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Biomedical subjects

L Appelgren

Publications and source records attributed to L Appelgren.

At least 37 records · Page 2Linked to original sources

Epidural versus intrathecal morphine-bupivacaine: assessment of consecutive treatments in advanced cancer pain.

Twenty-five patients with multifocal and multitype (somatic, visceral, and neurogenic) advanced cancer pain who experienced severe pain despite extradural (ED) morphine and bupivacaine were converted to intrathecal (IT) morphine and bupivacaine. The consecutive ED and IT periods (2-174 days, median = 50 days, and 1-305 days, median = 37 days, respectively) were assessed in clinical terms (daily analgesic dosages giving acceptable pain relief and quality of life expressed as sleeping hours and walking/daily activities). With the IT treatment, the total (all routes) opiate consumption and the daily doses of spinal morphine and spinal bupivacaine decreased significantly at the beginning of the treatment compared to the ED period, and continued to be significantly reduced for up to 1 wk for spinal opiate and bupivacaine and 6 mo for total opiate. The spinal opiate and bupivacaine doses were still lower in 50% of the patients at the end of the IT treatment compared to the end of the ED period. When final ED versus initial (2nd day) IT doses were assessed, the daily median dose ratios were 7.5 for total opiate and 4 for both spinal opiate and bupivacaine. Subsequently, lower daily volumes and higher concentrations were needed for IT administration of the drugs. During the first month of the IT treatment, sleeping and walking scores improved compared to ED treatment. Thus, the IT treatment gave more satisfactory pain relief, and--because of lower daily doses and volume--proved to be more suitable for treatment at home (continuous infusion from external pumps) than the ED treatment.

Adult↗

Epidural anaesthesia and postoperative colorectal motility--a possible hazard to a colorectal anastomosis.

The effects of epidural anaesthesia (EDA, mepivacaine) and EDA in combination with atropine and neostigmine on postoperative intestinal motility were studied in 17 patients undergoing operation for cancer of the rectum or sigmoid colon. Motility was recorded by a volumetric technique. Epidural anaesthesia (EDA) increased motor activity in the small bowel as well as in the left colon and rectum. Phasic motility dominated in the small intestine whereas tonic and segmental contractions were recorded from the large bowel. EDA induced a powerful tonic contraction with a concomitant shortening of the rectum. This effect was inhibited by atropine. The influence of atropine/neostigmine on left colonic motor activity was studied in six patients before and during EDA in a cross-over fashion. When administered alone, atropine/neostigmine did not cause any motility increase. Atropine/neostigmine administered during EDA, however, elicited a significant increase of motility. The increase of intestinal motor activity induced by EDA may expose a newly constructed colorectal anastomosis to undue strain in the immediate postoperative period. When EDA is used in combination with general anaesthesia, particular attention should be directed towards the use of neostigmine for reversing the effect of nondepolarizing muscle relaxants. Atropine appears under such circumstances not to protect from the excitatory effects of this drug on colorectal motility.

Aged↗

Acyclovir concentrations in serum and cerebrospinal fluid at steady state.

A long-term clinical trial of acyclovir, 800 mg tid, as a therapeutic agent in multiple sclerosis (MS) is in progress. In three patients paired serum and cerebrospinal fluid (CSF) specimens were sampled after one, four, eight and twelve months of continuous treatment. These samples were collected 1.5 h before or 1.5 h after an oral dose. Acyclovir concentrations were assessed by radioimmunoassay. In the CSF, the acyclovir concentration was relatively stable, with a mean of 0.83 microM, while the serum acyclovir concentration was variable with mean peak and trough concentrations of 4.08 and 2.47 microM, respectively. In two other MS patients the acyclovir concentration time profile in serum and CSF was studied at steady state during the 8 h dose interval. In this study the acyclovir concentration in the CSF was only slightly affected by the fluctuations in serum and the acyclovir CSF/acyclovir serum ratio was apparently not influenced by the blood-brain barrier function. We found no indication of an accumulation of acyclovir in cerebrospinal fluid after one to twelve months of oral treatment.

Acyclovir↗

Control of intraoperative hypertension with isoflurane in patients with coronary artery disease: effects on regional myocardial blood flow and metabolism.

The effect of isoflurane on regional myocardial metabolism and blood flow, when used as an adjunct to fentanyl-nitrous oxide anesthesia, to control intraoperative hypertension was investigated. Twenty-two patients with two- or three-vessel coronary artery disease with an ejection fraction greater than 0.5 and on beta-blockers up to the morning of surgery were studied during elective coronary artery by-pass grafting. Systemic and pulmonary hemodynamics, and regional (great cardiac vein, GCVF) myocardial blood flow and myocardial metabolic parameters were measured. In 10 patients, both GCVF and global (coronary sinus, CSF) myocardial blood flows were recorded. Measurements were made 1) after induction of anesthesia but prior to skin incision, 2) during sternotomy, and 3) during isoflurane administration after its use to reduce arterial pressure to the presternotomy level. The increase in systemic arterial pressure during sternotomy was due to an increase in systemic vascular resistance accompanied by increases in heart rate, pulmonary capillary wedge pressure, (PCWP) regional myocardial oxygen consumption and extraction, GCVF and total coronary vascular resistance. Isoflurane reduced systemic arterial pressure but not PCWP, to presternotomy levels within 6.9 +/- 0.7 minutes at an end-tidal concentration of 1.5 +/- 0.2%. Isoflurane induced a pronounced systemic and coronary vasodilatation and increases in cardiac index, heart rate and regional myocardial oxygen extraction while the GCVF/CSF ratio remained unchanged. While mean regional--MLE% values were not effected by sternotomy, in two patients myocardial lactate production was seen during sternotomy but not during isoflurane. In another two patients, isoflurane induced lactate production.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Sympathetic nervous influence on the internal anal sphincter and rectum in man.

The effect of sympathetic nerve block and efferent stimulation of the sympathetic nerves on anorectal motility was studied in 21 patients undergoing operation for rectal carcinoma. Anal pressure and rectal volume were simultaneously recorded before and after epidural anaesthesia and during nerve stimulation. Efferent electrical stimulation of the presacral hypogastric nerves (HGN) elicited a contraction of the internal anal sphincter (IAS) in 13 out of 15 patients. The contraction was preceded by a relaxation in seven patients. In the rectum stimulation of the HGN caused variable responses. A weak contraction was the most frequent response. Efferent stimulation of the periarterial lumbar colonic nerves (LCN) elicited a clear-cut contraction of the IAS, while rectal motor responses were only occasionally observed. Epidural anaesthesia encompassing the thoraco-lumbar region (EDA), when used to block the sympathetic discharge to the IAS and the rectum, caused a reduction of anal pressure (28 +/- 11%) and an increased rectal tone. The results imply that the human IAS receives a sympathetic excitatory innervation via both the HGN and the LCN. Furthermore, it appears that the HGN convey inhibitory fibres to the IAS. The rectal responses to EDA and sympathetic nerve stimulation also indicate the presence of both excitatory and inhibitory neurones in the sympathetic nerve supply to the rectum in man.

Aged↗

Effects of hemodilution on skeletal muscle blood flow and blood viscosity in vivo after splanchnic stasis.

Pressure-flow relationships and apparent viscosity in vivo were determined in the skeletal muscle of the dog in experimental shock induced by splanchnic venous stasis and after subsequent hemodilution with low molecular weight dextran. The calf muscles of one hind limb were surgically isolated and pressure-flow curves constructed for blood and a cell-free reference solution during vasodilation. The apparent viscosity in vivo was determined by comparing the flow values for blood and the reference solution at identical perfusion pressures. A shock state with hypotension and hemoconcentration was induced by laparotomy and splanchnic venous stasis. Hemodilution was subsequently produced by low molecular weight dextran. After splanchnic stasis, skeletal muscle blood flow decreased and viscosity in vivo increased disproportionately in relation to the increase in hematocrit. Hemodilution could reverse the flow and viscosity changes induced during the shock period. It is concluded that a shock state associated with hemoconcentration results in flow stagnation in the skeletal muscle with increased in vivo viscosity and that the changes can be reversed by hemodilution.

Animals↗

Intratumor distribution of capillary permeability surface area product (PS) correlated to tumor vascular space and blood flow.

The intratumor distribution of the capillary permeability surface area product (PS) correlated to the intratumor distribution of vascular space and of blood flow was studied by labeled albumin in a transplantable rat fibrosarcoma. A wide heterogeneity in intratumor distribution of PS was found. The tumor PS values were not significantly correlated to tumor vascular space or to blood flow values. This might suggest that intravascularly administered drugs could reach a comparative high intratissue concentration also in less vascularized tumor areas.

Albumins↗

Effects of increased plasma viscosity and red blood cell aggregation on blood viscosity in vivo.

The effects of increased plasma viscosity and induced red blood cell (RBC) aggregation on apparent viscosity of blood in vivo in the skeletal muscle of the dog were studied. Apparent viscosity in vivo was determined in the isolated and vasodilated calf muscles of one hindlimb by comparing pressure-flow relationships for RBC suspensions with pressure-flow relationships for a Newtonian solution of known viscosity. RBC suspensions of increased plasma viscosity with and without RBC aggregation were obtained by substituting plasma with isoviscous solutions of high- and low-molecular-weight dextran in saline. Hematocrits of the suspensions were adjusted to either 45 or 60%. The viscosities of the suspensions in vitro were determined in a Wells-Brookfield viscometer. Apparent viscosity of blood in vivo was found to be mainly dependent on the viscosity of plasma. RBC aggregation had no significant influence on the viscosity in vivo.

Animals↗

Blood flow and in vivo apparent viscosity in working and non-working skeletal muscle of the dog after high and low molecular weight dextran.

We studied the effect of high and low molecular weight dextran on blood flow and in vivo apparent viscosity in the vasodilated vascular bed of working and non-working skeletal muscle. In 12 mongrel dogs, the calf muscle of one hindlimb was isolated. Vasodilation was induced either by sciatic stimulation setting the muscle at rhythmic work or by intraarterial infusion of papaverine. Blood flow was measured electromagnetically at different perfusion pressures. In vivo apparent viscosity was calculated by comparing pressure-flow relationship for blood and a reference solution. Viscosity in vitro was determined in a cone-plate viscometer. A hyperviscous state was induced by intravenous infusion of high molecular weight dextran (HMWD). Hemodilution subsequently was produced by administration of low molecular weight dextran (LMWD). After HMWD, blood flow decreased to 30% of control values in the non-working group and to 45% of control values in the working group. After subsequent infusion of LMWD, blood flow returned to 60% of control values in the non-working group and to 70% of control values in the working group. In vivo apparent viscosity increased to values 250% above control in the non-working group and to 120% above control in the working group following HMWD. After subsequent infusion of LMWD in vivo, apparent viscosity decreased, but remained at values 65% above control in the non-working group and 45% above control in the working group. Thus, the flow impairment induced by HMWD was less pronounced in the working muscle, indicating a flow-preserving effect of rhythmic muscle contractions in this state of disturbed blood rheology. In contrast, the flow-improving effect of LMWD by hemodilution was more pronounced in the non-working muscle.

Animals↗

Influence of tranexamic acid on tumour blood flow.

The influence on the intratumour blood flow distribution in a transplantable rat sarcoma by a potent antifibrinolytic drug, tranexamic acid, administered intraperitoneally for 3 or 10 days was studied by the intratumour distribution of intravenously injected 86Rb. A local Xenon clearance technique was used to study the direct effect of tranexamic acid on local tumour blood flow. local tumour blood flow and the intratumour blood flow distribution after administration of tranexamic acid for 3 days were unchanged compared to controls. Prolonged administration of tranexamic acid changed the intratumour blood flow distribution significantly towards low flow values. This might be one mechanism behind the inhibiting effect of tranexamic acid in tumour growth rate, previously observed in both experimental and clinical studies.

Animals↗

The effect of polycythemia on blood flow in working and non-working skeletal muscle.

The effect of acutely induced polycythemia on blood flow and viscosity in the vasodilated vascular bed of working and non-working skeletal muscle was studied. In 12 mongrel dogs anesthetized with thiopental sodium the calf muscle of one hind limb was isolated. Vasodilation was induced either by sciatic stimulation setting the muscle at maximal work or by i.a. infusion of papaverine. Blood flow was measured at different perfusion pressure before and after infusion of 300 ml packed homologous red cells. Blood viscosity in vitro was determined in a coneplate viscometer. Apparent viscosity in vivo was analyzed by comparing pressure-flow relationships for blood and a reference solution. Polycythemia decreased blood flow by 35% in the non-working muscle but less than 10% in the working muscle at comparable perfusion pressures. Blood viscosity in vitro increased by 35% at low shear rates. Apparent viscosity in vivo increased by 35% in the non-working muscle but less than 10% in the working muscle. The flow impairment induced by polycythemia was far more pronounced in the non-working skeletal muscle indicating a flow facilitation by the rhythmic muscle contractions. Erythrocyte flow in fact increased in the working muscle after induced polycythemia while decreased in the non-working muscle.

Animals↗

Skeletal muscle microcirculation and oxygenation in experimental intestinal shock: A study on the efficacy of different plasma substitutes.

Shock was induced in 60 dogs by exteriorization of the small intestine for three hours. The relative effectiveness of various hemodiluting agents on the microcirculation was measured as skeletal muscle capillary blood flow (QXe) and capillary permeability (P) surface area (S) for plasma (PSp), as calculated from the clearances of two locally injected isotopes, 133 Xenon and 131 Iodide. Skeletal muscle oxygen tension (Pm(2) was measured with a tissue PO2 electrode. During shock QZe decreased to 26%, PSp to 31% of the initial values, and PmO2 dropped from 51 to 18 mmHg. The degree of recovery from shock was assessed after reposition of the intestine and the infusion of different plasma substitutes (albumin, dextran 40, dextran 70, gelatin, ACD-plasma, and Ringer's acetate). Return of the intestine to the abdominal cavity did not in itself improve the shock condition. Dextran 40 and dextran 70 infusion increased QXe, PSp, and PmO2 to or above control levels, PSp to 60%, and QXe to 40% of the control values. Ringer's acetate gelatin, and ACD-plasma did not improve QXe but increased PSq to 62-67% of control values. Albumin and dextran increased PmO2 significantly in relation to no-fluid infusion. Only dextran 40 and dextran 70 increased both QXe and PSp significantly in relation to no -fluid infusion.

Anesthesia↗

Polycythemia, viscosity and blood flow in working and non-working skeletal muscle in the dog.

The relationship between hematocrit and blood flow in the vasodilated working and non-working skeletal muscle at different perfusion pressures was studied. After acutely induced polycythemia in the flow decreased by 35% in the non-working muscle which was proportional to the increase of viscosity measured in vitro. In the working muscle there was only a small non-significant decrease of flow after polycythemia indicating flow improvement at increased hematocrit by rhythmic muscle contractions.

Animals↗

Correlation between tissue pH, cellular transmembrane potentials, and cellular energy metabolism during shock and during ischemia.

The relevance of two direct techniques for monitoring of cellular function during tissue hypoxia has been evaluated. Tissue pH and cellular transmembrane potentials were registered in canine skeletal muscle during intestinal exteriorization shock and during prolonged local tourniquet ischemia. The obtained pH and transmembrane potential changes were correlated to simultaneous changes in high-energy phosphagen (ATP + CP) and lactate levels in skeletal muscle. In control dogs no significant changes in either of the studied variables occurred. Intestinal exteriorization shock as well as local tourniquet ischemia resulted in a gradual increase in tissue lactate and a concomitant decrease in tissue pH and transmembrane potentials. In both experimental situations there was a close correlation between the transmembrane potential reduction and the tissue lactate increase. Tissue pH registrations, on the other hand, did not similarly reveal the full extent of the tissue lactate increase under the two experimental conditions. Possible reasons for this discrepancy are discussed. On the basis of the present results it may therefore be concluded that the transmembrane potential seems to be a better variable for revealing the full extent of cellular metabolic deterioration during various situations with tissue hypoxia.

Adenosine Triphosphate↗