) 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.
Introduction Liver transplantation is currently the only curative therapy for end-stage liver failure; however, establishment of alternative treatments is required owing to the serious donor organ shortage. Here, we propose a novel model of hybrid three-dimensional artificial livers using both human induced pluripotent stem cells (hiPSCs) and a rat decellularized liver serving as a scaffold. Methods Rat liver harvesting and decellularization were performed as reported in our previous studies. The decellularized liver scaffold was recellularized with hiPSC-derived hepatocyte-like cells (hiPSC-HLCs) through the biliary duct. The recellularized liver graft was continuously perfused with the culture medium using a pump at a flow rate of 0.5 mL/min in a standard CO 2 (5%) cell incubator at 37 °C. Results After 48 h of continuous perfusion culture, the hiPSC-HLCs of the recellularized liver distributed into the parenchymal space. Furthermore, the recellularized liver expressed the albumin ( ALB ) and CYP3A4 genes, and secreted human ALB into the culture medium. Conclusion Novel hybrid artificial livers using hiPSCs and rat decellularized liver scaffolds were successfully generated, which possessed human hepatic functions.
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.
This retrospective study analyzed the current practice of blood transfusion-free open-heart surgery in 536 children weighing 5-20 kg undergoing surgery between 2004 and 2007. A miniaturized cardiopulmonary bypass (CPB) circuit was used (priming volume; 300 ml for the flow rate <1,500 ml/min; 550 ml for the flow rate of 1500-2300 ml/min). Modified ultrafiltration was routinely performed. Criteria for blood transfusion during CPB included a hematocrit of <20% and/or mixed venous oxygen saturation of <65%. Transfusion during CPB was avoided in 264 (49.3%) of the 536 patients (5-10 kg group, 29.0%; 11-15 kg group, 67.4%; 16-20 kg group, 80.8%). There was no neurological complication related to hemodilution. Multiple logistic regression analysis revealed that body weight, preoperative hematocrit, priming volume of CPB circuit, CPB time, and lowest hematocrit during CPB predict requirement of blood transfusion (p < 0.01). Transfusion rate was lowest in the atrial septal defect group (5.6%) and highest in tetralogy of Fallot group (78.7%), being associated with complexity of diagnosis and procedure required. Blood transfusion-free open-heart surgery may be achieved in the half of the patients weighing 5-20 kg, and further miniaturization of CPB circuit and refinement of perfusion strategy might reduce transfusion rate in patients <10 kg and/or with complex congenital heart disease.
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