Vascular 5-HT1-like receptors mediating vasoconstriction and vasodilatation: their characterization and distribution in the intact canine cardiovascular system.

1. In anaesthetized dogs, intra-left atrial administration of 5-hydroxytryptamine (5-HT) and selected tryptamine analogues (5-carboxamidotryptamine, 5-CT; 5-methyl tryptamine, 5-MT; alpha-methyl 5-hydroxytryptamine, alpha-HT; sumatriptan, Sum) in the presence of ketanserin and MDL72222 (5-HT2 and 5-HT3 receptor antagonists, respectively), produced dose-related changes in carotid, coronary and renal vascular conductance mediated by vascular 5-HT1-like receptors. 2. In the carotid vascular bed, 5-HT, 5-MT, alpha-HT and Sum were vasoconstrictors with a rank order of potency (comparing ED50 values) of 5-HT = Sum > 5-MT > alpha-HT. By contrast in this vascular bed, 5-CT was a potent vasodilator. 3. In the coronary vascular bed, 5-HT, 5-CT, 5-MT and alpha-HT were vasodilators with a rank order of potency (comparing ED50 values) of 5-CT > 5-HT > 5-MT > alpha-HT. In this vascular bed, Sum was without effect. 4. In the renal vascular bed, 5-HT, 5-CT, 5-MT, alpha-HT and Sum were vasoconstrictors with a rank order of potency (comparing ED50 values) of 5-CT > 5-HT > Sum > 5-MT > alpha-HT. 5. The coronary (and carotid) vasodilator responses to 5-CT were antagonized by the 5-HT1-like receptor antagonists, spiperone (1 mg kg-1) and methiothepin (0.1 mg kg-1), whereas the renal vasoconstrictor responses to this tryptamine analogue were antagonized only by methiothepin. 6. It is concluded from these studies that agonist finger-printing in vivo, using tryptamine analogues,identifies and confirms the functional presence of at least two pharmacologically distinct subtypes of the 5-HT1-like receptor in the intact canine cardiovascular system. These two subtypes are located on the vascular smooth muscle and mediate direct vasoconstriction and vasodilatation responses in vivo.7. In addition, these studies confirm that the distribution of these subtypes within the major vascular beds, shows a marked heterogeneity. The carotid vascular responses to the tryptamine analogue sindicate the presence of both the vasodilator and the vasoconstrictor subtypes. The coronary vascular responses to these analogues are, however, consistent with presence of the vasodilator subtype, only. By contrast, the renal vascular responses to these analogues indicates only the presence of the vasoconstrictor subtype.

Historical perspectives of neonatal transport.

A personalized view of the growth and development of neonatal transport is presented. The public display of premature infants in France and Germany and the beginning of the transport incubators in Chicago are explained. How the policy of regionalization was developed and diluted during the readjustment phase is discussed.

The effects of combined angiotensin converting enzyme inhibition and beta-adrenoceptor blockade on plasma renin activity in anaesthetized dogs.

1. The effects of beta-adrenoceptor blockade on the changes in plasma renin activity (PRA) following angiotensin enzyme (ACE) inhibition were investigated in pentobarbitone-chloralose anaesthetized dogs. 2. ACE-inhibition, with enalapril (2 mg kg-1), caused a significant reduction in systemic arterial blood pressure (BP) with little or no effect on cardiac function, and a significant elevation of plasma renin activity (PRA). By contrast beta-adrenoceptor blockade with atenolol (1 mg kg-1), caused a similar reduction in BP but in addition, significantly reduced cardiac function and PRA. 3. A combination of enalapril with atenolol, caused a significant reduction in BP, cardiac function and PRA, hence there was no elevation of PRA, as was seen following ACE-inhibition with enalapril alone. 4. The observations with beta-adrenoceptor blockade alone, show that there is an important homeostatic role for the renal sympathetic innervation, mediated by beta-adrenoceptors, in controlling basal renin levels. Furthermore, the renal sympathetic innervation appears to be an important contributor to the renin release caused by an ACE-inhibitor as the additional presence of a beta-adrenoceptor blocking agent will prevent this release. 5. BW B385C (2 mg kg-1), which combines both ACE-inhibition and beta-adrenoceptor blocking properties, also produced reductions in BP and cardiac function similar to those seen with the enalapril/atenolol combination. In addition, for an equivalent degree of ACE-inhibition by BW 385C, to that seen with enalapril alone, the elevation of PRA was attenuated. 6. A combination of ACE-inhibition and beta-adrenoceptor blocking activity in a single entity, such as BW B385C, therefore also produces a reduced renin release when compared with an ACE-inhibitor, such as enalapril. This provides further confirmation of the importance of the renal sympathetic innervation in the renin response to ACE-inhibition, and supports the concept of combining ACEinhibition with beta-adrenoceptor blockade.

Outcome of very-low-birth-weight infants: does antepartum versus neonatal referral have a better impact on mortality, morbidity, or long-term outcome?

To evaluate the effect of aggressive intrapartum and early neonatal resuscitation on perinatal mortality, neonatal morbidity, and long-term outcome, we evaluated two groups of low-birth-weight infants who received different intrapartum and early neonatal care. One group of infants was delivered at a university-based regional perinatal center offering both high-risk obstetric and tertiary neonatal care. The second population consisted of infants from five community hospitals with level I nurseries. These two groups were selected because they differed in the ability to provide intrapartum and early neonatal care and because a total base population could be evaluated. During the 4-year study period, 174 infants with birth weights of 500 to 1499 gm were delivered at the university center and 297 infants were delivered at the community hospitals. At the university center, there was a significant reduction in fetal deaths, a delay in the time of neonatal deaths, and a reduction in hyaline membrane disease. Neonatal mortality rates at the university center were not reduced, and the incidence of sequelae was not affected. These data suggest that for the smallest infant, intrapartum and immediate neonatal care at a tertiary center may decrease fetal mortality and neonatal morbidity rates. Neonatal mortality and long-term outcome, however, may be less affected.

Outcome of very-low-birth-weight infants: are populations of neonates inherently different after antenatal versus neonatal referral?

Postnatal transfer of high-risk infants to a neonatal intensive care unit has been an accepted medical practice for more than two decades. More recently, antepartum maternal referral for the smallest infants has been recommended to reduce infant mortality, morbidity, and long-term handicaps. The limited data available to compare in utero and postnatal transfer suggest that maternal risk factors may also influence antenatal referral. We evaluated antepartum maternal and postnatal infant referrals from five metropolitan Denver hospitals with level I facilities. Mothers who were referred to the tertiary perinatal center before delivery were more likely to have one or more high-risk conditions. The presence of a maternal risk factor (preeclampsia, antepartum bleeding, prolonged rupture of the membranes, or chorioamnionitis) was significantly more common in the maternal transfer group (p less than 0.002). Neonatal weight was higher for the maternal referrals compared with neonatal referrals. Neonatal survival was independently improved by transport of mother or infant, increasing birth weight, and higher Apgar scores. We suggest that maternal risk factors were an important determinant in the choice of antenatal referral to our perinatal center for both the community and regional hospitals during this study period. Studies that compare outcome of infants after maternal and infant transfer must control for potentially inherent differences between the antenatally and postnatally transferred infants.

The cost of care of the less-than-1000-gram infant.

One of the most difficult ethical issues in neonatal intensive care concerns the treatment of extremely low birth weight infants (ELBW). Because of their extreme prematurity, aggressive medical intervention is needed to sustain life. Advances in perinatal medicine have made it possible for these extremely immature infants to survive. More importantly, although the mortality and long-term morbidity are high, particularly for infants less than 700 gm, many of the survivors are expected to become productive members of society and produce measurable economic benefit. The limits set for aggressive management of the VLBW infant have gradually been lowered in virtue of the successful survival at each birth weight. It appears that, with each reduction in the birth weight at which maximal efforts should be used, enough babies have survived to encourage us to continue. As we drive to bring the limit of viability to lower gestations and lower birth weights, we are finding some biologic limitations to extrauterine survival that present technology and knowledge cannot overcome. Unquestionably, there is a need for more comprehensive statistics to allow us to define the lower limit of survival. Because of the poor survival rate among infants weighing less than 700 gm, and because of the high cost of their care and statistically poor quality of life among many of the surviving infants, it has been suggested that perhaps a less aggressive approach should be adopted for those extremely immature infants. However, some recent data indicate that aggressive treatment is effective in saving lives, even at the lower spectrum of birth weight, and many of the survivors are normal or have mild handicaps. The importance of economic considerations to solve the ethical dilemma posed by the intensive care of ELBW infants is being questioned. Concerns that reflect moral absolutes cannot be adequately answered in terms of mere dollars and cents. Although the cost of neonatal intensive care is high on a per diem or per case basis, it appears to be reasonable in relation to the health benefits it provides. For infants in the weight class less than 750 gm, probably none would have survived in the absence of neonatal intensive care. We believe that a policy of benign neglect for the ELBW infant is not justified in the present era of perinatal medicine. Given these considerations, we think that aggressive treatment is reasonable, at least initially at birth.(ABSTRACT TRUNCATED AT 400 WORDS)

The management of antepartum haemorrhage (excluding placenta praevia).

A 3-year retrospective survey of patients presenting with an antepartum haemorrhage (APH) to The Royal Women's Hospital, Melbourne, was undertaken. Cases of placenta praevia were excluded from the series. The overall perinatal mortality (PNM) was 14.5%. There were 98 patients with accidental haemorrhage (PNM 23.4%) and 101 patients with an APH of unknown aetiology (PNM 6%). Generalized uterine tenderness and tenseness were the most consistent features associated with imminent fetal compromise and it is in this group that an early resort to Caesarean section may be beneficial. The routine use of a clotting profile was found to be of little value, especially in patients with a mild haemorrhage.

Who pays the bill for neonatal intensive care?

The Children's Hospital Newborn Emergency Service conducted 174 transports to the Newborn Center during a four-month period in 1976. The transport charge directly related to the distance between the referring hospital and the NBC. Two years after the NBC discharged the last study infant, 150 of 174 accounts have been paid in full. Insurance paid 85%, families paid 4%, and the hospital wrote off 11% of all hospital charges. The Children's Hospital referred 2% of all hospital charges to a bill collection agency. One hundred-forty-four infants (84%) survived and 27 (16%) died. The mean charge per day for survivors was $338; the mean charge per day for nonsurvivors was $607.