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Biomedical subjects

J Nowak

Publications and source records attributed to J Nowak.

At least 145 records · Page 8Linked to original sources
PubMed1985

Stimulatory cholinergic effect on the release of antiaggregatory activity into the circulation of cat and man and its modification by beta-adrenergic antagonists.

The release of PGI2-like activity into the circulation in response to cholinergic agonists and modification of this response by beta-adrenergic antagonists was investigated in anaesthetized cats and healthy humans. Antiaggregatory activity in the arterial blood was continuously assayed by measuring platelet aggregation on blood superfused collagen strip. In some of the human experiments, after the administration of the drugs, the conversion of [14C]-arachidonate to [14C]-prostaglandins in the pulmonary vascular bed was studied. Cholinergic agonists stimulated the release of PGI2-like activity into the circulation, which effect was potentiated in cats by beta-adrenergic antagonists. In humans the latter agents did not stimulate the conversion of [14C]-arachidonate to prostaglandins in the pulmonary circulation and, moreover, inhibited the stimulatory cholinergic effect. The results suggest that an interplay between cholinergic and beta-adrenergic mediators may be involved, although in a different way in cats and in humans, in the release of PGI2-like activity into the systemic circulation.

Acetylcholine↗
PubMed1985

Coronary flow regulation in patients with ischemic heart disease: release of purines and prostacyclin and the effect of inhibitors of prostaglandin formation.

The present investigation was undertaken to study cardiac release of adenosine and prostacyclin (prostaglandin [PG] I2) in patients with ischemic heart disease (IHD), and to assess coronary vascular resistance before and after inhibition of synthesis in such patients. In 48 patients with IHD, arterial and coronary sinus blood samples were taken at rest, during atrial pacing to angina, and after pacing. Levels of purines were determined by high-performance liquid chromatography and the PGI2 metabolite 6-keto-PGF1 alpha was measured with radioimmunoassay. Coronary sinus blood flow was determined with retrograde continuous thermodilution before and after oral administration of indomethacin, aspirin, naproxen, or ibuprofen. Atrial pacing induced myocardial ischemia, as evidenced by typical chest pain and arrested lactate extraction. Adenosine was extracted at rest, but during ischemia there was a significant release of its metabolite hypoxanthine, indicating increased myocardial breakdown of high-energy adenine nucleotides. Arterial and coronary sinus concentrations of 6-keto-PGF1 alpha were low and no significant differences between them were found. After administration of the PG-synthesis inhibitor indomethacin, coronary vascular resistance was elevated, as was the cardiac oxygen extraction. The three other PG-synthesis inhibitors (aspirin, naproxen, and ibuprofen) did not, however, induce any change in coronary vascular resistance or in the cardiac extraction of oxygen. On the basis of these data we suggest that in patients with IHD cardiac ischemia results in increased myocardial production and release of purines, cardiac ischemia does not elicit any detectable increase in coronary production of prostacyclin, and the increased coronary resistance induced by indomethacin does not reflect the involvement of locally formed PG in the maintenance of coronary flow, but is rather a direct effect of the drug.

Adenosine↗
PubMed1984

Central and peripheral haemodynamic effects of non-steroidal anti-inflammatory drugs in man.

The haemodynamic effects of non-steroidal anti-inflammatory (NSAI) drugs can be attributed either to their common property of inhibiting the formation of prostaglandins (PG) in the cardiovascular system, or to direct actions on the tone and sensitivity of the resistance vessels in various regions. Indomethacin (IND) is the most frequently studied NSAI drug, in animals and in man. Its cardiovascular effects differ somewhat from those of other NSAI, due to the fact that, besides inhibiting PG formation, IND acts as a direct vasoconstrictor. The stimulatory effect of IND in vascular smooth muscle results in an increased systemic vascular resistance which, although partially compensated by a decreased cardiac output, gives rise to a moderate increase in systemic blood pressure. The vasoconstrictor effect of IND is of particular interest in patients with ischemic heart disease, since it lowers their already decreased coronary flow, and may thereby accentuate the risk of myocardial infarction. Administration of IND also leads to a decreased blood flow in the splanchnic region, the kidneys, and the brain. The cerebral blood flow is lowered by 25-35%; in addition, IND almost entirely erases the hyperemic flow response to hypercapnia. Of other NSAI drugs, at least aspirin and naproxen are completely devoid of such actions on the cerebral circulation. A common vascular effect of all NSAI drugs is a diminution of reactive hyperemia, the local hyperemia that develops in a tissue subjected to a short period of arterial occlusion. Part of this hyperemic response is dependent on an intact vascular PG formation and consequently it is inhibited when PG formation is blocked. In contrast, NSAI drugs do not affect the functional increase in the blood flow in working skeletal muscle.

Adult↗
PubMed1984

Release of prostacyclin from the human pulmonary vascular bed in response to cholinergic stimulation.

The ability of the human pulmonary vascular bed to synthesize prostaglandins (PGs) in response to cholinergic stimulation was investigated in healthy male volunteers. In all of them, except controls, carbaminoylcholine (CCh) was injected subcutaneously at a dose of 5 micrograms/kg. In 3 subjects [1-14C]-labelled arachidonate was then infused at a constant rate into the right atrium between 10 and 15 min after the administration of the drug and the blood from the subclavian artery was sampled simultaneously. The arterial content of [14C]-labelled metabolites was extracted, separated by thin-layer chromatography and quantified using liquid scintillation spectrometry. In 8 other subjects PGI2-like activity after the administration of CCh was assayed in the arterial blood and in 1 subject in the venous blood, using a technique for continuous measurement of platelet aggregation on blood-superfused collagen strip. The major portion of [14C]-activity in the radiochromatograms migrated in parallel with the 6-keto-PGF1 alpha standard. No early defined peaks corresponding to any of the unlabelled PGs D2, E2 or F2 alpha, appeared, but in one chromatogram a minor radiopeak corresponding to authentic thromboxane B2 was observed. Also in the platelet aggregation experiments, 5-15 min after the administration of CCh, a significant increase in the PGI2-like activity was observed in the arterial as well as in the peripheral venous blood, which effect of the drug was abolished by pretreatment with atropine and acetylsalicylic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Effect of propranolol, practolol and atenolol on human platelet thromboxane formation and plasma levels of prostaglandins 6-keto-F1 alpha and E2.

The effects of three different beta-adrenergic blocking drugs, propranolol, practolol and atenolol on platelet thromboxane production and the release of prostacyclin and prostaglandin E2 into the circulation were investigated in healthy volunteers. The beta-adrenergic antagonists were administered intravenously at equipotent doses. The serum TxB2 levels after whole blood clotting and the arterial and venous plasma concentrations of 6-keto-PGF1 alpha and PGE2 were measured before and during a 60 min period after the administration of the drugs, using radioimmunoassay. Practolol and atenolol elicited a significant decrease in platelet thromboxane formation but remained without effect on plasma 6-keto-PGF1 alpha and PGE2 levels. In contrast, propranolol did not influence serum TxB2 concentrations but induced a significant increase in plasma content of 6-keto-PGF1 alpha and PGE2. The results indicate that beta-adrenergic antagonists alter the balance between the proaggregatory, vasoconstricting and antiaggregatory, vasodilating prostanoids in the human cardiovascular system. Although the direction of the action of these drugs seems to differ depending on the selectivity of the beta-adrenoceptor blocking properties the net effect of this action should be beneficial.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Release of prostacyclin into the coronary venous blood in patients with coronary arterial disease.

Voluntary patients with a history of myocardial infarction and with typical effort angina underwent catheterization of the coronary sinus and a brachial artery. Healthy young males, serving as controls, were subjected to the same procedure. Arterial and coronary venous blood was drawn at rest and during atrial pacing to angina (patients) or to a heart rate of 140 beats/min (healthy volunteers) for analysis of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) and prostacyclin-like activity (PILA). 6-Keto-PGF1 alpha levels were measured using radioimmunoassay; PILA in the blood was assayed by rapid preparation of platelet-rich plasma followed by determination of the ADP-induced platelet aggregation. Increased arterial levels of PILA and of radioimmunoactive 6-keto-PGF1 alpha (RIA-6-keto-PGF1 alpha) were observed in the patients at rest as well as during pacing. No obvious release of RIA-6-keto-PGF1 alpha occurred at rest, either in the patients or in the controls. However, during pacing, increased amounts of RIA-6-keto-PGF1 alpha appeared in the coronary venous blood of the patients. The results demonstrate that an increased cardiac prostacyclin formation prevails in patients with signs of impaired coronary flow and suggest that ischemic heart disease is characterized by an insufficient vascular response to this vasodilator prostaglandin rather than by its insufficient endogenous production.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Biosynthesis of prostaglandins in microsomes of human skeletal muscle and kidney.

The capacity of human skeletal muscle, renal cortical and renal medullary microsomes to synthesize prostaglandins (PGs) from exogenous precursor was investigated. The microsomal fractions were incubated with [1-14C]-labelled arachidonate ([14C]-AA) in the absence and in the presence of reduced glutathione (GSH). [14C]-PGs formed in the incubates were extracted, separated by thin-layer chromatography and quantified using liquid scintillation spectrometry. [14C]-labelled PGE2, PGF2 alpha and 6-keto-PGF1 alpha were found to be the principal products of microsomal PG formation and appeared in similar relative quantities in the incubates of all three tissues studied. In some incubates of renal cortical and renal medullary microsomes formation of smaller relative amounts of [14C]-PGD2 and thromboxane B2 was also noted. In addition, formation of substantial amounts of a polar, not yet identified compound was frequently observed in all incubates. In the absence of GSH, [14C]-6-keto-PGF1 alpha was the main PG formed by microsomes of all of the three tissues. At the expense of 6-keto-PGF, the addition of GSH resulted in an almost 2-fold stimulation of [14C]-PGF2 alpha formation in the skeletal muscle and renal cortical incubates, whereas in the renal medullary incubates an increase in the relative amounts of [14C]-PGE2 was observed. The PG synthetic capacity was highest in the skeletal muscle and lowest in the renal cortical microsomes. The results demonstrate a considerable capacity of human skeletal muscle and of the renal cortex and renal medulla to synthesize prostacyclin. Furthermore, the data reveal GSH-dependent differences in the expression of PG biosynthesis in these tissues. The GSH-dependent differentiation of PG synthesis may reflect a mechanism of adaptation of local PG production to the physiological processes.

Aged↗
PubMed1982

Effect of metoprolol and alprenolol on the metabolic, hormonal, and haemodynamic response to insulin-induced hypoglycaemia in hypertensive, insulin-dependent diabetics.

Insulin hypoglycaemia was induced three times in 6 insulin-dependent, hypertensive diabetics: before instituting antihypertensive long-term treatment and after obtaining a satisfactory blood pressure with either alprenolol or metoprolol given in a randomized order. The blood glucose concentration (1.6-1.9 mmol/l) at which the hypoglycaemia necessitated intravenous administration of glucose was almost identical on all three occasions. During hypoglycaemia the systolic and diastolic blood pressures increased significantly by a mean maximal rise of 27/14 mmHg on alprenolol treatment, but remained unchanged on metoprolol. The responses of adrenaline, noradrenaline, cortisol, and growth hormone did not differ significantly on the three occasions. None of the beta-adrenergic drugs counteracted the early hormone defence mechanisms in hypoglycaemia and the signs of hypoglycaemia were not masked. The haemodynamic response was altered only by the non-selective (alprenolol) and not by the selective beta-adrenergic blocking agent (metoprolol).

Adult↗
PubMed1981

Central haemodynamics during halothane and enflurane anaesthesia in vascular surgery.

Central haemodynamics were studied before and during reconstructive vascular surgery in 18 patients receiving halothane or enflurane anaesthesia (nine patients in each group). In both groups cardiac output (CO), stroke volume (SV), oxygen uptake (VO2) and arterial blood pressure fell significantly after induction of anaesthesia, whereas the arterio-venous oxygen difference (AVD) and the total peripheral resistance (TPR) remained unchanged. In spite of an average intraoperative blood loss of 600 ml, which had not been substituted for, surgery brought about an increase in CO, SV and VO2, while the AVD and TPR remained unchanged. Following transfusion of 900 ml of blood, CO and SV showed a further significant increase in both groups, whereas VO2 was unchanged and the AVD and TPR fell significantly. The pulmonary capillary venous pressure (PPCV) was stable during induction of anaesthesia and surgery but increased after blood transfusion. The changes in SV and PPCV were analyzed in relation to the concept of ventricular function curves. It is concluded that there were no fundamental differences in central haemodynamics between halothane and enflurane anaesthesia either before or during surgery. In both groups the changes in CO and SV were due mainly to a reduced demand of oxygen transport and expected changes in sympatho-adrenergic tone rather than to myocardial depression.

Aged↗
PubMed1981

Conversion of exogenous arachidonic acid to prostaglandins in the pulmonary circulation in vivo. A human and animal study.

The capacity of human lungs to synthetize prostaglandins (PGs) from exogenous arachidonic acid (AA) was investigated in healthy male volunteers. 14C-labelled AA was infused at a constant rate into the right atrium under simultaneous sampling of blood from the ascending aorta. The arterial content of 14C-AA metabolites was extracted, separated with thin-layer chromatography and quantified using fractionated liquid scintillation spectrometry. Conversion of exogenous AA to prostacyclin (PGI2) was also studied in the lungs of anaesthetized cats. In these experiments different doses of unlabelled AA were administered intravenously. Simultaneously PGI2-activity in the arterial blood was assayed using a technique for continuous measurement of platelet aggregation on blood superfused collagen strip. Radiochromatograms of the human arterial plasma revealed no clearly defined peaks corresponding to any of the unlabelled standards of PGD2, PGE2, 6-keto-PGF1 alpha, PGF2 alpha or TxB2. The 14C-activity in the chromatograms materialized only in one (apart from AA) prominent peak in parallel to 13,14-dihydro-15-keto-PGE2. Neither in cats did significant amounts of PGI2 appear in the arterial blood after administration of AA in moderate doses. Only very high AA doses caused a slight increase in arterial PGI2-activity. The results demonstrate that human lungs do not convert exogenous AA to PGs under physiological conditions. In cats the reluctance of the lungs to utilize exogenous precursor can only be overcome with high, non-physiological AA doses. The data may suggest the existence of special regulatory mechanisms which control release of PGs from the lungs and promote utilization of endogenous precursor.

Adult↗