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Biomedical subjects

A Wennmalm

Publications and source records attributed to A Wennmalm.

At least 109 records · Page 6Linked to original sources
PubMed1985

Adenosine-induced coronary release of prostacyclin at normal and low pH in isolated heart of rabbit.

Rabbit hearts were perfused by the Langendorff method with drug-free perfusion medium or with a medium containing adenosine (10(-7) M-10(-4)M) and the coronary and transmyocardial efflux rates of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were measured. Perfusion was performed both at pH 7.4 and 6.9. In other experiments the hearts were pre-labelled with [14C]-arachidonic acid and the coronary efflux of radioactivity and of labelled lipids and 6-keto-PGF1 alpha were determined. The basal coronary flow was elevated by almost 70% during tissue acidosis, in comparison to control. Adenosine induced a dose-dependent increase in the coronary flow, amounting to about 75% at normal pH and a drug concentration of 10(-5)M. The adenosine-induced increase in coronary flow was not facilitated by low pH. The base coronary efflux of 6-keto-PGF1 alpha from the hearts was 2.5--3.6 ng min-1. Adenosine (10(-6)-10(-5)M) significantly facilitated this efflux, up to 6.5 ng min-1. The efflux of 6-keto-PGF1 alpha was not changed by perfusion with acidic medium, either in the basal state or during perfusion with adenosine. The basal interstitial efflux of 6-keto-PGF1 alpha was 4.5-5.5 ng 3 min-1. This efflux was not affected by perfusion of the heart with adenosine-containing medium. In hearts pre-labelled with [14C]-arachidonic acid, adenosine (10 microM) induced a specific liberation of labelled lipid-extractable substances, including 6-keto-PGF1 alpha. 6 From these data we conclude that adenosine stimulates the liberation of 6-keto-PGFI. from the rabbit heart by increasing precursor availability and subsequent formation of prostacyclin in the coronary vessels. Furthermore, the increase in coronary flow induced by tissue acidosis is not related to an augmented formation of prostacyclin.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Prostacyclin infusion in patients with acute myocardial infarction.

To investigate whether prostacyclin protects ischaemic myocardium in humans the effect of prostacyclin or placebo was studied in two groups of patients with acute myocardial infarction who presented within six and 16 hours of the onset of symptoms. Intravenous infusion of prostacyclin or placebo was started immediately after admission at a rate corresponding to 4-5 ng/kg/minute. The infusion was maintained for 72 hours. Clinical status, electrocardiograms, plasma enzyme activity, infarct extension during the infusion, and reinfarction after the infusion were studied. Prostacyclin was well tolerated by most patients: neither systemic blood pressure nor heart rate differed between the two groups. In the 11 patients who received treatment within six hours of the onset of symptoms prostacyclin significantly lowered the maximum plasma activities of creatine kinase MB and lactate dehydrogenase. In the 19 patients who received treatment 6-16 hours after the onset of symptoms prostacyclin had no such effect. None of the patients receiving prostacyclin had an extension of the infarction during the infusion, whereas four patients receiving placebo did; this difference was significant. These data are the first to provide evidence that prostacyclin might limit myocardial injury in patients with acute myocardial infarction.

Adolescent↗
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

Effect of nicotine on the formation of prostacyclin-like activity and thromboxane in rabbit aorta and platelets.

The effect of nicotine on the bioformation of prostacyclin (PGI2) and of thromboxane (Tx)B2 in rabbit aorta and platelets, respectively, was investigated. Rabbit aortic rings were incubated with [14C]-arachidonic acid ( [14C]-AA) and the incubation products were separated with thin layer chromatography (t.l.c.). Alternatively, the aortic rings were incubated without substrate and their spontaneous formation of platelet anti-aggregatory activity was measured. Rabbit platelet microsomes were incubated with [14C]-AA and the products formed were separated with t.l.c. Rings of aorta were found to be incapable of converting added [14C]-AA to labelled 6-keto-PGF1 alpha (the stable hydrolysis product of PGI2). Rings of aorta incubated in saline medium spontaneously formed PGI2-like activity. This formation was dose-dependently inhibited by nicotine, with an I50 of about 10(-4) M. Platelet microsomes converted [14C]-AA to labelled TxB2. This formation was unaffected by nicotine. It is concluded that a true difference in sensitivity to nicotine exists between cyclo-oxygenase in rabbit aorta and platelets. The data also demonstrate a tissue difference between rabbit aorta and platelets concerning their utilization of exogenous AA as substrate in the formation of platelet active compounds.

Adenosine Deaminase↗
PubMed1984

Human renal allograft blood flow, oxygen extraction, and prostaglandin release: their bearing on graft function.

The intraoperative blood flow, oxygen extraction, and prostaglandin production were studied in 26 transplanted kidneys. Eleven were from related donors and 15 from cadavers. Postoperative dialysis was required by four of the five recipients of a cadaveric kidney having an intraoperative blood flow of less than 200 ml/min/100 gm of tissue. All the cadaveric kidneys with a blood flow greater than this produced urine immediately after revascularization. The blood flow in the cadaveric kidneys was related to the total ischemia time, with a lower rate in kidneys preserved for more than 24 hours. There was no difference in the oxygen extraction values for the kidneys in the related donors, in their associated recipients, and in the cadaveric organ recipients. During postoperative catheterization of the renal vein the oxygen extraction for the kidneys from related donors was practically normalized, while for the cadaveric kidneys it was increased though still subnormal. This difference was also reflected in the renal function at that time. No evidence was found that prostaglandins are involved in the regulation of the blood flow to the graft kidney.

Adolescent↗
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

Effect of different prostaglandin synthesis inhibitors on post-occlusive blood flow in human forearm.

The vascular relaxation response in the human forearm that follows a short period of arterial occlusion (reactive hyperemia) was investigated with respect to its dependence on an intact PG synthesis. In 10 healthy subjects, five men and five women, forearm blood flow was measured, using venous occlusion plethysmography, in the basal state and during the recovery phase following 5 min of obstructed arterial flow. The subjects were studied at nine different occasions. At six of these they were pre-treated with the highest recommended doses of either of the PG synthesis inhibitors acetyl-salicylic acid, diclofenac, ibuprofen, indomethacin, naproxen or piroxicam; the remaining occasions were controls, performed in the absence of drugs in the beginning, middle, and end of the series. All the drugs significantly decreased the total reactive hyperemia following 5 min of arterial occlusion. Ibuprofen was the most efficient agent, inhibiting the total reactive hyperemia by more than 70%, and naproxen was least active, producing about 35% inhibition. The rest of the drugs diminished the total reactive hyperemia by 55-65%. Basal forearm blood flow was not affected by either of the agents. From these data we conclude that drugs which inhibit PG synthesis in man have in common the capacity to decrease post-occlusive reactive hyperemia. This indicates that an activation of the local release of arachidonic acid, leading to formation of vasodilator PG, is one of the main factors behind the vascular smooth muscle relaxation response to arterial occlusion.

Adolescent↗
PubMed1983

Hypoxia elicits liberation of anti-aggregatory substances from isolated rabbit hearts.

The hypothesis was investigated that myocardial hypoxia stimulates the production of platelet anti-aggregatory substances in the heart. Rabbit hearts were perfused under normoxic or hypoxic conditions and the coronary and interstitial effluents from the hearts were separated. The occurrence of anti-aggregatory activity (AAA) in the interstitial effluent was detected in vitro from its capacity to inhibit ADP-induced platelet aggregation. The AAA in the effluent was deemed to be prostacyclin (PGI2) if its release was abolished by administration of indomethacin (5 X 10(-5) M) to the heart, and to be adenosine if it was abolished by incubation of the effluent with adenosine deaminase. During normoxic perfusion, only a minor efflux of AAA appeared from the heart; neither was the efflux appreciable during mild hypoxia (30 or 60% O2). Severe hypoxia (venous pO2 below 5 kPa), on the other hand, was associated with a marked release of AAA. Incubation of hypoxic effluent with adenosine deaminase resulted in a small loss of activity, indicating that the major part of the AAA was not ascribable to adenosine. After indomethacin treatment, significant amounts of AAA still appeared in the effluent during hypoxia. However, unlike the case before indomethacin, this AAA was completely destroyed by adenosine deaminase. From these data, we conclude that myocardial hypoxia can mobilize either of two independent mechanisms for protection against platelet aggregation: an activation of the synthesis and release of prostacyclin, and a more complete breakdown of ATP, leading to an increased formation and efflux of adenosine.

Adenosine↗
PubMed1983

Effect of cigarette smoking on reactive hyperaemia in the human finger.

The effect elicited by cigarette smoking on the reactive hyperaemia that develops following release of arterial occlusion in human skin was investigated, and compared to the corresponding effects elicited by oral administration of indomethacin (an inhibitor of the prostaglandin-forming enzyme cyclo-oxygenase) or nicotine, or by smoking of nicotine-free cigarettes. Finger blood flow was determined in human volunteers, using venous occlusion plethysmography, in the basal state and after 5 min of arterial occlusion. All subjects were studied before and after they had smoked two tobacco cigarettes, two herbal (nicotine-free) cigarettes, or chewed a nicotine chewing gum. The determinations before and after tobacco smoking were repeated after administration of indomethacin. In separate series, the effects of smoking on heart rate and systemic blood pressure were recorded. The basal finger blood flow was significantly (P less than 0.05) diminished following cigarette smoking, by about 35%, and so was the reactive hyperaemia (P less than 0.05), by about 55%. The reactive hyperaemia after administration of indomethacin in combination with cigarette smoking did not differ from that obtained after cigarette smoking alone. The reactive hyperaemia was not affected by oral administration of nicotine, or by smoking of two herbal cigarettes. Cigarette smoking elicited increases in heart rate and systemic blood pressure that were of similar magnitude before and after indomethacin. From these data, we conclude that cigarette smoking elicits an inhibitory effect on the reactive hyperaemia in the human finger. This effect is probably not caused by nicotine, and seems to act via blockade of the vascular relaxation normally medicated by locally formed cyclo-oxygenase products.

Adult↗
PubMed1983

Platelet aggregability in smoking and non-smoking subjects.

The hypothesis was investigated that the arachidonic acid (AA) system has a different impact on platelet function in smoking compared to non-smoking subjects. Arterial blood was sampled from smokers and non-smokers, and platelet-rich plasma (PRP) was prepared. There were no differences in sex and age distribution between the groups. One portion of the PRP was used to determine the lowest amount of AA required to induce platelet aggregation. In other portions the endogenous anti-aggregatory (prostacyclin/PGI2/-like) activity in the blood was determined, after reinforcing it with theophylline. There was no difference between smokers and non-smokers regarding the amount of AA required to induce platelet aggregation. In fresh PRP prepared from blood from non-smoking subjects theophylline (10(-4) M) induced a 12-17% inhibition of the ADP-induced aggregation of platelets, indicating the presence of endogenous subthreshold concentrations of PGI2-like activity in their blood. The corresponding inhibition in fresh PRP prepared from blood from smokers was significantly lower (4-7%), suggesting lower endogenous concentrations of PGI2-like activity in their blood, or alternatively, decreased platelet sensitivity to the action of such activity. From these data we conclude that smokers differ from non-smokers with regard to their platelet function: platelet aggregability in response to AA is unaffected, while the endogenous anti-aggregatory power in the plasma is decreased. These observations may be of significance for the cardiovascular hazards connected with smoking.

Adult↗