Cation channels trigger apoptotic death of erythrocytes.

Erythrocytes are devoid of mitochondria and nuclei and were considered unable to undergo apoptosis. As shown recently, however, the Ca(2+)-ionophore ionomycin triggers breakdown of phosphatidylserine asymmetry (leading to annexin binding), membrane blebbing and shrinkage of erythrocytes, features typical for apoptosis in nucleated cells. In the present study, the effects of osmotic shrinkage and oxidative stress, well-known triggers of apoptosis in nucleated cells, were studied. Exposure to 850 mOsm for 24 h, to tert-butyl-hydroperoxide (1 mM) for 15 min, or to glucose-free medium for 48 h, all elicit erythrocyte shrinkage and annexin binding, both sequelae being blunted by removal of extracellular Ca(2+) and mimicked by ionomycin (1 microM). Osmotic shrinkage and oxidative stress activate Ca(2+)-permeable cation channels and increase cytosolic Ca(2+) concentration. The channels are inhibited by amiloride (1 mM), which further blunts annexin binding following osmotic shock, oxidative stress and glucose depletion. In conclusion, osmotic and oxidative stress open Ca(2+)-permeable cation channels in erythrocytes, thus increasing cytosolic Ca(2+) activity and triggering erythrocyte apoptosis.

Cumulative effects of high cholesterol levels, high blood pressure, and cigarette smoking on carotid stenosis.

BACKGROUND: Single measurements of cardiovascular risk factors may not accurately reflect a person's past exposure to those risk factors. We therefore studied the long-term associations of cardiovascular risk factors such as high serum cholesterol levels, high blood pressure, and cigarette smoking with the prevalence of carotid stenosis. METHODS: We studied cross-sectional and longitudinal information from a sample of 429 men and 661 women in the Framingham Heart Study who underwent B-mode ultrasound measurements of the carotid artery. Their mean age was 75 years, and each had attended most of the biennial clinic examinations over the 34 years before the carotid ultrasound study. We used time-integrated measurements to assess the associations between various cardiovascular risk factors and the degree of carotid stenosis. RESULTS: Moderate carotid stenosis (> or =25 percent) was present in 189 men and 226 women. We assessed the odds ratios for this degree of stenosis as compared with minimal stenosis (<25 percent) according to increases in risk factors. In the men, the odds ratio for moderate carotid stenosis associated with an increase of 20 mm Hg in systolic blood pressure was 2.11 (95 percent confidence interval, 1.51 to 2.97). The odds ratio for an increase of 10 mg per deciliter (0.26 mmol per liter) in the cholesterol level was 1.10 (95 percent confidence interval, 1.03 to 1.16), and for an increase of five pack-years of smoking it was 1.08 (95 percent confidence interval, 1.03 to 1.13). The results were similar in the women. Time-integrated measurements of diastolic blood pressure showed significant associations with carotid stenosis in men and insignificant associations in women. CONCLUSIONS: Over the long term, high systolic blood pressure, high cholesterol levels, and smoking were associated with an increased risk of carotid stenosis in this elderly population.

Abnormal diastolic left ventricular posterior wall motion in left ventricular hypertrophy.

The left ventricular pressure-volume relationship is abnormal in left ventricular hypertrophy (LVH). As a result, the left atrium empties more slowly than normal during the rapid filling phase of diastole, producing a characteristic abnormality of diastolic aortic root motion. In order to determine whether this altered LV filling is accompanied by a derangement of diastolic LV wall motion which might be useful in identifying the presence of altered chamber compliance, the M-mode echocardiograms of 60 patients with LVH secondary to aortic stenosis, hypertrophic subaortic stenosis, or hypertension, and those of 36 normal individuals were evaluated. Patients with LVH demonstrated abnormal LV posterior wall motion manifested by prolonged phases of rapid ventricular filling and atrial contraction (p less than 0.01 and p less than 0.05, respectively). The early diastolic wall motion abnormality can be readily detected by visual inspection of the echocardiogram. These findings support the concept of diastolic dysfunction in LVH and represent another echocardiographic feature of that condition.

Diastolic aortic root motion in left ventricular hypertrophy.

The echocardiographic motion of the aortic root reflects, in part, left atrial filling and emptying. The echocardiograms of 60 patients with left ventricular hypertrophy (LVH) secondary to aortic stenosis, hypertrophic subaortic stenosis, and hypertension were compared with those of 36 normal subjects to determine whether the alterations of early rapid diastolic filling associated with LvH would alter motion of the posterior aortic root. Patients with LVH had a characteristic echographic pattern of motion of the posterior aortic root manifested by the attenuation of normal abrupt diastolic posterior aortic root motion. The atrial emptying index (AEI), defined as the fraction of passive posterior aortic wall motion occurring in the first third of diastole, was significantly reduced in patients with LVH (p less than 0.001), but did not discriminate among mild, moderate, and marked hypertrophy. The AEI may be useful in the identification of altered left ventricular filling associated with LVH. The changes associated with a decreased AEI are readily appreciated by visual inspection and provide a rapid method of qualitatively assessing left ventricular filling properties.

Echocardiogram analysis in a pattern recognition framework.

Echocardiogram analysis is treated in a pattern recognition framework. Anterior mitral leaflet waveforms are classified for the four-class problem consisting of the classes "normal," "mitral stenosis," "mitral valve prolapse," and "idiopathic hypertrophic subaortic stenosis." In addition, aortic root waveforms and left ventricular wall waveforms are classified for the two-class problem consisting of the classes "normal" and "idiopathic hypertrophic subaortic stenosis." One common method of analysis (Fourier analysis) underlies each classification scheme. Classification accuracy is sufficiently good to warrant the inference that successful automated decision-making based on the algorithms investigated is feasible.