浅谈二尖瓣交界分离术中监护和输液与复苏的关系

本文通过116例二尖瓣决窄分离术中监护和输液,从中体会到术中监护是心脏手术成功必不可少的条件。只有做好术中监护,才能及时了解病情发展,正确指导复苏和输液,提高手术的安全系数。     

A novel technique for measuring heart rate in a free swimming marine vertebrate

A mouth opening sensor incorporating a magnet and Hall sensor attached to a data logging unit was used to monitor the breathing and foraging behavior of a free-swimming leatherback sea turtle (Dermochelys coriacea). Analysis of these data revealed a rhythmic low amplitude oscillation. Further investigation of the frequency of this signal lead us to believe that the movements (< 0.1 mm) are caused by the movement of blood through the nearby blood vessels. Putative heart rate decreased during dive descent and increased considerably during dive ascent reflecting the bradycardia and anticipatory tachycardia recorded by other means in other air-breathing divers. Oscillation frequencies were also comparable to the heart rate recorded in leatherbacks by means of implanted electrodes. We therefore propose that this device which was already known to reliably record behaviour such as breathing, feeding and buccal oscillations in sea turtles also has potential for recording other signals which cause movement on the external surface of an animal.     

Embryonic atrial function is essential for mouse embryogenesis, cardiac morphogenesis and angiogenesis

The requirement for atrial function in developing heart is unknown. To address this question, we have generated mice deficient in atrial myosin light chain 2 (MLC2a), a major structural component of the atrial myofibrillar apparatus. Inactivation of the Mlc2a gene resulted in severely diminished atrial contraction and consequent embryonic lethality at ED10.5-11.5, demonstrating that atrial function is essential for embryogenesis. Our data also address two longstanding questions in cardiovascular development: the connection between function and form during cardiac morphogenesis, and the requirement for cardiac function during vascular development. Diminished atrial function in MLC2a-null embryos resulted in a number of consistent secondary abnormalities in both cardiac morphogenesis and angiogenesis. Our results unequivocally demonstrate that normal cardiac function is directly linked to normal morphogenic development of heart and vasculature. These data have important implications for the etiology of congenital heart disease.     

Microinjecting recombinant rainbow trout Ea4-peptide of pro-IGF-I into zebrafish embryos causes abnormal development in heart, red blood cells, and vasculature

E-peptides and mature insulin-like growth factors (IGFs) are produced from pre-pro-IGFs during post-translational processing and co-secreted into the circulation. Previously, we reported that introduction of a transgene encoding the secreted form of rainbow trout (rt) Ea4-peptide or human (h) Eb-peptide into newly fertilized eggs of medaka (Oryzias latipes) and zebrafish (Danio rerio) resulted in developmental defects in heart, red blood cells and vasculature. In addition to vasculature and red blood cell developmental defects, multiple phenocopies of heart developmental defects categorized by developmental arrest at cardiomyocyte, heart tube and heart looping stages were also observed. These results raise a question of whether rtEa4- or hEb-peptide exerts pleiotropic inhibitory effects on heart, vasculature and red blood cell development in fish embryos. To answer this question, various amounts of recombinant rtEa4-peptide were microinjected into zebrafish eggs at 1.5, 2.5 and 5.5 h post-fertilization (hpf). Although a dose-dependent developmental defect in heart, vasculature and red blood cells was observed in embryos microinjected with rtEa4-peptide at 1.5 and 2.5 hpf, the heart development in all of the microinjected embryos was arrested at the cardiomyocyte stage. Furthermore, the mRNA levels of Nkx2.5, GATA5, VEGF, GATA1 and GATA2 genes in defective embryos were significantly reduced by rtEa4-peptide. These results confirm our previous findings that rtEa4- or hEb-peptide exhibits pleiotropic effects in inhibiting heart, vasculature and red blood cell development in zebrafish embryos.     

Longitudinal Hemodynamic Measurements in Swine Heart Failure Using a Fully Implantable Telemetry System

Chronic monitoring of heart rate, blood pressure, and flow in conscious free-roaming large animals can offer considerable opportunity to understand the progression of cardiovascular diseases and can test new diagnostics and therapeutics. The objective of this study was to demonstrate the feasibility of chronic, simultaneous measurement of several hemodynamic parameters (left ventricular pressure, systemic pressure, blood flow velocity, and heart rate) using a totally implantable multichannel telemetry system in swine heart failure models. Two solid-state blood pressure sensors were inserted in the left ventricle and the descending aorta for pressure measurements. Two Doppler probes were placed around the left anterior descending (LAD) and the brachiocephalic arteries for blood flow velocity measurements. Electrocardiographic (ECG) electrodes were attached to the surface of the left ventricle to monitor heart rate. The telemeter body was implanted in the right side of the abdomen under the skin for approximately 4 to 6 weeks. The animals were subjected to various heart failure models, including volume overload (A-V fistula, n = 3), pressure overload (aortic banding, n = 2) and dilated cardiomyopathy (pacing-induced tachycardia, n = 3). Longitudinal changes in hemodynamics were monitored during the progression of the disease. In the pacing-induced tachycardia animals, the systemic blood pressure progressively decreased within the first 2 weeks and returned to baseline levels thereafter. In the aortic banding animals, the pressure progressively increased during the development of the disease. The pressure in the A-V fistula animals only showed a small increase during the first week and remained stable thereafter. The results demonstrated the ability of this telemetry system of long-term, simultaneous monitoring of blood flow, pressure and heart rate in heart failure models, which may offer significant utility for understanding cardiovascular disease progression and treatment.     

Development of electrical activity in cardiac myocyte aggregates derived from mouse embryonic stem cells

Embryonic stem cells differentiate into cardiac myocytes, repeating in vitro the structural and molecular changes associated with cardiac development. Currently, it is not clear whether the electrophysiological properties of the multicellular cardiac structure follow cardiac maturation as well. In long-term recordings of extracellular field potentials with microelectrode arrays consisting of 60 substrate-integrated electrodes, we examined the electrophysiological properties during the ongoing differentiation process. The beating frequency of the growing preparations increased from 1 to 5 Hz concomitant to a decrease of the action potential duration and action potential rise time. A developmental increase of the conduction velocity could be attributed to an increased expression of connexin43 gap junction channels. Whereas isoprenalin elicited a positive chronotropic response from the first day of spontaneous beating onward, a concentration-dependent negative chronotropic effect of carbachol only developed after approximately 4 days. The in vitro development of the three-dimensional cardiac preparation thus closely follows the development described for the mouse embryonic heart, making it an ideal model to monitor the differentiation of electrical activity in embryonic cardiomyocytes.     

Long-Term Stability of Visual Pattern Selective Responses of Monkey Temporal Lobe Neurons

Many neurons in primate inferotemporal (IT) cortex respond selectively to complex, often meaningful, stimuli such as faces and objects. An important unanswered question is whether such response selectivity, which is thought to arise from experience-dependent plasticity, is maintained from day to day, or whether the roles of individual cells are continually reassigned based on the diet of natural vision. We addressed this question using microwire electrodes that were chronically implanted in the temporal lobe of two monkeys, often allowing us to monitor activity of individual neurons across days. We found that neurons maintained their selectivity in both response magnitude and patterns of spike timing across a large set of visual images throughout periods of stable signal isolation from the same cell that sometimes exceeded two weeks. These results indicate that stimulus-selectivity of responses in IT is stable across days and weeks of visual experience.     

Genetic, environmental and maternal influences on embryonic cardiac rhythms

The relative roles of an animal's genetic constituents and environmental factors in influencing physiological variables such has heart rate have not been extensively investigated. This paper considers how heart rate patterns in the developing animal can be regulated, and how a combination of 'nature' and 'nurture' may interact to produce discrete patterns of heart rate change during development. The concept of the 'developmental trajectory' is evoked to generate a conceptual framework for how physiological development can be perturbed by environmental factors. Data are provided from three species showing how 'clutch-effects' (the fact that siblings perform physiologically much more similarly than non-siblings) can greatly influence the variance observed when collecting data on heart rate during development. Finally, so-called 'maternal effects', which are the influences on embryos of environmental experiences of the parents, are discussed as potentially confounding effects in the study of the genetic basis for physiological patterns of change during development.     

Cardiac pacemaker function of HCN4 channels in mice is confined to embryonic development and requires cyclic AMP

Important targets for cAMP signalling in the heart are hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels that underlie the depolarizing 'pacemaker' current, I(f). We studied the role of I(f) in mice, in which binding of cAMP to HCN4 channels was abolished by a single amino-acid exchange (R669Q). Homozygous HCN4(R669Q/R669Q) mice die during embryonic development. Prior to E12, homozygous and heterozygous embryos display reduced heart rates and show no or attenuated responses to catecholaminergic stimulation. Adult heterozygous mice display normal heart rates at rest and during exercise. However, following beta-adrenergic stimulation, hearts exhibit pauses and sino-atrial node block. Our results demonstrate that in the embryo, HCN4 is a true cardiac pacemaker and elevation of HCN4 channel activity by cAMP is essential for viability. In adult mice, an important function of HCN4 channels is to prevent sinus pauses during and after stress while their role as a pacemaker of the murine heart is put into question. Most importantly, our results indicate that HCN4 channels can fulfil their physiological function only when cAMP is bound.     

Inhibitory Synapses on Pacemaker Neurons in the Heart Ganglion of a Stomatopod, Squilla oratoria

The pacemaker neurons of the Squilla heart ganglion are innervated from the CNS through three pairs of extrinsic nerves. One of them, the α-nerve, is inhibitory to the heart beat. The effect of α-nerve stimulation on the pacemaker potential was examined with intracellular electrodes. Without extrinsic nerve stimulation the membrane potential of the pacemaker cell fluctuated spontaneously. On application of a tetanic train of stimuli to the α-nerve the membrane potential was shifted and fixed to a steady level, which with K₂SO₄-filled electrodes was near the peak of hyperpolarization after a spontaneous burst, but was less negative with KCl-filled electrodes. The shift of the membrane potential was due to the summated IPSP's. By changing the level of the membrane potential with injection of the polarizing current the IPSP could be reversed in sign, and the size of the IPSP was linearly correlated with the membrane potential level. During inhibition the membrane conductance increased. The increase depended on divalent cation concentrations in the outside medium. In Ca-rich saline the IPSP was greatly enhanced. In Mg-rich saline it was suppressed. The amplitude of antidromic spikes was reduced during inhibition especially when the spike frequency was high.     

Heterogeneous cellular expression of creatine kinase isoenzyme during normal rat heart development

The degree to which developmentally related alterations in cardiac creatine kinase (CK) activity reflect modification of CK isoenzyme gene expression remains uncertain. The present studies addressed this question by assessing multiple aspects of CK in rat heart during the perinatal to adult transition. In addition to whole tissue, isolated and purified muscle and nonmuscle cells were studied, as well as myofibrillar, mitochondrial, and cytosolic subcellular fractions. Whole homogenate CK enzyme specific activity nearly doubled during the weanling to adult developmental period. Muscle cell CK activity increased by a similar magnitude. Nonmuscle cell activity decreased. In the adult heart, both myofibrillar and mitochondrial CK activities were augmented versus the weanling heart. The cytoplasmic fraction activity held constant during development. Electrophoretic isoenzyme analyses of both weanling and adult cardiac muscle cells indicated the presence of mitochondrial CK and MM-CK isoforms. Weanling heart nonmuscle cells contained mitochondrial, MM, MB, and BB isoforms; however, BB isoform was not detected in the adult heart nonmuscle cells. Arrhenius plots provided information regarding heart muscle and nonmuscle cell alterations during development. CK activation energies were also determined for whole tissue, muscle/nonmuscle cells, myofibrils, mitochondria, and cytosol. Results demonstrate that heterogeneous muscle/nonmuscle cellular composition and differential myofibrillar/mitochondrial subcellular composition account for normal, developmentally related changes in heart CK enzyme activity. CK isoenzyme gene expression changes were not detected in cardiac muscle cells, and transition of CK-B to CK-M gene expression is limited to nonmuscle cells during normal, weanling to adult development in the rat heart.     

Measurement of intracellular calcium ion activity with neutral exchanger ion sensitive microelectrodes

Micropipettes filled with the neutral liquid ion exchanger ETH 1001 can be used to make microelectrodes that are sensitive to cytoplasmic levels of Ca2+. They are high resistance electrodes, so that care is required in order to record the low current signal. The electrodes often yield 10-15 mV change between intracellular Ca2+ activities of 10(-6) and 10(-7) M, according to a log relation. The microelectrodes are non-destructive, even in rather small cells, and can be used to monitor Ca2+ changes during experimental interventions.     

Fate Mapping Identifies the Origin of SHF/AHF Progenitors in the Chick Primitive Streak

Heart development depends on the spatio-temporally regulated contribution of progenitor cells from the primary, secondary and anterior heart fields. Primary heart field (PHF) cells are first recruited to form a linear heart tube; later, they contribute to the inflow myocardium of the four-chambered heart. Subsequently cells from the secondary (SHF) and anterior heart fields (AHF) are added to the heart tube and contribute to both the inflow and outflow myocardium. In amniotes, progenitors of the linear heart tube have been mapped to the anterior-middle region of the early primitive streak. After ingression, these cells are located within bilateral heart fields in the lateral plate mesoderm. On the other hand SHF/AHF field progenitors are situated anterior to the linear heart tube, however, the origin and location of these progenitors prior to the development of the heart tube remains elusive. Thus, an unresolved question in the process of cardiac development is where SHF/AHF progenitors originate from during gastrulation and whether they come from a region in the primitive streak distinct from that which generates the PHF. To determine the origin and location of SHF/AHF progenitors we used vital dye injection and tissue grafting experiments to map the location and ingression site of outflow myocardium progenitors in early primitive streak stage chicken embryos. Cells giving rise to the AHF ingressed from a rostral region of the primitive streak, termed region ‘A’. During development these cells were located in the cranial paraxial mesoderm and in the pharyngeal mesoderm. Furthermore we identified region ‘B’, located posterior to ‘A’, which gave rise to progenitors that contributed to the primary heart tube and the outflow tract. Our studies identify two regions in the early primitive streak, one which generates cells of the AHF and a second from which cardiac progenitors of the PHF and SHF emerge.     

Using multi-parameter flow cytometry as a novel approach for physiological characterization of bacteria in microbial fuel cells

This work demonstrates, for the first time, the potential of using multi-parameter flow cytometry to monitor changes in the microbial cytoplasmic membrane integrity and polarization during microbial fuel cells (MFC) operation. Such information is crucial to follow the dynamics of bacteria colonization of the electrodes and their viability maintenance during electrical current production. Interestingly, the results show that during voltage production, the electrostatic gradients of the bacteria cytoplasmic membrane are disturbed, leading to depolarization of a subpopulation (where less than 40% of the cells were polarized). Once the voltage dropped, due to substrate limitation, several cells in the anode supernatant restored their polarized state. This process was reversible and observed over more than 4 cycles of fresh substrate addition. Similar power outputs induced similar membrane polarization results, regardless of the substrate used. The percentage of non-viable cells was maintained constant during current production. This study opens new opportunities to monitor cell behavior, and thus increase the knowledge of dynamic mechanisms responsible for current production at the individual cell level. This technique could be of great interest for the development of new MFC configurations and optimization of MFC operation conditions toward increased performance.     

Some ethical issues at the population level raised by 'soft' eugenics, euphenics, and isogenics.

It is argued that at the population level there are three central genetic developments raising ethical issues. The first is the emergence of 'soft' eugenics, due primarily to the increasing ability to detect carriers of genetic diseases, to monitor their pregnancies, and to provide the option to abort a fetus predisposed to major genetic disease. The second development is the recognition of the extent to which many serious diseases of adult life are due to a disturbance of ancient genetic homeostatic mechanisms due to changing life style, raising the question of whether a society that increasingly pays the medical bills should attempt to impose healthier standards of living on its members. Such an attempt at 'euphenics' may be thought of as the antithesis to eugenics. The third development relates to recognition of the need to regulate the size of the earth's population to numbers that can be indefinitely sustained; this regulation in a fashion (isogenic) that will preserve existing genetic diversity.     

Blood pressure and heart rate determination by radiotelemetry in mice

Mice are not commonly used in cardiovascular physiology, especially in space physiology because of methodological problems. The initial studies that have monitored arterial pressure and heart rate in mice used the tail cuff plethysmography method or classical catheterization techniques with a catheter liable to an external pressure transducer. But for long term arterial pressure measurements the studies have been facilitated by the development of radiotelemetry. This is a less constraining method as classical one allowing to monitor in continuous in freely moving animal blood pressure, heart rate and temperature. This technique allows to record these parameters thank to an implanted transmitter without physical connection with the monitoring system. The aim of this work was to valid the use of the radiotelemetry in mice to evaluate arterial blood pressure and heart rate during different stress conditions (but only control data are described in this paper).     

Nkx2-5- and Isl1-expressing cardiac progenitors contribute to proepicardium

Correct delineation of the hierarchy of cardiac progenitors is a key step to understanding heart development, and will pave the way for future use of cardiac progenitors in the treatment of heart disease. Multipotent Nkx2-5 and Isl1 cardiac progenitors contribute to cardiomyocyte, smooth muscle, and endothelial lineages, which constitute the major lineages of the heart. Recently, progenitors located within the proepicardium and epicardium were reported to differentiate into cardiomyocytes, as well as smooth muscle and endothelial cells. However, the relationship of these proepicardial progenitors to the previously described Nkx2-5 and Isl1 cardiac progenitors is incompletely understood. To address this question, we performed in vivo Cre-loxP-based lineage tracing. Both Nkx2-5- and Isl1-expressing progenitors contributed to the proepicardium and expressed Wt1 and Tbx18, markers of proepicardial progenitor cells. Interestingly, Nkx2-5 knockout resulted in abnormal proepicardial development and decreased expression of Wt1, suggesting a functional role for Nkx2-5 in proepicardium formation. Taken together, these results suggest that Nkx2-5 and/or Isl1 cardiac progenitors contribute to proepicardium during heart development.     

Retinoids--their metabolites, action, and role in heart development

Retinoids constitute a group of active compounds known as vitamin A. Apart from an unquestionable function in adults, retinoids also play a profound role in many events during embryonic development for instancje in axial patterning and organogenesis. Retinoic acid is the most active biological form of vitamin A. Its signaling both in adults and during embryonic development occurs at different levels through interaction with specific proteins and nuclear receptors. Retinoic acid signaling in heart development occurs mostly via interaction with secondary heart field cells by restricting their spatial expansion and controlling proper addition of these cells to the cardiac tube. This signal requires precise level of local retinoic acid, excess or insufficiency of which causes various malformations of the embryo and embryonic heart. Although retinoid signaling in the developing heart is a highly significant developmental factor, it is not yet fully understood. The following review summarises recent developments regarding this subject.