Seven patients who had suffered head injury 3 to 5 days before the study was undertaken received clonidine (2.5 micrograms/kg iv over 10 min). This resulted in a reduction of plasma norepinephrine (p less than .05) and in normalization of plasma epinephrine (p less than .05). Neither common carotid blood flow nor diastolic blood flow as index of global cerebral perfusion as measured by pulsed Doppler changed. The reduction of sympathetic overactivity, probably due to the specific action of clonidine on alpha 2-adrenoceptors within the rostral ventrolateral medulla, may be of interest in the management of head injury because of the maintenance of cephalic hemodynamics.

In pentobarbital-anesthetized dogs with decentralized adrenal glands, sinoaortic baroreceptor deafferentation produced an increase in mean aortic blood pressure which reached a maximum (42 +/- 5 mm Hg, n = 6) within 5 min and then waned entirely within the subsequent 25 min. In contrast, in sham-operated dogs, the maximal pressor response due to deafferentation was of greater magnitude (63 +/- 6 mm Hg, n = 8) and of much longer duration (44 +/- 4 mm Hg, 60 min after deafferentation). Heart rate was only augmented slightly in both preparations. A marked elevation of epinephrine plasma concentration occurred 5 min after deafferentation and the magnitude of this effect was 8 times greater in dogs with innervated than denervated adrenal glands. Norepinephrine plasma concentration increased moderately and similarly in the two preparations. Administration of pergolide (30.0 micrograms/kg i.v.) 15 min before undertaking the deafferentation procedure induced a small, short-lasting increase in blood pressure and a small fall in heart rate in dogs in which the innervation to the adrenal glands was left either intact (sham-operated) or removed surgically. In dogs with adrenal gland denervated, pergolide blocked entirely the pressor response and the small elevation in plasma concentration of catecholamines evoked by sinoaortic deafferentation in the matched, saline-pretreated group. However, in sham-operated dogs (intact adrenal innervation), pergolide reduced partially (by 41%) the increase in blood pressure and plasma epinephrine concentration caused by deafferentation. The decrease in heart rate, produced by pergolide, was abolished by deafferentation in sham-operated and adrenal decentralized dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Numerous data have suggested that beta-adrenoceptor-mediated responses were decreased in uremia and that parathormone could be implicated in this phenomenon. In a previous paper we have shown that the beta2 receptor density of mononuclear cells of uremic patients is significantly increased despite a significant increase in plasma epinephrine, suggesting that an endogenous substance could interfere and disregulate the beta 2 receptor density. In order to further evaluate this phenomenon we have firstly studied the influence of one non uremic and five uremic plasma ultrafiltrates on the binding of (-)-[125I]iodocyanopindolol using rat lung beta adrenoceptors. The results show that uremic plasma ultrafiltrates induce a decrease in the Bmax value without any variation on the Kd value. In a second step we have assessed the ability of human synthetic 1-34 and 53-84 parathormone to interact directly with beta-adrenoceptors. No variation in the (-)-[125I]iodocyanopindolol binding parameters was observed. These results suggest that an uremic endogenous substance might interfere on the beta adrenergic receptors and that the alteration in the beta-adrenergic response in uremia is probably not due to a direct action of parathormone on the beta-adrenoceptors.

The release of platelet-derived vasoactive substances, particularly serotonin (5-HT), have been implicated in the pulmonary vasoconstrictor response following acute pulmonary embolism. Therefore, we studied the effects of infusing ketanserin, a 5-HT blocking agent, upon pulmonary and systemic hemodynamics and gas exchange in 10 patients with severe acute pulmonary embolism. These patients evidenced 45 +/- 17% mean angiographic pulmonary vascular obstruction. Ketanserin significantly decreased the mean pulmonary arterial pressure from 26 +/- 6 to 23 +/- 5 mm Hg (p less than 0.001). The total pulmonary vascular resistance decreased from 9.1 +/- 3.2 to 8.3 +/- 2.5 mm Hg/L X min X m2 (p less than 0.001). However, the mean cardiac index was unchanged. The systemic arterial and right atrial pressures were significantly decreased after ketanserin. The PaO2 increased in all patients from 60.5 +/- 12.6 to 66.5 +/- 13.6 mm Hg (p less than 0.05), whereas the venous admixture was unchanged. This was attributed to an increased PVO2 (27 +/- 7 to 30 +/- 5 mmHg, p less than 0.01) secondary to a reduction of calculated peripheral oxygen consumption during ketanserin infusion. The results indicate ketanserin is a mild pulmonary vasodilator and can reduce the pulmonary hypertension and increase the PaO2 after pulmonary embolism.

To assess the hormonal response to captopril pre-treatment during sodium nitroprusside (SNP) -induced hypotension, 12 patients were studied during a spinal surgical procedure. Haemodynamic data, plasma-renin activity, aldosterone, adrenaline and noradrenaline levels were measured. Patients were randomly allocated to two groups: Group I, control patients; Group II, 3 mg kg-1 captopril pre-treated patients. SNP requirement for the same level (mean arterial pressure (MAP) = 55 mmHg) and duration of hypotension (88.5 +/- 28.7 vs. 95.2 +/- 22.5 min) was significantly lower in Group II than in Group I (16.5 +/- 14.2 mg vs. 39.3 +/- 16.7 mg; P less than 0.05) and a lower SNP infusion rate was required to induce and to maintain hypotension. In Group II patients, MAP remained significantly lower than the control and Group I values for 30 min after SNP withdrawal. Cardiac index (CI) remained stable in both groups. Heart rate was not modified in Group II during hypotension. Plasma-renin activity rose more dramatically in Group II patients than in Group I both during hypotension (13.9 +/- 7.5 vs. 2.8 +/- 0.9 ng ml-1 h-1; P less than 0.05) and after hypotension (23.4 +/- 15.4 vs. 2.2 +/- 0.8 ng ml-1 h-1; P less than 0.05). Plasma catecholamine levels increased in both groups during hypotension and remained raised in captopril patients after SNP withdrawal. It can be concluded that recovery from hypotension may be delayed when using captopril and that sympathoadrenal activity induced by hypotension is not substantially altered by captopril pre-treatment, suggesting that sympathetic blockade might not be the mechanism by which captopril reduces SNP requirement during controlled hypotension for surgical procedure in man.

Previous investigations have suggested that beta-adrenoceptor-mediated responses were decreased in uremia. To evaluate this phenomenon further, beta 2-receptor density in mononuclear cells, plasma catecholamines and plasma parathyroid hormone were studied in two groups of normotensive patients: group U, twenty-five chronic uremic patients with end-stage renal failure; group C, twenty-eight control subjects. Each group was divided into three age and sex-matched subgroups. Beta 2-receptor density was determined using (-)125 iodocyanopindolol. Despite a significant increase in plasma epinephrine in the group of uremic patients, there was a significant increase in beta 2-adrenoceptor density. On the other hand the uremic state did not influence (-)125 iodocyanopindolol binding affinity and plasma norepinephrine. Parathyroid hormone, as expected, was significantly elevated in all the uremic subgroups. It can be concluded that the uremic state is associated with an unexpected upregulation of beta 2-receptor density in mononuclear cells. The role of an endogenous beta-blocking substance is suggested.

All patients admitted during a 33-month period to a multidisciplinary intensive care unit were prospectively studied in order to determine the incidence and severity of drug-induced illness leading to the admission. The role of underlying diseases was assessed and the avoidability of drug-induced illness considered. Out of 1651 patients, 97 (5.88%) were admitted because of drug-induced illness; 74 of these had serious underlying diseases. 13 (13.4%) of the 97 patients died, but underlying diseases accounted for 4 of the 13 fatalities. In nearly half of the cases, the drug-induced illness appeared potentially avoidable.

The effects of bromocriptine (BRC; 20 mg X kg-1, b.i.d., orally) on genetic hypertension development (GHD), cardiovascular hemodynamics, regional vascular reactivity to vasopressor agents and biological parameters have been investigated in spontaneously hypertensive rats (SHRs) treated from their 4th to 20th weeks of age. BRC only partially opposed GHD and this was due to a limitation of the progressive increase in peripheral resistance which normally develops in SHRs with ageing since simultaneously cardiac index was not modified. Renal blood flow was increased and renal and mesenteric vascular responsiveness to norepinephrine was reduced. BRC almost completely suppressed prolactin plasma levels and slightly reduced epinephrine and norepinephrine plasma levels. Plasma Na+ and urinary volume and ADH values were not modified. The discrepancy between the favourable antihypertensive profile of BRC and its limited preventive effects against GHD remains to be elucidated.

To determine (1) whether changes in plasma histamine occurred during provoked bronchospasm and (2) if so, whether such changes could be related to variations in plasma catecholamines, venous plasma histamine and catecholamines were measured during a dose-response carbachol challenge in eight healthy volunteers. A significant rise in plasma histamine was observed, whereas induced bronchoconstriction was small, 80% +/- 4% of initial specific airway conductance. There was no further increase in plasma histamine, whereas induced bronchoconstriction became more marked (70%, 60%, and 50% of specific airway conductance initial value). Plasma catecholamines did not change throughout the study. We conclude that mast cell degranulation occurs during a carbachol challenge, and that the variations in plasma histamine are not related to changes in plasma catecholamines.