Reduction of occlusive coronary artery thrombosis and myocardial ischemia by molsidomine in anesthetized dogs

1982 ◽  
Vol 60 (8) ◽  
pp. 1104-1111 ◽  
Author(s):  
Volker B. Fiedler
Keyword(s):  
Coronary Artery ◽  
Platelet Aggregation ◽  
Myocardial Ischemia ◽  
Diastolic Pressure ◽  
Thrombus Formation ◽  
Left Ventricular ◽  
Bolus Administration ◽  
Artery Thrombosis ◽  
Coronary Artery Thrombosis

The antianginal drug molsidomine was evaluated for its in vivo antithrombotic effects in barbiturate-anesthetized open-chest dogs by inducing left circumflex (LCX) coronary artery thrombosis with low-amperage stimulation (150 μA for 6 h) of the intimal surface of the vessel. Intravenous bolus administration of 0.10 mg/kg molsidomine 10 min prior to onset of electrical stimulation partially prevented occlusive LCX thrombosis and prolonged time to complete vessel occlusion by 45 min (p < 0.05). Intracoronary thrombus mass was reduced (14 ± 0.8 vs. 32 ± 4 mg in controls, p < 0.05). Final 6-h infarcts after complete LCX coronary artery thrombosis were measured by triphenyltetrazolium chloride (TTC) staining and were smaller after molsidomine pretreatment when related to left ventricular mass (14 ± 3 vs. 28 ± 2%, p < 0.02) or to the LCX vessel area at risk for infarction (18 ± 3 vs. 58 ± 4%, p < 0.01). Molsidomine did not induce hemodynamic alterations during time to complete thrombotic LCX coronary artery occlusion. In saline controls, heart rate and end-diastolic pressure increased whereas blood pressure and contractility decreased significantly. The percentage of ventricular ectopic beats concomitant to thrombus formation and myocardial ischemia was significantly reduced in the drug-treated dogs. Molsidomine also partially prevented the reduction in myocardial function parallel to blood flow diminution as measured with an ultrasonic technique. The drug further exerted significant ex vivo inhibition of collagen-induced platelet aggregation (p < 0.01 vs. control from 4 h after onset of LCX stimulation). In addition to established hemodynamic effects of molsidomine there may also be a direct effect on platelet aggregation and thrombus formation in vivo which delays coronary artery narrowing and occlusion as one primary cause for myocardial ischemia.

Prevention of Canine Coronary Artery Thrombosis with Echistatin, a Potent Inhibitor of Platelet Aggregation from the Venom of the Viper, Echis carmatus

1990 ◽  
Vol 64 (04) ◽  
pp. 576-581 ◽  
Author(s):  
Ronald J Shebuski ◽  
Denise R Ramjit ◽  
Gary R Sitko ◽  
Patricia K Lumma ◽  
Victor M Garsky
Keyword(s):  
Coronary Artery ◽  
Platelet Aggregation ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Artery Thrombosis ◽  
Coronary Artery Thrombosis ◽  
Canine Coronary Artery

SummaryA model of acute, platelet-dependent canine coronary artery thrombosis was utilized to assess the antithrombotic effect of a synthetic, RGD-containing 49-residue protein termed echistatin. This protein is derived from the venom of the viper, Echis carinatus. In vitro, echistatin inhibited ADP (10 ΜM)-induced platelet aggregation with IC50 values in human and canine platelet-rich plasma of 101 ± 4 and 127 ± 32 nM, respectively. In vivo, in the dog, infusion of echistatin for 30 min at 20 pg kg−1 min−1 or 2.6 nM kg−1 min−1 resulted in total abolition of acute platelet-dependent coronary thrombus formation in all dogs tested (n = 5). Infusion of a lower dose (10 pg kg−1 min−1) was not effective in prevention of thrombus formation. Blood samples were taken before and after infusion of echistatin in order to determine ex vivo platelet aggregatory responses. Echistatin (20 pg kg−1 min−1, i.v.) attenuated ex vivo platelet aggregation elicited by ADP, U-46619 and collagen and increased bleeding time by 2.9 ± 0.5-fold over control. Thus, in the dog, echistatin is an effective antithrombotic agent inhibiting both platelet aggregation in vivo in the coronary artery as well as ex vivo with a concomitant increase in bleeding time. Furthermore, the effects of echistatin on platelet aggregation and bleeding time are reversible with restoration to control levels occurring 30-60 min after termination of the infusion.

Anti-thrombotic Effects of CX-397, a Recombinant Hirudin Analog, in a Canine Model of Coronary Artery Thrombosis

1998 ◽  
Vol 79 (02) ◽  
pp. 423-430 ◽  
Author(s):  
Toshimitsu Hori ◽  
Mie Moriike ◽  
Taiji Asano ◽  
Hideya Hayashi ◽  
Kazunori Iwade ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Thrombus Formation ◽  
Specific Inhibitor ◽  
Canine Model ◽  
Control Group ◽  
Dependent Manner ◽  
Recombinant Hirudin ◽  
Artery Thrombosis ◽  
Coronary Artery Thrombosis ◽  
Intermediate Dose

SummaryCX-397, a recombinant hirudin analog, is a potent and specific inhibitor of human α-thrombin. We conducted a comparative study of CX-397 and heparin in a canine model of left circumflex (LCX) coronary artery thrombosis to evaluate the anti-thrombotic efficacy of CX-397. Administration of drugs (i. v.; bolus + infusion) was commenced 10 min prior to the initiation of LCX coronary artery electrolytic injury (100 μA for 300 min). All saline-treated control animals (7/7) developed thrombotic occlusion during the experimental period, leaving a residual thrombus mass of 15.4 ± 3.8 mg. Treatment with CX-397 at three incremental dose levels reduced the incidence of occlusion (4/7, 2/5 and 0/7) and decreased thrombus weight (12.6 ± 2.5 mg, 6.3 ± 3.0 mg and 2.1 ± 1.3 mg, respectively) in a dose-dependent manner. At the in termediate dose (15,000 ATU/kg + 15,000 ATU/kg/h) or higher, CX-397 showed significant anti-thrombotic effects (p <0.05 and p <0.01) and suppressed increases in thrombin-antithrombin III complex (TAT) levels (p <0.01 and p <0.001). In the heparin (80 U/kg + 60 U/kg/h)-treated group, the incidence of occlusion (5/7) and thrombus weight (14.1 ± 6.2 mg) did not differ significantly from the control group. Plas ma TAT levels in the heparin group decreased compared with the control group (p <0.01), but was less potent than the intermediate dose CX-397 (p <0.01). The anti-coagulation (activated partial thromboplastin time and activated clotting time) and template bleeding time prolongation effects of heparin were more potent than those of the intermediate dose CX-397 which showed significant anti-thrombotic effects. In conclusion, CX-397 dose-dependently suppressed thrombus formation by inhibition of thrombin activity in a canine coronary artery injury model. The anti-thrombotic efficacy of CX-397 was more potent than that of heparin at equivalent anti-coagulation dosage.

scholarly journals Triple Coronary Artery Thrombosis Presenting as Acute Anterior ST-Segment Elevation Myocardial Infarction

2017 ◽  
Vol 27 (04) ◽  
pp. 223-226
Author(s):  
Serkan Kahraman ◽  
Hakan Ucar ◽  
Sinem Ozyılmaz ◽  
Samir Allahverdiyev ◽  
Emrah Ermis
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Thrombus Formation ◽  
Circumflex Artery ◽  
Timi Flow Grade ◽  
St Segment Elevation ◽  
Segment Elevation Myocardial Infarction ◽  
Artery Thrombosis ◽  
Coronary Artery Thrombosis ◽  
St Segment

AbstractSimultaneous multivessel epicardial coronary artery thrombosis is an uncommon finding in acute ST-segment elevation myocardial infarction (STEMI). It generally leads to cardiogenic shock and sudden cardiac death in the hospital. We report a 42-year-old male patient presenting with acute anterior STEMI with triple coronary artery thrombosis. An emergency coronary angiogram showed total occlusion of the left anterior descending artery (LAD) with thrombus formation. At the same time, thrombus formations were also seen in the circumflex artery (CXA), the second obtuse marginal (OM2) branch, and the distal right coronary artery (RCA). We unsuccessfully attempted thrombus aspiration of the LAD. Subsequently, we decided to stent the LAD, and a successful percutaneous coronary intervention (PCI) was performed for the LAD. In a second procedure, RCA thrombosis regressed with 24-hour tirofiban (glycoprotein IIb/IIIa receptor inhibitor) perfusion, although CXA thrombosis and OM thrombosis did not regress. Therefore, we performed stenting of the CXA and OM with a newer provisional technique called the flower petal technique. Thrombolysis in myocardial infarction (TIMI) flow grade III was seen after stenting. The patient was discharged from the hospital 5 days after PCI without any symptoms.

Local proCPU (TAFI) Activation during Thrombolytic Treatment in a Dog Model of Coronary Artery Thrombosis can be Inhibited with a Direct, Small Molecule Thrombin Inhibitor (Melagatran)

2002 ◽  
Vol 87 (04) ◽  
pp. 557-562 ◽  
Author(s):  
J. A. Björkman ◽  
T. Abrahamsson ◽  
V. Nerme ◽  
K. Schatteman ◽  
J. Leurs ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Thrombus Formation ◽  
Coronary Vessels ◽  
Thrombin Inhibitor ◽  
Thrombolytic Treatment ◽  
Arterial Blood ◽  
Artery Thrombosis ◽  
Coronary Artery Thrombosis ◽  
Group 2 ◽  
Group 1

SummaryTo test the hypothesis that the direct thrombin inhibitor, melagatran is able to inhibit local pro-carboxypeptidase U (proCPU) activation that occurs during thrombolytic treatment, t-PA alone, or in combination with melagatran, was given to dogs with a coronary artery thrombosis. Blood samples from the great cardiac vein and aorta were collected at baseline, during thrombus formation, throughout the t-PA±melagatran infusion and during the patency period, for analysis of CPU activity using a novel assay. A higher CPU activity in venous compared to arterial blood (V-A difference) indicates CPU activation in coronary vessels.Efficacy was assessed by determination of time to lysis, duration of patency and blood flow during patency. Dogs (n = 26) were randomized to receive either 1) t-PA, 1 mg/kg as an intravenous 20-min infusion; 2) t-PA as in group 1,+ melagatran bolus, 0.3 mg/kg, followed by a 3-h infusion (0.15 mg/kg per h); 3) sham-operated but no coronary thrombus, and administered t-PA as for Group 1. All groups had similar baseline characteristics. Significant increases in CPU activity were observed in Groups 1 and 2 during thrombus formation, with V-A differences of 5.5 and 4.5 U/L, respectively. No significant V-A difference was observed in the sham-operated group. CPU activity increased in Group 1 during the t-PA infusion (V-A difference 15.9 U/L), whereas the V-A difference in Group 2 decreased to 2.6 U/L following melagatran treatment. These results demonstrate that melagatran attenuates generation of CPU in the coronary circulation. The mechanism is probably indirect, via inhibition of thrombin-mediated activation of proCPU.

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