Sudden cardiac death. A post mortem study. Part I. Evaluation of the methodology in assessing the age of myocardial ischemic necrosis.
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Biomedical subjects
Publications and source records attributed to S Stamatelopoulos.
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It has recently been reported that heparin administration to rabbits is followed by an inhibition of the Na, K-ATPase of the myocardial sarcolemma. Further investigation of this phenomenon in an experimental animal which enables measurement of changes in myocardial contractility are presented here. The left ventricular pressure and the quotient of its first derivative to its total value (dp/dt/P) were followed for 60 min in 16 anesthetized dogs administered with heparin (700-5000 i.u./kg), as well as in 10 non treated animals. All animals were then sacrificed and myocardial Mg and Na, K-ATPase were assayed. The measured (dp/dt/P)max(Vpm) changes in the heparin treated animals at the 60th min of the experiment were positively correlated to the dose of heparin. A significant increase of Vpm values was observed only in the animals treated with doses of heparin higher than 2000 i.u./kg compared to non heparin group. A significant animals of the heparin group only, this decrease was not dose dependent. It is concluded that very large doses of heparin increase heart contractility by a mechanism probably not directly related to that which caused the Na, K-ATPase inhibition observed following heparin administration. Evidence is presented suggesting that lysophosphatidylcholine (LPC) is involved in the mechanism of this inhibition.
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A new technique is described, utilizing an air-driven pump, connected to the left ventricle, without a valve and synchronized with the electrocardiogram. The pump is operated in brief (80 msecs) pulses. When applied at the end-diastolic phase it produces an increase in stroke volume and dp/dt/P and a marked improvement in the function curves of a failing left ventricle, without substantially increasing the mean left atrial pressure. Thus, mechanical assistance to the failing heart can also be based on this new principle, namely the inotropic effect of a brief left intraventricular end-diastolic pseudo-augmentation.
This study was planned to investigate whether part of the energy produced by cardiac contraction to propel blood toward the systemic circulation can be used to increase the coronary flow in systole. Ten devices (I-X) designed to divert laterally part of a flow column (without substantially increasing resistance to flow) were tested in a mock circulation and in nine anesthetized dogs. An increase of 11.69 +/- 1.97% (mean +/- SEM, P less than 0.005) in "coronary flow" and of 8.98 +/- 0.56% (mean +/- SEM, P less than 0.001) in coronary sinus flow were obtained with device I mounted on a stylet and placed above the "aortic valve" in the mock circulation and the dogs, respectively, without increasing the flow resistance. The results in;dicate the possibility of diverting part of the aortic flow toward the coronary arteries without increasing mean aortic pressure.
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In-antimyosin scintigraphy offers a valuable noninvasive method for early detection of clinically silent cardiac involvement in patients with systemic sclerosis, even in the absence of left ventricular dysfunction. In these patients with positive antimyosin study results, intense pharmacologic treatment with vasodilators may be warranted.
Although the combination of paclitaxel with doxorubicin has yielded high response rates in metastatic breast cancer, severe cardiotoxic events have been reported in several patients. The rationale for our study was to evaluate the activity of paclitaxel/doxorubicin combination in patients with this disease but to avoid excessive cardiotoxicity. Therefore, we administered 4 cycles of doxorubicin/paclitaxel followed by 6 cycles of standard cyclophosphamide, methotrexate and 5-fluorouracil (CMF) regimen. Study medication consisted of doxorubicin 60 mg/m2 as a 15-min intravenous infusion followed by paclitaxel 175 mg/m2 as a 3-hour infusion. CMF regimen consisted of cyclophosphamide 600 mg/m2 as 1-hour intravenous infusion followed by methotrexate 40 mg/m2 and 5-fluorouracil 600 mg/m2 bolus injection. The main toxicity of doxorubicin/paclitaxel treatment phase was neutropenia (WHO grade 3/4, 58%), but we observed only one cardiac adverse event. Toxicities of the CMF treatment phase were not significant. Of 24 patients evaluable for response, 2 (8%) had complete responses and 11 (46%) achieved partial response. Ten additional patients (42%) had stable disease. The median time to progression was 12 months and the median overall survival was 18.5 months. The sequential administration of doxorubicin and paclitaxel followed by CMF appeared active and well tolerated in patients with metastatic breast cancer.
The advent and wide application of new technology, especially noninvasive techniques, has enabled physicians to more completely investigate and clarify the etiopathogenic mechanisms of stroke. Such data have not been available until recently for Southeastern Europe. In addition, during the last decades, strategies for the modification of risk factors and primary prevention may have changed the prevalence of each subgroup of stroke as well. We investigated 1, 042 consecutive patients who had first strokes, during a period of 5 years (from June 1992 to May 1997) and classified them prospectively based on etiopathogenic mechanisms. Patients with transient ischemic attacks and subarachnoid hemorrhage were excluded. There were 613 male and 429 female patients, with a mean age of 70.2 +/- 11.9 years. Forty-six percent of the patients arrived within 3 h from stroke onset. The probable mechanisms were: large-artery atherosclerosis, 156 (15%); lacunes, 177 (17%); cardioembolic, 335 (32.1%); infarct of unknown cause, 182 (17.5%); miscellaneous causes, 35 (3.3%), and intracerebral hemorrhage (ICH), 157 (15.1%). In the cardioembolic group, nonvalvular atrial fibrillation (NVAF) was the probable cause in 225 patients, especially in patients older than 75 years (65%). The overall hospital mortality was 15.2% (from 0.6% for lacunar stroke to 34% for ICH). In our population, cardioembolism is the most frequent subtype of stroke. NVAF is the most likely source, especially in older patients.
BACKGROUND: Nitric oxide (NO) is a soluble gas produced by the activity of an enzyme found in neurons. It has been implicated in a great number of normal physiological functions (such as noradrenaline and dopamine release, memory and learning, regulation of the cerebrovascular system, modulation of wakefulness, modulation of nociception, olfaction, food intake and drinking) as well as pathologies (Alzheimer's, Huntington's disease, cerebral ischemia, stroke). Two reports have addressed the involvement of NO in depression. METHODS: The objective of the study was to examine the association between NO and specific depressive symptoms. For this purpose, in a sample of 28 end-stage renal failure patients (who have increased NO levels), we tested the hypothesis that the subgroup of patients with these specific depressive symptoms was differentiated from the patients without these symptoms with regard to serum levels of NO metabolites. The depressive symptoms were assessed using the Zung self-rating scale. RESULTS: Our study revealed an association of NO with the following depressive symptoms: sexual dysfunction, weight loss, psychomotor retardation, indecisiveness and irritability. CONCLUSION: The association between NO system and symptoms of depression does not necessarily imply a pathogenetic association between NO and depressive disorder. Further research is needed to verify these findings and study their possible pathogenetic implications.
OBJECTIVE: Cardiac involvement with myocardial-band necrosis is common in systemic sclerosis. One possible explanation is that an underlying vasomotor abnormality accounts for these histologic findings. To shed light on this issue we investigated the existence of "myocardial Raynaud's phenomenon" in such patients. METHODS: We examined 25 patients with systemic sclerosis and 14 patients with systemic lupus erythematosus or rheumatoid arthritis, using cold pressor and dipyridamole-thallium-201 scintigraphy. RESULTS: Twenty-three patients with systemic sclerosis and 13 patients with lupus erythematosus or rheumatoid arthritis had normal perfusion during dipyridamole imaging. Seven scleroderma patients with normal dipyridamole test presented cold-induced transient myocardial ischemia, while none of the control patients had cold-induced ischemia (p = 0.034). All patients with cold-induced ischemic defects presented long-standing Raynaud's phenomenon (> 5 years); of the 14 patients with long-standing Raynaud's phenomenon 7 presented ischemic thallium-201 defects; of the remaining 9 patients with Raynaud's phenomenon of short duration (< 5 years) none presented cold-induced ischemia (p = 0.019). CONCLUSION: Patients with systemic sclerosis and long-standing Raynaud's phenomenon, even in the presence of normal myocardial perfusion during pharmacological vasodilation with dipyridamole, may present cold-induced myocardial ischemia, a functional Raynaud's phenomenon of the heart.