We analyzed total Ca handling of the left ventricle (LV) in the mildly failing heart preparation induced by a temporary intracoronary Ca overloading intervention in eight excised and cross-circulated canine hearts. This Ca intervention consisted of interruption of coronary blood perfusion by Ca-free oxygenated Tyrode perfusion for 10 min followed by high-Ca (16mmol/l) oxygenated Tyrode perfusion for 5 min. This intervention decreased the LV contractility index, Emax (end-systolic maximum elastance), by 40% after restoration of the blood cross-circulation. We expected a Ca overload or paradox failing heart resembling the postischemic stunned heart and being characterized by an increased O2 cost of Emax. However, LV O2 consumption under mechanically unloading conditions decreased by 30% from control without increasing the O2 cost of Emax. To obtain a mechanistic view of this failing heart, we investigated cardiac total Ca handling by our integrative analysis method. In this method, we obtained the internal Ca recirculation fraction (RF) from the decay beat constant of the postextrasystolic potentiation following each sporadic spontaneous extrasystole in these failing LVs. We combined the RF with the decreased Emax and the unchanged O2 cost of Emax in our recently developed formula of total Ca handling. We found that these failing LVs had a slightly but significantly increased RF accompanied by either a slightly increased futile Ca cycling or a slightly decreased Ca reactivity of Emax, or both. Any of these three possible changes can account for the unchanged O2 cost of Emax. This result indicates that the present mildly failing heart has not yet fallen into a typical Ca overload or paradox by the temporary Ca overloading intervention.

Thirty-six hepatocellular carcinoma (HCC) tissues obtained from 34 patients were classified according to histological diagnosis into six well-differentiated HCC, 20 moderately differentiated HCC and 10 poorly differentiated HCC. High molecular weight DNA was prepared from each tumour and the corresponding non-tumour tissue. Loss of heterozygosity (LOH) on chromosomes 4q, 5q, 10q, 11p, 16q, 17p, mutation of the p53 gene and polymorphism of intron 25 of the retinoblastoma (RB) gene were simultaneously analysed. The patients were composed of three cases of small HCC (the diameter of which was < 3 cm) and 31 cases of advanced HCC. Twenty-nine of 34 (85.3%) patients analysed had been exposed to hepatitis B virus and/or hepatitis C virus. The frequencies of LOH on seven chromosomes were 57.9% in 17p13.3, 45.1% in 17p, 45.1% in 11p, 41.9% in 5q, 41.9% in 16q24, 29.0% in 4q, 25.8% in 10q in advanced HCC (four of well differentiated, 18 of moderately differentiated and nine of poorly differentiated carcinoma). In contrast, LOH was observed on 4q, 5q, 16q and 17p in 33% (1/3) of the small HCC (two of well differentiated and one of moderately differentiated carcinoma). The mutation of the p53 genes and polymorphism of the RB gene were present in 25.8% (8/31) and 12.9% (4/31) of the advanced tumours, respectively, but the mutation was not found in small HCC. LOH on every chromosome and the p53 mutation were observed more frequently in more advanced tumours, and the genetic changes accumulated with the increase of the histopathological grade.(ABSTRACT TRUNCATED AT 250 WORDS)

) was originally defined as the end-systolic pressure (ESP)/stroke volume (SV) ratio of the left ventricle (LV) [1][2][3]. E a is approximately equal to heart rate (HR) times total peripheral resistance (TPR) under stable hemodynamics [1][2][3]. E a has the same dimensions as an index of ventricular contractility (E max ) defined as the ESP/endsystolic volume (ESV) ratio [1][2][3][4][5][6]. E a proved to be powerful in evaluating the ventriculo-arterial coupling from the viewpoint of cardiac mechanoenergetics in regular beats [1][2][3][4][5][6]. The mechanical energy efficiency from LV total mechanical energy (PVA) to SV is maximal when E a equals E max [1][2][3][4][5][6][7][8][9][10][11]. The mechanical work efficiency from LV oxygen consumption to SV is maximal when E a is appropriately (around 50%) smaller than E max [3][4][5][6][7][8][9][10][11]. Both efficiencies are re- Abbreviations: AF, atrial fibrillation; CO, cardiac output; E a (ϭESP/SV), either effective arterial elastance conventionally, or effective afterload elastance in this study; E max , an index of ventricular contractility defined as the maximum or end-systolic elastance of the ventricle, or end-systolic pressure-volume ratio; EDP, end-diastolic pressure; EDV, end-diastolic volume; ESP, end-systolic pressure; ESV, end-systolic volume; G i (t), electrical conductance of intraventricular blood; G p , parallel conductance; HR, heart rate; LV, left ventricle; LVP, left ventricular pressure; LVV, left ventricular volume; PVA, total mechanical energy of contraction, or systolic pressure-volume area; RR, cardiac beat interval measured as the interval between two R waves of ECG; RR1 through RR6, first through sixth preceding RRs; SV, stroke volume; TPR, total peripheral resistance; V c , ventricular correction volume equivalent to parallel conductance Gp; V 0 , ventricular unstressed volume.

We previously found the frequency distribution of the left ventricular (LV) effective afterload elastance (E(a)) of arrhythmic beats to be nonnormal or non-Gaussian in contrast to the normal distribution of the LV end-systolic elastance (E(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(max) are the two key determinants of the LV O(2) consumption per beat. In the present study, we analyzed the frequency distribution of PVA during AF by its chi(2), significance level, skewness, and kurtosis and compared them with those of other major cardiodynamic variables including E(a) and E(max). We assumed the volume intercept (V(0)) of the end-systolic pressure-volume relation needed for E(max) determination to be stable during arrhythmia. We found that PVA distributed much more normally than E(a) and slightly more so than E(max) during AF. We compared the chi(2), 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(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.

We recently found that contractility ( E max) of an individual irregularly arrhythmic beat in electrically induced atrial fibrillation (AF) is reasonably predictable from the ratio of the preceding beat interval (RR1) to the beat interval immediately preceding RR1 (RR2) in the canine left ventricle. Moreover, the monotonically increasing relation between E max and the RR1-to-RR2 ratio (RR1/RR2) passed through or by the mean arrhythmic beat E max as well as the regular beat E max at RR1/RR2 = 1. We hypothesized that this E max-RR1/RR2 relation during irregular arrhythmia could be attributed to the basic characteristics of the mechanical restitution and potentiation. To test this, we adopted a known comprehensive equation describing the force restitution and potentiation as a function of two preceding beat intervals and simulated contractilities of irregular arrhythmic beats with randomized beat intervals on a computer. The simulated E max-RR1/RR2 relation reasonably resembled the one that we recently observed experimentally, supporting our hypothesis. We therefore conclude that the primary mechanism underlying the varying contractilities of irregular beats in AF is mechanical restitution and potentiation.

Many groups in both basic and clinical studies [1][2][3][4][5][6][7][8][9] have long investigated basic statistical characteristics, including the frequency distribution of arrhythmic beat interval (RR), during atrial fibrillation (AF). Mean RR has been used to evaluate the average RR during AF [9][10][11]. However, the minimal number of beats from which the mean RR has been reliably obtained varied widely between only 4 beats to as many as the number of beats for 2 min among investigators and their purposes [9][10][11]. In some of these studies, mean RR was obtained to characterize the average RR even either in case of the nonnormal distribution or without testing its normality [1,5,6,[8][9][10][11].We have recently studied the frequency distributions not only of RR, but also of ventricular contractility (E max ) [12] and effective arterial elastance (E a ) [13] in in situ ejecting left ventricles during AF [14]. We have found that not only RR, but also E max , E a , and ventriculo-arterial coupling (E a /E max ) distributed nonnormally with considerable skewness (lack of symmetry of a frequency distribution) and kurtosis (peakedness or flatness of a frequency distribution) [14]. Their meanϮSD values could not uniquely characterize their nonnormal frequency distributions [14], unlike a normal frequency distribution [15,16].We recognized in the present study the necessity of isovolumic contractions to scrutinize the frequency distributions of E max during AF for the following reason. Although E a and E a /E max require ejecting contractions whether in situ or ex vivo [13,14,17] Key words: arrhythmia, statistics, histogram, normality, variance.Abstract: Mean levels of left ventricular rhythm and contractility averaged over arrhythmic beats would characterize the average cardiac performance during atrial fibrillation (AF). However, no consensus exists on the minimal number of beats for their reliable mean values. We analyzed their basic statistics to find out such a minimal beat number in canine hearts. We produced AF by electrically stimulating the atrium and measured left ventricular arrhythmic beat interval (RR) and peak isovolumic pressure (LVP). From these, we calculated instantaneous heart rate (HRϭ60,000/RR), contractility (E max ϭLVP/isovolumic volume above unstressed volume), and beat interval ratio (RR1/RR2). We found that all their frequency distributions during AF were variably nonnormal with skewness and kurtosis. Their meansϮstandard deviations alone cannot represent their nonnormal distributions. A 90% reduction of variances of E max and RR1/RR2 required a moving average of 15 and 24, respectively, arrhythmic beats on the average, whereas that of RR and HR required 60 beats on the average. These results indicate that a statistical characterization of arrhythmic cardiodynamic variables facilitates better understanding of cardiac performance during AF.

In ulcerative colitis patients, the risk factors and indications for colectomy were different according to the patient's clinical background. Our findings may help to predict patients with ulcerative colitis who have a high risk for colectomy.

Our criteria incorporating specific histologic features and endoscopic disease extent reliably predict eventual clinical outcome, and are expected to prove useful in determining the necessity of surgery.