 10 +/- 1 W in six of seven patients. Using the large-tip electrode, an impedance rise occurred in five of 10 patients, but at 25 +/- 10 W and after 21 +/- 9 seconds. Atrioventricular block occurred before the impedance rise in three of these five patients. Complete atrioventricular block persisted in 15 of 16 patients at a mean follow-up of 8.7 months. Atrioventricular conduction returned at 1 month in one group 2 patient and was successfully ablated by a second procedure. Three group 1 patients died 0.5-2 months after ablation, and a fourth patient underwent cardiac transplantation after 10 months. Pathological examination of the heart in two of these patients showed necrosis of the atrioventricular node and origin of the His bundle, without injury to the middle or distal His bundle. All 10 group 2 patients are alive and subjectively improved after ablation. CONCLUSIONS: We conclude that catheter-delivered radiofrequency current effectively produces complete atrioventricular block (94%) without requiring general anesthesia or the risk of ventricular dysfunction or cardiac perforation. The large-tip electrode allows a threefold increase in delivered power and markedly decreases the number of pulses and time required to produce atrioventricular block.

Atrioventricular Node↗

PubMed1991

Effects of reducing uterine blood flow on fetal blood flow distribution and oxygen delivery.

We examined the effect of graded reduction in uterine blood flow on distribution of cardiac output and oxygen delivery to fetal organs and venous blood flow patterns in 9 fetal sheep using the radionuclide-labeled microsphere technique. We reduced uterine blood flow in two steps, decreasing fetal oxygen delivery to 70% and 50% of normal, and compared the results with those from a similar study from our laboratory on graded umbilical cord compression. With 50% reduction in fetal oxygen delivery, blood flow and the fraction of the cardiac output distributed to the brain, heart, and adrenal gland increased and that to the lungs, carcass, skin, and scalp decreased. Oxygen delivery to the brain and myocardium was maintained, while that to the adrenal doubled, and that to the brain stem increased transiently. The decrease in oxygen delivery to both carcass and lower body segment correlated linearly with oxygen consumption (P less than 0.001). The proportion of umbilical venous blood passing through the ductus venosus increased from 44.6% to 53% (P less than 0.05). The preferential distribution of ductus venosus blood flow through the foramen ovale to the heart and brain increased, but that to the upper carcass decreased so that ductus venosus-derived blood flow to the upper body did not change. Hence, the oxygen delivered to the brain from the ductus venosus was maintained, and that to the heart increased 54% even though ductus venosus-derived oxygen delivery to the upper body fell 34%. Abdominal inferior vena caval blood flow and its contribution to cardiac output decreased, but the proportion of the abdominal inferior vena caval blood distributed through the foramen ovale also increased from 23.0 to 30.9%. However, the actual amount of inferior vena caval blood passing through the foramen ovale did not change. There was a 70% fall in oxygen delivery to the upper body segment from the inferior vena cava. A greater portion of superior vena caval blood was also shunted through the foramen ovale to the upper body, but the actual amounts of blood and oxygen delivered to the upper body from this source were small. Thus, graded reduction of uterine blood flow causes a redistribution of fetal oxygen delivery and of venous flow patterns, which is clearly different from that observed previously during graded umbilical cord occlusion.

Animals↗

PubMed1990

Atrial natriuretic peptide response to ionic and nonionic contrast left ventriculography.

Atrial natriuretic peptide (ANP) levels were measured prior to and at 1 and 5 minutes postcontrast left ventriculography with an ionic contrast agent (diatrizoate), and a nonionic agent (iopamidol) and the results were compared. Since ionic contrast agents have been found to cause an increase in left ventricular end-diastolic pressure (LVEDP) and nonionic agents have been found to have less of an effect on LVEDP, we investigated the response of ANP levels, which have been found to increase secondary to increased LVEDP (atrial pressure), with both agents. A group of 38 patients who were scheduled for left heart catheterization for suspected coronary artery disease was included (19 in each group) and blood samples for ANP levels were drawn from the left ventricles. At the same time, heart rate, LVEDP, and left ventricular systolic pressure (LVSP) were also measured. It was found that the LVEDP increased significantly for both agents at 1 minute postventriculography, but no further change occurred at 5 min. Heart rate increased significantly in the diatrizoate group at 1 minute with a return of heart rate to preventriculography levels at 5 min, while the ANP level and LVSP remained unchanged at 1 minute postventriculography with both agents but increased significantly at 5 min in the diatrizoate group only. This difference in ANP response is not correlated with the LVEDP. The response of ANP may be related to heart rate and/or LVSP.

Atrial Natriuretic Factor↗

PubMed1990

Axonal branching of medullary swallowing neurons projecting on the trigeminal and hypoglossal motor nuclei: demonstration by electrophysiological and fluorescent double labeling techniques.

The projections of ventral medullary reticular neurons on both trigeminal (Vth) and hypoglossal (XIIth) motor nucleus were studied in sheep anesthetized with halothane. In a first series of experiments, extracellular microelectrodes were used to record the activity of medullary swallowing interneurons (SINs) located in the ventral region (around the nucleus ambiguus) of the swallowing center. Antidromic activation after electrical stimulation of the Vth and XIIth nuclei was tested in 83 SINs. For 38 SINs a clear antidromic activation was observed and for 8 of them the response was triggered by stimulation of either nucleus. As confirmed by the reciprocal collision test, these 8 SINs had branched axons sending information to both nuclei tested. Average latencies for antidromic activation of branched SINs after stimulation of the XIIth and the Vth motor nucleus were 2.2 +/- 0.6 ms and 2.7 +/- 0.8 ms respectively. The axonal conduction velocity of these neurons was 4.4 +/- 1.3 m/s for the collateral to the Vth motor nucleus and 2.7 +/- 0.7 m/s for axons projecting to the XIith motor nucleus. In a second series of experiments the double retrograde labeling technique was used to confirm the existence of neurons with branched axons in the medullary regions corresponding to the swallowing center. Small and well localized injections of Fast Blue (FB) and Diamidino Yellow (DY) fluorescent tracers were made in the Vth and in the XIIth motor nucleus respectively. A relatively large number of double-labeled cells was found in the ventral region of swallowing center (reticular formation around the nucleus ambiguus, 2-4 mm in front of obex).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Ig/EBP-1: a ubiquitously expressed immunoglobulin enhancer binding protein that is similar to C/EBP and heterodimerizes with C/EBP.

We report the isolation and characterization of cDNA clones that encode a protein with the same DNA binding specificity as the immunoglobulin heavy chain enhancer binding protein E (muEBP-E). We call the gene encoding this protein Ig/EBP-1. A fusion protein encoded by the cDNA binds specifically to muEBP-E-binding sites (E sites) in both the IgH enhancer and the VH1 promoter. Sequence analysis reveals that Ig/EBP-1 is a member of the "basic-zipper" family of DNA-binding proteins that are characterized by basic regions and heptad repeats of leucine residues. Among known family members, Ig/EBP-1 demonstrates highest homology to C/EBP throughout the DNA-binding domain and leucine repeat region. Ig/EBP-1 and C/EBP have highly overlapping binding specificities; both cloned proteins bind to the IgH enhancer and the VH1 promoter E sites, and Ig/EBP-1 binds to previously characterized C/EBP binding sites in the Rous sarcoma virus (RSV) LTR and the murine albumin promoter. Consistent with their homology in the leucine repeat region, Ig/EBP-1 and C/EBP form heterodimers; Ig/EBP-1 is the first member of this family that has been found to heterodimerize with the well-characterized C/EBP. Ig/EBP-1 mRNA is present in all tissues and cell lines examined, although its levels vary almost 20-fold from different sources, with highest levels in early B cells. In tissues where Ig/EBP-1 and C/EBP are both present, heterodimers may be functionally important. The presence of Ig/EBP-1 in fibroblasts and other tissues where C/EBP is not expressed suggests that Ig/EBP-1 may be functionally important for the activity of the RSV enhancer in these cell types. Finally, elevated expression of Ig/EBP-1 in early B cells may explain in part the enhancer-independent activity of VH promoters early in B-cell development.

Amino Acid Sequence↗

PubMed1990

Structural characteristics of the variable regions of immunoglobulin genes encoding a pathogenic autoantibody in murine lupus.

We have studied several monoclonal anti-double-stranded (ds) DNA antibodies for their ability to accelerate lupus nephritis in young NZB X NZW F1 female mice and to induce it in BALB/c mice. Two identified as pathogens in both strains have characteristics previously associated with nephritogenicity: expression of IgG2a isotype and IdGN2 idiotype. Both pathogenic antibodies used the combination of genes from the VHJ558 and VK9 subfamilies. Two weak pathogens failed to accelerate nephritis in young BW mice, but induced lupus nephritis in BALB/c mice. They both express IdGN2; one is cationic and an IgG3, the other is an IgG2a. Additional MAbs (some IgG2a, one IdGN2-positive) did not accelerate or induce nephritis. We have cloned and sequenced the variable regions of the immunoglobulin genes of one pathogenic autoantibody. No unique V, D, or J gene segments and no evidence of unusual mechanisms in generating diversity were used to construct this antibody. These data argue against use of unique abnormal Ig genes by systemic lupus erythematosus individuals to construct pathogenic autoantibody subsets. Instead, the major abnormality may be immunoregulatory.

Animals↗

PubMed1990

Pulmonary vascular effects of exogenous atrial natriuretic peptide in sheep fetuses.

In the adult, atrial natriuretic peptide (ANP) regulates renal and cardiovascular function when blood volume is expanded, when atrial pressure is increased, and when arterial oxygen content is decreased. In late gestation fetal sheep, plasma ANP concentrations are higher than in pregnant adults; however, ANP function in the fetus is unclear. To assess the possible role of ANP in mediating changes in pulmonary blood flow, we studied six chronically cannulated fetal sheep at 132-134 d gestation (term 145 d). We infused ANP in doses of 4.0 +/- 0.48, 16.0 +/- 1.9, and 64.0 +/- 7.7 ng/kg/min, and vehicle into all fetuses. ANP increased hematocrit, which suggests that blood volume decreased. Pulmonary blood flow, measured by the radionuclide-labeled microsphere technique, increased in response to the 4.0, 16.0, and 64.0 ng/kg/min dose ANP infusions from a control value of 126.5 +/- 32.2 to 141.8 +/- 26.9 to 170.4 +/- 37.2 to 300.8 +/- 84.8 mL/min/100 g (p less than 0.05), respectively, and calculated pulmonary vascular resistance decreased from a control value of 0.45 +/- 0.08 to 0.42 +/- 0.08 to 0.43 +/- 0.09 to 0.21 +/- 0.04 (p less than 0.05) mm Hg/mL/min/kg, respectively. Pulmonary blood flow decreased to 54.5 +/- 6.0 mL/min/100 g and calculated pulmonary vascular resistance increased to 0.81 +/- 0.09 mm Hg/mL/min/kg during the recovery period. Mean pulmonary and carotid arterial blood pressures, venous blood pressure, and heart rate did not change significantly. Thus, ANP may play a role in maintaining right ventricular output in the fetus by increasing pulmonary blood flow through its ability to decrease pulmonary vascular resistance.

Animals↗

PubMed1990

Leukotrienes C4, D4, and E4 in fetal lamb tracheal fluid.

Previously, we demonstrated that either putative leukotriene receptor antagonists or a synthesis inhibitor markedly decreased pulmonary vascular resistance in the near-term fetal lamb and concluded that leukotrienes may play a role in maintaining the high pulmonary vascular resistance in the fetus. To further investigate the role of leukotrienes, we measured concentrations of leukotriene (LT) C4, LTD4, and LTE4 in 17 tracheal fluid samples from 8 of 9 near-term (129-139 days, term = 145 days), chronically-catheterized, fetal lambs during normoxia to evaluate their possible role in regulating resting tone and in seven of the nine before and during hypoxia to evaluate their possible role in hypoxic vasoconstriction. The tracheal fluid samples collected by gravity over 1-3 min, on ice, were immediately treated with cold ethanol, centrifuged, and the supernatant covered with N2 and stored in a -70 degrees C freezer for a maximum of 3 weeks. Purification and separation of leukotrienes was done by reverse-phase high performance liquid chromatography using a gradient elution method, and fractions corresponding to LTC4, LTD4, and LTE4 standards were quantified immediately by radioimmunoassay. During normoxia (descending aortic PaO2 2.9 +/- 0.3 kPa [21.5 +/- 2.5 mmHg]; mean +/- SD), all 3 leukotrienes were detected in 16 of the 17 samples: LTC4 29 +/- 28 pg/ml (range 0-119 pg/ml); LTD4 66 +/- 51 pg/ml (range 9-177 pg/ml); and LTE4 43 +/- 50 pg/ml (range 0-204 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Activator proteins which regulate immunoglobulin heavy chain gene transcription in B lymphocytes.

While our results do not completely explain the B-cell specificity or other regulated aspects of IgH transcription, they show that IgH transcriptional factors belong to several different DNA-binding families which are capable of dimerization. It may be that formation of heteromultimers provides an additional level of regulation which might confer functional tissue specificity. Our results also suggest that enhancers and promoters may interact through protein-protein interactions, looping out the intervening DNA. Finally, we have shown that the same protein may regulate several genes including IgH and c-myc, indicating that transcriptional regulatory mechanisms for different genes are both complex and interconnected.

Animals↗

PubMed1989

Modulation of synaptic transmission in the rabbit coeliac ganglia by gastric and duodenal mechanoreceptors.

The involvement of duodenal and gastric mechanoreceptors in the modulation of synaptic transmission was investigated in a rabbit sympathetic prevertebral ganglion. The present study was performed in vitro on the coeliac plexus connected to the stomach and the duodenum. The electrical activity of ganglionic neurons was recorded using intracellular recording techniques. The patterns of synaptic activation of these ganglionic neurons in response to the activation of mechanoreceptors by gastric or duodenal distension were investigated. Although gastric or duodenal distension was unable to elicit any fast synaptic activity in ganglionic neurons, it produced either an inhibition or a facilitation of the fast nicotinic excitatory postsynaptic potentials elicited by stimulation of the thoracic splanchnic nerves. In addition, this distension triggered long-lasting (3-11 min) modifications in the electrical properties of the ganglionic neurons, i.e. slow depolarizations (6-18 mV) or slow hyperpolarizations (3-6 mV), which were sometimes associated with a decrease in the input membrane resistance. After cooling of the nerves connecting the coeliac ganglia to the stomach, the activation of gastric or duodenal mechanoreceptors was no longer able to modify the fast synaptic activation or the electrical properties of the ganglionic neurons. The results demonstrate that gastric and duodenal mechanoreceptors project onto neurons of the coeliac ganglia and change their excitability as well as the central inputs they receive. The long duration of these modifications suggests that gastric and duodenal mechanoreceptors can modulate the activity of the neurons of the coeliac ganglia.

Action Potentials↗

PubMed1989

Influence of increased pulmonary vascular pressures on the closure of the ductus arteriosus in newborn lambs.

Neonatal conditions associated with increased pulmonary artery pressure have an increased incidence of patent ductus arteriosus. We operated on 15 near term fetal lambs and placed mechanical occluders into or around both branch pulmonary arteries so that main pulmonary artery blood pressure could be controlled. The lambs were delivered and ventilated for 4 h. In seven lambs, the branch vessels were obstructed so that pulmonary artery pressure increased to equal aortic pressure; in eight lambs (control), the branch vessels were not obstructed. There were no significant differences between the two groups in circulating prostaglandin E2 or 6 keto F1 alpha concentrations, PaO2, pH, or PaCO2. Despite these similarities, ductus resistance in the lambs with elevated pulmonary pressure was significantly less than that in the control lambs. After the 4 h measurements, we studied the ductus in vitro. We have previously found that ductus arteriosus constriction produces ischemia of its muscle wall that limits its ability to dilate or constrict any further. Ductus from lambs with elevated pulmonary pressure had a significantly increased ability to respond to oxygen, prostaglandin E2, and indomethacin compared with ductus from control lambs; these findings are consistent with less ductus constriction in vivo. Thus, the high incidence of patent ductus arteriosus in neonates with elevated pulmonary vascular resistance may be due in part to the increased pulmonary vascular pressure, which opposes ductus constriction and preserves ductus responsiveness. Conversely, the normal drop in pulmonary pressure that occurs in full term infants may facilitate the closure of the ductus after delivery.

Animals↗

PubMed1989

Effect of acute umbilical cord compression on hepatic carbohydrate metabolism in the fetal lamb.

Although the liver plays a central role in glucose homeostasis in the adult, its importance in fetal glucose homeostasis during acute reductions of substrate delivery is unknown. To examine this, we studied eight fetal lambs at 121 +/- 2 d gestation. We placed catheters in the descending aorta, inferior vena cava umbilical vein and the left (n = 6) or right (n = 2) hepatic vein, and a balloon occluder around the umbilical cord. At least 4 d after surgery, before and during umbilical cord compression, we measured blood oxygen saturation, glucose, lactate, and Hb concentrations, and blood flows using the radiolabeled microsphere technique. Gluconeogenesis was assessed by infusion of [U14C]lactate. Reducing umbilical flow by 50-60% from a control value of 181 +/- 20 mL/min/kg (mean +/- SD) caused a dramatic decrease in hepatic blood flow from 332 +/- 99 to 94 +/- 77 mL/min/100 g (p less than 0.05). Oxygen delivery to the fetus fell by 50% and that to the liver by 73%. However, hepatic O2 consumption was maintained by increased extraction. Glucose delivery to the liver fell from 67 +/- 24 to 20 +/- 13 mg/min/100 g (p less than 0.001), but lactate delivery did not change. In spite of the maintenance of lactate delivery, net hepatic lactate uptake fell significantly from 3.3 +/- 1.7 to 1.4 +/- 0.9 mg/min/100 g (p less than 0.05). This could account, in part, for the increase of blood lactate concentration from 16 +/- 4 to 27 +/- 7 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Aortic balloon valvuloplasty.

Fifty-eight patients with severe aortic stenosis underwent successful aortic balloon valvuloplasty. The mean aortic valve gradient was reduced from 65 +/- 22 to 32 +/- 13 mmHg with symptomatic improvement. The procedure is an effective palliative procedure for patients with high surgical risk.

Aged↗

PubMed1989

Effect of cortisol on hepatic gluconeogenesis in the fetal sheep.

To determine whether the prenatal surge in cortisol induces the onset of gluconeogenesis in the fetal sheep, we performed studies in eight fetal sheep of 124 +/- 3 days gestational age. Catheters were inserted chronically in the descending aorta, inferior vena cava, and hepatic and umbilical veins, allowing the measurement of substrate flux across the liver and placenta. Cortisol was infused over a 48-h period, raising plasma cortisol concentrations from 3.5 +/- 2.5 ng/ml to 78 +/- 22 ng/ml at 24 h and 111 41 ng/ml at 48 h. At 24 and 48 h, [14C]lactate was infused into the inferior vena cava, and blood samples were obtained to measure plasma concentrations and specific activities of glucose and lactate. Comparison of the cortisol-treated group with an untreated control group of animals revealed no differences in blood gases, haemoglobin concentrations, or glucose and lactate levels. Similarly, there were no differences between groups in liver oxygen consumption, glucose and lactate flux, or gluconeogenesis from lactate. In two animals we demonstrated hepatic glucose production from lactate. One of these was in active labor at the time of study, and one aborted within hours of the study. We conclude that the prenatal cortisol surge alone is not responsible for the onset of hepatic gluconeogenesis in the perinatal period. However, cortisol may have a permissive action, promoting hepatic gluconeogenesis in response to other hormonal stimuli.

Animals↗

PubMed1988

Butyrate infusions in the ovine fetus delay the biologic clock for globin gene switching.

The switch from fetal to adult hemoglobin expression is regulated in many mammalian species by a developmental clock-like mechanism and determined by the gestational age of the fetus. Prolonging fetal globin gene expression is of considerable interest for therapeutic potential in diseases caused by abnormal beta-globin genes. Butyric acid, which is found in increased plasma concentrations in infants of diabetic mothers who have delayed globin gene switching, was infused into catheterized fetal lambs in utero during the time of the normal globin gene switch period. The globin gene switch was significantly delayed in three of four butyrate-treated fetuses compared with controls and was entirely prevented in one fetus in whom the infusion was begun before the globin switch was under way. These data provide a model for investigating and arresting the biologic clock of hemoglobin switching.

Animals↗

PubMed1988

Indomethacin and patent ductus arteriosus: effects on renal function in preterm lambs.

To examine the independent effects of a patent ductus arteriosus and of indomethacin therapy on the renal function of the preterm newborn, we created a preterm lamb model in which ductus diameter could be regulated. We studied 24 preterm newborn lambs. Eight lambs (group 1) had their ductus closed at delivery and received no indomethacin. Eight lambs (group 2) had their ductus closed and then received indomethacin (0.3 mg/kg) at 5.5 h; eight lambs (group 3) had their ductus kept open and then received indomethacin at 5.5 h. Hemodynamic and renal function measurements were made at 5 h (pretreatment) and at 12.5 h. In group 2 lambs there was a significant reduction in inulin clearance (GFR) and osmolal clearance after indomethacin. In contrast, lambs with an open ductus (group 3), when compared with lambs with a closed ductus (groups 1 and 2) at 5 h, already had significantly decreased blood pressure, GFR, urine volume, and osmolal clearance. Following indomethacin treatment, group 3 lambs showed no further decrease in renal function. We suggest that in preterm lambs with patent ductus, the apparent lack of renal dysfunction following indomethacin treatment reflects underlying diminished renal function.

Animals↗

PubMed1988

The role of beta-adrenoreceptor stimulation and contractile state in the preterm lamb's response to altered ductus arteriosus patency.

A model of patent ductus arteriosus in premature lambs was created to study the relative importance of beta-adrenoreceptor stimulation and increased myocardial contractility. In 39 fetal lambs (133 +/- 2, +/- SD days gestation, term 145 days), the ductus arteriosus was infiltrated with formalin, and a snare was placed around it to regulate its patency. One day later, the lambs were delivered, given sheep surfactant, paralyzed, and mechanically ventilated. Microsphere measurements of left ventricular output were made between 4 and 6 h after delivery. When the ductus was opened, there was no change in heart rate, but there were significant increases in left ventricular output, stroke volume, left ventricular end-diastolic pressure, and peak dP/dt. The increase in peak dP/dt due to opening the ductus was greater than that due to an increase in left ventricular end-diastolic pressure alone and was accompanied by an increase in norepinephrine secretion from the left ventricle. Propranolol (1 mg/kg) was used to evaluate the effect of beta-adrenergic tone on left ventricular output and contractility. The left atrium was paced in both control and propranolol-treated lambs. When the ductus was closed, propranolol significantly decreased stroke volume and peak dP/dt without changing left ventricular end-diastolic pressure or systemic vascular resistance. During a saline volume load (50 ml/kg over a 3-min period), propranolol-treated lambs had a reduced stroke volume and peak dP/dt despite similar values of left ventricular end-diastolic pressure and resistance as those of control lambs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗