Ventricular function in noncardiacs with alcoholic fatty liver: role of ethanol in the production of cardiomyopathy.

Since many patients with cardiomyopathy have a history of chronic ethanolism often associated with malnutrition, we have evaluated left ventricular (LV) function in alcoholics with fatty liver, who had no clinical evidence of cardiac or nutritional disease. During an afterload test of LV function the pressor response to angiotensin evoked a threefold rise of enddiastolic pressure in the alcoholic group which was substantially greater than the 4 mm Hg rise in control subjects. The stroke volume and stroke work response in the noncardiac alcoholic was significantly less than in controls. Diminished LV function was corroborated in the noncardiac alcoholic at rest, using a contractility index. To evaluate the dose-response relationship of ethanol in the production of cardiac malfunction, two groups of noncardiac alcoholic subjects were studied acutely at low and moderate dose levels. After 6 oz, ventricular function, myocardial blood flow, and metabolism were not significantly affected. After 12 oz, there was a progressive rise of end-diastolic pressure and decrease of stroke output at a mean blood alcohol level of 150 mg/100 ml, reverting toward control by 4 hr. The coronary effluent transiently evidenced leakage of cell constituents, despite an increase of coronary blood flow, suggesting a direct but reversible cardiac injury. Myocardial extraction of triglyceride was enhanced, whereas FFA uptake was reduced. A possible role of myocardial triglyceride accumulation in heart muscle was considered in pathogenesis. Chronic ingestion of 16 oz of Scotch daily by an alcoholic subject while on a normal diet produced, after 12 wk, a progressive increase of heart rate and size, circulation time, and venous pressure, and a ventricular diastolic gallop. Normal values were restored within 7 wk after interrupting alcohol. These several studies suggest that the cumulative effects of repeated ingestion of ethanol in intoxicating doses can produce diminished LV function before clinical evidence of cardiac abnormality, or heart disease not necessarily related to malnutrition.

Patterns of drug resistance among patients with tuberculous pleural effusion in Greece.

SETTING: Data on the relationship between pleural tuberculosis (TB) and anti-tuberculosis drug resistance are scarce. OBJECTIVE: To determine the patterns of drug resistance among pleural Mycobacterium tuberculosis isolates in Greece and the incidence of tuberculous pleural effusion (TPE) among patients with multidrug-resistant (MDR) or extensively drug-resistant (XDR) pulmonary TB. DESIGN: Drug susceptibility testing (DST) results recorded in the database of the National Reference Centre for Tuberculosis in Athens, Greece, over a 9-year period (2003-2011) were reviewed. Chest X-rays from hospitalised patients with pulmonary MDR/XDR-TB during the same period were also reviewed for the presence of TPE. RESULTS: Resistance to at least one first-line drug was observed in 11% of the cases (MDR-TB 3%, XDR-TB 1%), while 29% of the patients with pulmonary MDR/XDR-TB presented with TPE during the course of their disease, the majority ipsilateral to the lung lesions, which responded to guided anti-tuberculosis treatment. CONCLUSION: The prevalence of drug resistance among pleural M. tuberculosis isolates in Greece highlights the importance of DST prior to treatment selection in TPE patients. In our study population, TPE that developed in one third of the patients with pulmonary MDR/XDR-TB usually resolved with DST-guided anti-tuberculosis treatment.

Relation of platelets to catecholamine induced myocardial injury.

To test the thesis that myocardial injury, induced by catecholamines, is ischaemic in origin due to platelet accumulation in the coronary microvasculature, sustained left intracoronary and systemic infusion of catecholamines in toxic dosage was given to dogs previously infused with autologous 51Cr-labelled platelets. Subsequent determination of tissue radioactivity and electrolytes, as well as electronmicrography, indicated that the induced myocardial injury was not related to microvascular occlusion by platelets.

Chronic smoking in an animal model. Effects on clotting and fibrinolysis.

The effects of chronic smoking upon fibrinogen turnover and other clotting parameters, were studied prospectively in an animal model maintained on a chronic program for a period of 18 months. The animal received the equivalent on a weight basis of 11/2 packs of cigarettes daily, smoked by a human subject with the weight of 70 kg. The obtained results suggested significant enhancement of the coagulation mechanism in the smoking animals developing over the period of observation particularly when combined with high lipid diet.

Hemodynamic effects of staged hematocrit reduction in patients with stable cor pulmonale and severely elevated hematocrit levels.

Patients with cor pulmonale and high hematocrit levels are often subjected to phlebotomy in the belief that the adverse effects of high viscosity may outweigh the benefit of increased oxygen carrying capacity. To evaluate this, 12 patients with stable cor pulmonale and hematocrit values greater than 55 per cent were studied before and after a series of venesections. Right heart and aortic pressures, cardiac output and blood gases were measured at three mean hematocrit levels, 61 per cent (stage I), 50 per cent (stage II) and 44 per cent (stage III), with blood volume unchanged. From stages I to II, there were significant decreases in both man pulmonary artery pressure and total pulmonary resistance. Oxygen transport fell but not oxygen consumption. Right ventricular end-diastolic pressure and cardiac output did not change. Right ventricular work either fell or was maintained by increased output. Frank-Starling performance (supine exercise) improved. No significant changes occurred with further reduction in hematocrit to normal levels (stage III). The findings of this study support the concept of overcompensating erythrocytosis in cor pulmonale, and the effects of moderate hematocrit reduction should not be overlooked in these severely ill patients.

Cardiovascular effects of long-term cigarette smoking and nicotine administration.

The nature of the cardiovascular risk in cigarette smokers has not been characterized. To compare the relative effects of long-term smoking and nicotine administration on the cardiovascular system, 18 month old beagle littermates were prepared with a permanent tracheostomy. They were classified into three groups: I, seven control dogs; II, nine dogs that smoked seven cigarettes/day; and III, eight dogs that received an equivalent amount of nicotine. After a period of up to 22 months, the animals were catheterized under anesthesia for assessment of left ventricular function and volumes by indicator-dilution technique. Heart rate, stroke volume, left ventricular end-diastolic pressure and volume and intraventricular conduction times did not differ significantly in the three groups. Left ventricular ejection fraction was 44 +/- 3 percent (mean +/- standard error of the mean) in the control group, 35 +/- 3 percent in the dogs that smoked cigarettes (P less than 0.05) and 27 +/- 3 percent in those given nicotine (P less than 0.01) despite similar values for end-diastolic variables in the three groups. The first derivative of left ventricular pressure (dP/dt) normalized for pre- and afterload was 2.4 +/- 0.2 cm/sec -1 in the control group, 1.41 +/- 0.12 in the cigarette-smoking group (P less than 0.005) and 1.34 +/-0.08 in the nicotine group (P less than 0.01). Although mean aortic pressure was significantly elevated in both the smoking (127 +/- mm Hg) and nicotine (127 +/- 10 mm Hg) groups, there was no significant correlation with the contractility indexes. Reduction of afterload to normal levels did not affect the abnormal ventricular performance. Hypertrophy, inflammation and abnormalities of cell ultrastructures were not present, and myocardial lipid and cation composition were normal. Since interstitial fibrosis was evident in both experimental groups, an alteration of elastic elements may be operative. These cardiovascular abnormalities appear to be predominantly dependent on the nicotine of cigarettes.

Nonplatelet effects of aspirin during acute coronary occlusion: electrophysiologic and cation alterations in ischemic myocardium.

BACKGROUND: Mortality after acute myocardial ischemia has been reduced by aspirin (ASA) but mechanisms other than the antiplatelet effect have not been established. This article evaluates an antiarrhythmic action during sympathetic stimulation in the intact anesthetized dog with and without ischemia. METHODS AND RESULTS: The ventricular fibrillation threshold (VFT) was examined before and after epinephrine (E) in normals (group I). A VFT reduction during E was normalized after 1 week of ASA (P<.01). Regional myocardial ischemia for 1 hour resulted in similar hypoperfusion in controls of group II and after ASA. Action potential responses in isolated superfused ischemic tissue showed prolonged repolarization (APD90) in response to E, which was normalized after ASA (P<.01). To assess the antiarrhythmic role of the anion in group III, Na salicylate was given. During 1 hour of ischemia, the VF incidence was reduced and cation abnormalities diminished in ischemic myocardium compared with untreated ischemia. CONCLUSIONS: ASA antagonizes the reduction of the VFT induced by catecholamine in normals as well as the repolarization abnormality elicited by E during acute ischemia. The salicylate anion appears to be the active component in view of the efficacy in preventing VF during the early ischemic period.

Diabetic cardiomyopathy: experimental and clinical observations.

Heart failure, arrhythmia, or chest pain can be a consequence of diabetes independent of coronary disease or hypertension. Diastolic myocardial dysfunction is common, contributing to the high mortality during acute infarction. The authors discuss diabetic cardiomyopathy and its management.

Secreted phosphoprotein-1 directly provokes vascular leakage to foster malignant pleural effusion.

Secreted phosphoprotein-1 (SPP1) promotes cancer cell survival and regulates tumor-associated angiogenesis and inflammation, both central to the pathogenesis of malignant pleural effusion (MPE). Here, we examined the impact of tumor- and host-derived SPP1 in MPE formation and explored the mechanisms by which the cytokine exerts its effects. We used a syngeneic murine model of lung adenocarcinoma-induced MPE. To dissect the effects of tumor- versus host-derived SPP1, we intrapleurally injected wild-type and SPP1-knockout C57/BL/6 mice with either wild-type or SPP1-deficient syngeneic lung cancer cells. We demonstrated that both tumor- and host-derived SPP1 promoted pleural fluid accumulation and tumor dissemination in a synergistic manner (P<0.001). SPP1 of host origin elicited macrophage recruitment into the cancer-affected pleural cavity and boosted tumor angiogenesis, whereas tumor-derived SPP1 curtailed cancer cell apoptosis in vivo. Moreover, the cytokine directly promoted vascular hyper-permeability independently of vascular endothelial growth factor. In addition, SPP1 of tumor and host origin differentially affected the expression of proinflammatory and angiogenic mediators in the tumor microenvironment. These results suggest that SPP1 of tumor and host origin impact distinct aspects of MPE pathobiology to synergistically promote pleural fluid formation and pleural tumor progression. SPP1 may present an attractive target of therapeutic interventions for patients with MPE.