HEART-RATE-VARIABILITY IN PATIENTS WITH ORTHOTOPIC HEART-TRANSPLANTATION - LONG-TERM FOLLOW-UP

To evaluate heart rate variability (expressed as the standard deviation of RR intervals) within 5 years of follow-up, we studied 20 patients (14 males, 6 females, mean age 44 +/- 12 years) who underwent orthotopic heart transplantation. Six measurements were taken: one in the first 3 weeks after transplantation, and the others once annually, for 5 years. Twenty healthy subjects (mean age 44 +/- 7 years) constituted the control group. Heart rate variability increased significantly in the first 3 years of follow-up (7.2 +/- 1 vs. 11.1 +/- 4, p0.001; 11.1 +/- 4 vs. 15.2 +/- 4, p0.01; 15.2 +/- 4 vs. 18.9 +/- 5, p0.05); in the following years this trend slackened and values did not reach a statistically significant difference (18.9 +/- 5 vs. 21.4 +/- 5; 21.4 +/- 5 vs. 22.5 +/- 5). The mean standard deviation was invariably greater in the control group (63.6 +/- 12). These findings show that sinus rhythm variability in the denervated heart progressively increased over 5 years of follow-up. The absence of presynaptic uptake, which is responsible for adrenergic hypersensitivity to circulating catecholamines and intrinsic cardiac reflexes, does not appear to cause this phenomenon, since these mechanisms are not able to evolve in time after cardiac transplantation. Therefore, an enhanced beta-adrenergic receptors density or affinity to circulating catecholamines or a limited sympathetic reinnervation may be the more probable underlying mechanism

Simulation of chronic mitral regurgitation

In mitral regurgitation the left ventricle enlarges in order to increase its stroke volume because of the regurgitation through the mitral valve. The amount of this volume increase, and of the consequent increase in left ventricular mass, its dependent upon the amount of the regurgitant volume, but many other factors come into play, such as left ventricular pumping capability (contractility), the level of peripheral pressure, resistance and compliance of the arterial tree. The aim of this study is to predict the final left ventricular volumes and mass given the amount of mitral regurgitation. The predicted results are compared with actual data in real patients. In most cases prediction is fairly good; some discrepancies can be interpreted as an index of advanced decompensation

Analytical expression of effective afterload in aortic and mitral regurgitation

Effective arterial elastance (Ea) is the coupling parameter between the left ventricle and peripheral circulation in normal subjects. If left ventricular end systolic pressure (Pes), contractility (Es) and Ea are known, left ventricular end diastolic volume (LVEDV) and ejection fraction of the ventricle are completely determined. The aim of this study was to give an analytical expression for Ea in patients with mitral and aortic regurgitation, and predict both LVEDV and the effect of vasodilator therapy on LVEDV. Twenty-three subjects with atypical chest pain, 15 patients with mitral insufficiency and 11 with aortic insufficiency underwent diagnostic cardiac catheterization, coronary angiography, and left ventricular cineangiography, which was analyzed quantitatively. Ea was 2.05 +/- 0.63 in normal subjects, while it was 1.28 +/- 0.71 and 1.57 +/- 0.87 in patients with mitral and aortic insufficiency, respectively. All these groups differed with ANOVA test (p = 0.0031). We tested the ability of the analytical expressions for Ea in normal subjects, and patients with mitral insufficiency or aortic insufficiency to predict measured Ea and LVEDV. Ea and LVEDV were predicted rather accurately in every case (p < 0.0001). We used published data to test the effect of resistance modulation on LVEDV. Predicted and measured LVEDV were linearly correlated both in aortic (p < 0.0001) and mitral insufficiency (p = 0.027). Moreover, in some cases a left ventricular enlargement after vasodilator therapy could be anticipated because of an unbalanced decrease in resistance and heart rate. Ea seems to be the coupling parameter between the left ventricle and the peripheral circulation not only in normal subjects, but also in patients with mitral or aortic regurgitation; its measurement before administering vasodilating drugs may be useful in order to predict the effects on LVEDV, and achieve an optimal ventriculoarterial coupl

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field