Biomedical subjects

G Valen

Publications and source records attributed to G Valen.

At least 37 records · Page 2Linked to original sources

PubMed2000

Effects of cardiac surgery on some clinically used inflammation markers and procalcitonin.

One hundred and ten patients were investigated prospectively in a study aimed at creating reference curves for inflammation markers (serum C-reactive protein (CRP), blood leukocyte count, iron, transthyretin and procalcitonin). Blood samples were taken daily and the patients were monitored for signs of infection. Ninety-six patients had no postoperative infections. CRP and leukocyte counts peaked on the third and second postoperative days, respectively. Neither patients operated on off-pump (n = 4) nor patients with minor infections (n = 11) differed from the non-infected group. Two out of three patients with major postoperative infection exhibited a secondary peak in CRP and leukocyte count. Iron and transthyretin decreased initially, followed by a slow increase without any difference between the groups. Procalcitonin was high in some non-infected patients and low in some infected patients. CRP and leukocyte count had a predictable course with a secondary peak in major infections but the other markers did not provide any valuable information.

Adult↗

PubMed2000

Glucocorticoid pretreatment protects cardiac function and induces cardiac heat shock protein 72.

Acute administration of glucocortiocoids reduces inflammation. Increasing knowledge of the mechanisms of action indicate that pretreatment with glucocorticoids could have organ-protective effects. We investigated whether pretreatment with methylprednisolone (MP) protected the heart against ischemia-reperfusion dysfunction, and we hypothetized that this protection might be due to induction of the cardioprotective heat shock protein 72 (HSP72). Rats were given vehicle or MP-40 mg/kg im as a double injection starting either 24 or 120 h (5 days) before their hearts were excised for Langendorff perfusion (n = 6-11 hearts in each group). MP improved left ventricular function and coronary flow during reperfusion after 30 min of global ischemia and reduced infarct size. Cardiac HSP72 gradually increased in a 24-h time course after MP treatment, and the increase was sustained 5 days afterward (immunoblotting). HSP72 mRNA was either reduced or unchanged, indicating a posttranscriptional regulation. Pretreatment with hydrocortisone or dexamethasone (n = 7-8 hearts of each) similarily increased cardiac HSP72 24 h afterward. This paper demonstrates that glucocorticoids increase cardiac HSP72 and protect organ function against ischemia-reperfusion injury.

Animals↗

PubMed1999

Hydrogen peroxide induces endothelial cell atypia and cytoskeleton depolymerization.

Reactive oxygen intermediates induce cell injury in a variety of pathophysiological conditions. Human umbilical cord vein endothelial cell (HUVEC) cultures were exposed to 1 or 200 microM H2O2 for 15 min, and observed after 15 min, or 1, 4, 24, or 120 h. Factor VIII and the cytoskeletal proteins vimentin and tubulin were visualized immunocytochemically. Release of lactate dehydrogenase (indices of cell membrane injury) did not increase after H2O2 exposure; nor was cellular expression of factor VIII affected. 200 microM H2O2 induced cell contraction after 15 min which disappeared after 1 and 4 h, but was evident again after 24 h. Immediately after exposure, the filamentous structure of vimentin and tubulin disappeared, but normalized after 1 h. After 120 h, the cytoskeleton filaments were coarsened and disorganized, and an abundance of multinucleated giant cells were observed. Catalase (150 U/ml) abolished all effects of H2O2. One microM H2O2 did not induce any changes in HUVEC. Thus, the present concentrations of H2O2 did not induce cell necrosis or altered expression of factor VIII. Early, reversible cell contraction and depolymerization of cytoskeletal proteins were observed, followed by a delayed contraction and cell atypia after 200 microM H2O2.

Antibodies, Monoclonal↗

PubMed1999

Post-ischaemic dysfunction does not correlate with release of cardiac troponin T in isolated rat hearts.

Cardiac troponin T (cTnT) is a highly sensitive and specific serum marker of irreversible cardiomyocyte injury. It is not clear whether cTnT also is a suitable marker of subtle, reversible injury. In the present investigation the relationship between cTnT release and function during the first 30 min of reperfusion after 30 min of global ischaemia, was investigated in isolated, retrogradely perfused rat hearts. Left ventricular systolic (LVSP), end-diastolic (LVEDP) and developed (LVDP) pressures, heart rate (HR), and coronary flow (CF) were measured. In one series of experiments (n=7) the kinetics of cTnT release during 30 min of reperfusion was investigated. An early, short-lasting peak of cTnT release appeared after 30 s of reperfusion. Then cTnT release gradually increased with a maximum after 20 min (from 0.08 +/- 0.03 before ischaemia to 2.16 +/- 0.40 ng min-1) (mean +/- SEM). In a second series of experiments (n=52) the relationship between cTnT release and cardiac function was investigated after 20 min of reperfusion. At this time point LVEDP increased (0 to 62 +/- 3 mmHg) and LVDP decreased (84 +/- 2 to 33 +/- 3 mmHg), but without any correlation with cTnT release. cTnT release was positively correlated to LVSP (P < 0.04, r=0.29), and negatively correlated to HR (P < 0.03, r=-0.31). cTnT concentration in the coronary effluent increased in parallel to increasing CF (P < 0.03, r=0.31). In conclusion, during the early reperfusion period there was no consistent correlation between cTnT release and dysfunction after global ischaemia in the isolated rat heart. Release of cTnT and post-ischaemic function appear to provide supplementary information in this particular model.

Animals↗

PubMed1999

Mechanical conversion of post-ischaemic ventricular fibrillation: effects on function and myocyte injury in isolated rat hearts.

Ventricular fibrillation (VF) and ventricular tachycardia (VT) are common phenomena during reperfusion. In experimental research many hearts have to be excluded from haemodynamic evaluation because of severe arrhythmias. Theoretically, electroconversion or mechanical conversion (MC) might be used to convert VF or VT. MC induces a physical shock analogous to a chest thump. The aim of this study was to investigate the efficacy of MC in isolated, perfused rat hearts, and to see whether MC itself induced myocardial cell injury and functional impairment. Langendorff-perfused rat hearts (n = 89) from several experimental series subjected to 30 min of global ischaemia and 60 min of reperfusion were retrospectively analysed. Left ventricular systolic (LVSP), end-diastolic (LVEDP), and developed (LVDP) pressures, coronary flow (CF), and heart rate (HR) were measured. If VF or VT continued for 1 min during reperfusion, MC was attempted by a flick of the forefinger to the right ventricle. If VF or VT still occurred, MC was repeated. Hearts that did not have regular beating after 20 min of reperfusion were excluded. Release of cardiac troponin T (cTnT) was measured before ischaemia and after 20 min of reperfusion. Forty-four out of 89 hearts had VF or VT during reperfusion. Thirty-five hearts were converted, 18 of which were converted by one or two MCs only. The higher the total number of MCs employed, the more cTnT was released. After 20 min of reperfusion, LVEDP, LVDP and CF were better in hearts with a higher number of MCs and with increased release of cTnT. After 60 min of reperfusion, LVEDP was still improved in hearts with more cTnT release, whereas LVSP was lower, and LVDP and CF were independent of the number of MCs. There was no consistent correlation between release of cTnT and heart dysfunction. In conclusion, MC effectively converted VF or VT. MCs increased post-ischaemic myocardial cell damage, as judged from increased cTnT release. Post-ischaemic dysfunction was partly attenuated in hearts with multiple MCs, and did not correlate with release of cTnT. We feel that MCs should not be used in isolated, perfused hearts.

Animals↗

PubMed1999

Hydrogen peroxide induces mRNA for tumour necrosis factor alpha in human endothelial cells.

Reactive oxygen intermediates are important mediators of inflammation. We investigated if hydrogen peroxide (H2O2) induces tumour necrosis factor alpha (TNFalpha) expression in cultured human cells from umbilical vein endothelium (HUVEC), aortic smooth muscle cells (SMC), peripheral blood mononuclear cells (PBMC), or the cell line Mono Mac 6. Cultures were stimulated with 200 micromol/L H2O2 for 15 min. After 4 h cells were harvested, mRNA extracted, and amplified by semiquantitative reverse transcription polymerase chain reaction (RT-PCR) with histone (H3) as reference gene. In HUVECs, mRNA for TNFalpha increased with a factor of 4 after stimulation (p < 0.001), in PBMC with a factor of 2 (p < 0.05), while mRNA from SMC and Mono Mac 6 did not increase significantly. Cellular TNFalpha protein in HUVECs was measured with flow cytometry (FACS) before and 6, 12, and 24 h after stimulation. TNFalpha protein was detectable in small, but reproducible amounts 12 h after stimulation, and increased further after 24 h. However, no secretion of TNFalpha was detected by ELISA. FACS analysis of the passaged HUVEC cultures did not reveal any contamination with non-endothelial cells. In conclusion, H2O2 induces TNFalpha mRNA in HUVECs and PBMC. In HUVECs an increase of intracellular TNFalpha protein was also detected, indicating that endothelial cells can produce small amounts of TNFalpha.

Cells, Cultured↗

PubMed1999

Does hypothermia or hyperkalemia influence the preconditioning response?

Ischemic preconditioning (IPC) is a potent mode of myocardial protection, but not in all models of cold cardioplegia. The present study investigates possible effects of hypothermia and hyperkalemia on the preconditioning response. Langendorff-perfused rat hearts were preconditioned (2 min global ischemia and 5 min reperfusion) or control-perfused prior to 35 min normothermic, global ischemia (series 1, n = 17 in each group); 50 min normothermic cardioplegia (St. Thomas's II) (series 2, n = 10 in each); 75 min 23 degrees C, global ischemia (series 3, n = 7 in each); or 5 h 6-8 degrees C, global ischemia (series 4, n = 9 in each). Left ventricular developed (LVDP) and end-diastolic (LVEDP) pressures, coronary flow (CF), heart rate, incidence of severe reperfusion arrhythmias, and release of troponin T (TnT) were measured. IPC attenuated reduction of LVDP and CF, and increase of LVEDP during reperfusion in series 1-3. TnT release was reduced by IPC in series 3 only. IPC did not attenuate dysfunction after hypothermic ischemia (series 4). Neither hyperkalemia nor moderate hypothermia alone inhibited the preconditioning response, but IPC was not protective in deep hypothermia.

Animals↗

PubMed1998

Measurements of plasma glutaredoxin and thioredoxin in healthy volunteers and during open-heart surgery.

Thioredoxin (Trx) and glutaredoxin (Grx) are both multifunctional redox-active proteins. In this study, Grx was identified in human plasma by immunoaffinity purification. The affinity-purified material from human plasma displayed a band of 12 kDa identical to recombinant human Grx by Western blotting and its glutathione-dependent reducing activity of beta-hydroxyethyl disulfide. Competitive enzyme-linked immunosorbent assays (ELISA) showed that plasma levels (mean +/- SD) of Grx and Trx in healthy volunteers (n = 41) were 456 +/- 284 ng/ml and 28.5 +/- 12.6 ng/ml, respectively. In cardiac surgical patients (n = 17), plasma Grx levels did not significantly change during cardiopulmonary bypass (CPB). In contrast, Trx levels in arterial plasma measured by sandwich ELISA and corrected for hemolysis were elevated during reperfusion of the postcardioplegic heart (p = .0001 at maximum), whereas by competitive ELISA Trx increased during surgical preparation for CPB, but decreased during CPB. When recombinant Trx was oxidized, immunoreactive Trx levels were decreased by competitive ELISA but not changed by sandwich ELISA. These results suggest that oxidized Trx is released into plasma during CPB. There was no significant difference in Trx and Grx levels between arterial and intracoronarial plasma samples, indicating no specific release by the post-cardioplegic heart. Trx and Grx may be important components in the plasma defense against oxidative stress.

Adult↗

PubMed1998

Effects of a novel, low-molecular weight inhibitor of lipid peroxidation on ischemia-reperfusion injury in isolated rat hearts and in cultured cardiomyocytes.

We investigated the effect of H290/51, a novel, low-molecular-weight inhibitor of lipid peroxidation, on cardiac ischemia-reperfusion injury. Lactate dehydrogenase (LD) release from cultured cardiomyocytes exposed to 1 h hypoxia and 4 h reoxygenation was measured after pretreatment with different concentrations of H290/51. In another series, Langendorff-perfused rat hearts were exposed to 30 min global ischemia and 60 min reperfusion (n=minimum 10 in each group): 1. Control ischemia-reperfusion. 2. Vehicle throughout the experiment. 3. Vehicle during stabilization, and H290/51 (10(-6) mol/l) during reperfusion. 4. H290/51 throughout the experiments. During reoxygenation of isolated cardiomyocytes, H290/51 dose dependently inhibited LD release with an pIC50 value of 7.2+/-0.4 (mean+/-SEM), with 10(-6) mol/l as the lowest efficient concentration. In isolated hearts ischemia-reperfusion induced severe reperfusion arrhythmias, reduced left ventricular developed pressure (LVDP) and coronary flow (CF), and increased LV end-diastolic pressure (LVEDP). LD activity in the effluent increased. H290/51 throughout perfusion (group 4) reduced the occurrence of severe reperfusion arrhythmias (p < .0001), attenuated the decrease of LVDP (p < .008), and CF (p < .006), the increase of LVEDP (p < .008), and the release of LD (p < .002). Tissue contents of thiobarbituric acid-reactive substances did not increase during reperfusion in controls, but was reduced in group 4 (p < .004). H290/51 given only during reperfusion (group 3) tended to improve cardiac function, but significantly so only for increase of CF (p < .01). The lipid peroxidation inhibitor H290/51 attenuated cardiac injury induced by ischemia-reperfusion.

Animals↗

PubMed1998

Preconditioning does not attenuate cardiac dysfunction after global ischaemia in the guinea-pig.

Ischaemic preconditioning reduces infarct size, but the effects on cardiac function after global ischaemia are more controversial. Additionally, species differences may exist. The present study investigates the effects of preconditioning on cardiac performance in the globally ischaemic, Langendorff-perfused guinea-pig heart. Hearts were stabilized for 25 min, and divided into the following groups: (1) (n = 8) control perfusion for 16 min before 30-min global ischaemia and 30-min reperfusion, (2) (n = 7) two episodes of 3-min ischaemia and 5-min reperfusion before global ischaemia, (3) (n = 7) 5-min ischaemia and 10-min reperfusion before ischaemia, (4) (n = 8) control perfusion before 40-min ischaemia and 30-min reperfusion, (5) (n = 8) Preconditioning as group 2 before ischaemia as group 4, (6) (n = 9) Control perfusion before 50-min ischaemia and 30-min reperfusion, (7) (n = 10) Preconditioning as group 2 before ischaemia as group 6. A dose-dependent reduction of left ventricular systolic pressure, and increase of end-diastolic pressure was observed during reperfusion after 30-, 40- and 50-min ischaemia. Preconditioning did not influence these changes, nor did it attenuate the incidence of severe reperfusion arrhythmias or reduction of coronary flow. In conclusion, ischaemic preconditioning does not improve cardiac function during reperfusion of the globally ischaemic, isolated guinea-pig heart.

Animals↗

PubMed1998

Preconditioning with hydrogen peroxide (H2O2) or ischemia in H2O2-induced cardiac dysfunction.

The possible cardioprotective effects of preconditioning by ischaemia (IPC) or a low dose of H2O2 (HPC) prior to a high dose of H2O2 was investigated. Langendorff-perfused rat hearts (n = 10 in each group) were subjected to 10 min of 140 micromol/L H2O2 and 30 min recovery after either (1) control perfusion, (2) 20 micromol/L H2O2 for 10 min, recovery 10 min, or (3) 2 x 2 min global ischaemia and 5 min reperfusion. 140 micromol/L H2O2 increased left ventricular end-diastolic pressure from 0 to 68+/-8 mmHg in controls (mean+/-SEM), which was attenuated by IPC (46+/-9 mmHg, p<0.001) and HPC (18+/-4 mmHg, p < 0.001 compared to controls, p < 0.01 compared to IPC). HPC, but not IPC, improved coronary flow (p < 0.02) and left ventricular developed pressure (p < 0.001) during recovery. Troponin T release was similar in all groups. Tissue thiobarbituric acid reactive substances, antioxidant capacity, catalase, and glutathione peroxidase were not influenced by 140 micromol/L H2O2. H2O2 decreased the level of tissue glutathione. This reduction was augmented by HPC (p <0.02) and attenuated by IPC (p < 0.02). H2O2 increased superoxide dismutase (p < 0.04). The increase was attenuated by IPC (p < 0.05), but not influenced by HPC. HPC efficiently protected cardiac function in H2O2-induced cardiac injury, while IPC had only a small protective effect. The functional protection cannot be explained by reduction of irreversible injury, attenuation of lipid peroxidation, or modification of tissue antioxidant parameters.

Animals↗

PubMed1997

Oxidative stress and release of tissue plasminogen activator in isolated rat hearts.

UNLABELLED: To evaluate the potential of tissue plasminogen activator (t-PA) as a marker of endothelial activation or injury, the dose-response relationship between reactive oxygen intermediates and t-PA release was investigated in isolated rat hearts. After stabilization the hearts were perfused for 10 minutes with different concentrations of hydrogen peroxide (H2O2) (0 (control perfusion), 20, 40, 80, 120, 160, or 200 microM) (n = 8 hearts/group), followed by 30 minutes recovery. Higher concentrations than 80 microM induced cardiac dysfunction and a dose-dependent release of lactate dehydrogenase, indicating myocyte injury. H2O2-concentrations of 80 microM and more caused a significant, but temporary t-PA release. Peak t-PA release occurred more rapidly with higher concentrations, but otherwise there was no difference dependent on the H2O2-dose. The effects of H2O2 (120 or 200 microM) on t-PA release were also compared to the effects of bradykinin. Both were given for 10 minutes as above, and the procedure was repeated after 10 minutes recovery. Bradykinin (50 or 500 nM) released t-PA with the same magnitude, but with peak values occurring earlier than t-PA release induced by H2O2. Bradykinin, but not H2O2, induced t-PA release during the second exposure, suggesting different mechanisms of release. IN CONCLUSION: Perfusion with H2O2 leads to a dose-dependent myocardial injury in isolated rat hearts. H2O2 also causes an acute t-PA release without dose-dependency, suggesting an all or nothing response of the endothelium. t-PA may be used as an indicator of, but cannot quantify endothelial activation or injury.

Animals↗

PubMed1997

Can reactive oxygen species precondition the isolated rat heart against arrhythmias and stunning?

Ischaemic preconditioning has cardioprotective effects. Reactive oxygen species may be possible mediators. The present study investigated whether low doses of exogenous hydrogen peroxide could mimic preconditioning in isolated, Langendorff-perfused rat hearts. Hearts were subjected to two episodes of 3 min global ischaemia and 5 min reperfusion (n = 17), or were given 10 (n = 15), 20 (n = 10), 30 (n = 20), 40 (n = 18), 80 (n = 17) or 160 microM (n = 10) hydrogen peroxide for 10 min, followed by 10 min recovery, before 25 min global ischaemia and 60 min reperfusion, and compared with ischaemic controls of matching perfusion time (n = 17 and n = 23). Cardiac performance was assessed by heart rate, left ventricular systolic, end-diastolic and developed pressures, and coronary flow. Severe reperfusion arrhythmias occurred frequently in control hearts, and was attenuated by ischaemic preconditioning. All hearts pretreated with 160 microM hydrogen peroxide had severe arrhythmias throughout reperfusion, while these were not seen in any heart perfused with 20 microM hydrogen peroxide (P < 0.01 compared to controls). Ischaemia and reperfusion induced a minor decrease in heart rate, left ventricular systolic and developed pressures, and increased end-diastolic pressure. Ischaemic preconditioning attenuated the decrease of heart rate and the increase of end-diastolic pressure, and increased coronary flow, while hydrogen peroxide did not significantly attenuate these changes. In conclusion, a low dose of exogenous hydrogen peroxide before global ischaemia inhibited severe reperfusion arrhythmias, but had no other protective effects. The present work does not suggest that reactive oxygen species are important mediators of the preconditioning effects on stunning and arrhythmias in the rat heart.

Animals↗

PubMed1997

Preconditioning the globally ischaemic, isolated rat heart: the impact of the preconditioning model on post-ischaemic systolic and diastolic function.

In studies of preconditioning, a variety of models have been used. The aim of the present study was to find the optimal preconditioning model for preservation of cardiac function during reperfusion of globally ischaemic, Langendorff-perfused rat hearts. Cardiac function was assessed by the occurrence of severe reperfusion arrhythmias (ventricular fibrillation or asystolia), heart rate (HR), left ventricular systolic (LVSP), end diastolic (LVEDP), and developed pressures (LVDP = LVSP - LVEDP), as well as coronary flow (CF). Series 1 (n = 17) in each group: control perfusion for 20 min without preconditioning or 2 episodes of 2, 3, 4, or 5 min of ischaemia, each followed by 5 min reperfusion, before 25 min ischaemia and 60 min reperfusion. Preconditioning reduced the incidence of reperfusion arrhythmias, attenuated the reperfusion-induced increase of LVEDP, and increased CF, but did not influence LVSP, LVDP, or rate x pressure-product (RPP = LVSP x HR) during reperfusion. The greatest effect was found by 2 min ischaemia and 5 min reperfusion. In series 2 (n = 17 in each group) control perfusion for 7 or 28 min, or preconditioning with 1-4 episodes of 2 min ischaemia and 5 min reperfusion before 35 min ischaemia and 60 min reperfusion were compared. Reduction of severe reperfusion arrhythmias and LVEDP elevation, as well as improvement of CF, LVDP, and HR in preconditioned hearts were observed in series 2. Optimal cardioprotection was achieved by only one episode of preconditioning. In conclusion, preconditioning before global ischaemia improved cardiac function during reperfusion of isolated rat hearts. The most marked effects were reduction of severe reperfusion arrhythmias and attenuation of diastolic dysfunction. Although all preconditioning models employed were cardioprotective, 1 episode of 2 min ischaemia provided optimal protection.

Animals↗

PubMed1997

Release of creatine kinase, troponin-T, and tissue plasminogen activator in arterial and coronary venous blood during coronary artery bypass surgery.

Tissue plasminogen activator (t-PA) as a possible marker of endothelial injury during elective coronary artery bypass surgery was studied. T-PA antigen and activity were measured in arterial and coronary venous plasma in 14 patients, and compared to the markers of myocyte injury creatine kinase (CK-MB) and troponin-T (TnT). Cardiopulmonary bypass (CPB) lasted 86 (55-107) min, and aortic cross-clamping (cold, crystalloid cardioplegia) lasted 41 (25-62) min (median (central 90% percentile)). Blood flow in the great cardiac vein was measured by retrograde thermodilution, and increased from 49 (27-90) ml/min before CPB to a maximum of 92 (55-125) ml/min 40 min after declamping (not significant). CK-MB, TnT, and t-PA antigen and activity all increased during CPB, and were significantly higher in coronary sinus than arterial plasma after declamping the aorta. Net cardiac release ([coronary sinus-arterial concentration] x coronary flow) of TnT increased after the aorta was declamped, and was higher in the seven patients with the longest cross-clamping time than in the seven with the shortest time (p < 0.01). Cardiac release of CK-MB and t-PA antigen also increased after declamping, but with no significant difference between long and short cross-clamp times. t-PA activity, however, increased more in the patients with the longest cross-clamp times (p < 0.008). In conclusion, CK-MB, TnT and t-PA were released from the postcardioplegic heart. Release of t-PA indicates that postcardioplegic coronary endothelial activation or injury occurred t-PA activity as well as TnT increased more in patients with long times of cross-clamping, indicating that t-PA activity may be a possible marker of postcardioplegic endothelial injury or activation.

Aged↗

PubMed1997

Release of markers of myocardial and endothelial injury following cold cardioplegic arrest in pigs.

Cold cardioplegic arrest causes reperfusion injury to both endothelium and myocardium. We investigated release of troponin-T (TnT), tissue plasminogen activator activity (t-PA) and histamine (HA) from the heart before and after 2h of cold crystalloid cardioplegia in eight Swedish landrace pigs. Coronary sinus blood flow was measured in an external shunt between the coronary sinus and the right atrium. TnT, t-PA and HA were measured concomitantly in arterial and coronary sinus plasma, and the cardiac release was calculated. Cardiac release of TnT increased from 18 (15-25) micrograms/min (median (central 90% percentile)) before cold cardioplegia to maximum 281 (132-510) micrograms/min 30 min after aortic declamping (p < 0.02 vs initial value). t-PA rose from -4 (-52-34) to maximum 249 (75-691) IU/min 2 min after declamping (p < 0.01) and thereafter returned to baseline levels. The net cardiac release of HA was 72 (-80-1321) nmol/min before cardioplegia, rising to 234 (-188-524) after 2 min of reperfusion (p < 0.02) and returning to baseline after 30 minutes. We conclude that the porcine heart releases t-PA, Tn-T and HA during postcardioplegic reperfusion. The differing kinetics of their release may indicate different affection of the myocardium and the endothelium. Tn-T, t-PA and HA are potential markers of myocardial and endothelial injury in the porcine heart.

Animals↗

PubMed1996

Systemic release of thrombomodulin, but not from the cardioplegic, reperfused heart during open heart surgery.

Thrombomodulin is a potential marker of endothelial injury. Plasma thrombomodulin was measured in concomitant arterial and coronary sinus samples in 9 patients undergoing elective coronary artery bypass surgery with cardiopulmonary bypass (CPB, 88 +/- 14 min) (mean +/- SD) and cold, crystalloid, antegrade cardioplegia (44 +/- 14 min). Arterial thrombomodulin was 17 +/- 6 ng/ml before surgery, and decreased to 10 +/- 5 ng/ml after heparinization (p < 0.008 compared to initial value). During CPB thrombomodulin increased, with a maximal level of 23 +/- 7 ng/ml (p < 0.008 vs initial value) 40 min after aortic declamping. No difference between arterial and coronary sinus concentrations was detected during reperfusion of the heart. In conclusion, plasma thrombomodulin is decreased by heparin, and increased during CPB. Consequently, thrombomodulin may be used to evaluate endothelial injury during CPB. However, as there is no specific intracoronary release of thrombomodulin during reperfusion, thrombomodulin is not a suitable marker of coronary endothelial injury after cardioplegia.

Aged↗

PubMed1996

Release of tissue plasminogen activator during reperfusion after different times of ischaemia in isolated, perfused rat hearts.

Tissue plasminogen activator (t-PA) is a potential marker of endothelial cell activation or injury. The relationship between duration of ischaemia and release of t-PA during reperfusion was investigated in isolated rat hearts exposed to either 5, 10, 20, 30, 40, or 60 min of global, normothermic ischaemia followed by 30 min of reperfusion (n = 8 in each group). t-PA activity was measured (chromogenic peptide substrate assay) in the effluent before ischaemia, and after 2.5, 5, 7.5, 10, 20, and 30 min of reperfusion. Release of lactate dehydrogenase (LD), a marker of myocyte injury, was measured before ischaemia and after 5 min reperfusion. Left ventricular pressures were measured by a balloon in the left ventricle. Ischaemia for 20 min or less had only minor effects on cardiac function. Thirty min or more of ischaemia induced ventricular fibrillation during reperfusion in most hearts. After ischaemia t-PA outflow increased, but without any significant difference between groups. Peak release occurred after either 2.5 or 5 min of reperfusion. After 10 min reperfusion the release was not different from the basal value. In contrast, postischaemic release of LD correlated to the length of ischaemia. To conclude, t-PA release from the ischaemic-reperfused rat heart is independent of the length of ischaemia. Thus the potential of t-PA to quantify endothelial injury appears to be limited.

Animals↗