Comparative study on the cardio-respiratory change during prostaglandin E1-induced hypotension in the patients in the supine and prone position

Prostaglandin E₁-induced hypotension (25% reduction from the preadministration level in mean arterial pressure) was applied to thirteen patients. Eight patients among them were operated in the supine position (group I) and other five in the prone position (group II). The maintenance dose of PGE₁ was considerably lower in group II than in group I (0.067µg·kg^–1·min^–1 vs. 0.119µg·kg^–1·min^–1). In group I, there was a significant increase in CI, with a significant decrease in SVRI and PVRI during PGE₁-induced hypotension. Such a high dose of PGE₁ (0.119µg·kg^–1·min^–1) was considered to have a direct dilating action on the systemic resistance bed as well as on the pulmonary vasculature. It was considered that the suppression of hypoxic pulmonary vasoconstriction could be a mechanism to increase venous admixture during PGE₁-induced hypotension. In group II, there was no significant increase in CI, and no significant decrease in SVRI and PVRI. PGE₁-induced hypotension can be safely applied to the anesthetized patients, but we should be careful to apply it to the patients in the prone position, because lower dose of PGE₁ can induce severe hypotension, which is not accompanied by the increase in CI as occures in the patients in the supine position.(Hirose M, Yoda K, Sakai K, et al.: Comparative Study on the cardio-respiratory change during prostaglandin E₁-induced hypotention in the patients in the supine and prone position. J Anesth 5: 30–35, 1991)     

Serum α1-microglobulin and β2-microglobulin for the estimation of fetal glomerular renal function

As proteins cannot cross the placenta levels of the microproteins ₁-microglobulin (₁MG) and ₂-microglobulin (₂MG) can be used to assess fetal glomerular renal function. ₁MG, ₂MG and creatinine were routinely determined in cord and maternal blood of 133 newborns [gestational age (GA) 25–42 weeks]. Twenty-nine patients with suspected impaired maternal or fetal renal function were studied separately and two fetuses were studied in utero. The mean fetal ₂MG concentration fell from 3.87±0.56 mg/l in the 25–31 weeks GA group to 2.60±0.50 mg/l in the mature newborn group. ₁MG concentration fell from 3.10±0.51 to 2.25±0.49 mg/dl. In contrast, the mean maternal ₁MG concentration rose from 1.73±0.69 mg/l in the 25–31 weeks GA group to a mean of 1.83±0.48 mg/l in the mature newborn group; ₁MG rose from 3.96±0.58 to 4.33±1.6 mg/dl. Maternal and fetal creatinine levels were identical. Fetal microprotein levels fall during intra-uterine development as glomerular filtration rate (GFR) rises. There is no correlation between cord blood and maternal ₁MG or ₂MG concentrations. In 13 children with urological anomalies only 1 had elevated microprotein levels and he later developed renal insufficiency. Determination of microprotein levels in fetal serum can be used to detect severe renal function disturbances and to estimate GFR independently of maternal renal function.     

The ONG capsular lens,report of 100 implantations

This Capsular Lens (ONG, type IV, to be called O.C.L.) has been developed for routinely performed extracapsular cataract extraction with lens implantation. The fundamental surgical procedure was based on continuing experience with the bimanual aspiration-irrigation technique and system developed by the author in 1971. The biomechanical properties of the asymmetric partly flexible, haptic loops are designed to give tensionfree fixation in two capsular pockets. The plano-anterior position of the lens ensures well-defined irido-lenticular clearance and proper alignment of the convex side with the posterior capsule. Consequently no iridectomy or iridotomy is needed for proper aqueous flow.     

Binding ofβ-adrenoceptor blocking drugs to human serum albumin,to α1-acid glycoprotein and to human serum

Summary The binding of 8 -adrenergic blocking drugs to human serum albumin, to ₁-acid glycoprotein and to serum from normal volunteers and from patients with rheumatoid arthritis was studied. Protein binding was determined in vitro using equilibrium dialysis of labelled drug at 25° C. Oxprenolol and propranolol were highly bound to serum, alprenolol, pindolol and timolol to a lesser degree, and atenolol, metoprolol and sotalol were negligibly bound. For the five compounds which were appreciably bound, the mean binding was significantly higher in serum from patients with rheumatoid arthritis than in serum from normal volunteers. For those drugs, binding to ₁-acid glycoprotein was higher than to human serum albumin, and binding to a mixture of both proteins approached that to serum from healthy volunteers. For each of these drugs there was a strong correlation between the serum ₁-glycoprotein concentration and the percentage binding.     

Binding of aprindine and moxaprindine to human serum, α1-acid glycoprotein and serum of healthy and diseased humans

Summary A comparison was made between the binding of the anti-arrhythmic agents aprindine and moxaprindine to human serum, to human serum albumin (HSA), to ₁-acid glycoprotein (₁-AGP) and to a mixture of HSA and ₁-AGP. In serum from healthy volunteers (n=4) the binding of aprindine-HCl 5 µg/ml (13.8 µM) was 93.8% (SD±1.0), and that of moxaprindine-HCl 5 µg/ml (12.8 µM) was 94.1% (SD±1.1). Their binding to the mixture of ₁-AGP and albumin approximated their binding to serum. For ₁-AGP, the binding was similar for both compounds, whereas for HSA the binding of aprindine was more pronounced than that of moxaprindine: for both products the affinity coefficient for binding to ₁-AGP was about 100 times greater than that for binding to albumin. In serum from rheumatoid patients and from patients with renal failure a small but significant increase in binding of aprindine and moxaprindine was observed, approximately 1%. Increased and decreased binding was seen in serum from cirrhotic patients; for example, for aprindine the range in cirrhosis was 96.7%–79.8%, and the range in controls was 95.0%–92.4%. Free drug fraction and ₁-AGP concentration were inversely correlated. The results show that ₁-AGP plays an important role in the binding of aprindine and moxaprindine, and that alteration in the binding of the two compounds in disease states to a large extent can be explained by changes in serum ₁-AGP concentration.     

Metabolic aspects of maximal exercise performance after slow release metoprolol and after atenolol

Summary Maximal exercise performance by eight healthy male subjects was tested after one week of medication with slow-release metoprolol 200 mg/d (metoprolol-SR), atenolol 200 mg/d or placebo, in a double blind crossover trial. The maximal working capacity was significantly decreased after atenolol and metoprolol-SR. Plasma glucose and FFA concentrations during the exercise test did not change: either after placebo therapy or after beta-blockade. The anaerobic threshold did not change after beta-blockade, but the changes in lactate due to the exercise were less after beta-blockade. Neither beta-blocker affected the exercise-induced alteration in airway resistance. Both drugs caused a small but significant ventilatory depression at rest and at 75% of maximal exercise. It is concluded that the limiting factor in maximal exercise performance after ₁-adrenergic blockade does not lie in oxygen transport to the working muscles via ventilation and the circulation, but is most probably due to anaerobic metabolism.     

Serum concentration and protein binding of thioridazine and its metabolites in patients with chronic alcoholism

Summary The blood chemistry and clinical pharmacokinetics of thioridazine and its metabolites, side-chain sulphoxide, side-chain sulphone and ring sulphoxide, were studied in 31 alcoholics and were compared with values in 17 thioridazine-treated controls without alcoholism. Pathological blood chemistry values, including abnormal liver function and protein concentrations, were common among the alcoholics. In relation to dosage, the majority had a low serum concentration of thioridazine and at a given concentration of thioridazine they had high serum concentrations of its metabolites. Positive intercorrelations were found between pathological liver function tests, prolonged serum half-life and increased serum concentration of thioridazine. The free fractions of thioridazine, side-chain sulphoxide and ring sulphoxide were significantly higher and those of the side-chain sulphone lower in the alcoholics than in the controls. The free fractions of side-chain and ring sulphoxide were significantly increased in patients with a low concentration of ₁-acid glycoprotein.     

Benzamide action at α2-adrenoceptors modifies catecholamine-induced contraction and relaxation of circular smooth muscle from guinea-pig stomach

Summary Dopamine was shown to act on the circular smooth muscle of the stomach body to cause contraction at a yohimbine-sensitive site (₂) and a relaxation at a prazosin-sensitive site (₁). Metoclopramide and tiapride failed to modify either response, failed to antagonise a relaxation to phenylephrine at 1(₁ sites in the same tissue, and failed to modify the contractions caused by dopamine and phenylephrine at an ₂-adrenoceptor site in the pyloric sphincter. However, (+)- and (–)-sultopride and (+)-sulpiride antagonised the dopamine-induced contractions of the stomach body indicating an ₂-antagonist action. An ability to attenuate the relaxation of this tissue may reflect a displacement of the contraction curve to the right rather than an ₂-antagonist action since the response to phenylephrine was not antagonised either in this tissue or in the pyloric sphincter. Within the central nervous system the (–)-enantiomers of sultopride and sulpiride have a highly selective dopamine receptor blocking action. This cotrasts with the present findings in the stomach musculature of a non-stereospecific antagonism at ₂-type adrenoceptors.     

Alpha adrenoceptors in rat brain: Direct identification with prazosin

Summary Tritiated prazosin was used to characterize high affinity binding sites with characteristics similar to ₁ adrenoceptors in rat brain membranes. These sites were compared with ₂ adrenoceptors labeled with tritiated clonidine. The prazosin sites had an association constant of 2 nM^–1 and bound the ligand optimal around pH 7.0. The density of the sites was 300 fmoles per mg of protein; the half time of dissociation of prazosin was 7 min at 30° C. The order or potencies of agonists, determined from binding-inhibition experiments with labeled prazosin, was: naphazoline > clonidine > adrenaline > noradrenaline > phenylephrine > -methylnoradrenaline > dophamine. The order of potencies of antagonists was: prazosin > phenoxybenzamine > phentolamine > clozapine > yohimbine. Sodium ions and divalent cations as well as guanyl nucleotides have little or no effect on the binding of the labeled antagonist. This is in contrast to the binding of the labeled agonist clonidine (Glossmann and Presek, 1979a, 1979b). Labeled prazosin may be a useful tool to characterize ₁ adrenoceptors.This is part of the thesis of R. H. to be presented to the Fachbereich Humanmedizin, Justus Liebig-Universität Giessen, in partial fulfillment of the requirements for a Doctor of Medical Science degreee     

Effects of sympathectomy on the in vivo α and β-responses of the parotid gland

Summary Salivary secretion in response to noradrenaline and isoprenaline was measured in innervated and chronically sympathectomized parotid glands of the rat. In innervated glands, the responses to isoprenaline lasted longer than those to noradrenaline. Chronic sympathetic denervation enhanced the responses to both noradrenaline and isoprenaline. The magnitude of the supersensitivity to isoprenaline was related to the dose and the time at which the responses were analyzed. Supersensitivity was greater for the initial than for the total secretion elicited by isoprenaline. Propranolol (1 mg/kg) and phenolamine (5 mg/kg) were used in order to determine the relative participation of and -adrenoceptors in the enhanced responses to isoprenaline. The results suggest that postjunctional supersensitivity for the secretory responses of this organ to isoprenaline is mainly mediated through -adrenoceptors of the secretory cells and -adrenoceptors of the myoepithelial cells.