Biomedical subjects

C Roman

Publications and source records attributed to C Roman.

At least 19 recordsLinked to original sources

PubMed2005

Fecal tumor necrosis factor-alpha and calprotectin as differential diagnostic markers for severe diarrhea of small infants.

OBJECTIVE: The etiology of early-onset diarrhea of neonates and small infants that persists despite bowel rest is heterogeneous. Two different categories of disorders presenting with diarrhea in the first weeks of life can be distinguished: constitutive intestinal epithelial disorders (microvillus atrophy [MVA] or epithelial dysplasia [ED]) and immune-inflammatory disorders, (autoimmune enteropathy [AIE] or inflammatory colitis [IC]). We aimed to evaluate in a prospective manner the use of fecal inflammatory markers in the differential diagnosis of severe persistent diarrhea. MATERIAL AND PATIENTS: Twenty-five patients (17 males) were enrolled in this study (median age 8 months). Fourteen children had a constitutive enterocyte disorder (group 1: MVA = 8, ED = 6), and 11 patients had an immuno-inflammatory disease (group 2: AIE = 5, IC = 6). Stool samples were collected at the time of diagnosis and stored at -80 degrees until tumor necrosis factor (TNF)-alpha and calprotectin were measured by enzyme-linked immunoadsorbent assay. RESULTS: No significant differences in age at onset of diarrhea or in stool volumes were observed between both groups. In group 1, fecal TNF-alpha was undetectable/normal in 14 of 14 children, whereas group 2 showed dramatically elevated TNF-alpha levels (mean 3,104, range 237-18,078 pg/g) in 8 of 11 patients. Similarly, calprotectin levels were undetectable/normal in 14 of 14 patients in group 1 and highly raised in 11 of 11 patients in group 2 (median 1,145, range 375-3,095 mug/g), P < 0.01. Under therapy, these inflammatory parameters normalized. CONCLUSIONS: Determination of fecal inflammatory markers is a simple method helping to distinguish constitutive from immuno-inflammatory etiologies of severe persistent diarrhea. These data also suggest that constitutive enterocyte disorders are not accompanied by an inflammatory mucosal reaction.

Age of Onset↗

PubMed2001

Fructose- 1,6-bisphosphate did not affect hippocampal neuronal damage caused by 10 min of complete umbilical cord occlusion in fetal sheep.

Fructose-1, 6-bisphosphate (FBP) has a neuroprotective effect in neonatal and adult rats. The purpose of this study was to examine the effects of FBP on hippocampal neuronal damage in fetal sheep asphyxiated by 10 min of complete umbilical cord occlusion. Thirteen fetal sheep at 124 days of gestation were surgically instrumented with catheters. Cardiorespiratory parameters were monitored, and biochemical analyses were performed with the blood samples. During the insult seven fetuses were given FBP (500 mg/kg) and six were given iso-osmotic saline, and hippocampal neuronal damage was examined histologically and scored. Cardiorespiratory changes were the same in both groups, and there was no neuroprotective effect of FBP in this study. However the decrease of serum total Ca level implied the Ca- chelating effect of FBP.

Animals↗

PubMed2001

In utero remodeling of the fetal lamb ductus arteriosus: the role of antenatal indomethacin and avascular zone thickness on vasa vasorum proliferation, neointima formation, and cell death.

BACKGROUND: The ductus arteriosus (DA) of newborn infants exposed in utero to indomethacin is resistant to postnatal indomethacin; we hypothesized that this is due to ductus constriction in utero, with subsequent remodeling of the vessel. METHODS AND RESULTS: Infusion of fetal lambs with indomethacin for 48 hours constricted the DA and increased the thickness of the avascular zone of the DA, which in turn induced the expression of vascular endothelial growth factor, endothelial nitric oxide synthase (due to ingrowth of vasa vasorum), neointima formation, and loss of smooth muscle cells; moderate degrees of DA constriction in utero increased NO production, which inhibited DA contractility. Marked degrees of DA constriction decreased tissue distensibility and contractile capacity. CONCLUSIONS: DA patency is no longer controlled primarily by prostaglandins once it has been exposed to indomethacin in utero.

6-Ketoprostaglandin F1 alpha↗

PubMed2001

TGF-beta and colorectal carcinogenesis.

There is substantial evidence to support the contention that the Smad portion of the TGF-beta signal transduction pathway provides an important tumor-suppressor function. Mutational loss of function of Smad pathway members have been associated with the development of human cancers and appear to be causative in selected rodent carcinogenesis models. TGF-beta also has multiple other actions that appear to be independent of the growth-inhibitory/tumor suppressor effects. The predominant effect of TGF-beta appears to be dependent on the context of the responding cell. Once transformation has occurred, TGF-beta effects may be detrimental and may actually promote tumor cell survival, invasion, and metastasis. Recent work suggests that these effects may involve TGF-beta regulation of COX-2 and other pathways that may contribute to tumor cell aggressiveness. In gaining a better understanding of the mechanisms by which TGF-beta may promote tumor progression, it is likely that new therapeutic strategies may be developed that preserve tumor-suppressor function of TGF-beta while inhibiting the tumor-promoting effects.

Adenoma↗

PubMed2001

LY393615, a novel neuronal Ca(2+) and Na(+) channel blocker with neuroprotective effects in models of in vitro and in vivo cerebral ischemia.

In the present studies we have examined the effects of a new calcium channel blocker, LY393615 ((N-Butyl-[5,5-bis-(4-fluorophenyl)tetrahydrofuran-2-yl]methylamine hydrochloride, NCC1048) in a model of hypoxia-hypoglycaemia in vitro and in a gerbil model of global and in two rat models of focal cerebral ischaemia in vivo. Results indicated that LY393615 protected against hypoxia-hypoglycaemic insults in brain slices and also provided significant protection against ischaemia-induced hippocampal damage in gerbil global cerebral ischaemia when dosed at 10, 12.5 (P<0.05) or 15 mg/kg i.p. (P<0.01) 30 min before and 2 h 30 min after occlusion. The compound penetrated the brain well after a 15 mg/kg i.p. dose and had a half-life of 2.5 h. In further studies LY393615 was protective 1 h post-occlusion when administered at 15 mg/kg i.p. followed by 2 doses of 5 mg/kg i.p. 2 and 3 h later. LY393615 dosed at 15 mg/kg i.p. followed by 2 further doses of 5 mg/kg i.p. (2 and 3 h later) also produced a significant reduction in the infarct volume following Endothelin-1 (Et-1) middle cerebral artery occlusion in the rat when administration was initiated immediately (P<0.01) or 1 h (P<0.05) after occlusion. The compound was also evaluated in the intraluminal monofilament model of focal ischaemia. The animals had the middle cerebral artery occluded for 2 h, and 15 min after reperfusion LY393615 was administered at 15 mg/kg i.p. followed by 2 mg/kg/h i.v. infusion for 6 h. There was no reduction in infarct volume using this dosing protocol. In conclusion, in the present studies we have reported that a novel calcium channel blocker, LY393615, with good bioavailability protects against neuronal damage caused by hypoxia-hypoglycaemia in vitro and both global and focal cerebral ischaemia in vivo. The compound is neuroprotective when administered post-occlusion and may therefore be a useful anti-ischaemic agent.

Animals↗

PubMed2001

Factors that increase the contractile tone of the ductus arteriosus also regulate its anatomic remodeling.

Permanent closure of the full-term newborn ductus arteriosus (DA) occurs only if profound hypoxia develops within the vessel wall during luminal obliteration. We used fetal and newborn baboons and lambs to determine why the immature DA fails to remodel after birth. When preterm newborns were kept in a normoxic range (Pa(O(2)): 50-90 mmHg), 86% still had a small patent DA on the sixth day after birth; in addition, the preterm DA wall was only mildly hypoxic and had only minimal remodeling. The postnatal increase in Pa(O(2)) normally induces isometric contractile responses in rings of DA; however, the excessive inhibitory effects of endogenous prostaglandins and nitric oxide, coupled with a weaker intrinsic DA tone, make the preterm DA appear to have a smaller increment in tension in response to oxygen than the DA near term. We found that oxygen concentrations, beyond the normoxic range, produce an additional increase in tension in the preterm DA that is similar to the contractile response normally seen at term. We predicted that preterm newborns, kept at a higher Pa(O(2)), would have increased DA tone and would be more likely to obliterate their lumen. We found that preterm newborns, maintained at a Pa(O(2)) >200 mmHg, had only a 14% incidence of patent DA. Even though DA constriction was due to elevated Pa(O(2)), obliteration of the lumen produced profound hypoxia of the DA wall and the same features of remodeling that were observed at term. DA wall hypoxia appears to be both necessary and sufficient to produce anatomic remodeling in preterm newborns.

6-Ketoprostaglandin F1 alpha↗

PubMed2001

Case reports. Six cases of infection due to Trichophyton verrucosum.

Dermatophyte infections due to Trichopkyton verrucosum are not frequent in Europe. Six cases observed in Italy in the period 1995-99 are reported. Two were cases of tinea barbae, two of tinea corporis and two of tinea capitis, one of which had been preceded by tinea faciei. In three cases the source of contagion was horses, in two it was cattle and in one case it was another person. The two cases of tinea barbae were initially interpreted and treated as bacterial infections, a diagnostic error reported with increasing frequency in the literature regarding dermatophytosis due to T. verrucosum.

Adolescent↗

PubMed2000

Effects of lingual nerve afferents on swallowing in sheep.

We investigated in sheep the effects of stimulation of the thick afferent fibers running through the lingual nerve (LN) upon the activity of some of the muscles and medullary interneurons or motoneurons which are active during swallowing. Using electromyography (EMG), and extra- and intracellular neuronal recording, we demonstrated that LN stimulation inhibited triggering and/or distal progression of deglutition reflexly induced by stimulation of the superior laryngeal nerve (SLN). This inhibition appeared as a delay, or the interruption or total suppression, of the EMG and neuronal swallowing activities, depending on the interval between SLN and LN stimulation. It was apparent at the level of the muscles and motoneurons of the nucleus ambiguus, as well as at the level of the interneurons of the dorsal medulla within or around the nucleus of solitary tract, which are assumed to be the core of the organizing system for swallowing, the so-called central pattern generator (CPG). Taking into account the stimulation parameters used in our experiments, it was likely that only LN-mechanosensitive fibers were excited. These fibers were involved in the jaw-opening reflex, and possibly in mastication regulation. Therefore, inhibition of swallowing could result from interactions between the hindbrain mastication and swallowing CPGs. However, it was also possible that mechanosensitive afferents acted upon the swallowing CPG directly or indirectly through supramedullary, especially cortical, loops.

Afferent Pathways↗

PubMed2000

How do types of employment relate to health indicators? Findings from the second European survey on working conditions.

STUDY OBJECTIVE: To investigate the associations of various types of employment with six self reported health indicators, taking into account the part played by demographic variables, individual working conditions and four ecological indicators at the country level. DESIGN: Cross sectional survey (structured interview) of a sample of the active population of 15 European countries aged 15 years or over. Main independent variables were nine types of employment categorised as follows: small employers, full and part time permanent employees, full and part time fixed term employees, full and part time sole traders and full and part time temporary contracts. Main outcome measures were three self reported health related outcomes (job satisfaction, health related absenteeism, and stress) and three self reported health problems (overall fatigue, backache, and muscular pains). Logistic regression and multilevel models were used in the analyses. SETTING: 15 countries of the European Union. PARTICIPANTS: 15 146 employed persons aged 15 or over. MAIN RESULTS: Precarious employment was consistently and positively associated with job dissatisfaction but negatively associated with absenteeism and stress (as compared with full time permanent workers). Fatigue, backache and muscular pains also tended to be positively associated with precarious employment, particularly with full time precarious employment. Small employers reported high percentages of stress and fatigue, but absenteeism was relatively low. Sole traders generally reported high percentages of all outcomes, except for absenteeism, which was low. For each type of employment (except temporary contracts), full time workers tended to report worse health outcomes than part time workers. Patterns were generally consistent across countries. Associations persisted after adjustment for individual level working conditions and were not modified by country level variables. CONCLUSIONS: This study is the first to examine the relations between various types of employment and six health related indicators for all 15 member states of the European Union. Suggestive patterns worthy of further exploration have been found. Standardised definitions of types of underemployment and health related outcomes, more potent epidemiological designs and the inclusion of socioeconomic information (for example, social security systems, incapacity benefit schemes) at the regional level are proposed for inclusion in further research.

Adolescent↗

PubMed2000

Mechanisms of calcitonin gene-related peptide-induced increases of pulmonary blood flow in fetal sheep.

Fetal pulmonary blood flow is regulated by various vasoactive substances. One, calcitonin gene-related peptide (CGRP), increases pulmonary blood flow. We examined four key physiological mechanisms underlying this response using the blocker drugs CGRP receptor blocker (CGRP(8-37)), nitric oxide synthase inhibitor [N(omega)-nitro-L-arginine (L-NNA)], adenosine triphosphate-dependent potassium (K(ATP)) channel blocker (glibenclamide), and cyclooxygenase inhibitor (indomethacin) in 17 near-term fetal sheep. Catheters were placed in the left (LPA) and main pulmonary arteries, and an ultrasonic flow transducer was placed around the LPA to measure flow continuously. CGRP was injected directly into the LPA (mean 1.02 microgram/kg) before and after blockade, and responses to CGRP were statistically compared. Before blockade, CGRP increased LPA blood flow from 23 +/- 25 to 145 +/- 77 ml/min (means +/- SD), and these increases were significantly attenuated by CGRP(8-37) (n = 6; 91% inhibition), L-NNA (n = 6; 86% inhibition), and glibenclamide (n = 6; 69% inhibition). No significant changes were found with indomethacin (n = 6; 4% inhibition). Thus, in the fetal pulmonary circulation, CGRP increases pulmonary blood flow not only through its specific receptor but also, in part, through nitric oxide release and K(ATP) channel activation.

Adenosine Triphosphate↗

PubMed2000

Cyclooxygenase-2 inhibitors constrict the fetal lamb ductus arteriosus both in vitro and in vivo.

Nonselective cyclooxygenase (COX) inhibitors are potent tocolytic agents; however, they also have adverse fetal effects such as constriction of the fetal ductus arteriosus. Recently, selective COX-2 inhibitors have been used in the management of preterm labor in the hope of avoiding fetal complications. However, both COX-1 and -2 are expressed by cells of the ductus arteriosus. We used fetal lambs (0.88 gestation) to assess the ability of selective COX-2 inhibitors celecoxib and NS398 to affect the ductus arteriosus. Both selective COX-2 inhibitors decreased PGE(2) and 6ketoPGF(1alpha) production in vitro; both inhibitors constricted the isolated ductus in vitro. The nonselective COX-1/COX-2 inhibitor indomethacin produced a further reduction in PG release and an additional increase in ductus tension in vitro. We used a prodrug of celecoxib to achieve 1.4 +/- 0.6 microg/ml, mean +/- standard deviation, of the active drug in vivo. This concentration of celecoxib produced both an increase in pressure gradient and resistance across the ductus; celecoxib also decreased fetal plasma concentrations of PGE(2) and 6ketoPGF(1alpha). Indomethacin (0.7 +/- 0.2 microg/ml) produced a significantly greater fall in ductus blood flow than celecoxib and tended to have a greater effect on ductus resistence in vivo. We conclude that caution should be used when recommending COX-2 inhibitors for use in pregnant women, because COX-2 appears to play a significant role in maintaining patency of the fetal ductus arteriosus.

6-Ketoprostaglandin F1 alpha↗

PubMed1999

Stimulation of the chewing area of the cerebral cortex induces inhibitory effects upon swallowing in sheep.

Mastication and swallowing are two tightly integrated components of food intake behavior. We investigated the effects of stimulating the chewing area of the fronto-orbital cortex (CCx) on some muscles and medullary interneurons (Ins) or motoneurons (Mns) active during swallowing. For the purpose of comparison, the lingual nerve (LN) was also stimulated during the experiments. Electromyography (EMG) and extracellular neuronal recording were used, and swallowing was reflexly induced (RIS) by stimulation of the superior laryngeal nerve (SLN). RIS was almost totally abolished during long-lasting repetitive stimulation of CCx or LN, and was strongly facilitated after stimulation cessation. Short-duration stimulation (one or a few pulses) of both the CCx and LN also inhibited triggering of deglutition when delivered just before the onset of RIS. This inhibition appeared as a delay or total suppression of the EMG and neuronal swallowing activities. It was obvious at the level of the muscles, the hypoglossal Mns and the premotoneurons (PMns; Ins of the ventral medulla near the nucleus ambiguus), as well as at the level of the Ins of the dorsal medulla (within or around the solitary tract nucleus) which are assumed to be the core of the 'central pattern generator' (CPG) for swallowing. In addition to the 'chewing-related inhibition', many ventral Ins exhibited a short latency synaptic activation after CCx and/or LN stimulation. Therefore, these Ins may play a pivotal role for reflex or cortical fast control of tongue (and jaw) muscles, and for coordinating their contractions in the context of mastication-deglutition interactions.

Animals↗

PubMed1999

[Partial inpatient cardiologic after-care].

In Germany the in-hospital rehabilitation of patients with cardiac diseases is standard. Especially because of criticism of effectiveness and wasting of resources we evaluated in a pilot study a rehabilitation program with an in-hospital start, followed facultatively on ambulatory basis at the same institution, at the cardiac rehabilitation clinic. The aims of the study were to find out the acceptance of the the program by the patients, the safety and the impact of the facultative ambulatory rehabilitation program on cardiovascular risk factors. From January 1993 to December 1995 the primary enclosing criteria (cardiac disease suitable for rehabilitation, age < 70 years, lodging < 40 km) were fulfilled by 612 patients, 122 female. 268 (43.8%) were disclosed on medical grounds because of the rigid pilot character of the study, for 74 (12.1%) patients was the participation on organisational grounds not possible. Sixty-six of the remaining 270 patients preferred the facultative continuation of the rehabilitation on ambulatory basis for 1 or 2 weeks, the entire rehabilitation lasting up to 4 weeks. During the ambulatory phase the patients slept at home, otherwise these patients followed the same procedure as the in-hospital participants. Despite of severe medical concerns 4 further patients wished to participate on facultative ambulatory continuation of the rehabilitation, among these were 2 women, only 5 of the total 70 patients of the facultative ambulatory program group being female. There were no significant differences among 24 patients with CAD of both groups during the rehabilitation and in a control after 14.8 months (Table 3). The impact on serum total cholesterol and LDL cholesterol was positive (Table 2), albeit after 14.8 months no more significant. Over the control period there were a negative development of serum triglyceride level and significant negative effects on the body weight. There were no complications among the 66 patients during the facultative ambulatory phase of the rehabilitation, in contrast to those 37 of 268 patients who had to be disclosed because of medical concerns (Table 1). During the rehabilitation the drug therapy was optimized for many participants. The control after 14.8 months revealed that these remedies were followed with great accuracy by the physicians at home (Figure 1). In conclusion, a cardiac rehabilitation program with an in-hospital start of 2 weeks, going over to ambulatory rehabilitation for 1 to 2 weeks, is as effective and safe as an in-hospital cardiac rehabilitation. As known, amelioration of the long-term results has yet to be achieved.

Adult↗

PubMed1999

Effects of nitroglycerin and indomethacin on fetal-maternal circulation and on fetal cerebral blood flow and metabolism in sheep.

OBJECTIVE: Our purpose was to evaluate the effects of maternal administration of nitroglycerin and indomethacin on maternal and fetal hemodynamics and on fetal cerebral blood flow and metabolism in sheep. STUDY DESIGN: Invasive vascular and fetal carotid flow monitoring was established in 12 gravid ewes. Isotonic sodium chloride solution, nitroglycerin, and indomethacin were infused maternally, and maternal and fetal heart rate, blood pressure, blood gas values, fetal carotid blood flow, and flow variability were measured. Fetal cerebral uptake of oxygen, glucose, and lactate were calculated. RESULTS: Nitroglycerin infusion caused a significant increase in maternal and fetal heart rate and a significant decrease in maternal and fetal mean arterial pressure at a dosage of 10 microram/kg per minute, without a change in blood gas values. Neither drug had any effect on fetal carotid blood flow, flow variability, or cerebral substrate metabolism. CONCLUSION: Maternal administration of nitroglycerin and indomethacin caused no adverse maternal or fetal circulatory changes and did not alter fetal carotid blood flow or substrate metabolism.

Animals↗

PubMed1999

Mechanisms of adrenomedullin-induced increase of pulmonary blood flow in fetal sheep.

Mechanisms of adrenomedullin-induced increases in fetal pulmonary blood flow were examined in 19 near-term fetal sheep using four key blocker drugs: nitric oxide synthase inhibitor (N(omega)-nitro-L-arginine), calcitonin gene-related peptide (CGRP) receptor blocker, ATP-dependent potassium (K(ATP)) channel blocker (glibenclamide), and cyclooxygenase inhibitor (indomethacin). Catheters were inserted into the left pulmonary artery and superior vena cava to administer drugs and into the main pulmonary and carotid arteries to measure pressures and heart rate. An ultrasonic flow transducer was placed around the left pulmonary artery to measure flow continuously. Adrenomedullin (mean 1.06 microg/kg) was injected into the left pulmonary artery before and after infusion of N(omega)-nitro-L-arginine (mean 96.5 mg/kg, n = 6), glibenclamide (mean 11.8 mg/kg, n = 6), CGRP receptor blocker (mean 312.0 microg/kg, n = 6), and indomethacin (mean 1.7 mg/kg, n = 8). Blockade was confirmed by appropriate agonist injection. The adrenomedullin-induced response in left pulmonary artery blood flow was inhibited by N(omega)-nitro-L-arginine (inhibition rate 99%) and significantly attenuated by glibenclamide (inhibition rate 44%); however, no significant changes were found with CGRP receptor blocker or indomethacin (inhibition rate 0 and 17%, respectively). The responses of the main pulmonary and carotid arterial pressures were similarly affected by those blockers. Our data suggest that in the fetal pulmonary circulation, the adrenomedullin-induced increase in pulmonary blood flow depends largely on nitric oxide release and partly on K(ATP) channel activation, and does not involve the CGRP receptor or a cyclooxygenase-mediated mechanism.

Adrenomedullin↗

PubMed1999

Effect of beta-adrenergic stimulation on oxygen metabolism in the fetal lamb.

Catecholamines, which are released into the circulation during stress, increase fetal metabolism. This effect appears to be related to beta-adrenoreceptor stimulation. We examined the effect of isoproterenol infusion on umbilical blood flow, oxygen delivery and consumption, and glucose and lactate uptake in late-gestation fetal lambs. Isoproterenol increased umbilical blood flow, but oxygen delivery to the fetus did not increase. Umbilical venous oxygen content fell linearly with the increase in umbilical blood flow. It is proposed that oxygen delivery to the sheep fetus is at or near a maximum and that oxygen delivery cannot be raised by increasing umbilical blood flow because oxygen diffusion at the placental site is limited. Fetal oxygen consumption increased initially but returned to control levels with an increase in infusion rate. Blood glucose concentration increased during isoproterenol infusion; this was due to release of glucose and not because of increased placental uptake. Fetal blood pH values fell in association with elevated lactate levels. It is proposed that elevated glucose concentrations resulted in increased metabolism of glucose, and because oxygen delivery could not be enhanced, increased anaerobic glycolysis caused lactate concentration to rise.

Animals↗

PubMed1999

Perinatal myocardial DNA and protein changes in the lamb: effect of cortisol in the fetus.

Myocardial growth during fetal life is accomplished by proliferation of the number of myocytes (hyperplasia). Shortly after birth, normal growth of the heart is predominantly due to increase in cell size (hypertrophy), and myocytes largely lose the capability to replicate. This change is characterized by a decrease in myocardial DNA concentration and an increase in protein/DNA concentration ratio. Among many of the events associated with birth is an increase in plasma cortisol concentrations in the few days before delivery of the fetus. To determine the possible role of cortisol in the postnatal change in myocardial growth, we measured DNA and protein concentrations in the free walls of the left (LV) and right (RV) ventricles in normal fetal lambs, normal newborn lambs, and in fetal lambs in which cortisone was infused for 72-80 h into the left coronary artery, which we showed does not perfuse the RV free wall. Normally, fetal RV DNA is higher than LV DNA concentration, and DNA/protein ratio is lower in RV than in LV. It is suggested that this could be related to the greater load on the RV. Postnatally, protein concentrations increase progressively, but DNA remains the same in both ventricles, and protein/DNA ratios increase. Cortisol, infused to achieve normal prenatal levels in LV myocardium, markedly decreases LV DNA without affecting RV DNA concentrations. The present study indicates that cortisol inhibits myocyte replication and that cortisol simulates the change in myocardial growth pattern normally occurring after birth. It raises concerns regarding prenatal administration of glucocorticoids to mothers to mature the fetal lungs before preterm delivery.

Animals↗

PubMed1998

Calcitonin gene-related peptide increases pulmonary blood flow in fetal sheep.

Calcitonin gene-related peptide (CGRP) may play a role in regulation of pulmonary vascular tone in adults. We set out to establish whether or not CGRP has any effect on the fetal pulmonary circulation. Hemodynamic effects of exogenous CGRP were studied in seven near-term fetal sheep. Single CGRP injections into left pulmonary artery (LPA), compared with acetylcholine, and five repeated CGRP injections were studied. Single CGRP injections (1.36 +/- 0.13 micrograms/kg) increased LPA blood flow (transit time ultrasound) significantly, from 26 +/- 22 to 202 +/- 86 ml/min (P < 0.05), and decreased pulmonary and aortic pressures, from 58 +/- 5 to 48 +/- 6 mmHg and from 56 +/- 3 to 46 +/- 5 mmHg, respectively (P < 0.05). LPA resistance decreased from 3.69 to 0.24 mmHg.min.ml-1 (P < 0.05). These changes were similar to those with acetylcholine. Five CGRP injections at 5-min intervals increased LPA flow significantly, in stepwise fashion, and LPA resistance decreased. Heart rate increased stepwise, without changes in pulmonary or carotid arterial pressures. Exogenous CGRP is a potent pulmonary vasodilator in fetal sheep and increases pulmonary flow. CGRP-induced increases in heart rate are not secondary to decreased systemic blood pressure but reflect a positive chronotropic effect. These findings suggest a role for endogenous CGRP in the remarkable decrease in pulmonary vascular resistance during the transition to extrauterine life.

Acetylcholine↗