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Efficient regioselective synthesis of β-amino alcohol derivatives, including enantioenriched ones, by a tetraarylphosphonium salt-catalyzed coupling reaction of epoxides with trichloroacetonitrile is described. Formal [3+2] cycloaddition, followed by hydrolysis, proceeded smoothly to afford N-protected β-amino alcohols in good yields. [ABSTRACT FROM AUTHOR]

Lewis acids, especially rare earth metal triflates, were found to be extremely effective in promoting and accelerating the cycloaddition reactions of carbonyl ylides generated by intramolecular carbenoid-carbonyl cyclization with imine dipolarophiles. This methodology enables less reactive carbonyl ylides, to be reacted with imine dipolarophiles.

Assessment of left ventricular systolic and diastolic pump properties is fundamental to advancing the understanding of cardiovascular pathophysiology and therapeutics, especially for heart failure. The use of end-systolic and end-diastolic pressure-volume relationships derived from measurements of instantaneous left ventricular pressure-volume loops emerged in the 1970s as a comprehensive approach for this purpose. As invasive and noninvasive techniques for measuring ventricular volume improved over the past decades, these relations have become commonly used by basic, translational, and clinical researchers. This review summarizes 1) the basic concepts underlying pressure-volume analysis of ventricular and myocardial systolic and diastolic properties, 2) deviations from ideal conditions typically encountered in real-life applications, 3) how these relationships are appropriately analyzed, including statistical analyses, and 4) the most common problems encountered by investigators and the appropriate remedies. The goal is to provide practical information and simple guidelines for accurate application and interpretation of pressure-volume data as they pertain to characterization of ventricular and myocardial properties in health and disease. systole; diastole; ventricular mechanics; end-systolic pressure-volume relationship; end-diastolic pressure-volume relationship

We previously found the frequency distribution of the left ventricular (LV) effective afterload elastance ([E.sub.a]) of arrhythmic beats to be nonnormal or non-Gaussian in contrast to the normal distribution of the LV end-systolic elastance ([E.sub.max]) in canine in situ LVs during electrically induced atrial fibrillation (AF). These two mechanical variables determine the total mechanical energy [systolic pressure-volume area (PVA)] generated by LV contraction when the LV end-diastolic volume is given on a per-beat basis. PVA and [E.sub.max] are the two key determinants of the LV [O.sub.2] consumption per beat. In the present study, we analyzed the frequency distribution of PVA during AF by its [chi square], significance level, skewness, and kurtosis and compared them with those of other major cardiodynamic variables including [E.sub.a] and [E.sub.max]. We assumed the volume intercept ([V.sub.o]) of the end-systolic pressure-volume relation needed for [E.sub.max] determination to be stable during arrhythmia. We found that PVA distributed much more normally than [E.sub.a] and slightly more so than [E.sub.max] during AF. We compared the [chi square], significance level, skewness, and kurtosis of all the complex terms of the PVA formula. We found that the complexity of the PVA formula attenuated the effect of the considerably nonnormal distribution of [E.sub.a] on the distribution of PVA along the central limit theorem. We conclude that mean (SD) of PVA can reliably characterize the distribution of PVA of arrhythmic beats during AF, at least in canine hearts. end-systolic elastance; effective afterload elastance; frequency distribution; normality

Neiguan (PC-6) is a traditional acupoint in each forearm and overlies the trunk of the median nerve. Previous studies show that electroacupuncture (EA) at the Neiguan acupoint could improve not only myocardial ischemic dysfunction by inducing a depressor response but also recover hemorrhagic hypotension by inducing a pressor response. However, their physiological mechanisms are not yet elucidated. We investigated the pressor effect of Neiguan EA and its mechanism by focusing on left ventricular (LV) performance in a canine hemorrhagic hypotension model. We hemorrhaged 36 anesthetized and thoracotomized mongrel dogs and decreased LV end-systolic pressure (ESP) to ~70 mmHg (35% decrease). We obtained LV pressure-volume (P-V) data with a micromanometer catheter and a conductance catheter. One-hour Neiguan EA significantly recovered the decreased ESP, end-diastolic volume, and stroke volume by 32 [+ or -] 13%, 27 [+ or -] 13%, and 39 [+ or -] 17%, respectively (P < 0.05), without changing heart rate and the slope of the end-systolic P-V relation. Neiguan EA inhibited a hemorrhage-induced increase in plasma catecholamines. However, vecuronium (neuromuscular blocking agent) administration abolished the antihypotension effect of Neiguan EA. Furthermore, Neiguan EA was much more effective than a nonacupoint thigh EA. We conclude that Neiguan EA achieved the antihypotension effect by improving LV filling of the hemorrhage-depressed LV performance despite the inhibition of the hemorrhage-increased plasma catecholamines. This pressor effect seemed to accompany an increased venous return by Neiguan EA-increased vasomotor tone and muscle pump. This study demonstrated a scientific basis for the therapeutic efficacy of acupuncture in the treatment of hemorrhagic hypotension and shock. Neiguan acupoints; left ventricular performance; vasomotor tone; cardiovascular response; muscle pump

Pressure overload cardiac hypertrophy may be a compensatory mechanism to normalize systolic wall stress and preserve left ventricular (LV) function. To test this concept, we developed a novel in vivo method to measure myocardial stress ([sigma])-strain ([epsilon]) relations in normal and hypertrophied mice. LV volume was measured using two pairs of miniature omnidirectional piezoelectric crystals implanted orthogonally in the endocardium and one crystal placed on the anterior free wall to measure instantaneous wall thickness. Highly linear [sigma]-[epsilon] relations were obtained in control (n = 7) and hypertrophied mice produced by 7 days of transverse aortic constriction (TAC; n = 13). Administration of dobutamine in control mice significantly increased the load-independent measure of LV contractility, systolic myocardial stiffness. In TAC mice, systolic myocardial stiffness was significantly greater than in control mice (3,156 [+ or -] 1,433 vs. 1,435 [+ or -] 467 g/[cm.sup.2], P < 0.01), indicating enhanced myocardial contractility with pressure overload. However, despite the increased systolic performance, both active (time constant of LV pressure decay) and passive (diastolic myocardial stiffness constant) diastolic properties were markedly abnormal in TAC mice compared with control mice. These data suggest that the development of cardiac hypertrophy is associated with a heightened contractile state, perhaps as an early compensatory response to pressure overload. systolic myocardial stiffness; contractility; cardiac mechanics; transgenic mice

Temperature-dependent postextrasystolic potentiation and [Ca.sup.2+] recirculation fraction in canine hearts. Am J Physiol Heart Circ Physiol 282: H403-H413, 2002; 10.1152/ajpheart.00427.2000.--We have found that cardiac temperature proportionally changes [O.sub.2] cost of contractility, defined as [O.sub.2] consumption for myocardial total [Ca.sup.2+] handling normalized to contractility in terms of the end-systolic pressure-volume ratio (maximal elastance, [E.sub.max]), in the canine left ventricle (temperature sensitivity, [Q.sub.10] = 2). We have separately found that a decrease in the recirculation fraction (RF) of [Ca.sup.2+] within myocardial cells underlies an increased [O.sub.2] cost of [E.sub.max] in stunned hearts. We therefore hypothesized that a similar change in RF would underlie the [Q.sub.10] of [O.sub.2] cost of [E.sub.max]. We tested this hypothesis by analyzing RF calculated from an exponential decay component of the transiently alternating postextrasystolic potentiation in the canine left ventricle. RF decreased from 0.7 to 0.5 as cardiac temperature increased from 33 to 38 [degrees] C with [Q.sub.10] of 0.5, reciprocal to that of [O.sub.2] cost of [E.sub.max]. We conclude that [Q.sub.10] of ATP-consuming reactions involved in [Ca.sup.2+] handling and [E.sub.max] response to it could reasonably account for the reciprocal [Q.sub.10] of RF and [O.sub.2] cost of [E.sub.max]. excitation-contraction coupling; calcium handling; ventricular contractility; sarcoplasmic reticulum

Left ventricular diastolic dysfunction in type 2 diabetes mellitus model rats. Am J Physiol Heart Circ Physiol 282: H138-H148, 2002.--To gain insight into the pathogenesis of diabetic cardiomyopathy, we investigated cardiac function in terms of the coupling of left ventricular mechanical work and the energetics in Otsuka Long-Evans Tokushima Fatty rats, which are well known as a model of type 2 diabetes mellitus (DM). Neither left ventricular systolic function and mean coronary flow nor coronary flow reserve differed even in late DM rats. The amount of oxygen required for mechanical work and contraction was unaltered, although myosin isozyme was finally transformed from [V.sub.1] to [V.sub.3]. The maximum pacing rate was decreased from 300 to 240 beats/min, and the left ventricular relaxation rate was significantly (P < 0.05) slower only in late DM rats, resulting in decreased oxygen consumption per minute for total [Ca.sup.2+] handling in excitation-contraction coupling mainly consumed by sarco(endo)plasmic reticulum [Ca.sup.2+]-ATPase (SERCA2) without significant changes in basal metabolism or in mitochondrial oxidative phosphorylation. The protein level of SERCA2 in membranes was significantly (P < 0.001) lower in severe DM rats. We conclude that the only lusitropic dysfunction due to the depressed expression of SERCA2 is related to generating diabetic cardiomyopathy even in the present type 2 diabetic rats. oxygen consumption; sarcoplasmic reticulum [Ca.sup.2+]-ATPase

The 2-oxazoline-4-carboxylates are discussed relative to cis- and enantioselective synthesis using formal (3 + 2) cycloaddition of 5-alkosyoxazoles with aldehydes catalyzed by Lewis acid. Synthetically useful 2-osazoline-4-carboxylates were synthesized by the methlaluminum beta-binaphthoxide-catalyzed reaction of 2-aryl-5-alkoxyoxazoles with substituted benzaldehydes.