Is stiffness increased during ischemia?

Possible sources of increased ventricular stiffness can be more easily appreciated when pressure and volume patterns are considered as a function of time. A discussion on sources of effective or apparent stiffness or stiffness changes includes viscoelastic properties and active behavior at the muscular level. Chamber geometry and coronary vascular pressure and flow are intrinsic ventricular components. Together with the pressure head and crosstalk as extraventricular components, all these properties are integrated to determine intact heart behavior in late relaxation and diastole.     

Postextrasystolic potentiation worsens fast filling of the hypertrophied left ventricle in aortic stenosis and hypertrophic cardiomyopathy

Impaired left ventricular (LV) filling in aortic stenosis (AS) and in hypertrophic cardiomyopathy (HCM) is caused by slow LV pressure decay, which could be explained by depressed inactivation of hypertrophied myocardium. Postextrasystolic potentiation (PESP), which increases activator calcium, could lead to further deterioration of LV relaxation. The influence of PESP on LV filling dynamics was, therefore, investigated in normal controls and in patients with LV hypertrophy caused by AS or by HCM. LV hemodynamics and LV hemodynamic relaxation indexes were determined during normal sinus rhythm (NSR) and after PESP. LV pressures were recorded by micromanometer tip catheters (controls, n = 10; AS, n = 17; HCM, n = 11). Simultaneous mitral flow Doppler echocardiograms were obtained in patients with LV hypertrophy (AS, n = 8, HCM, n = 5). Despite significant increases of LV dP/dtmax after PESP in all three study groups, PESP affected LV hemodynamic relaxation indexes differently. The time constant of LV pressure decay (TPB) derived from exponential curve fits with nonzero asymptote pressure remained unaltered after PESP in normal controls, rose from 62 +/- 17 to 74 +/- 21 msec (p less than 0.02) in patients with AS, and rose from 74 +/- 18 to 84 +/- 19 msec (p less than 0.02) in patients with HCM. Early diastolic LV pressure decay was measured by phi (phase of the first harmonic of a Fourier transform applied to the diastolic LV pressure waves) and by t (time interval from LV dP/dtmin to LV minimum diastolic pressure). After PESP, phi remained unaltered in normal controls but decreased in AS from 42.8 +/- 19.1 degrees to 24.0 +/- 28.8 degrees (p less than 0.001) and in HCM from 39.7 +/- 15.4 degrees to 26.9 +/- 15.7 degrees (p less than 0.001). Similarly, t was unchanged after PESP in normal controls but prolonged in AS from 146 +/- 48 to 205 +/- 86 msec (p less than 0.001) and in HCM from 168 +/- 40 to 208 +/- 53 msec (p less than 0.02).(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of damaging the endocardial surface on the mechanical performance of isolated cardiac muscle

The mechanical properties of mammalian ventricular cardiac muscle have been studied in the presence and in the absence of an intact endocardial surface. Isotonic and isometric twitch contractions were obtained from papillary muscles of the right ventricle of cat at 29 degrees and 37 degrees C, at different extracellular calcium concentrations ([Ca2+]o), and at different initial muscle lengths. The endocardial surface was damaged by gentle abrasion of the muscle surface with a plastic blade or by brief immersion for 1 second with 1% Triton X-100. Although there was no evidence of damage to myocardial cells, damaging the endocardial surface resulted in an immediate and irreversible abbreviation of the twitch contractions with, except at the highest ([Ca2+]o, a decrease in peak isometric twitch tension. These changes induced 1) an asymmetrical shift of the tension-[Ca2+]o relation towards increasing [Ca2+]o but with no effect at the highest [Ca2+]o, and 2) a rightward and downward shift of the length-tension relation. Both shifts were significantly more pronounced at 37 degrees C than at 29 degrees C; they were not accompanied by significant changes in Vmax. The asymmetrical shift of the tension-[Ca2+]o relation suggests that the endocardium-mediated chain of events may be mediated by changes in the sensitivity of the contractile proteins to Ca2+. This hypothesis is also supported by the similar pattern of changes (i.e., modulation of the onset of early tension decline) induced by decreasing length at each [Ca2+]o and by the removal of a functional endocardium. Accordingly, the endocardium may help to control the performance of the heart by modulating peak contractile performance and relaxation of the underlying myocardium.     

In vitro and in vivo metabolism and detection of 3‐HO‐PCP,a synthetic phencyclidine,in human samples and pooled human hepatocytes using high resolution mass spectrometry

The new psychoactive substance (NPS) 3‐HO‐PCP, a phencyclidine (PCP) analog, was detected in a law enforcement seizure and in forensic samples in Denmark. Compared with PCP, 3‐HO‐PCP is known to be a more potent dissociative NPS, but no toxicokinetic investigations of 3‐HO‐PCP are yet available. Therefore, 3‐HO‐PCP was quantified in in vivo samples, and the following were investigated: plasma protein binding, in vitro and in vivo metabolites, and metabolic targets. All samples were separated by liquid chromatography and analyzed by mass spectrometry. The unbound fraction in plasma was determined as 0.72 ± 0.09. After in vitro incubation with pooled human hepatocytes, four metabolites were identified: a piperidine‐hydroxyl‐and piperidine ring opened N‐dealkyl‐COOH metabolite, and O‐glucuronidated‐ and O‐sulfate‐conjugated metabolites. In vivo, depending on the sample and sample preparation, fewer metabolites were detected, as the O‐sulfate‐conjugated metabolite was not detected. The N‐dealkylated‐COOH metabolite was the main metabolite in the deconjugated urine sample. in vivo analytical targets in blood and brain samples were 3‐HO‐PCP and the O‐glucuronidated metabolite, with 3‐HO‐PCP having the highest relative signal intensity. The drug levels of 3‐HO‐PCP quantified in blood were 0.013 and 0.095 mg/kg in a living and a deceased subject, respectively. The 3‐HO‐PCP concentrations in deconjugated urine in a sample from a living subject and in post‐mortem brain were 7.8 and 0.16 mg/kg, respectively. The post mortem results showed a 1.5‐fold higher concentration of 3‐HO‐PCP in the brain tissue than in the post mortem blood sample.     

Application of artificial intelligence in screening for adverse perinatal outcomes: A protocol for systematic review

The article presents a systematic review protocol. The aim of the study is an assessment of current studies regarding the application of artificial intelligence and neural networks in the screening for adverse perinatal outcomes. We intend to compare the reported efficacy of these methods to improve pregnancy care and outcomes. There are more and more studies that describe the role of machine learning in facilitating the diagnosis of adverse perinatal outcomes, like gestational diabetes or pregnancy hypertension. A systematic review of available literature seems to be crucial to compare the known efficacy and application. Publication of a systematic review in this category would improve the value of future studies. The studies reporting on artificial intelligence application will have a major impact on future prenatal practice.     

Relaxation and diastole of the heart

In the present review, we adopted the viewpoint of the physiologist looking at the global function of the heart, during relaxation and diastole, as an integrated muscle-pump system. We first focused our attention on properties of relaxation and diastole at the subcellular (SR, contractile proteins), cellular, and multicellular scales of cardiac muscle and then at the scale of the ventricle and intact global heart. At each lower scale we derived properties from experimental facts and examined the extent to which these properties could be extrapolated conceptually to the higher scale. From this muscle-pump approach, we learned that a general and fundamental property of relaxation of the heart as a muscle-pump system is load dependence, i.e., the mutually independent behavior of the time patterns of slow force decline and pressure fall and of rapid lengthening and rapid filling. Load dependence is found at all hierarchic scales, irrespective of whether it is examined under strictly isotonic-isometric or isometric-isotonic or auxotonic loading conditions and despite often substantial nonuniformity. Relaxation is governed by the interaction of the loading conditions and the two major determinants of the inactivation process, i.e., Ca2+ reuptake by the SR and the properties of the contractile proteins. Load dependence is the mere mechanical expression of the unequal contribution, during the two phases of relaxation, of these three interacting determinants of relaxation (load, SR, and contractile proteins). During force decline in isolated muscle and pressure fall in the ventricle, the properties of the contractile proteins predominate over load and SR; during muscle lengthening and rapid ventricular filling, load and SR become more important. As the relative importance of the phenomena above is different during pressure fall in comparison to rapid filling, it is not surprising that directional changes in pressure fall may not predict those in filling. We also saw that the overall time pattern of pressure fall in contrast to rapid filling may sometimes be markedly altered, e.g., with simultaneous increases in peak-dP/dt, indicating more rapid early pressure relaxation, and prolonged time constant tau, indicating slower late pressure relaxation, or vice versa. From this muscle-pump approach, it should also be remembered that optimal efficiency of the heart limits the extent to which nonuniformity may exist. At all hierarchic scales, variations in the degree of nonuniformity, however small, constitute an important physiological modulator of performance throughout systole and diastole.(ABSTRACT TRUNCATED AT 400 WORDS)