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Biomedical subjects

W Heller

Publications and source records attributed to W Heller.

At least 37 records · Page 2Linked to original sources
PubMed1999

Action of aprotinin in myocardial ischemia - an investigation using a plasma-free model.

BACKGROUND: The protease inhibitor aprotinin has been reported to have an anti-ischemic effect on left-ventricular myocardium in patients undergoing cardiopulmonary bypass operation. To examine the anti-ischemic properties beside its antifibrinolytic and inhibitory action on the kallikrein-bradykinin system, we investigated this substance in buffer-perfused rat hearts. METHODS: 24 isolated isovolumically contracting rat hearts received a 10-minute infusion of either 10000 units aprotinin or pure saline followed by 30 minutes of no-flow global ischemia and 45 minutes of reperfusion. Hemodynamics, high-energy phosphates, and troponin T as molecular marker of cardiac injury were studied. RESULTS: During 15 minutes of reperfusion steady state function was identical in both groups, with a recovery of the developed left-ventricular pressure to 81.9+/-1.5% after protease inhibition and 83.0+/-2.6% in the controls. Coronary flow, myocardial oxygen consumption, and contractile reserve after maximum Ca++ stimulation were also identical. High-energy phosphates were comparably reduced in both groups (adenine nucleotides: 3.1+/-0.3 micromol/g ww after aprotinin vs. controls 2.7+/-0.4 micromol/g ww and creatine phosphate: 6.5+/-0.9 micromol/g ww vs. controls 4.7+/-1.1 micromol/g ww). However, release of the cardiac specific marker troponin T was lower after ischemia at several measurements (p<0.05). The total release of troponin T was 44+/-10 ng in the aprotinin treated hearts vs. 90+/-17 ng in the postischemic control hearts (p<0.05). CONCLUSIONS: The findings demonstrate that aprotinin in a moderate dose is effective in reducing postischemic troponin release in a non-blood perfused system. Measurement of myocardial high-energy phosphates after aprotinin use was performed for the first time and indicates that not a reduction in severity of direct myocardial ischemic intensity but a beneficial action on processes causing release of troponin is the mode of action of this effect.

Adenosine Triphosphate↗
PubMed1999

A twin study of individual differences in perceptual asymmetry.

Individual differences in perceptual asymmetry have been associated with individual differences in cognitive abilities, personality characteristics, and psychiatric symptoms, for which between-person variation appears to be genetically influenced. Perceptual asymmetry scores are also associated with direction of handedness, for which between-person variation does not appear to be genetically influenced. To assess whether between-person variation of perceptual asymmetry scores is genetically influenced, we examined asymmetry on a freevision task of face processing, the Chimeric Faces Task (CFT), in a sample of 31 monozygotic (MZ) and 20 same-sex dizygotic (DZ) twin pairs. MZ and DZ within twin-pair resemblances were compared to assess genetic and familial influences on asymmetric hemispheric function. We found that twins within a pair were no more likely to resemble each other than were unrelated individuals. The results suggest that the between-person variation in CFT perceptual asymmetry is not influenced by genes or shared environment.

Journal Article↗
PubMed1999

Contrasting patterns of brain activity in anxious apprehension and anxious arousal.

Evidence suggests that a distinction between anxious apprehension (worry) and anxious arousal (somatic anxiety) might account for some discrepancies in the literature examining brain activity in anxiety. In the current study, we compared the regional brain activity of groups of anxious apprehension and anxious arousal participants, selected on the basis of self-report measures previously shown to be psychometrically distinct from each other and from a specific measure of depression. Patterns of hemispheric asymmetry in electroencephalogram alpha distinguished the two types of anxiety, with the anxious arousal group showing more right than left activity. No significant asymmetry was found for the anxious apprehension group. The results provide further support for contrasting patterns of brain activity in distinct types of anxiety. Research is needed to specify further the topography and functional significance of this distinction.

Adolescent↗
PubMed1999

Activation markers of coagulation and fibrinolysis: alterations and predictive value in acute coronary syndromes.

Several alterations of the coagulation, of the fibrinolysis and of inflammation are known in patients with acute coronary syndromes. To extent current knowledge of the pathophysiology and to optimize therapeutical strategies, the new molecular markers can be used in clinical studies. Furthermore, several studies were undertaken to assess the prognostic value of activation markers of these systems for patients with unstable angina pectoris and acute myocardial infarction with or without thrombolytic therapy. The majority of studies focussed on markers of thrombin activation, fibrinogen, fibrin degradation products and t-PA and its main inhibitor PAI-1. While there are stimulating results from larger studies, the value for prognosis for the individual patient still is limited by the overlap of patients with good versus a poor outcome.

Acute Disease↗
PubMed1998

Thrombolytic therapy in acute myocardial infarction: comparison of procoagulant effects of streptokinase and alteplase regimens with focus on the kallikrein system and plasmin.

BACKGROUND: Thrombolytic therapy in patients with acute myocardial infarction (AMI) is hampered by procoagulant effects. In vitro studies have indicated that plasmin stimulation activates the kallikrein-contact-phase system, resulting in thrombin activation. This prospective comparative study was designed to examine the procoagulant effects of streptokinase or alteplase in AMI. METHODS AND RESULTS: Sixty-one patients with AMI received 1.5 million U of streptokinase or front-loaded alteplase (up to 100 mg) and systemic heparin. Twenty-four patients with AMI and no thrombolytic therapy and 30 control subjects were examined for comparison. Molecular markers of thrombin, plasmin activation, and coagulation activities were determined before therapy and serially for up to 10 days. Moderate thrombin (initial thrombin-antithrombin [TAT] complex 18+/-5 versus 4+/-0.3 microg/L, P<0.05) and kallikrein (up to 45+/-4 versus 30+/-1 U/L at 3 hours, P<0.01) activation occurs in patients with AMI. D-Dimers are increased (P<0.01), and plasmin is stimulated (P<0.01). Streptokinase and alteplase increase TAT to 50+/-17 and 51+/-18 microg/L at 3 hours and to 50+/-17 and 33+/-14 microg/L at 6 hours, respectively (P<0.01). Kallikrein activity is elevated (P<0. 01) to 76+/-5 and 71+/-7 U/L at 3 hours and 64+/-6 and 47+/-5 U/L by streptokinase and alteplase, respectively, at 6 hours. Reductions in fibrinogen and increases in D-dimers and plasmin-antiplasmin complexes are more marked (P<0.05 and 0.01) after streptokinase versus alteplase. Correlations were found among TAT, kallikrein activity, and plasmin activation (P<0.01). CONCLUSIONS: The data indicate a more marked procoagulant action of the streptokinase regimen compared with front-loaded alteplase, thus supporting the hypothesis of a plasmin-mediated kallikrein activation with consecutive procoagulant action in vivo.

Acute Disease↗
PubMed1998

Endothelial tissue-type plasminogen activator release in coronary heart disease: Transient reduction in endothelial fibrinolytic reserve in patients with unstable angina pectoris or acute myocardial infarction.

OBJECTIVES: We sought to examine whether the disturbed fibrinolytic system in patients with an acute coronary syndrome is associated with a reduced endothelial fibrinolytic capacity. BACKGROUND: Intracoronary thrombus formation is a frequent finding in acute coronary syndromes. Systemic alterations of coagulation and fibrinolysis are known to occur, but possible disturbances of endothelial fibrinolytic function have not been investigated. METHODS: We compared 42 patients with an acute coronary syndrome (acute myocardial infarction in 11 and unstable angina pectoris in 31) with 25 patients with stable angina. Venous blood was sampled serially for determination of markers of the fibrinolytic system and of hypercoagulability from admission to day 10. An occlusion test to determine the maximal endothelial tissue-type plasminogen activator (t-PA) release was also performed. RESULTS: Both on day 0 and day 10, patients with an acute coronary syndrome had a marked elevation of t-PA mass concentration (mean value +/- SEM 14.4 +/- 1.6 [day 0], 18.9 +/- 2.5 ng/ml [day 10]) and of plasminogen activator inhibitor (PAI) (9.4 +/- 2.2 [day 0], 11.3 +/- 2.6 AU/liter [day 10], p < 0.05 vs. patients with stable angina). There was also a hypercoagulative state with elevated thrombin activity and increased D-dimers (p < 0.05 vs. patients with stable angina). Maximal endothelial t-PA release was initially reduced (p < 0.05 vs. patients with stable angina) to 2.3 +/- 0.9 ng/ml, but levels recovered during follow-up to 4.4 +/- 1.4 ng/ml (vs. 5.7 +/- 1.5 ng/ml in patients with stable angina). CONCLUSIONS: Despite the known prolonged systemic alteration of fibrinolysis in acute coronary syndromes, endothelial fibrinolytic capacity is reduced only during the acute phase and becomes normalized during follow-up, and thus is linked more to intravascular thrombus formation than to steady state levels of markers of the fibrinolytic system.

Angina, Unstable↗
PubMed1998

Memory effects in the action of ozone on conifers.

Conifers are known to possess relative ozone tolerance in short-term experiments. A scenario for ozone damage of conifers is now derived from the first exposure experiments in which both the initial biochemical response phase and delayed visible symptom development were studied. A number of early biochemical ozone responses could be detected in Norway spruce (Picea abies [L.] Karst.) and Scots pine (Pinus sylvestris L.). The stress metabolite catechin persisted over several months. In the year following ozone treatment of spruce, decreases in pigment content and photosynthetic capacity, as well as development of visible symptoms (chlorosis, banding), were determined in the needle age classes previously exposed to an accumulated hourly ozone dose above 40 ppb (AOT40) of >/=60-80 ppm small middle doth. The visible symptoms developed during spring emergence of the new flush. In the case of Scots pine, an ozone dose (AOT40) of >/=30 ppm small middle doth caused the premature shedding of needles 9 months after treatment. The delayed symptoms of both spruce and pine occurred during known phases of endogenous stress. The symptoms appeared to reflect an ozone "memory" imprinted by the induced early stress reactions. Ambient AOT40 ozone doses in Central Europe are in the range 4 and 50 ppm small middle doth per growing season. Ozone is proposed to potentially damage conifers through memory effects ("abiotic" pathway) or through predisposition for pathogen attack ("biotic" pathway).

Catechin↗
PubMed1998

Streptokinase-induced activation of the kallikrein-kinin system and of the contact phase in patients with acute myocardial infarction.

Thrombolytic therapy in acute myocardial infarction (AMI) is hampered by a considerable reocclusion rate. Thrombin activity is enhanced, and contact-system activation via plasminemia might be possible. Prospectively we examined the contact phase and the kallikrein-kinin system and additional molecular markers of hemostasis and fibrinolysis in AMI. In 22 patients with AMI, blood sampling was performed at admission and < or =10 days afterward. Eleven patients received 1.5 Mio U streptokinase (group A) and were compared with 11 AMI patients without thrombolytic therapy (group B). All patients had systemic heparinization (5,000 IU bolus, i.v.; 1,000 IU/h, i.v.). In group A (vs. group B), the kallikrein-factor XII system was significantly activated (3 h after start of therapy): kallikrein activity 140 +/- 41 (vs. 43 +/- 8) U/L (p < 0.05); kallikrein inhibition 87 +/- 9 (vs. 113 +/- 7%; p < 0.05), and factor XII 70 +/- 14 (vs. 94 +/- 6%). C1 inhibitor and factor XII inhibition were decreased. High-molecular-weight kininogen consumption indicating bradykinin generation was enhanced (p < 0.01). In group A, thrombin activity (TAT) was increased, and a hypercoagulative state with increased fibrin degradation products (d-dimer) was found. Plasmin activation in group A was reflected by decreased plasminogen and antiplasmin levels (p < 0.01). The findings indicate that streptokinase induces activation of the contact phase-kinin system in vivo associated with a consecutive increase of thrombin and bradykinin generation. Activation of this pathway might substantially contribute to reocclusion after initially successful thrombolytic therapy and to hypotensive reactions observed after streptokinase.

Acute Disease↗
PubMed1998

A new intermediate in the mineralization of 3,4-dichloroaniline by the white rot fungus Phanerochaete chrysosporium.

Phanerochaete chrysosporium ATCC 34541 has been reported to be unable to mineralize 3,4-dichloroaniline (DCA). However, high mineralization is now shown to occur when a fermentation temperature of 37 degrees and gassing with oxygen are used. Mineralization did not correlate with lignin peroxidase activity. The latter was high under C limitation and low under N limitation, whereas the reverse was true for mineralization. The kinetics of DCA metabolism was studied in low-N and low-C and C- and N-rich culture media by metabolite analysis and 14CO2 determination. In all cases, DCA disappeared within 2 days, and a novel highly polar conjugate termed DCAX accumulated in the growth medium. This metabolite was a dead-end product under C and N enrichment. In oxygenated low-C medium and in much higher yield in oxygenated low-N medium, DCAX was converted to DCA-succinimide and then mineralized. DCAX was purified by high-performance liquid chromatography and identified as N-(3,4-dichlorophenyl)-alpha-ketoglutaryl-delta-amide by high-performance liquid chromatography and mass spectroscopy, gas chromatography and mass spectroscopy, and nuclear magnetic resonance spectroscopy. The formation of conjugate intermediates is proposed to facilitate mineralization because the sensitive amino group of DCA needs protection so that ring cleavage rather than oligomerization can occur.

Aniline Compounds↗
PubMed1998

Effects of the combinations propofol/alfentanil and midazolam/fentanyl on blood pressure and contact phase system during coronary surgery.

Perioperative haemodynamic changes leading to severe circulatory problems during open-heart surgery still represent dreaded complications. The aim of this study was to examine the relationship between the use of applied anaesthetic agents and alterations of the contact phase of the intrinsic blood-clotting system, as changes within the kallikrein-kinin system can lead to a fall in blood pressure. In a randomized study, parameters of the kallikrein-kinin system, coagulation and fibrinolysis were determined for 36 patients with aortocoronary bypass operations. The patients had been given either midazolam/fentanyl or propofol/alfentanil to maintain anaesthesia. Perioperative blood pressure values were registered at seven fixed points. The measured values of the factor XIIa-like activity and the kallikrein-like activity suggested a higher activation of the contact phase, when propofol/alfentanil was given. From the start of the extracorporeal circulation (ECC) to the end of the operation, the kallikrein-like activities in the propofol/alfentanil group were significantly higher than those of the midazolam/fentanyl group. Also, the results of the kallikrein inhibition capacity and the indicators of fibrinolysis (t-PA and D-dimers) indicate a stronger activation of the contact phase--at least at the beginning of recirculation--and as a result of it, a stronger fibrinolysis within the propofol/alfentanil group. In addition, the hypotensive side-effects differed significantly between the two groups. Patients receiving propofol/alfentanil needed the triple amount of antihypotonicum to maintain the mean arterial blood pressure above 75 mmHg. With the results of this study, a correlation between the application of propofol/alfentanil, contact phase activation, with activation of the kallikrein-kinin-bradykinin system and the observed hypotension, can be presumed.

Alfentanil↗
PubMed1997

Patterns of regional brain activity differentiate types of anxiety.

Previous studies have reported hemispheric asymmetries in brain activity in anxiety, but the direction of asymmetry has been inconsistent. A distinction between anxious apprehension (e.g., worry) and anxious arousal (e.g., panic), as types of anxiety, may account for some of the discrepancies. To test this proposition, the authors selected participants with self-reported anxious apprehension and experimentally manipulated anxious arousal. Regional brain activity was examined by recording electroencephalograms during rest and during an emotional narrative task designed to elicit anxious arousal. Overall, anxious participants showed a larger asymmetry in favor of the left hemisphere than did controls. In contrast, during the task, anxious participants showed a selective increase in right parietal activity. The results support the hypothesis that anxious apprehension and anxious arousal are associated with different patterns of regional brain activity.

Anxiety↗
PubMed1996

Influence of heparin, heparin plus aprotinin and hirudin on contact activation in a cardiopulmonary bypass model.

In the present study we used an in vitro cardiopulmonary bypass model to compare activation of the FXII-plasma kallikrein systems, coagulation pathway and blood cell changes, with heparin (3 U/ml), heparin plus aprotinin (3 U/ml and 250 KIU/ml) and recombinant hirudin (6 micrograms/ml). After 90 min circulation the results showed that with heparin plus aprotinin and with hirudin the activation of these cascade reactions was markedly lower. In particular kallikrein-like activities and PMN-Elastase-alpha 1-PI levels were significantly lower in the latter two groups. The least activation was detected with hirudin. Our results confirm that the contact systems of blood are activated during CPB with heparin as anticoagulant, that aprotinin reduces this activation, and that recombinant hirudin may be preferred to heparin as an anticoagulant in cardiac surgery.

Aprotinin↗
PubMed1996

The quality of autotransfused chest-drainage blood after cardiac surgery: a study of coagulation factors.

A wide range of experience, dating back as far as 1978, has been gained with both the hard-shell cardiotomy reservoir of the heart-lung machine and the Sorensen autotransfusion system as retransfusion systems. Three remains, however, a lack of knowledge regarding the quality of retransfused blood in systems of less complex construction which are already available on the market and involve the use of a pouch (Sentinel-Seal autotransfusion system and Pleur-evac collecting system). The present study entailed the investigation of blood from the chest drainages of twenty patients after cardiac surgery by using a simple retransfusion system (Sentinel-Seal autotransfusion system). In two postoperative groups of patients with low and high blood loss from chest drainage, we determined, in addition to free plasma hemoglobin, the following: factor XII, kallikrein-like activity, thrombin-antithrombin III complex, tissue-plasminogen and d-dimers. In the collective with a low blood loss, we found remarkable cell alterations as well as highly activated and advanced coagulation and an extraordinary fibrinolytic activity. If done at all, retransfusion by the Sentinel-Seal autotransfusion system should be restricted to the first four postoperative hours in cases of high blood loss.

Antithrombin III↗
PubMed1996

Radiographic contrast media and the coagulation and complement systems.

Intravascular contrast agents have several side effects including alterations of the hemostasis and the complement system. The effects on these systems may be one of the main causes of the "adverse contrast agent reaction." In vitro and in vivo evidence is provided that both ionic and nonionic contrast media activate the plasma kallikrein with consecutive activation of the factor XII-contact phase and stimulation of the bradykinin generation. Furthermore, activation of the complement cascade via the classic and the alternative pathways was described to a various extent for intravascular application of contrast agents. In non-reactors, these alterations are transient and only have a limited extent indicating that these reactions are within the regulatory capacity of the kallikrein-kinin-factor XII system. In reactors, however, significant evidence for an extended activation of the kallikrein system is associated with reduced levels of C1-esterase inhibitor. Therefore, patients with alterations in these systems should be regarded as candidates for adverse contrast agent reactions. Furthermore, contrast media influence the blood coagulation, especially in contact to artificial surfaces (plastic or glass). In vitro findings suggest that there is a broad scope of modifications caused by contrast agents indicating a modification of the risk of thromboembolism during angiography. Preliminary data suggest that an inhibition of clot formation is more effective with ionic compared with nonionic contrast agents. In summary, radiographic contrast agents have an impact both on the hemostasis and the complement systems. The effects may be of importance for adverse reactions as well as for thromboembolic complications during angiography.

Blood Coagulation↗
PubMed1995

Alterations of coagulation and fibrinolytic and kallikrein-kinin systems in the acute and postacute phases in patients with unstable angina pectoris.

BACKGROUND: Unstable angina pectoris is frequently associated with intracoronary thrombus formation. In a prospective study, we investigated in 35 patients with unstable angina pectoris markers of coagulation and the kallikrein-kinin and fibrinolytic systems in the acute and postacute phases. METHODS AND RESULTS: We determined serially in the patients up to 10 days after admission factor XII and the beta-factor XIIa inhibition, kallikrein-like activity, prekallikrein, C1-esterase inhibitor, kallikrein inhibition, high molecular weight kininogen as indicators of the contact phase and bradykinin generation, thrombin-antithrombin III (TAT) complex as marker of the activated coagulation cascade, fibrinogen, plasminogen, plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (TPA), and D-dimers as indicators of the fibrinolytic system. Data were compared with those from control subjects (n = 25) and from patients with stable angina pectoris (n = 25). In patients with unstable angina pectoris, initially the contact phase and the kallikrein-kinin system were markedly elevated (factor XII, 96 +/- 5% versus 117 +/- 5%; kallikrein-like activity, 35.7 +/- 2.9 versus 27.4 +/- 1.3 U/L; high molecular weight kininogen, 52.7 +/- 5.2% versus 87.7 +/- 3.9%; P < .01 versus control subjects). Contact-phase activation persisted for the following 10 days, whereas the initially enhanced bradykinin generation normalized after 2 days. Furthermore, we had evidence of a hypercoagulative state (TAT, 10.9 +/- 3.1 versus 4.5 +/- 0.7 micrograms/L, P < .05; D-dimer, 474 +/- 81 versus 272 +/- 71 ng/mL) persisting longer than the clinically symptomatic period in association with disturbed fibrinolysis (TPA, 15.9 +/- 1.9 versus 5.1 +/- 0.4 ng/mL; P < .01; PAI-1, 9.9 +/- 2.6 versus 4.6 +/- 1.6 AU/mL; P = NS) in the presence of elevated fibrinogen levels. CONCLUSIONS: Our data indicate that in patients with unstable angina pectoris, intracoronary thrombus formation is associated with a hypercoagulative state, including activation of the contact phase and of the kallikrein system and increased bradykinin generation. The persistence of this hypercoagulative state, together with a disturbed fibrinolysis, might indicate an increased risk for further coronary events.

Acute Disease↗
PubMed1995

Lower cardiac troponin T levels in patients undergoing cardiopulmonary bypass and receiving high-dose aprotinin therapy indicate reduction of perioperative myocardial damage.

Nowadays in many European heart centers the activation of the fibrinolytic system, always occurring during cardiopulmonary bypass, is routinely reduced by high-dose application of the proteinase inhibitor aprotinin (total of > 4 million KIU). In this study parameters of myocardial ischemic injury were investigated with the aim of identifying further benefits of aprotinin, particularly the protection of the myocardium during the ischemic period of aortic crossclamping. Forty patients with coronary artery disease who underwent aorta-coronary bypass grafting were randomly and in a double-blind fashion divided into two groups, one that received high-dose aprotinin therapy and one that received only saline solution. Markers such as troponin T, with high specificity for detection of myocardial ischemia and infarction, and markers with more general specificity such as creatine kinase, its isoenzyme, and lactate dehydrogenase showed significantly increased values after ischemia in both groups. In patients who received high-dose aprotinin therapy 3 days after cardiopulmonary bypass all parameters measured showed significantly lower levels compared with those in the control group. Therefore we can presume that the application of high-dose aprotinin provides myocardial protection from perioperative ischemic injury.

Aprotinin↗