RESUMO
Since histamine has recently been shown to play an important role in the pathogenesis of atherosclerosis in experimental nonketotic diabetes, and since leukocytes and platelets contain most of the histamine in blood, we have determined the levels of histamine in these cells from patients with peripheral vascular disease (PVD), insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). The leukocyte and platelet histamine concentration in PVDs was significantly greater than that in controls, IDDMs and NIDDMs. Histamine content of leukocytes and platelets from IDDMs and NIDDMs did not differ from that in control subjects. The higher histamine content of leukocytes and platelets in PVD may lead to a greater release of this amine at sites of vascular endothelial damage. Increased histamine release may increase endothelial permeability and contribute to further vascular injury as observed in experimental models of diabetes and hypercholesterolemia.
Assuntos
Plaquetas/metabolismo , Histamina/sangue , Claudicação Intermitente/sangue , Leucócitos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Permeabilidade Capilar , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
In a double-blind placebo-controlled trial, buflomedil was shown to cause a significant increase both in median claudication provoking time from 63 sec (range: 24-136 sec) to 124 sec (range: 53-261 sec) (p less than 0.01), and in maximum walking distance (MWD) from 169m (range: 157-308 m) to 293 m (range: 107-429 m) (p less than 0.01). The MWD after three months' buflomedil treatment was also significantly (p = 0.05) prolonged when compared with the MWD in the appropriate placebo group. In contrast, treatment with the placebo caused no significant change in these indices. Subjective improvement was observed in 12 out of 14 patients on buflomedil, whilst it occurred in only 6 out of 14 patients on the placebo (p less than 0.05). The clinical improvement was not associated with an increase in the ankle pressure index or a reduction in platelet aggregation and thromboxane A2 release.
Assuntos
Claudicação Intermitente/tratamento farmacológico , Pirrolidinas/uso terapêutico , Idoso , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Feminino , Humanos , Claudicação Intermitente/fisiopatologia , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária/efeitos dos fármacos , Tromboxano A2/sangueRESUMO
A 46 year old man with intermittent claudication due to severe peripheral vascular disease had a circulating lupus like anticoagulant (LLAC), thrombocytopenia (79 X 109/1), markedly reduced platelet survival and a normal bone marrow. He was treated with intravenous prostacyclin (PGI2) infusions which resulted in improvement of the patient's exercise tolerance and normalisation of his platelet count (300 X 109/1) and platelet aggregation could then be assessed. The platelets were markedly hyperaggregable and generated supranormal quantities of thromboxane A2. A diagnosis of consumptive thrombocytopenia secondary to peripheral vascular disease and platelet hyperaggregability was made. Despite therapy with aspirin and dipyridamole, gradual and progressive reduction in platelet count followed and his exercise tolerance declined over the next three months. Immunoglobulin prepared from the patient's serum did not inhibit vascular PGI2 synthesis in vitro. To our knowledge this is the first reported case of consumptive thrombocytopenia due to severe peripheral vascular disease and platelet hyperaggregability. PGI2 administration caused a transient resolution of these features which was not sustained by aspirin and dipyridamole.
Assuntos
Arteriosclerose Obliterante/fisiopatologia , Fatores de Coagulação Sanguínea/antagonistas & inibidores , Epoprostenol/uso terapêutico , Claudicação Intermitente/fisiopatologia , Trombocitopenia/sangue , Arteriosclerose Obliterante/tratamento farmacológico , Transtornos da Coagulação Sanguínea/sangue , Fatores de Coagulação Sanguínea/análise , Testes de Coagulação Sanguínea , Epoprostenol/biossíntese , Humanos , Inibidor de Coagulação do Lúpus , Masculino , Pessoa de Meia-Idade , Testes de Função Plaquetária , Trombocitopenia/tratamento farmacológico , Trombocitopenia/fisiopatologiaRESUMO
Echocardiography and thallium-201 imaging with coronary vasodilators such as dipyridamole have been shown to be useful in detecting the presence and prognostic significance of coronary artery disease. Adenosine, a potent and direct coronary vasodilator, has a shorter physiologic half-life than dipyridamole, which exerts its effect by blocking the cellular uptake of adenosine. Because of the potential advantage of dipyridamole, we undertook this study to determine the correlation of adenosine echocardiography with thallium scintigraphy. Forty-two patients (18 men and 24 women; mean age 64) who were unable to undergo treadmill exercise and were known or suspected to have coronary artery disease were studied. A baseline echocardiogram was obtained in four standard views followed by adenosine infusion at a rate of 140 micrograms/kg/min for 6 minutes. Thallium-201 was administered 3 minutes into the infusion while a second echocardiogram was performed. Thallium-201 imaging was begun immediately after the infusion of adenosine and repeated 4 hours later. Sixteen patients underwent coronary angiography within 1 month of the adenosine echocardiogram and thallium-201 study. At the peak infused dose of adenosine there was a significant increase in heart rate (12 beats/min; p = 0.0001) and rate-pressure product (1.3 x 10(3) beats/min x mm Hg; p = 0.02) and statistically insignificant decreases in systolic and diastolic blood pressures. Sixty-two percent of patients experienced side effects during the adenosine infusion, with chest pain, shortness of breath, and flushing occurring most frequently. These side effects resolved within 1 to 2 minutes after the infusion was stopped. Ischemic electrocardiographic changes occurred in 19% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Adenosina , Doença das Coronárias/diagnóstico por imagem , Ecocardiografia/métodos , Tomografia Computadorizada de Emissão de Fóton Único , Adenosina/efeitos adversos , Adenosina/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia Coronária , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Radioisótopos de TálioRESUMO
We have previously demonstrated that platelets obtained from patients with anorexia nervosa or severe peripheral vascular disease are hyperaggregable. Since conventional heparins are known to activate platelets in vitro and occasionally induce thrombosis and consumptive thrombocytopenia in vivo, we have investigated the direct effect of a conventional heparin on platelets obtained from patients with anorexia nervosa or severe peripheral vascular disease. Heparin at therapeutic concentrations was found to induce platelet aggregation of such platelets in vitro. In contrast, a recently developed low molecular weight heparinoid (Org 10172), at therapeutic concentrations, had no effect on these hyperaggregable platelets. We conclude that: heparin may be potentially harmful to patients with hyperaggregable platelets; thrombocytopenia and thrombosis associated with heparin therapy may be mediated through a direct effect of heparin on platelets; it is unlikely that heparin induced thrombocytopenia is always mediated by classical immunological mechanisms, especially in patients with hyperaggregable platelets; and low molecular weight heparinoids may be safer anticoagulants in patients with platelet hyperaggregability.