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Biomedical subjects

A Wennmalm

Publications and source records attributed to A Wennmalm.

At least 127 records · Page 7Linked to original sources
PubMed1983

Prostaglandin-mediated inhibition of noradrenaline release. VII. Effect of indomethacin on some cardiovascular reflexes in man.

The effect of indomethacin, a prostaglandin (PG) synthesis inhibitor, on some cardiovascular reflexes was studied in healthy subjects. Heart rate (HR) and respiratory sinus arrhythmia (RSA) in the basal state and during carotid stimulation (neck suction), Valsalva ratio, and changes in heart rate and blood pressure (BP) during an orthostatic test were measured before and one hour after administration of indomethacin (1.5 mg/kg). The efficacy of the PG synthesis inhibitor was monitored by analysis of platelet aggregation induced by arachidonic acid. Following indomethacin no change was observed in basal HR. Carotid stimulation depressed the HR and this effect was of the same amplitude before and after indomethacin. The amplitude of RSA was not affected by indomethacin, either in the basal state or during carotid stimulation. The Valsalva ratio and the changes in HR and BP during the orthostatic test were similar before and after the drug. Circulating levels of noradrenaline were unaffected by indomethacin. These data demonstrate that inhibition of PG bioformation in man does not affect major cardiovascular reflexes. Consequently they disfavour the hypothesis that endogenously formed PG would be involved in the normal activity of the afferent, central or efferent pathways for cardiovascular regulation.

Adult↗
PubMed1983

Release of two vasodilators, adenosine and prostacyclin, from isolated rabbit hearts during controlled hypoxia.

The release of two locally formed vasodilators, adenosine and prostacyclin (PGI2), from hearts subjected to different degrees of hypoxia was investigated. Isolated rabbit hearts were perfused according to Langendorff with Tyrode solution, saturated with gas mixtures containing 8-95% O2 and 5% CO2 in N2. Coronary flow rate, O2 extraction and uptake, and cardiac production of lactate, purines and 6-keto-PGF1 alpha (the stable metabolite of PGI2) were determined. During perfusion of the hearts with a solution saturated with 95% O2, release of lactate, 6-keto-PGF1 alpha and purines was very low: lactate was liberated at a rate of about 5 mumol/100 g . min, purine release corresponded to 2% of the total adenosine nucleotide content of the heart per hour and the release of 6-keto-PGF1 alpha was about 150 mumol/100 g . min. During hypoxia there was a graded release of lactate and purines from the heart, as well as a liberation of 6-keto-PGF1 alpha. Mild hypoxia (60% O2 in the gas mixture) elicited a 160% increase in the formation of lactate and a 40% increase in the release of purines. During severe hypoxia (8% O2 in the gas mixture) the release of lactate and purines increased by more than 2000%. In contrast, the release of 6-keto-PGF1 alpha never increased more than 80% at any degree of hypoxia, neither did it correlate to the severity of the hypoxia. From these data we conclude that of the two vasodilating agents formed in the heart, adenosine and prostacyclin, the former is probably more important in the regulation of coronary flow.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Effect of cigarette smoking on basal and carbon dioxide stimulated cerebral blood flow in man.

The effect of cigarette smoking on the basal cerebral blood flow (CBF) and on the cerebral hyperemia induced by CO2 breathing was investigated in healthy human volunteers. CBF was measured with the N2O-wash-in technique in the basal state and during inhalation of 5% CO2, before and after smoking of two commercial filter tipped cigarettes. In parallel the (arterial-jugular venous) difference in O2 content, arterial and jugular venous pCO2, pulmonary ventilation, heart rate and systemic blood pressure were followed. During smoking there was a 10-15 mmHg increase in systemic blood pressure and a parallel elevation of heart rate (+ 20 beats/min). Cerebral blood flow increased by about 25%, and cerebral vascular resistance fell about 15%. The cerebral metabolic rate of oxygen (CMRO2) was elevated by about 30% above control. Inhalation of 5% CO2 by itself markedly increased CBF and decreased cerebral vascular resistance, while leaving CMRO2 unaffected. Cigarette smoking did not significantly change either of these effects of CO2 breathing. From these data it is concluded that cigarette smoking elevates systemic blood pressure and decreases cerebral vascular resistance, and thereby augments basal CBF. This flow-promoting effect of smoking is probably due to an increased cerebral consumption of oxygen. Furthermore, the data demonstrate that smoking does not interfere with the cerebral vascular response to increased arterial pCO2.

Adult↗
PubMed1981

Pulmonary formation of prostacyclin in man.

The pulmonary formation of prostacyclin (PGI2), as reflected by the difference in concentration of pulmonary and systemic arterial radioimmunoassayed 6-keto-PGF1 alpha, was determined in six healthy waking subjects. The systemic arterial 6-keto-PGF1 alpha levels were low (less than or equal to 50 pg/ml), and no evidence of pulmonary formation and release of the compound was noted. In other experiments systemic arterial 6-keto-PGF1 alpha levels were determined in patients prior to and during artificial ventilation, as well as during and after occlusion of the pulmonary circulation (extra-corporeal circulation, ECC). The arterial 6-keto-PGF1 alpha concentration prior to artificial ventilation was 17 +/- 4 pg/ml, i.e. within the range observed in the healthy subjects. During artificial ventilation the arterial levels of 6-keto-PGF1 alpha increased to 191 +/- 21 pg/ml, suggesting that pulmonary formation of PGI2 was stimulated. In the patients subjected to ECC with occluded pulmonary circulation the arterial content of 6-keto-PGF1 alpha was stabilised at an elevated level (120-170 pg/ml). Following re-establishment of the pulmonary circulation the arterial concentrations of 6-keto-PGF1 alpha increased markedly, to 284 +/- 50 pg/ml. It is suggested that the basal pulmonary formation of PGI2 in man is low or non-existent, and that enhanced formation of the compound in the lungs is a consequence of intervention with normal pulmonary ventilation of perfusion.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

Oxygen consumption in rabbit Langendorff hearts perfused with a saline medium.

Isolated rabbit hearts were perfused according to Langendorff at a temperature of 38 degrees C and a pressure of 5.9 kPa with gassed Tyrode solution. Gas mixtures containing 5% CO2 and 15, 20, 30, 60, or 95% O2 in N2 were used to saturate the perfusion medium. In some cases lactate (50 or 500 microM) was present in the medium perfusing the heart. Coronary flow (CF), oxygen pressure in the perfusion medium and in the cardiac effluent and lactate in the effluent were analysed in all experiments. The oxygen uptake in the hearts perfused with a medium equilibrated at atmospheric pressure with 95% O2 and 5% CO2 (oxygen pressure approximately 87 kPa, oxygen content 19 ml X 1(-1)), averaged 3 ml X 100 g w.w. -1 X min-1. Reduction of the oxygen pressure in the perfusion medium resulted in an increase in CF and in the fractional extraction of oxygen from the medium, making it possible to maintain the heart's oxygen uptake (VO2) down to an oxygen pressure in the perfusion medium of about 24 kPa (oxygen content approximately 5 ml X 1(-1), the perfusion medium equilibrated with 20% O2 and 5% CO2 in N2). Myocardial lactate production was low during perfusion at pO2 approximately 87 kPa but increased rapidly when the oxygen pressure was lowered. The addition of lactate (500 microM) to the perfusion medium at pO2 approximately 87 kP induced a fractional uptake of about 20%. It is concluded that the VO2 observed during perfusion at pO2 approximately 87 kPa mainly reflects aerobic myocardial metabolism in this preparation. This assumption is based on the facts that coronary flow and fractional oxygen extraction are submaximal and that a considerable uptake of lactate occurs concurrently with a very limited production. However, even moderate reduction of the oxygen pressure in the perfusion medium (to approximately 61 kPa) is followed by a significant increase in lactate production, indicating that myocardial oxygenation is inefficient.

Animals↗
PubMed1980

Transitory failure of ADP to induce platelet aggregation in plasma from a young healthy woman.

Platelet rich plasma was prepared from venous blood sampled from a healthy young female. ADP(2.5 - 250 microgram) failed to induce platelet aggregation when added to the plasma shortly after the collection of blood, but later addition of ADP induced normal aggregation. Serial dilution of the female's platelet-rich plasma with plasma of normal aggregability was followed by a progresively increasing aggregation amplitude. It is suggested that the impaired aggregation observed shortly after blood sampling was due to a transitory high concentration of prostacyclin in the female's plasma.

Adenosine Diphosphate↗
PubMed1980

Cardiac synthesis of prostaglandins from arachidonic acid in man.

The bioformation of PGs in the human heart was studied in 7 male volunteers by constant rate infusion of 14C-labelled arachidonic acid (AA) into the aortic root and simultaneous blood sampling from the coronary sinus. After conventional extraction of lipids from the plasma samples, the various 14C-PGs formed were separated and quantified by means of thin layer chromatography and fractionated liquid scintillation spectrometry. The infused arachidonic acid was metabolized and well defined chromatographic peaks of 14C-PGs were obtained. Apart from a chromatographic peak corresponding to 14C-PG metabolites, 6-keto-PGF1 alpha constituted the main 14C-PG formed (23 +/- 8%) reflecting a considerable synthesis of prostacyclin in the heart. 14C-PGs of the D, E and F series were formed in roughly equal amounts (14--19%). In a 54-year-old subject, 6-keto-PGF1 alpha constituted a greater proportion of 14C-PGs (60%) than in the other subjects. This can reflect a general effect of ageing or it can indicate the presence of ischemic heart disease in this subject.

Adult↗
PubMed1980

Nicotine inhibits hypoxia- and arachidonate-induced release of prostacyclin-like activity in rabbit hearts.

1 Rabbit hearts were perfused by the Langendorff technique and the interstitial effluent content of platelet anti-aggregatory activity (prostacyclin-like activity) was assayed at regular intervals. 2 Perfusion was performed with a solution containing 5% CO2 in O2. At regular intervals it was changed to solution containing 12% O2 and 5% CO2 in N2. Alternatively, perfusion with 5% CO2 in O2 was maintained during the entire experiment and sodium arachidonate was infused (5 to 15 microgram/min) at intervals. Under the basal conditions no efflux of prostacyclin-like activity was observed in the interstitial cardiac effluent, but both perfusion with a hypoxic solution and infusion of arachidonate induced such release. 3 Nicotine (5 X 10(-5) M) in the solution perfusing the heart markedly inhibited the efflux of prostacyclin-like activity into the cardiac interstitial effluent, induced by hypoxia or by infusion of arachidonate. 4 It is suggested that nicotine counteracts the formation of prostacyclin-like activity in the rabbit heart by interfering with the enzymatic conversion of arachidonate to prostacyclin.

Animals↗
PubMed1980

Inhibition by nicotine of the formation of prostacyclin-like activity in rabbit and human vascular tissue.

1 Rings of vascular tissue (from rabbit aorta or human peripheral vein) were incubated at room temperature in Tyrode solution in the absence or presence of nicotine or indomethacin. 2 Addition of portions of the incubates to human platelet-rich plasma (HPRP) elicited a decrease in adenosine 5'-diphosphate (ADP)-induced platelet aggregation in this plasma. Authentic prostacyclin (PGI2) also induced such a decrease. The decreased aggregation amplitudes that followed the addition of the vascular tissue incubates and of PGI2 were equally potentiated by theophylline (10(-4) M). 3 Both nicotine and indomethacin counteracted the formation of platelet anti-aggregatory activity in the vascular tissue incubates. The IC50S of nicotine and of indomethacin on the formation of platelet antiaggregatory activity were 2 X 10(-5) M and 6 X 10(-6) M, respectively. 4 Nicotine failed to affect the platelet anti-aggregatory effect induced by authentic PGI2 in HPRP. 5 It is concluded that nicotine counteracts the formation of platelet anti-aggregatory activity in rabbit aorta and human peripheral vein by eliciting an inhibitory effect on the bioformation of prostacyclin in these types of vascular tissue.

Adenosine Diphosphate↗
PubMed1980

Effect of nicotine on the formation of prostaglandins in the rabbit kidney.

The effect of nicotine on the bioformation of prostaglandins (PG) in the rabbit kidney was investigated. Rabbit kidneys were homogenized and the low-speed supernatant was incubated with 14C-labelled arachidonic acid (14C-AA), a PG precursor. Nicotine was added to the incubations to produce final concentrations of 5 x 10(-7) M to 5 x 10(-4) M. Control incubations without nicotine were also performed. 14C-PG formed were separated and evaluated on thin layer radiochromatography. In control experiments 14C-labelled PGD2, PGE2 and PGF2 were formed, the relative amounts in between them being 16, 31 and 53%, respectively. Nicontine dose-dependently depressed the formation of all PG formed in the kidney. At 5 x 10(-7) M the formation of 14C-PG was depressed to 45-80% of control and at a concentration of 5 x 10(-4) M it was depressed to 40% or less of control. It is concluded that nicotine elicits an overall depressive effect on the rabbit kidney formation of PG, probably by inhibiting cyclo-oxygenation of AA.

Animals↗