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Biomedical subjects

S Thelin

Publications and source records attributed to S Thelin.

At least 55 records · Page 3Linked to original sources
PubMed1994

Biocompatibility of heparin-coated circuits used in cardiopulmonary bypass.

The combined effect of heparin coating of cardiopulmonary bypass (CPB) circuits and reduced dose of systemic heparin on activation of the complement system and blood leukocytes was investigated in 19 patients undergoing coronary bypass surgery and randomly allocated to two groups. A heparin-coated CPB circuit together with a 50% reduction of the standard heparin dose were used for ten patients (HC group), and a standard CPB circuit with a standard heparin dose (300 IU/kg) for nine (C group). Significant rise in the levels of neutrophil-derived myeloperoxidase, lactoferrin and calprotectin were observed during CPB in both groups, but the total accumulated levels were significantly lower in the HC than in the C group (p < 0.05). Complement activation, assessed from levels of C3a and terminal complement complexes was similar in both groups. The lower levels of myeloperoxidase, lactoferrin and calprotectin during CPB in the HC group indicate that surface modification with end-point attached heparin enhances the biocompatibility of CPB.

Biocompatible Materials↗
PubMed1993

Heparin coating reduces blood cell adhesion to arterial filters during coronary bypass: a clinical study.

Deleterious effects of cardiopulmonary bypass (CPB) are partly sequelae of blood-foreign surface reactions. Coating the inner surfaces of CPB sets with heparin has been shown to decrease activation of humoral cascade systems. The aim of this study was to investigate whether the heparin-coated CPB sets influence adhesion of blood cells to surfaces of arterial filters during CPB. Thirty-one patients undergoing coronary artery bypass grafting were studied. In the control group (C) standard CPB sets and standard doses of heparin (300 IU/kg) were employed; in the HC (heparin-coated) group, heparin-coated CPB sets and reduced heparin doses (range, 150 to 225 IU/kg) were used. Two additional groups were also studied; group FC (coated filter), with standard CPB sets and heparin-coated arterial filters (heparin dose, 300 IU/kg), and group OC (uncoated filter), with heparin-coated CPB sets and standard arterial filters (heparin dose, 300 IU/kg). The inner surfaces of the arterial filters were examined after CPB with scanning electron microscopy. Scanning electron microscopy demonstrated almost clean surfaces in heparin-coated filters even when other parts of the circuit were uncoated. Using an arbitrary adhesion score, significant differences between the groups were noted in the adhesion grade; it was lowest in group HC (2.2 +/- 0.27 [mean +/- standard error of the mean]) versus group C (5.4 +/- 0.53; p < 0.001). In group FC it was marginally higher than in group HC but almost significantly lower than in group OC (2.6 +/- 0.68 versus 5.4 +/- 0.81; p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Biocompatible Materials↗
PubMed1992

Characterization of the molecular mechanism involved in the activation of hyaluronan synthetase by platelet-derived growth factor in human mesothelial cells.

The molecular mechanism involved in the stimulation of hyaluronan synthetase in normal human mesothelial cells was investigated. Exposure of mesothelial cells to platelet-derived growth factor (PDGF)-BB stimulated hyaluronan synthetase activity, measured in isolated membrane preparations, as well as hyaluronan secretion into the medium. The effect on hyaluronan synthetase was maximal after 6 h of treatment. In contrast, the stimulatory effect of transforming growth factor-beta 1 reached a maximum after 24 h. The stimulatory effect of PDGF-BB was inhibited by cycloheximide. The phosphotyrosine phosphatase inhibitor vanadate was found to stimulate hyaluronan synthetase activity, and to potentiate the effect of PDGF-BB. The protein kinase C (PKC) stimulator phorbol 12-myristate 13-acetate (PMA) also stimulated hyaluronan synthetase; furthermore, depletion of PKC by preincubation of the cells with PMA led to an inhibition of the PDGF-BB-induced stimulation of hyaluronan synthetase activity. Thus the PDGF-BB-induced stimulation of hyaluronan synthetase activity is dependent on protein synthesis and involves tyrosine phosphorylation and activation of PKC.

Cell Membrane↗
PubMed1992

Biochemical and functional effects of creatine phosphate in cardioplegic solution during aortic valve surgery--a clinical study.

During myocardial ischemia there is a drop in high-energy phosphates in the myocardium. Cold potassium cardioplegia decreases but does not altogether prevent this reduction. Supplementation of cardioplegic solutions with the high-energy compound creatine phosphate (10 mmol/L) compared to plain cardioplegic solutions was investigated in this study. Thirty patients scheduled for aortic valve replacement were included. The patients were randomized to group I (creatine phosphate) or group II (control). Postoperative hemodynamic evaluation revealed no significant differences between the groups. However, group I exhibited a tendency toward a better stroke-work index (135 +/- 18% vs. 102 +/- 5% recovery 15 minutes after bypass and 145 +/- 16% vs. 119 +/- 11% recovery 105 min after bypass). There were fewer patients in group I (5/15) needing inotropic support compared to group II (9/14). The myocardial content of ATP and creatine phosphate showed no significant differences during ischemia and reperfusion. It is concluded that the myocardial protection during ischemia was sufficient to prevent significant reductions of myocardial ATP and creatine phosphate irrespective of supplementation with CP.

Adenosine Triphosphate↗
PubMed1992

Heparin-coated cardiopulmonary bypass circuits and 25% reduction of heparin dose in coronary artery surgery--a clinical study.

Cardiopulmonary bypass with systemic heparinization causes trauma to blood cells and coagulation defects. Artificial surfaces could be coated by end-linkage binding of heparin (Carmeda Bioactive Surface, CBAS). Use of such surfaces during cardiopulmonary bypass in animals resulted in less postoperative blood loss and better preservation of blood cells. In this study heparin-coated circuits were employed during coronary artery grafting in 7 patients (Group HC). Concomitantly, the heparin dose was reduced by 25% and an activated clotting time (ACT) of 300 sec was accepted. Additional 7 patients were operated with standard circuits (Group C), requiring ACT above 400 sec with normal doses of heparin. There were no thromboembolic complications in Group HC. The postoperative bleeding was generally low and without significant intergroup differences. Coagulation parameters displayed significantly lower ACT and anti-Factor Xa during bypass in Group HC. A tendency towards less blood cell trauma was observed with heparin-coated circuits. The protamine dose could be reduced by 50%, which significantly reduced the protamine/heparin quotient. This study indicates that routine cardiopulmonary bypass could be performed safely with heparin-coated circuits and reduced intravenous doses of heparin and protamine. It is suggested that the use of heparin-coated circuits may lead to less blood cell trauma.

Blood Cells↗
PubMed1992

Experimental dynamic cardiomyoplasty in sheep.

To evaluate electrically stimulated muscle grafts for augmenting ventricular function in cardiac insufficiency, dynamic cardiomyoplasty was performed in nine sheep, using latissimus dorsi (LD) muscle wrapped as a pedicle around the left ventricle. Beginning 2 weeks postoperatively, LD was stimulated synchronously with the heart. After 6 and 12 weeks of stimulation, hemodynamic evaluation was done and biopsies were taken for histochemical and biochemical analysis. With intact heart function, stimulation of the muscle was not hemodynamically beneficial. During induced heart failure, cardiomyoplasty increased cardiac output by 25% in two sheep. Eight LD muscles contracted vigorously in synchrony with the heart, one was fibrosed and all were fixed to the thoracotomy incision by scar tissue. ATPase stain showed gradual transformation of muscle fibers into fatigue-resistant Type I. At 12 weeks only Type I were seen. Quantitative enzymatic analyses revealed increase in oxidative and decrease in glycolytic enzymes. Chronic electrical stimulation is concluded to change the muscle characteristics towards those of mainly oxidative and fatigue-resistant muscle, thereby improving opportunities for assisting the depressed heart. Dynamic cardiomyoplasty involves risks of adhesions to adjacent tissues and muscle trauma from chronic stimulation.

Animals↗
PubMed1992

Decreased blood loss after cardiopulmonary bypass using heparin-coated circuit and 50% reduction of heparin dose.

In a randomized, double-blind study of patients undergoing elective coronary artery grafting, the effect of heparin-coated circuit combined with 50% reduction of systemic heparin bolus was investigated. Ten patients comprised group HC (heparin-coated) and ten group C (controls). The mean total doses of heparin were 172 IU/kg in group HC and 416 IU/kg in group C and the respective protamine doses were 0.96 and 3.96 mg/kg (both p < 0.001). Activated clotting times during cardiopulmonary bypass were significantly shorter in group HC, and both intra- and postoperative bleeding was significantly less than in group C (7.7 vs. 11.7 ml/kg, p = 0.036, and 6.9 vs. 9.7 ml/kg, p = 0.004). Hemoglobin loss via the drains was 22.5 g in group HC and 43.7 g in group C (p < 0.005). Hemolysis at the end of bypass was significantly greater in group C. Apart from one perioperative myocardial infarction in group HC the postoperative course was uneventful. Use of a heparin-coated circuit is concluded to permit complication-free reduction of heparin and protamine doses and to decrease both intra- and postoperative bleeding, which may favorably influence the outcome of coronary artery grafting.

Blood Coagulation↗
PubMed1992

Heparin-coated circuits reduce activation of granulocytes during cardiopulmonary bypass. A clinical study.

Activated granulocytes release highly active enzymes such as myeloperoxidase and lactoferrin, which can be involved in tissue destruction mediated by oxygen free radicals. Cardiopulmonary bypass has been reported to activate granulocytes. Bypass circuits coated with heparin have been shown to reduce release of granulocyte factors in experimental studies. In the present study, heparin-coated circuits were compared with noncoated circuits. In seven patients undergoing coronary bypass, heparin-coated circuits were used (group HC), and seven served as control patients (group C). In group HC the heparin dose was reduced to 75% (225 IU/kg). Group C had the standard dose of 300 IU/kg. No preoperative differences in myeloperoxidase and lactoferrin were observed between the groups. At the end of bypass in both groups, there was a significant increase of these enzymes (p less than 0.001) followed by a later decrease. In group HC, however, the release of myeloperoxidase was significantly lower than in group C (215 +/- 24 versus 573 +/- 133 micrograms/L, mean +/- standard error of the mean). The release of lactoferrin was significantly lower in group HC than in group C both at the end of cardiopulmonary bypass (659 +/- 79 versus 1448 +/- 121 micrograms/L) and 3 hours after bypass (224 +/- 37 versus 536 +/- 82 micrograms/L). Granulocytes as well as total number of leukocytes continued to increase until 1 hour after bypass (p less than 0.001) and then manifested a slow decrease. It was concluded that the use of heparin-coated circuits reduced the release of granulocyte factors because of lower activation of leukocytes.

Biochemical Phenomena↗
PubMed1991

Heparin-coated cardiopulmonary bypass circuits reduce blood cell trauma. Experiments in the pig.

Blood cell trauma and postoperative bleeding remain important problems in cardiopulmonary bypass (CPB). We compared heparin-coated with non-coated circuits in the pig. Twenty animals were perfused for 2 h at normothermia using membrane oxygenators (Bentley Bos 50). Two groups were studied. In the non-coated group (NC, n = 11) the CPB circuits used were without a heparin coating. This group had systemic heparinization of 400 IU/kg to maintain an ACT (activated clotting time) of over 400 s during CPB. In the coated group (C, n = 9), all surfaces exposed to blood in the CPB circuits were heparin-coated. This group had the heparin dose reduced to 25% (100 IU/kg) without further administration regardless of ACT. During CPB, group C displayed shorter ACT (per definition), higher platelet count, platelet adhesion and lower fibrinolysis and haemolysis (P less than 0.05) as compared to group NC. No thromboembolic events were detected during CPB. Three animals in group NC and 4 animals in group C were weaned from CPB and protaminized. Four hours postoperatively, the leucocyte consumption was two-fold greater and blood loss about four-fold greater in group NC as compared with group C (P less than 0.05). Perfusion with heparin-coated surfaces reduces blood cell trauma. The decreased postoperative blood loss observed in group C is probably explained by the reduced dosages of heparin and protamine.

Animals↗
PubMed1991

Effects of adenosine infusion on the pig heart during normothermic ischemia and reperfusion.

Possible enhancement of myocardial protection during ischemia and reperfusion by administration of adenosine was evaluated in a pig heart model. Adenosine (100 micrograms/kg/min) was infused into the aortic root during ischemia in group AI (n = 5) and into the right atrium during reperfusion in group AR (n = 6). Group C (n = 6) served as controls. During cardiopulmonary bypass the hearts were subjected to 30 min of normothermic ischemia and 15 min of reperfusion before weaning. In group AI the stroke work index 30 and 90 min after ischemia and the mean arterial pressure 30 min after ischemia were significantly higher than in group C. These parameters did not differ significantly between groups AR and C. All groups showed decrease in myocardial adenosine triphosphate (ATP) and adenylate charge potential (ACP) during ischemia and partial (ATP) or complete (ACP) restoration after ischemia. Adenosine infusion into the aortic root during ischemia (adenosine cardioplegia) thus resulted in improved postischemic heart function, although biochemical correlates in ATP and ACP were not apparent.

Adenosine↗
PubMed1990

Heparin-coated equipment reduces complement activation during cardiopulmonary bypass in the pig.

Complement activation was studied during cardiopulmonary bypass (CPB) in the pig. One group of animals was perfused for 2 h using a standard extracorporeal circuit including a hollow fiber membrane oxygenator with full systemic heparinization. Another group was treated in the same way, except that bypass was performed through a heparin-coated CPB circuit (Carmeda Bio-Active Surface, CBAS) and systemic heparinization was reduced by 75%. It was found that complement activation during CPB, measured as changes in the ratio C3d/C3, was significantly less in the CBAS group, most probably reflecting a better biocompatibility.

Animals↗
PubMed1988

Laser Doppler flowmetry estimating myocardial perfusion after internal mammary artery grafting.

Myocardial perfusion in the anteroapical part of the left ventricle was monitored intraoperatively with laser Doppler flowmetry in ten patients after grafting of the internal mammary artery to the left anterior descending artery. The myocardial perfusion after declamping of only the mammary artery averaged 61% of the perfusion found after declamping also the aorta. Laser Doppler flowmetry is proposed to offer a means of monitoring regional myocardial perfusion in the phase immediately after internal mammary artery grafting.

Coronary Artery Disease↗
PubMed1987

Improved myocardial protection by creatine phosphate in cardioplegic solution. An in vivo study in the pig during normothermic ischemia.

The effect of creatine phosphate in potassium cardioplegia was studied in a pig heart model in vivo. Fifteen pigs divided into two groups were placed on cardiopulmonary bypass and subjected to 1 hour of cardioplegic arrest at normothermia. In group I (control), in which a potassium cardioplegic solution was used, only two out of eight animals could successfully be weaned from bypass. In group II, on the other hand, in which creatine phosphate (10 mmol/l) was added to the cardioplegic solution, six out of seven animals could be weaned from bypass and the heart performance assessed by volume loading. Group II also exhibited better maintenance of high-energy phosphates during ischemia, with significantly higher adenylate charge potential, than group I. In all animals weaned from bypass--two in group I and six in group II--the ventricular performance was decreased compared with that before induction of ischemia. The results indicate that creatine phosphate could be an effective constituent in potassium cardioplegia.

Animals↗
PubMed1987

Functional effects of phosphoenolpyruvate and ATP on pig hearts in cardioplegia and during reperfusion. An in vivo study with cardiopulmonary bypass.

The effects of phosphoenolpyruvate (PEP) and ATP in cardioplegia and during early reperfusion were studied in pigs. Twenty pigs divided into three groups were placed on cardiopulmonary bypass and subjected to 2 h of hypothermic cardioplegic arrest. Group I (n = 7) served as a control. In group II (n = 7) PEP (14.4 mM) and ATP (0.067 mM) were added to the cardioplegic solution. Group III (n = 6) was given PEP (28.8 mM) and ATP (0.134 mM) with 500 ml of isotonic NaCl in the aortic root during early reperfusion. All animals in group III were weaned from bypass compared with 6 of 7 in group I and 5 of 7 in group II. Forty minutes after ischemia group III was assessed to be the only group with an unchanged aortic flow and stroke volume. The total peripheral resistance and arterial pressure were reduced in this group. The results demonstrate that PEP and ATP administered during reperfusion have a beneficial effect and that this may be exerted both on the myocardium and on the peripheral vessels.

Adenosine Triphosphate↗