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C Thiemermann

Publications and source records attributed to C Thiemermann.

178 records · Page 10Linked to original sources
PubMed1989

Endothelin-1 releases prostacyclin and inhibits ex vivo platelet aggregation in the anesthetized rabbit.

The effects of porcine endothelin (endothelin-1, ET-1; 1 nmol/kg i.a.) on ex vivo platelet aggregation and platelet cAMP/cGMP levels were investigated in the anesthetized rabbit. ET-1 inhibited ADP-induced platelet aggregation by 83 +/- 9% within 5 min (p less than 0.01). This ET-1-induced inhibition of platelet aggregation lasted for 30 min and was associated with a significant (five- to sixfold) increase in platelet cAMP. However, platelet cGMP levels were unaffected. Indomethacin (5 mg/kg i.v., 20 min prior to ET-1) abolished the ET-1-induced inhibition of ex vivo platelet aggregation as well as the corresponding augmentation of platelet cAMP. Thus, ET-1 inhibits platelet function in vivo due to the release into the circulation of antiplatelet cyclo-oxygenase products, such as prostacyclin (or PGD2).

Anesthesia↗
PubMed1989

Eicosanoids in myocardial ischemia.

Arachidonic acid (AA) accumulation in the ischemic myocardial tissue. Its release and subsequent metabolization into several classes of eicosanoids and lipid peroxides occurs in parallel with the development of myocardial ischemic injury and may be initiated by the loss of energy-rich phosphates. The profile of eicosanoid release during ischemia and reperfusion differs both quantitatively and qualitatively from that seen under non-ischemic conditions. This is at least partially due to the presence of stimulated inflammatory cells and platelets with a considerable activity of AA-metabolizing enzymes as well as endothelial injury. Thus, cardiac eicosanoid release in nonischemic conditions is primarily beneficial, resulting in more effective adaption of its function to the needs of the circulation. Eicosanoid release in acute ischemia is primarily deleterious and enhances inflammatory reactions and functional disturbances.

Animals↗
PubMed1988

The thromboxane receptor antagonist, daltroban, protects the myocardium from ischaemic injury resulting in suppression of leukocytosis.

The cardioprotective action of the new selective inhibitor of thromboxane receptors, daltroban (BM 13.505), was studied in cats subjected to 3 h of coronary artery ligation followed by 2 h of reperfusion. In comparison with vehicle (physiological saline)-treated cats, daltroban (20 mg/kg per h i.v.) reduced the ischaemia-induced rise in the ST segment and prevented the development of a Q-wave in the ECG during reperfusion. This was paralleled by a significantly improved preservation of creatine-phosphokinase activity in the ischaemic myocardium. Daltroban significantly attenuated platelet ATP secretion, the U-46.619-induced contraction of the cat thoracic aorta ex vivo and the myeloperoxidase-associated generation of reactive oxygen species ex vivo. These effects could be largely attributed to the inhibition of ischaemia-induced leukocytosis. It is concluded that daltroban protects the myocardium from ischaemic injury and that this effect involves prevention of ischaemia-induced leukocytosis.

Adenosine Triphosphate↗
PubMed1988

Protection of the ischemic myocardium from reperfusion injury by prostaglandin E1 inhibition of ischemia-induced neutrophil activation.

This study investigates the action of intravenous PGE1 on myocardial reperfusion injury and the possible involvement of antineutrophil activities. Cats were subjected to 3 h of temporary ligation of the left anterior descending coronary artery, followed by 2 h of reperfusion. Animals were treated with PGE1 (5 micrograms/kg x min) or vehicle (saline solution), starting 0.5 h after coronary artery occlusion. Vehicle-treated cats exhibited a significant loss of cardiac creatine phosphokinase specific activity at 5 h, accompanied by a significant ischemia-induced rise in the ST segment of the ECG and development of a Q wave after starting reperfusion. All of these alterations were largely prevented by PGE1 treatment. PGE1 exerted some blood-pressure-lowering activity at 5 h (P greater than 0.05) but did not reduce myocardial contractile force and oxygen consumption. PGE1 modestly antagonized ischemia-induced formation of platelet aggregates. However, PGE1 prevented the rise in peripheral white blood cell count during ischemia and reperfusion and inhibited the generation of reactive oxygen species (myeloperoxidase assay) from zymosan-stimulated whole blood ex vivo. The ratio of generation of reactive oxygen species/white blood count remained unchanged. It is concluded that PGE1 protects the ischemic myocardium from acute reperfusion injury and that this effect involves an action of the compound on neutrophils, probably by improved myocardial tissue preservation, resulting in reduced formation of chemotactic products and, consequently, less local neutrophil accumulation and release of noxious metabolites.

Alprostadil↗
PubMed1988

The effects of endothelium-dependent vasodilators on cardiac output and their distribution in the anaesthetized rat: a comparison with sodium nitroprusside.

1. The effects of sodium nitroprusside, acetylcholine and bradykinin on cardiac output and its distribution were studied in the anaesthetized, vagotomised rat preparation by use of 113Sn-labelled microspheres. 2. All three vasodilators lowered peripheral arterial blood pressure, but only bradykinin significantly reduced total peripheral resistance without reducing cardiac output. Bradykinin caused tachycardia, but this was offset by a reduction in stroke volume. These effects of bradykinin were not altered by indomethacin (4 mg kg-1). Acetylcholine and sodium nitroprusside both caused significant (P less than 0.05) reductions in stroke volume and cardiac output. 3. Bradykinin reduced vascular resistance in the liver, stomach, small intestine, large intestine, pancreas/mesentery, epididimides, skeletal muscle and fat. These responses were not affected by indomethacin, whereas, the reduction in vascular resistance in the brain induced by bradykinin was abolished by indomethacin. 4. Acetylcholine caused a reduction in renal vascular resistance, where bradykinin had no effect. However, acetylcholine did not cause any haemodynamic changes in the bradykinin-sensitive intestinal vasculature. 5. Acetylcholine caused vasoconstriction in the coronary and epididymal vasculature. Bradykinin in the presence of indomethacin induced vasoconstriction in the skin. 6. In conclusion, the data show that, with the possible exception of the brain and the skin, the vasodilator actions of bradykinin can adequately be transduced (presumably by endothelium-derived relaxing factor, EDRF) in the absence of prostacyclin synthesis. Additionally, these results indicate that the vasculature of the stomach, pancreas/mesentery, epididimides and skeletal muscle are equally sensitive to both acetylcholine and bradykinin, whereas the kidneys showed selectivity towards acetylcholine and the intestines towards bradykinin. These results may indicate differential receptor populations.

Acetylcholine↗
PubMed1988

Protection of the ischaemic myocardium from reperfusion injury by defibrotide and its possible mechanism of action.

The following study was designed to investigate the therapeutic value of defibrotide (32 mg/kg bolus + 32 mg/kg x h i.v.) in a cat model of acute myocardial ischaemia (MI) and reperfusion and to elucidate its possible mechanism(s) of action. Infusion of defibrotide (DEF), starting 30 min after the onset of ischaemia, had no effect on any of the hemodynamic parameters measured. In comparison with vehicle-treated animals, DEF largely attenuated the MI-associated ST-segment elevation and completely prevented the development of a pathological Pardee-Q-wave upon reperfusion. Furthermore, DEF largely antagonized the loss of creatine phosphokinase from the ischaemic reperfused myocardium. DEF significantly reduced the MI-induced thrombocytopenia and inhibited the collagen-induced platelet ATP-secretion ex vivo. Interestingly, DEF-treatment did not modify the MI-induced leucocytosis or the release of reactive oxygen radicals from activated neutrophils. These findings indicate that stimulation of endogenous prostacyclin formation by DEF reduces myocardial reperfusion injury independently of any direct effects of the compound on neutrophil activation.

Animals↗
PubMed1986

Successful treatment of acute myocardial ischaemia with teopranitol--a novel organic nitrate.

The present study was designed to examine the effects of a new organic nitrate, teopranitol, in acute myocardial ischaemia. Adult cats were subjected to 5 h of myocardial ischaemia by permanent ligation of the left anterior descending coronary artery (LAD). Teopranitol (10 mg kg-1 X h) or physiological saline (vehicle) was infused i.v., beginning 30 min after LAD occlusion and continued until the end of the experiment. All animals subjected to myocardial ischaemia showed a significant elevation of the ST-segment within 20 min of LAD occlusion. In the LAD-vehicle group, the ST-segment elevation continued to increase; teopranitol attenuated this increase and significantly reduced the ST-segment elevation at 4 and 5 h (P less than 0.05). The loss of creatine phosphokinase-specific activity from the ischaemic myocardium was significantly reduced by teopranitol (P less than 0.05), indicating an improved preservation of myocardial tissue. There was a significant initial reduction in mean arterial blood pressure by teopranitol in sham-operated cats but no consistent change of this parameter, heart rate or the computed pressure-rate product in LAD-occluded cats. Teopranitol did completely reverse the ischaemia induced formation of platelet aggregates at 1 to 5 h (P less than 0.05). It is concluded that teopranitol exerts a significant protective effect in acute myocardial ischaemia in vivo that is independent of changes in systemic haemodynamics and might be associated with the generation of an antiplatelet activity in vivo.

Animals↗
PubMed1986

Treatment of acute myocardial ischaemia with a selective antagonist of thromboxane receptors (BM 13.177).

In order to elucidate the role of endogenous thromboxane A2 in myocardial ischaemia, cats were subjected to 5 h of permanent occlusion of the left anterior descending coronary artery (LAD) and treated with the thromboxane receptor antagonist BM 13.177 (5 mg kg-1 h-1, i.v.). In comparison with vehicle-treated LAD-occluded cats, BM 13.177 significantly attenuated the loss of creatine phosphokinase-specific activity from the ischaemic myocardium and antagonized the ischaemia-induced rise in the ST-segment of the electrocardiogram. BM 13.177 at the dose used did not reduce plasma thromboxane levels or ischaemia-induced platelet aggregate formation but considerably antagonized thromboxane-dependent platelet secretion ex vivo. The study demonstrates some beneficial effects of selective blockade of thromboxane receptors on biochemical and electrophysiological parameters of acute myocardial ischaemia.

Adenosine Triphosphate↗
PubMed1985

Usefulness of defibrotide in protecting ischemic myocardium from early reperfusion damage.

Defibrotide, a partially depolymerized polydeoxyribonucleotide obtained from mammalian lungs, was found to stimulate prostacyclin (PGI2) production and to possess significant antithrombotic and fibrinolytic activities. The present study was designed to evaluate the actions of defibrotide on feline myocardial ischemia, produced by 3 hours of occlusion of the left anterior descending coronary artery (LAD) and followed by 2 hours of reperfusion. Intravenous administration of defibrotide (32 mg/kg/hour subsequent to a 32 mg/kg bolus injection), beginning 30 minutes after LAD occlusion, resulted in a 60% reduction in loss of CK specific activity from ischemic myocardium at 5 hours, while the nonischemic myocardium remained unaffected. Defibrotide largely antagonized the increase in ST segment during LAD occlusion and prevented the appearance of a Q wave during early reperfusion, which was found in all vehicle-treated cats. Although 2 of 8 vehicle-treated cats died from ventricular fibrillation and another had severe ventricular tachyarrhythmia, none of the defibrotide-treated cats had similar severe changes in the electrocardiogram and all 7 cats survived the 5-hour observation period. Defibrotide had no direct action on general hemodynamic functions. In a separate set of experiments, defibrotide (0.1 mg/ml) produced an 8- to 10-fold stimulation of PGI2 release. The data suggest a remarkable protective potential of defibrotide on reperfusion damage of the ischemic myocardium, which may be associated with a PGI2-related mechanism.

Adenosine Triphosphate↗
PubMed1984

Comparison of the thromboxane synthetase inhibitor dazoxiben and the prostacyclin mimetic iloprost in an animal model of acute ischaemia and reperfusion.

The thromboxane (TX) synthetase inhibitor dazoxiben (80 micrograms/kg X min) and the prostacyclin analogue iloprost (0.6 micrograms/kg X min) were investigated in a cat model of acute myocardial ischaemia (MI) plus reperfusion. The agents were i.v. infused starting 30 min after LAD occlusion until the end of the observation period (5h). Dazoxiben significantly reduced the MI-induced increase in TXB2 and platelet ATP secretion. Dazoxiben did not influence the MI-induced depression in platelet count (PC), the fall in CK-specific activity or the ECG alterations associated with reperfusion whereas iloprost resulted in a nearly complete recovery of these parameters. These data suggest an efficacy of PGI2 administration but not of TX synthetase inhibition in preserving the myocardium from reperfusion injury. These data indicate that reperfusion-induced tissue damage appears not to be a thromboxane-dependent phenomenon.

Adenosine Triphosphate↗
PubMedDate not supplied

Induction of nitric oxide and tetrahydrobiopterin synthesis by lipoteichoic acid from Staphylococcus aureus in vascular smooth muscle cells.

Lipoteichoic acid (LTA), a component of the membrane of gram-positive bacteria, induces an isoform of nitric oxide (NO) synthase (iNOS) in vascular smooth muscle; this process may be associated with the vascular failure observed in gram-positive septic shock. The aim of the present work was to study the cellular mechanisms involved in the induction of NO synthesis by LTA from Staphylococcus aureus in cultured rat vascular smooth muscle cells. LTA induces the gene expression of iNOS and GTP cyclohydrolase I (GTPCH) as well as the formation of NO and tetrahydrobiopterin (BH4), effects which are synergistic with interferon-gamma. 2,4-Diamino-6-hydroxypyrimidine (DAHP), a selective inhibitor of GTPCH, inhibits both the increase in cellular levels of BH4 as well as the concomitant formation of NO caused by LTA in combination with interferon-gamma. This inhibition by DAHP is reversed by co-addition of sepiapterin which is a substrate for BH4 synthesis. Thus, BH4 synthesis is an absolute requirement for the induction of NO synthesis by LTA in vascular smooth muscle. Our findings also suggest that interrupting pterin synthesis may be an effective target for pharmacologic interventions aimed at limiting NO overproduction in gram-positive shock.

Animals↗