National differences in screening programmes for cardiovascular risks could obstruct understanding of cardiovascular prevention studies in Europe.

INTRODUCTION: In North-West Europe, cardiovascular disease is still a major cause of death and despite several efforts (e.g. European guidelines and conferences) cardiovascular risk factors are still inconsistently diagnosed and treated. METHODS: We evaluated the first consultations of patients in two cardiovascular referral clinics in France and the Netherlands, while evaluating the differences in national guidelines and between the profiles of patients at their first consultation. RESULTS: Notable differences exist between the two locally used guidelines in their programmes of cardiovascular risk assessment and their definition of LDL-cholesterol target levels. With regard to the LDL-cholesterol levels, more patients are 'on target' when using the French guideline than when using the Dutch guideline. Evaluation of the patient's profile at first presentation showed that the LDL-cholesterol levels were significantly lower in the Dutch patients (n = 77) compared with the French patients (n = 119). Dutch patients used significantly more statins than French patients. CONCLUSION: Despite the small study population included in this study, we found that comparison of daily care (as part of a primary prevention programme) is rather difficult due to several national differences in the approach to patients. All these factors combined should be taken into account, when discussing and extrapolating results obtained from analysis of cardiovascular prevention programmes.

Plasma methionine enkephalin levels in the human newborn at birth.

Plasma met-enkephalin immunoreactivity (MET-ENKi) and catecholamine levels were measured in umbilibal cord blood from 46 healthy newborn infants. Clinical data including Apgar scores, birth weight, gestational age, route of delivery, fetal heart tracings and arterial blood gas values were also obtained. Thirty-nine infants were delivered by the vaginal route. All but 1 infant delivered by cesarian section had undergone a trial of labor. Plasma MET-ENKi in the newborn infants was markedly greater than levels found in healthy adult volunteers: 360 +/- 25 versus 25 +/- 2 pg/ml, respectively. MET-ENKi levels were similar in umbilical arterial and umbilical venous blood, and in infants delivered vaginally or by cesarian section.

Pulmonary clearance of norepinephrine in lambs.

The lungs play an important role in the metabolism of vasoactive substances including endogenous amines. The role of pulmonary clearance of circulating norepinephrine has not been well defined in the young lamb (7-8 d of age). Using radiolabeled tracer norepinephrine in acutely instrumented lambs, we determined the in vivo pulmonary clearance and spillover rate of norepinephrine under baseline and hypoxic conditions. The fractional extraction of norepinephrine, the percent removed on a single pass through the pulmonary circulation, was 23 +/- 2%. The corresponding pulmonary clearance rate was 61 +/- 10 mL/kg/min and the net pulmonary norepinephrine removal rate was 0.41 +/- 0.14 nmol/kg/min. This clearance represented over 70% of whole body norepinephrine clearance. The spillover of synaptic norepinephrine was 0.22 +/- 0.13 nmol/kg/min. During hypoxia, animals showed significant increases in pulmonary artery pressure and resistance. Fractional extraction and norepinephrine decreased to 16 +/- 3%, p less than 0.005. Pulmonary clearance decreased to 31 +/- 7 mL/kg/min, and net pulmonary norepinephrine removal rate decreased to 0.27 +/- 0.07 nmol/kg/min. These results demonstrate that pulmonary clearance plays a significant role in norepinephrine clearance in 1-wk-old lambs. Alteration of norepinephrine clearance during physiologic states such as hypoxia may be important in the pathophysiology of altered pulmonary vascular resistance in newborn animals.

Neonatal adaptation: cardiac adrenergic effector mechanisms after birth in newborn sheep.

At birth, there is a marked increase in circulating plasma catecholamine concentrations. This increase is critical to many of the physiologic adjustments to postnatal life. Because the levels observed are higher than those seen in most other physiologic conditions in adults, previous investigators have suggested that the newborn is less sensitive to adrenergic stimulation or that desensitization to adrenergic stimulation occurs rapidly. To investigate this question, we designed experiments to measure myocardial beta-adrenergic receptor density and sensitivity before and after exposure to the catecholamine surge at birth in term newborn sheep. We also measured the status of sympathetic innervation, reflected by myocardial norepinephrine content. At birth, plasma catecholamines increased 4- to 6-fold with associated increases in heart rate, blood pressure, and cardiac output. Myocardial beta-adrenergic receptor at birth (135 fmol/mg protein) did not change significantly by 6 h of life (157 fmol/mg protein). Myocardial adenyl cyclase activity, reflecting receptor sensitivity, and myocardial sympathetic innervation also did not change. These results suggest that, despite exposure to sustained adrenergic stimulation, myocardial adrenergic effector mechanisms do not change in the newborn sheep at birth.

Fetal catecholamine responses to maternal hypoglycemia.

The present studies were designed to determine the fetal catecholamine and metabolic responses to insulin-induced maternal hypoglycemia. Maternal hypoglycemia was induced by a primed constant infusion of insulin and glucose administered to pregnant ewes to maintain maternal glucose at 20-25 mg/dl. Maternal and fetal samples for measurement of catecholamine, glucose, and free fatty acid levels and arterial blood gas analysis were collected before insulin infusion and at intervals thereafter for 6 h. Maternal and fetal plasma catecholamine levels increased significantly in response to hypoglycemia (analysis of variance, P less than 0.01). Fetal insulin and glucagon levels did not change despite a 50% reduction in fetal whole blood glucose concentration. Fetal free fatty acid levels increased significantly during hypoglycemia (P less than 0.05). There were no significant changes in maternal or fetal heart rate, blood pressure, or arterial blood gases during hypoglycemia. These results suggest that the fetus is capable of responding to hypoglycemia with an increase in catecholamine and free fatty acid levels. These results are consistent with the interpretation that the fetus is able to mobilize alternative energy substrates in response to maternal insulin-induced hypoglycemia.

The effects of hypoxia on (methionine) enkephalin peptide and catecholamine release in fetal sheep.

The effect of hypoxia on plasma met-enkephalin and catecholamine levels was studied in chronically catheterized fetal sheep. Maternal and fetal hypoxia was maintained for 20 min. We found hypoxia significantly increased the plasma levels of large mol wt met-enkephalin containing peptides from 1755 +/- 229 pg/mL during baseline to 4408 +/- 1426 pg/mL by 15 minutes of hypoxia. The levels of the met-enkephalin pentapeptide were unchanged during hypoxia from a baseline value of 168 +/- 56 pg/mL. Norepinephrine and epinephrine levels increased 5- and 10-fold, respectively, by 15 min of hypoxia. These observations suggest cosecretion of the large mol wt met-enkephalin peptides with catecholamines during stress in developing animals.

Free and sulfoconjugated catecholamine responses to hypoxia in fetal sheep.

Plasma catecholamines circulate either in conjugated or unconjugated forms. In adult humans, sulfoconjugated catecholamines predominate; however, there is considerable variation between species. In a variety of pathophysiological states catecholamine conjugation is believed to represent an important mechanism of inactivation of high circulating catecholamine levels. To date, there have been few data in developing animals or humans on catecholamine sulfoconjugation. We studied the differences in free and sulfoconjugated catecholamines in full term (141 +/- 1 days) and preterm (123 +/- 1 days) chronically catheterized fetal sheep and determined the changes in free and sulfoconjugated catecholamines in response to hypoxia. The results demonstrate that term and preterm animals have a comparable percentage of basal circulating sulfoconjugated catecholamines (free-to-total ratio 50-60%). In response to hypoxia, both free and sulfoconjugated catecholamines were promptly elevated with significant increases in each by 5 min of hypoxia. This was true for both term and pretern animals. The proportion of free and total catecholamines remained relatively constant during hypoxia despite a 5- to 10-fold increase in circulating levels of each. These data demonstrate that fetal sheep, as early as 80% gestation, have a well developed mechanism for sulfoconjugation and subsequent inactivation of the high circulating levels of catecholamines seen during fetal and newborn life.