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Biomedical subjects

S Steen

Publications and source records attributed to S Steen.

At least 73 records · Page 4Linked to original sources
PubMed1991

Pulmonary sequelae of prolonged total venoarterial bypass: evaluation with a new experimental model.

Total normothermic venoarterial bypass was established in 6 healthy pigs over a period of 18 hours. A heparin-coated closed extracorporeal system was used and no heparin was administered systemically. During the bypass period the main pulmonary artery was occluded and the heart was maintained in a beating state. All the animals maintained stable hemodynamics and normal blood gases during the entire period of bypass. In the postbypass period, the central hemodynamics continued to be stable while the arterial oxygen tension (inspired oxygen fraction = 0.21) decreased significantly (p less than or equal to 0.05). The total body oxygen uptake, on the other hand, remained unaltered. All the animals died within 4 hours after weaning off the venoarterial bypass circuit on account of pulmonary edema in 2 and cardiac arrest in 4. Death was preceded by progressive pulmonary hypertension and lactacidosis in all the animals. Histological examination of the lungs showed pulmonary parenchymal damage ranging from interstitial edema to intraalveolar hemorrhage and parenchymal necrosis involving more than 80% of the pulmonary parenchyma. A normothermic total venoarterial bypass of 18 hours duration or more produces pulmonary edema of varying severity, pulmonary hypertension, pulmonary parenchymal necrosis, and lactacidosis in healthy juvenile pigs, resulting uniformly in their death. Despite these sequelae the systemic arterial hypoxemia may only be mild to moderate.

Acidosis↗
PubMed1991

Might free arterial grafts fail due to spasm?

The rat femoral artery was used as a free graft and was studied after 2, 7, 14, 30, and 60 days. The patency of the grafts was 100% (2 days, n = 6), 78% (7 days, n = 9), 63% (14 days, n = 8), 33% (30 days, n = 12), and 18% (60 days, n = 11). Histology showed an intimal thickening after 14 days and the media, which in the controls consisted of eight to ten layers of myocytes, was reduced to six to eight cell layers. During the first 2 weeks the graft segments had an impaired contraction when exposed to Krebs solution with 124 mmol/L K+, whereas after 1 month and later the graft segments approached the controls or had even higher contractile force. The thromboxane mimic U-46619 elicited full contractile force at all times whereas the potency was significantly lower during the first 14 days. Noradrenaline was unable to induce contraction in the graft segments during the first 14 days, but at 30 and 60 days it had regained full contractile force and was significantly more potent (approximately 60 times) in the graft segments compared with the controls. This study suggests that intimal thickening and hypercontractility might be a problem in free muscular arterial grafts.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1991

High potassium contents in organ preservation solutions cause strong pulmonary vasocontraction.

Euro-Collins (ECS) and UCLA-formula organ preservation solutions induced strong vasocontraction in porcine pulmonary arteries when studied in organ baths at temperatures of 37 degrees C and 30 degrees C. At 20 degrees C ECS induced a 30% contraction, but at 6 degrees C no contraction (n = 5) or a weak contraction (n = 1) was elicited. Neither prostaglandin E1 nor nifedipine caused any significant reduction of the vasocontraction elicited by ECS and UCLA. Krebs solution, enriched with potassium in amounts corresponding to those in ECS (115 mmol/L) or UCLA (30 mmol/L), induced vasocontraction comparing well with those induced by ECS or UCLA, indicating that it is the high potassium content that causes the vasocontraction. In a second experiment lung segments were stored at 4 degrees C for 9 hours in ECS, UCLA, or Krebs solution. Pulmonary arterial segments were then studied in organ baths at 37 degrees C. The choice of preservation solution did not significantly affect the contractile properties of potassium, noradrenaline, or the thromboxane mimic U-46619. To conclude, high potassium contents in organ preservation solutions induce strong pulmonary vasocontraction in lung temperatures greater than 20 degrees C but not in temperatures less than 10 degrees C. These vasocontractions are not significantly reduced by prostaglandin E1 or nifedipine. We suggest that the initial preservation solution used to cool down the lungs should contain 4 mmol/L or no potassium. When the lung temperature is less than 10 degrees C, a second perfusion might be done, and then a high potassium content (if thought to be essential) will not cause vasocontraction.

Alprostadil↗
PubMed1991

Contractile properties of lymphatics from the human lower leg.

Lower leg lymphatics, taken from seven volunteers, were investigated in vitro. Isometric contractions were induced by noradrenaline, 5-hydroxytryptamine (5-HT), prostaglandin F2 alpha (PGF2 alpha), and the thromboxane A2 (TXA2)-mimetic U-44069. Noradrenaline induced phasic contractions in 6 of 7 segments. The amplitude of the contractions were up to 100% of a previous K+ (124mM)-induced contraction and the frequency at 10(-6)M of noradrenaline was 5-13 min-1. These contractions were unaffected by propranolol (10(-6)M), but they were abolished by phentolamine (10(-6)M). Noradrenaline had an Emax (tonic contraction) of 7% of the K+ (124mM) contraction (n = 7) and the pEC50-value was 6.9 (n = 3). The corresponding values for 5-HT were 21% (n = 5) and 6.4 (n = 3). PGF2 alpha elicited contractions in all segments investigated (Emax = 87%, pEC50 = 5.8, n = 5). U-44069 had high contractile capacity and potency in all investigated segments (Emax = 137%, pEC50 = 8.9, n = 7). Phasic contractions were elicited also by 5-HT, PGF2 alpha and U-44069. Compared to earlier studies of human peripheral lymphatics, these results show that there are regional differences in susceptibility to these vasoactive agents.

Adult↗
PubMed1991

In vitro effects of a thromboxane A2-analogue U-46619 and noradrenaline on contractions of the human thoracic duct.

A piece of a human thoracic duct removed at operation was investigated in organ baths. The duct was cut in 8 ring segments each about 1mm long and isometric tension recorded. The segments were exposed to a potassium rich (124mM) Krebs buffer solution. In only two of the segments were contractions induced (7.2 and 1.0mN, respectively). Noradrenaline and the thromboxane mimetic U-46619 induced tonic and phasic contractions. At a noradrenaline concentration of 10(-5)M the phasic contractions had a frequency of 5 min-1. The highest frequency, 9 min-1, was recorded with 3 x 10(-10)M of U-46619 present in the bath. Noradrenaline had a mean Emax of 50% of the previous K+ (124mM)-induced contraction, and the mean pEC50-value was 6.7. The Emax and pEC50-values of U-46619 were 142% and 9.5, respectively. Postjunctional alpha-adrenoceptors and thromboxane A2-receptors may play a role in the contractility of the human thoracic duct.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1991

Veno-right ventricular bypass as total extracorporeal lung assistance. An experimental study.

Efficacy of veno-right ventricular bypass as a total extracorporeal lung assistance was studied for a period of 24 hours in six healthy pigs with a mean weight of 60 kg. A covalently bonded heparin-coated extracorporeal membrane oxygenation system and a roller pump were used for the bypass. No local or systemic heparin was administered. The bypass was established with an open chest with two 28F venous cannulas and one 24F arterial cannula. The arterial cannula was placed in the right ventricle across the tricuspid valve. With the lung function totally disabled, this extracorporeal lung assistance maintained normal systemic arterial and mixed venous blood gases during the entire 24-hour period in all the animals. No significant tricuspid insufficiency was observed, and the animals maintained normal central hemodynamics. There was no hemolysis, and the platelet counts remained essentially unaltered. Multiple foci of clot formation were observed in all the oxygenators, but no macroscopic thrombosis or embolization was seen either in the heart or in the lungs. A veno-right ventricular bypass offers total extracorporeal lung assistance in 60 kg juvenile pigs for a period of 24 hours. Tricuspid valve competence is an important prerequisite for the success of this procedure.

Animals↗
PubMed1990

Effects of alpha-adrenoceptor active drugs, prostaglandin F2 alpha and vasopressin on cystic and hepatic arteries of pig and man.

Human and pig cystic and pig hepatic arteries were suspended in tissue baths and the effect of alpha-adrenoceptor selective drugs, prostaglandin F2 alpha (PGF2 alpha) and vasopressin were investigated. Prazosin fulfilled the criteria for competitive antagonism in concentrations 10(-9)-10(-7) M. The pA2-values were 9.53 in human cystic, 9.74 in pig cystic, and 9.57 in pig hepatic artery. Rauwolscine had no significant effect in the different arteries. In human cystic artery noradrenaline had significantly (P less than 0.05) higher Emax and pEC50-values (135% of the preceding K(+)-induced contraction and 6.4, respectively) compared with pig cystic (106% and 5.7, respectively) and pig hepatic artery (116% and 5.9, respectively). Vasopressin had no effect in the cystic arteries, whereas it had a high potency (pEC50 was 8.5) but low intrinsic activity (Emax was 14%) in pig hepatic artery. Prostaglandin F2 alpha had a significantly higher Emax in human than in pig arteries. No differences were found in pEC50-values. This study indicates a similarity in pharmacological characteristics of some vasoactive drugs especially between pig cystic and hepatic arteries. If this is also true in man, the easily obtainable cystic artery can be used for screening the effect of drugs on the hepatic artery.

Adrenergic alpha-Agonists↗
PubMed1990

Reversal of lethal citrate intoxication by intravenous infusion of calcium. An experimental study in pigs.

Intravenous infusions of 750 and 1000 ml 2.2% sodium citrate were given over a 60 min period to 17 pigs to study its effect on aortic pressure, electrocardiogram, ionised calcium, and citrate clearance. In group 1 (seven pigs) the animals did not receive calcium and the median survival time was 30 min (range 20-70 min). In groups 2 and 3 (five in each group) the pigs were treated with calcium chloride infusions (1 ml 10% calcium chloride to 10 ml citrate) and they all survived. In group 1 the ionised calcium concentrations in blood fell to values below 0.4 mmol/l, after which the blood pressure dropped abruptly. In the animals treated with calcium the mean ionised calcium concentration fell to 0.6 mmol/l, whereas total calcium increased to more than 7 mmol/l. The aortic pressure was consistently within normal values in the groups treated with calcium, but in the group that was not treated the blood pressure fell dramatically. There was no correlation between electrocardiographic changes and ionised calcium concentrations. In summary, calcium was an effective antidote to lethal citrate intoxication, and the only reliable method of determining the necessary dose of calcium was monitoring of ionised calcium concentrations.

Animals↗
PubMed1990

Intraoperative collection of shed blood with citrated compresses for autotransfusion. An experimental study in pigs.

Six pigs were used to study whether the collection of shed blood by means of surgical compresses instead of suction traumatizes such blood. In an in vivo part of the study, the whole blood volume of the pigs was retransfused after treatment with citrated compresses, and in an in vitro part the blood was treated extensively with compresses and analyzed. All animals survived, with a minor fall in hemoglobin after 48 hours and a rise in serum citrate concentration at the end of the experiment. A study of the coagulation system revealed no important change after retransfusion of compress-treated blood. In the in vitro part of the study, repeatedly squeezing blood from the compresses increased the concentration of free hemoglobin to a maximum of 5 g/l after ten squeezes, whereas platelets were numerically unchanged. The study indicates that collecting shed blood by means of surgical compresses may be a safe and efficient method.

Animals↗
PubMed1989

Cerebral function monitoring in rats with a critical hepatic injury treated with pneumatic antishock garment and infusion.

Twenty-nine rats were subjected to a severe standardized hepatic injury and divided into four groups. In addition to controls, the animals were treated with PASG inflated to 40 mm Hg, PASG and infusion of Ringer's acetate, or PASG and infusion of Ringer's acetate and Dextran 70 in combination. The aim of the infusion therapy was to stabilize the mean aortic blood pressure at 60 mm Hg. PASG significantly prolonged the survival time and the time during which a sensory evoked response could be observed. The PASG also prolonged the time before the EEG amplitude began to decrease or a burst-suppression pattern appeared in the EEG. Intravenous infusion of Ringer's acetate did not prolong these times compared to when PASG was used alone; when Dextran 70 was added to the infusion therapy these times were reduced. Changes in the EEG were recorded at a mean aortic pressure of 60 mm Hg when infusions were given, whereas the aortic pressure had to fall to 40 mm Hg before any changes could be observed when no infusions were used.

Acute Disease↗
PubMed1989

The strong contractile effect of the thromboxane receptor agonist U-46619 in isolated human pulmonary arteries and its competitive antagonism by BM-13.505.

Ring segments (I mm in diameter) of the pulmonary artery obtained from 16 patients undergoing thoracic surgery were mounted in tissue baths. Cumulative concentration-response curves of some prostanoids and amines were obtained, and Emax and pEC50 values calculated. Noradrenaline, phenylephrine, clonidine and serotonin (5-HT) showed low intrinsic activities. Prostaglandin F2 alpha (PGF2 alpha) induced strong contractions with an Emax of 126% of the preceding K+ (124 mM)-induced contraction, but its potency was low (pEC50 = 5.70). The thromboxane receptor agonists U-46619 and U-44069 induced strong contractions (Emax = 139% and 133% respectively) and were significantly more potent than the other drugs used (pEC50 = 8.43 and 8.30 respectively). The thromboxane receptor antagonist BM-13.505 (10(-8) to 10(-6) M) caused rightward parallel shifts of the U-46619 concentration-response curves without reduction of Emax, indicating competitive antagonism.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1989

Comparative effects of the alpha-adrenoceptor agonists noradrenaline, phenylephrine and clonidine in the human saphenous vein in vivo and in vitro.

The alpha-adrenoceptor-mediated contractile effects of noradrenaline (alpha 1 + alpha 2), phenylephrine (alpha 1) and clonidine (alpha 2) on human saphenous veins were investigated in vivo and in vitro. By infusion (0.3 ml min-1) of the drugs (increasing concentrations in the infused solution) into distended (40 mmHg) saphenous veins in six healthy subjects, local vasoconstriction was induced, measured by a photo-electric device. The drugs induced dose-dependent contractions in all subjects, and dose-response curves were constructed. These were compared with concentration-response curves based on in-vitro results. Macroscopically normal saphenous veins, taken at saphenousectomies, were used, and the preparations were contracted isometrically in organ baths by the agonists. From the curves obtained in vivo and in vitro, the relative potencies of phenylephrine and clonidine (in relation to noradrenaline) were calculated and compared. The relative potencies of phenylephrine in vivo (76%) and in vitro (82%) did not differ significantly. However, the relative potency of clonidine was significantly (P less than 0.05) lower in vivo (90%) than in vitro (99%). Thus, it is concluded that there are differences between the results obtained in vivo and in vitro, stressing the importance of comparative in vivo-in vitro studies.

Adrenergic alpha-Agonists↗
PubMed1989

Direct evidence of active sympathetic vasodilatation in the skin of the human foot.

1. During operative aorto-femoral vascular reconstructions on sixteen patients, the sympathetic chain was stimulated electrically between the L2 and L4 ganglia while blood flow was monitored by laser doppler flowmeters from the skin on the sole of the foot and the ankle and by an electromagnetic flowmeter from the deep femoral artery. Epidural anaesthesia to at least the T6 level was used which excluded reflex effects. 2. Stimulation (10 Hz) at 1-12 mA current strengths for 30 s evoked both reductions and increases of blood flow in glabrous and hairy skin. Initial short-lasting flow increases (durations 9-19 s) followed by sustained decreases were common: sometimes there were sustained flow increases at low and decreases at high current strengths. 3. In the deep femoral artery (supplying predominantly muscle) only flow reductions were evoked. 4. The results provide evidence for sympathetically mediated vasodilatation in the skin of the human foot whereas leg muscles may be supplied by vasoconstrictor nerves only.

Aged↗
PubMed1989

Antagonism of thromboxane receptor induced contractions in isolated human groin lymphatics.

In vitro studies were performed on lymphatics obtained from the groin in 19 patients undergoing vascular surgery. The lymphatics were mounted in tissue baths, and isometric contractions were induced by increasing concentrations of the thromboxane A2 (TXA2) mimetic U-46619. In comparison to K+ (124mM)-induced contraction, which were used as an internal standard, the response to U-46619 had an Emax of 105 +/- 5.9%. The pEC50-value was 8.14 +/- 0.09. The effects of two thromboxane receptor (TP-receptor) antagonists, L-636,499 and BM-13,505, were investigated. Both antagonists caused concentration-dependent right-ward shifts without depression of Emax of the U-46619 concentration-response curves. The slopes of the regression lines in a Schild plot for both antagonists did not differ from one, indicating competitive antagonism. The pA2-value of BM-13,505 (7.89) was 65 times higher than that of L-636,499 (6.08). The results suggest that the receptor involved in the prostanoid contraction in human groin lymphatics is of the TP-subtype.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1989

Contractility of human leg lymphatics during exercise before and after indomethacin.

Subcutaneous lymphatics in the lower leg were catheterized in the retrograde direction in 6 healthy male subjects. The catheter was connected to a pressure transducer, and pressure was measured during three stages of exercise including standing, tip-toeing, and running in place. Before the third stage, indomethacin (50mg) was given i.v. Rhythmic pressure waves were registered in each subject. During the second stage, when the subjects were "warmed up," the frequency (min-1) was 2.4 +/- 0.5 (mean +/- SEM). The corresponding values during tip-toeing and running were 5.8 +/- 0.7 (p less than 0.05) and 5.4 +/- 0.5 (p less than 0.05), respectively. The amplitudes (mean values between 3.2-4.7mmHg while standing) were not consistently altered during tip-toeing or running in any of the three stages. During standing there was a negative correlation between frequency and amplitude. No such correlation was found during tip-toeing or running, or after injection of indomethacin. Indomethacin did not significantly alter any of the measured parameters, but in two subjects the frequencies and amplitudes were decreased (about 50%) during standing, tip-toeing, and running.

Adult↗
PubMed1988

The effects of pneumatic antishock garments in the treatment of critical abdominal injuries in rats.

Thirty rats were subjected to a standardized critical aortic injury and divided into six groups. In addition to controls, the animals were treated with a pneumatic antishock garment (PASG), massive intravenous or intra-aortic saline infusion, or PASG in combination with either massive intravenous or intra-aortic saline infusion. Twenty-six rats were subjected to a standardized hepatic injury and divided into four groups. In addition to controls, the animals were treated with PASG, massive intravenous saline infusion, or PASG in combination with massive intravenous saline infusion. These animals were allowed to bleed for 5 minutes before the treatment was started. The treatment with PASG alone prolonged the median survival time significantly from 7 min in the control group to greater than 120 min in the PASG group in rats with an aortic injury and from 33 to greater than 120 min in rats with a hepatic injury. Intravenous infusion of saline did not prolong the median survival time. Intravenous infusion in combination with PASG did not have any positive effects on median survival time or median mean aortic pressure and failed to prolong the median survival time significantly in rats with a liver injury, as six out of eight animals developed a lethal pulmonary edema.

Abdominal Injuries↗
PubMed1988

Hemoconcentration by ultrafiltration during open-heart surgery.

Ultrafiltration was used during extracorporeal circulation (ECC) with heart-lung machine in 17 critically ill cardiac patients. In ultrafiltration (hemofiltration), water and small molecules (e.g. urea, creatinine and electrolytes), are separated from the blood by hydrostatic pressure generated on the blood side of a semipermeable membrane. The patients had severe water overload for three reasons, viz. congestive heart failure (10), renal failure (6) or iatrogenic extreme hemodilution (1). On average 2090 (800-5700) ml water was filtered off, increasing the hematocrit from 25 to 33%. Three indications for ultrafiltration during ECC and two modes of such treatment are exemplified in three case reports. No negative effect of the treatment was observed. Ultrafiltration during ECC thus may help to improve the postoperative course in patients with severe water overload due to congestive heart failure, renal failure or iatrogenic extreme hemodilution.

Aged↗