Role of normal serum in the binding of lipopolysaccharide to IgG fractions from rabbit antisera to Escherichia coli J5 and other gram-negative bacteria.

Because lipopolysaccharide (LPS) bound to lipoprotein is less active than unbound LPS in multiple assay systems, the binding of radiolabeled LPS to lipoproteins in sera prepared from normal rabbits and rabbits made hyperimmune to Escherichia coli J5 were compared. LPS-lipoprotein binding in hyperimmune sera to E. coli J5 was not greater than that in normal serum as assessed by ultracentrifugation, but more LPS was precipitated from hyperimmune antisera than normal sera under conditions designed to precipitate LPS-lipoprotein complexes with calcium and dextran. Radiolabeled LPS was precipitated by delipidated antisera and fractions of IgG purified by anion exchange chromatography, but the precipitation was dependent on the presence of normal serum in the reaction mixture. These data suggest that a fluid-phase RIA done in the presence of normal serum may facilitate the detection of IgG in antisera raised to E. coli J5 that binds to heterologous smooth LPS.     

Prediction of left ventricular mass from the electrocardiogram.

Multiple stepwise regression methods were used to derive electrocardiographic (ECG) models for prediction of the echocardiographic left ventricular (LV) mass index from standard 12-lead ECG measurements using data files of 203 men and 252 women. The correlation between echocardiographic and ECG estimates of LV mass index was R2 = 0.58 for men and R2 = 0.42 for women. A separate logistic regression model was derived for classification of LV hypertrophy as a dichotomized dependent variable. This classifier chose R (aVL), T (V6), and S (V1) for men and R (aVL), T (V6), and S (I) for women and produced a moderate sensitivity (53.7% for men and 63.4% for women) and specificity (94.9% for men and 92.9% for women). We conclude that the initial performance of these and other recently developed multivariate estimators of LV mass and LV hypertrophy classifiers is promising enough to subject them to further studies to evaluate their utility as risk predictors.     

Decreased intracellular calcium mediates the histamine H3-receptor-induced attenuation of norepinephrine exocytosis from cardiac sympathetic nerve endings

Activation of presynatic histamine H(3) receptors (H(3)R) down-regulates norepinephrine exocytosis from cardiac sympathetic nerve terminals, in both normal and ischemic conditions. Analogous to the effects of alpha(2)-adrenoceptors, which also act prejunctionally to inhibit norepinephrine release, H(3)R-mediated antiexocytotic effects could result from a decreased Ca(2+) influx into nerve endings. We tested this hypothesis in sympathetic nerve terminals isolated from guinea pig heart (cardiac synaptosomes) and in a model human neuronal cell line (SH-SY5Y), which we stably transfected with human H(3)R cDNA (SH-SY5Y-H(3)). We found that reducing Ca(2+) influx in response to membrane depolarization by inhibiting N-type Ca(2+) channels with omega-conotoxin (omega-CTX) greatly attenuated the exocytosis of [(3)H]norepinephrine from both SH-SY5Y and SH-SY5Y-H(3) cells, as well as the exocytosis of endogenous norepinephrine from cardiac synaptosomes. Similar to omega-CTX, activation of H(3)R with the selective H(3)R-agonist imetit also reduced both the rise in intracellular Ca(2+) concentration (Ca(i)) and norepinephrine exocytosis in response to membrane depolarization. The selective H(3)R antagonist thioperamide prevented this effect of imetit. In the parent SH-SY5Y cells lacking H(3)R, imetit affected neither the rise in Ca(i) nor [(3)H]norepinephrine exocytosis, demonstrating that the presence of H(3)R is a prerequisite for a decrease in Ca(i) in response to imetit and that H(3)R activation modulates norepinephrine exocytosis by limiting the magnitude of the increase in Ca(i). Inasmuch as excessive norepinephrine exocytosis is a leading cause of cardiac dysfunction and arrhythmias during acute myocardial ischemia, attenuation of norepinephrine release by H(3)R agonists may offer a novel therapeutic approach to this condition.     

Five-year effect of medical and surgical therapy on resting left ventricular function in stable angina: Veterans administration cooperative study

The effect of coronary artery bypass grafting (CABG) and medical therapy on 5-year resting left ventricular (LV) function was studied in 194 randomized patients with stable angina in the Veterans Administration Study of Coronary Artery Bypass Surgery. LV ejection fraction (EF) was determined in a central laboratory. The 92 medical and 102 surgical patients were comparable at entry with respect to historic, angiographic and electrocardiographic prognostic indicators. Twenty-eight percent of the medical and 30% of the surgical patients had a baseline EF of < 50%. There was no significant change in mean EF between baseline and 5-year values in either treatment group. The base-line and 5-year values were 56 and 58% in each treatment group. Intervening myocardial infarction (MI) had an adverse effect in medically treated patients (59 to 46%, p < 0.01) and in surgically treated patients with late Ml (58 to 47%, difference not significant). Perioperative MI was not associated with a decrease in EF (56 to 58%, difference not significant). These findings extend the similar results of previous short-term studies of the effect of coronary bypass surgery on resting LV function to 5 years, and provide data in a comparable medical control group.