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Biomedical subjects

D A Gorog

Publications and source records attributed to D A Gorog.

12 recordsLinked to original sources
PubMed2006

Enhanced spontaneous thrombolysis: a new therapeutic challenge.

Spontaneous thrombolysis is an endogenous protective mechanism against lasting arterial thrombotic occlusion, which is implicated in the pathogenesis of myocardial infarction and acute coronary events. Novel therapies for coronary heart disease (CHD) targeting atherosclerosis and thrombosis, together with cardiovascular prevention programs targeting risk-factors and lifestyle provide evidence that CHD is preventable. Although reduced fibrinolytic activity is a recognized risk-factor for ischemic cardiovascular events, it has so far been neglected. Our knowledge of the fibrinolytic effect of drugs commonly used for CHD such as antiplatelet agents (aspirin, ticlopidine, clopidogrel), anti-diabetic biguanides (phenformin, metformin) or anti-hypertensive drugs is scanty and conflicting. This is mainly due to the lack of a global test of spontaneous thrombolysis, as opposed to fibrinolysis of plasma or whole blood, i.e. the assessment of various activators and inhibitors of the fibrinolytic system. A recently described technique allows the measurement of spontaneous thrombolysis, that is, lysis of an autologous platelet-rich thrombus in the absence of added plasminogen activators. Early results suggest that this test may have significant clinical potential both in identifying those at risk of fatal cardiac events and in finding new therapeutic avenues or lifestyles to improve spontaneous thrombolytic activity.

Animals↗
PubMed2003

Treatment of iatrogenic aortic dissection by percutaneous stent placement.

During elective cardiac catheterization via the right femoral artery, difficulty was encountered advancing the guidewire beyond the aortic arch and the procedure abandoned. The patient later developed back pain and hypotension. A contrast-enhanced spiral computed tomography scan confirmed aortic dissection, extending from an entry point in the external iliac artery to the arch. We hypothesized that the entry site was responsible for filling the dissection in the thoraco-abdominal component. A stent was placed in the iliac artery, occluding the entry point. This is the first report of aortic dissection, a rare complication of angiography, managed by percutaneous stenting of the entry point.

Aortic Dissection↗
PubMed2002

Platelet membrane glycoprotein Ibalpha gene -5T/C Kozak sequence polymorphism as an independent risk factor for the occurrence of coronary thrombosis.

OBJECTIVE: To explore the potential of the GPIbalpha gene variable number tandem repeat (VNTR) and -5T/C Kozak polymorphisms to act as independent risk factors for myocardial infarction. METHODS: 256 patients aged 33-80 years (180 caucasian, 76 Indian Asian) were recruited at cardiac catheterisation for any diagnostic indication, and divided into two groups: group A, with confirmed previous myocardial infarction evident on ECG or ventriculogram (88 patients, 79 men, 9 women) and group B, with no evidence of myocardial infarction (168 patients, 101 men, 67 women). RESULTS: There was no significant difference in race, age, hypertension, smoking status, or family history between the infarct and non-infarct groups, though there was a significant difference in sex (89.8% male in group A, 60.1% male in group B, p < 0.001). Genotype analysis showed a strong association between the GPIbalpha Kozak homozygous TT genotype and the occurrence of myocardial infarction (group A: TT 85.2%, TC 12.5%, CC 2.3%; group B: TT 67.3%, TC 32.7%, p = 0.001). No significant association was found between myocardial infarction and the GPIbalpha VNTR, although analysis of the CC VNTR genotype against all other GPIbalpha VNTR genotypes showed a marginal association with myocardial infarction (p = 0.059). There was no association between the Kozak sequence polymorphism (p = 0.797) or GPIbalpha VNTR (p = 0.714) and the degree of vessel disease. CONCLUSIONS: The homozygous TT Kozak genotype may be a significant factor in the outcome of coronary artery disease completed by myocardial infarction. Conversely, the Kozak C allele in the heterozygous state TC may confer some protection against myocardial infarction.

Adult↗
PubMed2000

A potential role for endothelin-1 in peripheral vascular disease.

The distribution of endothelin-1 (ET-1) and its receptors (ET(A)/ET(B)) has been studied in segments of femoral artery obtained from patients undergoing operation for peripheral vascular disease (PVD) using a combination of immunohistochemistry and autoradiography. Both receptor subtypes were located on the tunica media of vessel segments, with ET(A)-receptors predominating. Densitometric analysis showed that there was no difference in receptor binding to proximal/distal arterial segments from PVD patients. High-resolution autoradiography identified ET(B) binding to vascular nerves and vasa vasorum, mainly in distal portions of femoral arteries. Immunoreactive ET-1 was also identified that was associated with the vasa vasorum.

Autoradiography↗
PubMed1999

Platelet reactivity and streptokinase resistance following antecedent streptokinase therapy for myocardial infarction.

AIMS: To assess the efficacy of second-time administration of streptokinase (SK). First-time thrombolysis with SK in myocardial infarction (MI) is established but the efficacy of subsequent SK is unknown. METHODS AND RESULTS: Platelet reactivity to shear stress, spontaneous and SK-induced thrombolysis were measured in vitro in 28 patients who had received SK for MI and compared to 15 controls. SK antibody (Ab) titres were inversely related to time from MI. Platelet reactivity was greatly enhanced in patients (p < 0.0001). Spontaneous thrombolysis in patients was poor and in 17 failed to occur. In contrast, thrombolysis occurred in all but 1 control. In patients platelet reactivity was strongly related to thrombolytic activity (r = -0.516; p = 0.0029). SK in vitro was at least 4 times more effective in controls than in patients. CONCLUSION: The chances of achieving patency with second administration of SK are poor. Ab titre is not a reliable predictor of resistance.

Adult↗
PubMed1998

Raised factor VIII is associated with coronary thrombotic events.

Coagulation is triggered during the onset of myocardial infarction, resulting in vascular occlusion. However, a causal role for individual haemostatic factors in the development of thrombotic occlusion is not established. Three cases (all relatively young women) are reported of raised factor VIII associated with myocardial infarction. Two patients presented acutely with myocardial infarction at a relatively young age with no preceding history of angina. The other patient had had venous thrombosis when young and activated protein C resistance (APCR), without the presence of factor V Leiden. A functional relation exists between APCR and factor VIII; therefore, raised factor VIII may contribute to APCR and the increased thrombotic risk in patients without factor V Leiden. Factor VIII is an important risk factor for atherothrombotic events, including sudden death, in patients with vascular disease. These cases support the association of raised factor VIII with acute thrombotic events, even in patients without significant underlying atheromatous disease.

Activated Protein C Resistance↗
PubMed1995

Thrombotic status analyser. Measurement of platelet-rich thrombus formation and lysis in native blood.

A physiologically relevant global in vitro test is described which allows the overall assessment of both thrombotic and thrombolytic activities of blood. In principle, native blood is drawn in pulses through a capillary tube where haemodynamic forces induce a platelet reaction culminating in vessel occlusion. Dislodgement/disintegration of the stabilised thrombus under pressure is a reflection of thrombolysis. Evidence is presented for the platelet-rich nature of the occlusion and that disruption of the thrombus and re-established patency is the result of thrombolysis, that is fibrinolysis with significant contribution from platelets. This test sensitively detects hypercoagulability (stasis); platelet hyperreactivity (coronary artery disease); anti-platelet effect (aspirin, prostacyclin) and the thrombolytic effect of, thrombin generation by, and resistance to streptokinase. Therefore, this overall assessment of thrombotic status could be of great diagnostic and therapeutic benefit in clinical practice.

Adult↗
PubMed1994

Activation of the phagocytic system increases intimal proliferation in hypercholesterolemic rabbits.

The effect of in vivo stimulation of the phagocytic system (neutrophils, monocytes and hepatic Kupffer-cells) by inducing phagocytosis of intravenously administered latex particles on lipid peroxidation and aortic intimal proliferation was tested in cholesterol-fed rabbits. Three weeks after starting the diet, aortic intimal proliferation was measured by the intimal to medial ratios and by the incorporation of [3H]thymidine, infused into the circulation for the preceding 14 days. Intimal to medial ratios were increased (0.473 +/- 0.023 vs. 0.282 +/- 0.011, P < 0.01) and aortic [3H]thymidine contents were higher (66.8 +/- 3.5 vs. 27.8 +/- 49 counts/min per mg, P = 0.0001) in latex bead-treated than in control animals. Injection of beads transiently increased plasma lipid peroxide levels. At the end of the 3 week experiment, plasma lipid peroxide levels were still elevated and lipid peroxide contents of the aortic walls were higher in the latex-treated rabbits (82.8 +/- 5.8 vs. 46.4 +/- 4.9 nmol/mg cholesterol, latex-treated vs. controls, P = 0.004). These data suggest a significant acceleration of atherogenesis by the stimulated phagocytic system, the mechanism of which may involve lipid peroxidation.

Animals↗
PubMedDate not supplied

Thrombin generation following arterial injury is a critical initiating event in the pathogenesis of the proliferative stages of the atherosclerotic process.

Vascular injury, activation of the coagulation system and thrombosis are common initial events in the accelerated atherosclerotic process. The role of thrombin generated at the site of aortic injury in the subsequent neointimal proliferation was studied in rabbits (n = 16) 3 weeks after balloon catheter injury. In half of these animals, potent thrombin antagonists, r-hirudin and P-PACK, were administered to prevent acute thrombotic events. Compared to aortas with intact endothelium (n = 8), aortas de-endothelialised 21 days earlier showed neointimal hyperplasia as measured by the intimal/medial ratio (0.68 vs. 0.04, injured vs. normal aortas) and an increase in both total cholesterol (4.08 vs. 3.31 mg/g, p < 0.05) and lipid peroxide content (31.3 vs. 1.1 nmol/g; p < 0.001). Neointimal hyperplasia following endothelial denudation was inhibited in rabbits treated with thrombin-antagonists (0.27 vs. 0.68, treated vs. untreated, p = 0.012) and neither total cholesterol (3.48 mg/g) nor lipid peroxide content (1.5 nmol/g) differed significantly from that of intact arteries. By demonstrating a strong relationship between thrombin generation following de-endothelialisation and the progressive intimal proliferation, this study supports the hypothesis that thrombin is an important contributor to restenosis after vascular injury. The highly atherogenic lipid peroxidation seems to be linked to the early, thrombin-mediated events, as it was completely prevented by adequate thrombin antagonism.

Animals↗