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Biomedical subjects

J Modig

Publications and source records attributed to J Modig.

At least 19 recordsLinked to original sources

[A case report. Hypotensive reaction caused by albumin infusion].

Hypotensive reactions during surgical procedures cause diagnostic problems in establishing whether the hypotension is due to blood loss or pharmaceuticals or other causes. A case of hypotension probably due to an albumin infusion is described. Bradykinin effects are probably the cause of many hypotensive reactions. Angiotensin-converting enzyme (ACE) inhibitors reduce degradation of bradykinin and thus increase the risk of hypotensive reactions. When possible, doctors should consider withholding ACE inhibitors 24 hours before surgical procedures likely to require albumin transfusions.

Angiotensin-Converting Enzyme Inhibitors↗

Retinyl palmitate injections reduce serum levels and effects of endotoxin on systemic haemodynamics and oxygen transport in the pig.

BACKGROUND: Retinyl palmitate [(RP) 230 IU.kg(-1)] modulates the circulatory and respiratory responses of a subsequent infusion of endotoxin in the pig. The aims of this study were: I. To determine if RP (2300 IU.kg(-1)) affects the serum endotoxin levels in this model. II. To evaluate the effect of this dose of RP on circulatory and respiratory variables in our porcine model. III. To investigate the levels of RP and neutrophil count in porcine endotoxaemia. METHODS: Ten anaesthetized pigs were randomly given 2300 IU.kg(-1) of RP or the solvent i.m. prior to the continuous i.v. infusion of E. coli endotoxin (10 microg.kg(-1).h(-1)). Another 4 sham animals were given either i.m. RP (n=2) or i.m. solvent (n=2) followed by an infusion of saline. Haemodynamics and oxygen extraction were monitored and samples taken for analysis of endotoxin, RP and blood cells. RESULTS: I. Endotoxin levels in serum were lower (P<0.001) in the RP-pretreated pigs. II. These animals had higher cardiac index (P<0.05), mean arterial pressure and left ventricular stroke work index (both P<0.001), and lower oxygen extraction (P<0.01). III. RP-Pre=pretreatment caused a paradoxical decrease in serum retinyl (P<0.001) and a more rapid restitution of neutrophil count (P<0.05). CONCLUSION: Pretreatment with RP (2300 IU.kg(-1)) counteracts the progressive increase in serum endotoxin levels in porcine endotoxaemia.

Animals↗

Renal vascular response to left atrial injection. An experimental study in the pig.

It has previously been shown that a rapid, transient and pronounced reduction in superficial renal cortical blood flow can be elicited by injection of 1 ml of plasma into the left atrium of the anaesthetized pig. This renal vascular response might constitute an important error in measurements of renal blood flow by means of the microsphere technique. In the present study we have investigated total renal (ultrasonic Doppler) and superficial renal cortical (laser Doppler flowmetry) blood flow after left atrial injections of saline and autologous blood. The average reductions in total renal blood flow were 4.7 +/- 2.4% (mean +/- s.d.) and 18.4 +/- 12.5% (mean +/- s.d.) for the blood and saline injections, respectively. The flow reduction was more pronounced in the superficial renal cortex with average reductions of 17.4 +/- 26.0% (mean +/- s.d.) and 59.4 +/- 38.5% (mean +/- s.d.) for blood and saline, respectively (laser Doppler flowmetry). Furthermore, two consecutive injections of microspheres were performed. The results from the second injection were compared with those from the first injection. In the superficial renal cortex the second injection indicated a significant reduction in blood flow and an significantly increased heterogeneity in the blood flow in two different tissue volumes. No corresponding differences were found in the juxtamedullary cortex. These results indicate that the renal vascular response to a left atrial injection is detectable as a reduction in total renal blood flow and is most pronounced in the superficial renal cortex. All these results taken together constitute an important error in measurements of superficial renal cortical blood flow by the microsphere technique.

Animals↗

Variations in superficial renal cortical blood flow and tissue oxygenation: an experimental porcine model.

Renal cortical microcirculation and its relation to inulin clearance, central haemodynamics and pulmonary gas exchange were studied in eight pigs under continuous intravenous chlormethiazole-pancuronium anaesthesia. The animals were studied during six consecutive 30-min periods. Four of the animals were also studied 19 h after the first period. In the superficial renal cortex, regional blood flow (Qsrc) was measured by laser Doppler flowmetry (LDF) and tissue oxygenation (PtO2) by surface microelectrode technique. Central haemodynamics and pulmonary gas exchange values were distributed within normal ranges. The importance of stable central haemodynamics in order to perform accurate microcirculatory measurements in the renal cortex was documented. A significant relation between Qsrc and pulmonary capillary wedge pressure (PCWP) was found (P less than 0.0001) despite the fact that PCWP was distributed within a range of only 0.7 kPa (all values were well within the normal range for pigs). No other relationships were found between central haemodynamics or pulmonary gas exchange variables and renal microcirculatory parameters. Concerning renal microcirculation and inulin clearance, at least 2-3 h may be required for stabilization after surgery. The average temporal variability between measurements performed every 30 min in each animal was 6 +/- 7% (s.d.) in the LDF values and 21 +/- 21% in the PtO2 values (mean PtO2). No correlations were found between Qsrc or PtO2 and inulin clearance. Since the haemodynamic parameters, pulmonary gas exchange variables and haematocrit were distributed within narrow ranges, we regard the temporal microcirculatory variability obtained here as normal in this experimental situation, and consider the porcine model well suited for further studies concerning renal microcirculation.

Anesthesia, Intravenous↗

Effects of diltiazem on postischaemic renal cortical microcirculation in the pig.

Diltiazem--a calcium entry blocker--was tested in a porcine model under continuous chlormethiazole-pancuronium anaesthesia as protection against renal failure following 60 min of renal ischaemia. Fourteen pigs were randomly allocated to one experimental (diltiazem and ischaemia) and one control group (only ischaemia) (n = 7 in each). Diltiazem was administered as a continuous intravenous infusion started before the ischaemic insult. In two additional animals diltiazem was given but ischemia was not induced. The postischaemic renal cortical microcirculation was simultaneously investigated in four different regions in the left kidney during the first 4 h of reperfusion. Laser Doppler flowmetry (LDF) was performed in two different regions and measurement of tissue oxygenation was done in two other regions. In the two animals treated with diltiazem without ischaemia, only minor variations in central haemodynamic and renal microcirculatory parameters were evident. In the control group (ischaemia), superficial renal cortical blood flow (Qsrc) decreased from 49 +/- 11 (s.d.) arbitrary units at baseline to 24 +/- 4 arb. units 4 h after start of reperfusion (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Postischaemic renal cortical microcirculation and tissue oxygenation in the pig.

Porcine and human renal physiology are similar in important aspects. Renal cortical microcirculation and its relation to inulin clearance (CIn) was therefore studied before and after renal ischaemia in 28 pigs under continuous intravenous chlormethiazole-pancuronium anaesthesia. The anaesthesia used provided essential stability in central haemodynamics. The animals were studied for 90 min of reperfusion following 0, 30 or 60 min of renal ischaemia. Twelve of the animals (four were subjected to each duration of ischemia) were also studied 18 h after start of reperfusion. Regional blood flow in the superficial renal cortex was measured by laser Doppler flowmetry (LDF), and tissue oxygenation (PtO2) by surface microelectrode technique. These techniques allow continuous or repeated measurements. During the first 90 min of reperfusion, superficial renal cortical blood flow measured by LDF (Qsrc) underwent considerable temporal variation which followed a certain pattern. Thus, when the renal arterial blood flow was restored after ischaemia, we observed an instant peak in Qsrc followed by a decreasing flow until a minimum value (Qmin) was reached between 3 and 9 min after start of reperfusion (tQmin). Thereafter, Qsrc increased until a maximal value (Qmax) was reached between 11 and 64 min after start of reperfusion (tQmax). The parameters tQmin and tQmax were related to inulin clearance 18 h after start of reperfusion (P less than 0.05 and P less than 0.01, respectively). Thus, it might be possible soon after start of reperfusion--to evaluate the severity of ischaemic damage. This could be useful in the evaluation of different prophylactic strategies, since the full extent of the ischaemic damage, as assessed by clearance determinations, cannot be established until hours later.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗

Postischaemic regional microvascular variations in the porcine renal cortex.

Regional microcirculatory differences in the superficial renal cortex were studied before and during 4 h following 60 min of renal ischaemia in seven pigs under continuous intravenous chlormethiazole-pancuronium anaesthesia. Superficial renal cortical blood flow (Qsrc) was measured by laser Doppler flowmetry (LDF) in two different regions. In two other different regions tissue oxygenation (PtO2) was measured by surface electrodes. Thus, microcirculatory measurements were simultaneously carried out in each animal in four different regions of the left kidney. After 60 min of renal ischaemia, pronounced renal cortical microcirculatory disturbances were found. The regional microcirculatory differences were notable, especially after ischaemia. On average, Qsrc was 49 +/- 11 (s.d.) arbitrary units at baseline and decreased to 24 +/- 4 arb. units 4 h after start of reperfusion (P less than 0.05). Before ischaemia the average difference between Qsrc simultaneously measured in two different parts of the renal cortex was 26 +/- 15% of the mean of both measurements, and it was 30 +/- 22% 4 h after start of reperfusion (n.s.). Mean PtO2 (m-PtO2) was on average 4.5 +/- 1.3 kPa at baseline and 2.4 +/- 1.5 kPa 4 h after start of reperfusion (P less than 0.05). The average difference between m-PtO2 simultaneously measured in two different parts of the renal cortex at baseline was 24 +/- 13% of the mean of both measurements and 57 +/- 49% 4 h after start of reperfusion (n.s.). In each of the two measured regions of the renal cortex m-PtO2 was calculated from 160 small tissue volumes distributed within a surface area of about 1 mm2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ringer's acetate and dextran-70 with or without hypertonic saline in endotoxin-induced shock in pigs.

The effects of Ringer's acetate, 6% dextran-70, 7.5% NaCl, and the combination of 7.5% NaCl and dextran-70 were tested in resuscitation from endotoxin shock induced by continuous iv infusion of Escherichia coli endotoxin in pigs. After about 3 h, a reproducible shock state was achieved and treatment was started, governed by the left atrial pressure. The hypertonic solutions (7.5% NaCl and 7.5% NaCl in dextran-70) did not show any overall advantages over the isotonic solutions (Ringer's acetate and dextran-70). Only transient beneficial hemodynamic effects lasting less than 30 min after infusion were seen. When dextran-70 was administered, cardiovascular function was markedly improved and oxygen delivery (DO2) and survival were significantly higher compared with the crystalloid groups (Ringer's acetate and 7.5% NaCl). Administration of large amounts of Ringer's acetate resulted in an immediate deterioration of pulmonary function. It was difficult to elevate left atrial pressure or even to keep it at baseline level, and cardiac index was only transiently increased. The overall result was a deterioration of DO2 and poor survival compared with the dextran-70 treated pigs. We conclude that dextran-70 is superior to Ringer's acetate in resuscitation from endotoxin-induced shock in pigs. Furthermore, we found no role for the use of hypertonic saline, alone or in combination with dextran, in the treatment of this type of prolonged endotoxin shock.

Animals↗

Disturbances in renal cortical perfusion with reference to the microsphere technique.

The microsphere technique for studying renal blood flow is based on injection of a small volume containing radioactively labelled microspheres into the left atrium, left ventricle or possibly the root of the aorta. In the present methodological study, superficial renal cortical blood flow and tissue oxygenation were measured in anaesthetized pigs by laser Doppler flowmetry and by oxygen surface electrode technique. Rapid and profound transient decreases in superficial renal cortical blood flow and tissue oxygenation were found after injection of small volumes of plasma and saline into the left atrium. This response was present also when solutions without microspheres were injected. The reaction was not abolished by careful adjustment of the injectate temperature. When the rapid onset of flow reduction is related to the estimated time of delivery of the bolus with microspheres, the validity of regional blood flow measurements using the microsphere technique within the superficial renal cortex must be seriously questioned.

Animals↗

Intrapulmonary deposition of aerosolized Evans blue dye and liposomes in an experimental porcine model of early ARDS.

In early ARDS (Adult Respiratory Distress Syndrome) and other inflammatory pulmonary disorders the lung might benefit from a high local deposition of an active drug, in order to optimize the local concentration without systemic side effects. In this methodological study we used pigs under controlled ventilation. The study was carried out in two steps. In the first part Evans blue dye in NaCl was delivered in aerosolized form. In the second part a dry powder containing FITC (fluorescein-isothiocyanate)-labelled-liposomes in NaCl was delivered in the same way. We evaluated whether there was an even, central, peripheral and/or alveolar deposition, whether the procedure was reproducible, and whether there was an interaction with alveolar macrophages. Sixteen animals under chlormethiazole anaesthesia and intermittent positive pressure ventilation (IPPV) were included in the study. Four animals were sacrificed after nebulization and baseline measurements. Five animals served as controls and received saline i.v. Six animals received endotoxin i.v. (18 micrograms.kg-1.h-1). One animal underwent broncho-alveolar lavage 15 min and 2 h after liposome administration. At the end of each experiment the lungs were inflated with air, excised and dried in a microwave oven. The left lung of each animal was sliced in a reproducible manner and lung-pieces from different regions were analyzed. The Evans blue dye or the phospholipid fraction of the lungs (containing liposomes), was extracted and analyzed spectrofluorometrically. This study shows that it is possible, under reproducible conditions, to administer aerosolized Evans blue dye and liposomes and to achieve a deposition in the terminal airways and/or alveolar spaces. The broncho-alveolar lavage demonstrated an interaction of liposomes with alveolar macrophages. The results imply that liposomes carrying active drugs and administered by inhalation may be used for local pulmonary treatment in early ARDS and other related inflammatory pulmonary diseases.

Aerosols↗

Conjunctival oxygen tension monitoring in experimental septic shock.

Continuous non-invasive monitoring of conjunctival oxygen tension (PcjO2) versus 'conventional' invasive hemodynamic and oxygen transport variables was evaluated in a porcine model of septic shock induced by a continuous i.v. infusion of E. coli endotoxin over 2 hours. Seventeen pigs under ketamine anesthesia and breathing air spontaneously were investigated. PcjO2, which reflects local oxygen tension at tissue level, correlated significantly at baseline and throughout the septic course with mixed venous oxygen saturation and oxygen utilization coefficient. All these correlations were significant at the 1% level. The corresponding correlations between PcjO2 and cardiac output were significant at the 5% level. A finding of great importance was that changes in PcjO2 preceded major changes in the intermittently measured physiological variables such as SvO2 and cardiac output. We conclude that PcjO2 monitoring is a valuable non-invasive method and which can provide a continuous assessment of the hemodynamic and oxygenation status in experimental septic shock.

Animals↗

Increased hyaluronic acid production in lung--a possible important factor in interstitial and alveolar edema during general anesthesia and in adult respiratory distress syndrome.

The tremendous swelling potential of hyaluronic acid (HA) is well established, however, the possible role of HA for interstitial and alveolar edema of the lung during general anesthesia and in adult respiratory distress syndrome (ARDS) has not received attention. Bronchoalveolar lavage (BAL) was therefore performed on 28 apparently lung-healthy patients; first 24 h prior to induction of general anesthesia and then--in the same lung segment--approximately 30 min after anesthesia induction with endotracheal intubation and mechanical ventilation with N2O in O2. The second BAL was undertaken prior to surgery. Another group of 11 patients with ARDS was also subjected to BAL. A third control group of 10 patients was investigated with BAL 24 h apart to see if a prior BAL influenced the second BAL. Prominent findings were that induction of general anesthesia was associated with significantly (P less than 0.001) increased amount of HA in BAL, on average 77 micrograms/l (range 24-181 micrograms/l) as compared with HA-level 24 h before anesthesia, where all values were below 20 micrograms/l. ARDS patients ranged from 72 to 1636 micrograms/l with a mean of 515 micrograms/l, which was significantly (P less than 0.001) higher than HA-level after induction of anesthesia. The control group that had BAL of the same lung segment 24 h apart did not show any increase in HA-level during the second BAL; with HA-level below 20 micrograms/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

True shunt in relation to venous admixture in an experimental porcine model of early ARDS.

Using the multiple inert gas elimination technique, ventilation/perfusion (V/Q) relationships were studied in an experimental porcine model of the early Adult Respiratory Distress Syndrome (ARDS) to establish the nature of the increased venous admixture. Six animals served as controls and revealed no major changes apart from a 10% decrease in cardiac output during the 4-h observation period. All control animals showed a shift to a higher mean V/Q of perfusion (Qmean) and a maintained log standard deviation (QSD) throughout the experiment. The distribution was unimodal and centered around a V/Q ratio of 1.0. The share of perfusion to V/Q ratio less than 0.005 (i.e. true shunt, Qs) remained unchanged at 6-7% of cardiac output. Nine animals, given a continuous infusion of E. coli endotoxin, showed a significant decrease of 53% in cardiac output (Qt) at 4 h. Mean pulmonary artery pressure (MPAP) showed a 2-phase reaction with a peak level at 0.5 h, and a second gradual increase from 2 h onwards. Venous admixture doubled at 0.5 h, after which it declined but remained elevated throughout the observation period. All endotoxin animals showed a shift in perfusion to a higher Qmean with a significantly wider QSD at 0.5, 2 and 4 h. The distribution was unimodal and centered around a V/Q ratio of 1.0. True shunt was unchanged at 6-7% of cardiac output throughout the study. The increase in venous admixture in this experimental ARDS model is consequently explained by the widening of the V/Q scatter and is due to a perfusion shift to lower ventilation/perfusion ratios rather than to an increase in true shunt.

Animals↗

Accumulation of hyaluronan (hyaluronic acid) in the lung in adult respiratory distress syndrome.

The concentrations of hyaluronan (HA) were measured in bronchoalveolar lavage (BAL) fluid and serum from 12 patients with adult respiratory distress syndrome (ARDS). The median BAL fluid HA concentration was 353 micrograms/L, about six times higher than that seen in control patients (p less than 0.001). The median serum HA value was 619 micrograms/L, which was a 30-fold increase compared with that in the control patients (p less than 0.001). Another connective tissue component, type III procollagen peptide, was not recovered in significant amounts during lavage in patients with ARDS, but it appeared in the bloodstream in increased concentrations (p less than 0.001). Obtained recovery of HA during lavage of patients with ARDS cannot be explained by an enhanced passive leakage from the bloodstream because of increased alveolar-capillary permeability, but rather could reflect a mobilization of HA from lung interstitial tissue because of hydrostatic mechanisms. Alternatively, the appearance of HA in the alveolar space in ARDS might reflect an enhanced lung synthesis of HA. An increased HA production can possibly be mediated, directly or indirectly, by activated complement components, since a significant relationship was seen between increased plasma concentrations of C3a des Arg and BAL fluid HA (r = 0.61; p less than 0.05). The observed accumulation of HA in the small airways in ARDS may be expected to immobilize water and thereby contribute to the interstitial and alveolar edema. The inverse correlation (r = 0.71; p less than 0.01) seen between BAL fluid HA and pulmonary oxygenation index (PaO2/inspired oxygen fraction) supports such a hypothesis.

Adult↗

Differences in coagulation and fibrinolysis after traumatic and septic shock in man.

In a prospective investigation of 19 patients with traumatic (n = 11) and septic (n = 8) shock admitted to the Intensive Care Unit of the University Hospital of Uppsala, differences in coagulation and fibrinolysis between the two conditions were evaluated. It was found that plasma coagulation variables such as thrombotest, normotest and antithrombin III were significantly lower in the septic patients, thus indicating a more intense and/or altered intravascular coagulation. Significantly higher levels of the von Willerbrand factor were found in septic patients, indicating a greater release from endothelial cells and platelets. The plasminogen activator inhibitor and the plasminogen-binding form of alpha 2-antiplasmin showed significantly higher values in septic patients, indicating a greater fibrinolysis inhibition in these patients. The greater disturbance in the protease-inhibitor balance in septicaemia was also verified by significantly lower levels of plasminogen and alpha 2-macroglobulin than after traumatic shock. Two out of 11 patients in traumatic shock developed the adult respiratory distress syndrome with a slow onset and benign course, whereas six out of eight septic shock patients developed a similar syndrome with a rapid onset and malignant course. These laboratory and clinical results lend further support to the hypothesis that the differences in coagulation and fibrinolysis systems reflect partly different pathogenic mechanisms underlying septic- and traumatic-induced adult respiratory distress syndrome.

Adolescent↗

Influence of regional anesthesia, local anesthetics, and sympathicomimetics on the pathophysiology of deep vein thrombosis.

Studies have shown that lumbar epidural and spinal anesthesia seem to offer two distinct clinical advantages over general anesthesia, particularly in total hip replacement patients. These major regional blocks reduce the frequency of deep vein thrombosis and pulmonary embolism and reduce intraoperative and postoperative blood losses. The beneficial effects on thromboembolism are probably explained by several factors, such as hyperkinetic blood flow in the lower legs, reduced tendency to coagulation, and improved fibrinolytic function. The effects of local anesthetics on leukocytes, platelets, erythrocytes, and plasma proteins and on the interactions among various blood cells and endothelial cells are other factors in the protection against thromboembolism. Sympathicomimetic agents (i.e., epinephrine in the local anesthetic solution together with ephedrine given prophylactically to maintain a stable blood pressure) probably also play a significant role, notably on fibrinolytic function. The reduction in blood loss and thus in transfusion requirements may also be important.

Anesthesia, Conduction↗