Cardiac-restricted expression of the carboxyl-terminal fragment of GRK3 Uncovers Distinct Functions of GRK3 in regulation of cardiac contractility and growth: GRK3 controls cardiac alpha1-adrenergic receptor responsiveness

G protein-coupled receptor kinase-2 and -3 (GRK2 and GRK3) in cardiac myocytes catalyze phosphorylation and desensitization of different G protein-coupled receptors through specificity controlled by their carboxyl-terminal pleckstrin homology domain. Although GRK2 has been extensively investigated, the function of cardiac GRK3 remains unknown. Thus, in this study cardiac function of GRK3 was investigated in transgenic (Tg) mice with cardiac-restricted expression of a competitive inhibitor of GRK3, i.e. the carboxyl-terminal plasma membrane targeting domain of GRK3 (GRK3ct). Cardiac myocytes from Tg-GRK3ct mice displayed significantly enhanced agonist-stimulated alpha(1)-adrenergic receptor-mediated activation of ERK1/2 versus cardiac myocytes from nontransgenic littermate control (NLC) mice consistent with inhibition of GRK3. Tg-GRK3ct mice did not display alterations of cardiac mass or left ventricular dimensions compared with NLC mice. Tail-cuff plethysmography of 3- and 9-month-old mice revealed elevated systolic blood pressure in Tg-GRK3ct mice versus control mice (3-month-old mice, 136.8 +/- 3.6 versus 118.3 +/- 4.7 mm Hg, p < 0.001), an observation confirmed by radiotelemetric recording of blood pressure of conscious, unrestrained mice. Simultaneous recording of left ventricular pressure and volume in vivo by miniaturized conductance micromanometry revealed increased systolic performance with significantly higher stroke volume and stroke work in Tg-GRK3ct mice than in NLC mice. This phenotype was corroborated in electrically paced ex vivo perfused working hearts. However, analysis of left ventricular function ex vivo as a function of increasing filling pressure disclosed significantly reduced (dP/dt)(min) and prolonged time constant of relaxation (tau) in Tg-GRK3ct hearts at elevated supraphysiological filling pressure compared with control hearts. Thus, inhibition of GRK3 apparently reduces tolerance to elevation of preload. In conclusion, inhibition of cardiac GRK3 causes hypertension because of hyperkinetic myocardium and increased cardiac output relying at least partially on cardiac myocyte alpha(1)-adrenergic receptor hyper-responsiveness. The reduced tolerance to elevation of preload may cause impaired ability to withstand pathophysiological mechanisms of heart failure.     

The effect of craniotomy on the intracranial hemodynamics and cerebrospinal fluid dynamics in humans

The goal of the research was to study the effect of the trephination of the human cranial cavity on the intracranial hemodynamics and cerebrospinal fluid (CSF) dynamics. The sample comprised 15 patients of a neurosurgical clinic in whom a trephine opening in the cranial bones was made for medical indications. In these patients, at rest and during an appropriate functional load, we recorded pulse changes in blood circulation (by transcranial Doppler sonography) and in the ratio between the pulse fluctuations in the blood and CSF volumes (by rheoencephalography) before and after surgery. Simultaneous recording of these parameters followed by computer pattern and phase analyses allowed evaluation of the complex biomedical compliance of the cranium during successive phases of the cardiac rhythm: the inflow of arterial blood, the redistribution of blood/CSF volumes, and the outflow of venous blood. Analysis of the results showed a beneficial influence of craniotomy on the intracranial hemodynamics and CSF dynamics. This was reflected in an increase in the cranial compliance, which increased the pulse increment in the volume of the arterial blood in the skull almost twofold. After craniotomy, the cross-flow of CSF between the cranial and spinal cavities decreased significantly, giving way to volumetric compensatory translocations of blood and CSF within the cranial cavity per se during the cardiac cycle, which increased the intracranial utilization of the energy of the cardiac output and contributed to the outflow of venous blood from the cranium. The results suggest a beneficial effect of craniotomy on the physiological mechanisms of the circulatory and metabolic maintenance of the brain activity.     

The pharmacodynamic response of the basal skin potential to quinidine gluconate

The basal skin potential (BSP) was explored as an indirect means of continuously monitoring the cardiac response of quinidine gluconate. A method was developed to follow the BSP using a high impedance, recording polygraph and nonpolarizing calomel electrodes. Intravenous administration of quinidine gluconate caused time dependent changes in the BSP. Further studies showed that blood levels during the elimination phase and the QT interval of the electrocardiogram (ECG) over their entire time period were highly correlated with the BSP. Optimal correlation with the QT interval occurred when the BSP curve was shifted to earlier times by approximately 10 minutes, reflecting possible differences in the accessibility or mechanism of the respective pharmacologic compartments. Further application of the BSP for pharmacodynamic monitoring will require electrode refinements and an increased understanding of its mechanism of action.     

Chronotherapy in Coronary Heart Disease: Comparison of Two Nitrate Treatments

The purpose of this study was to assess the ischemic burden and the hemodynamic changes during daily activities in patients with coronary heart disease. Three exercise tests were performed during the day (10:00 a.m., 2:00 p.m., 6:00 p.m.), recording ST-segment depression, pulmonary artery pressure, pulmonary wedge pressure, and cardiac output as well as heart rate and systemic blood pressure during placebo and nitrate therapy. With placebo as well as nitrate therapy there was a gradual increase of ischemia and preload and a decrease of cardiac output during the day. High nitrate concentrations led to a significant reduction of both preload and ST depression with a marked circadian phase dependency of cardiovascular effects.     

Chronotherapy in Coronary Heart Disease: Comparison of Two Nitrate Treatments

The purpose of this study was to assess the ischemic burden and the hemodynamic changes during daily activities in patients with coronary heart disease. Three exercise tests were performed during the day (10:00 a.m., 2:00 p.m., 6:00 p.m.), recording ST-segment depression, pulmonary artery pressure, pulmonary wedge pressure, and cardiac output as well as heart rate and systemic blood pressure during placebo and nitrate therapy. With placebo as well as nitrate therapy there was a gradual increase of ischemia and preload and a decrease of cardiac output during the day. High nitrate concentrations led to a significant reduction of both preload and ST depression with a marked circadian phase dependency of cardiovascular effects.     

A simple VCG system with temporal dimension,directional reference and display of component loops

A vectorcardiogram (VCG) represents the cardiac electrical activity as continuous vector loops in three mutually perpendicular planes, namely frontal, transverse and sagittal.This technical note describes a simple system developed to record VCG with an ordinary x-y oscilloscope and simple camera. Facilities exist for recording VCG with temporal dimension, directional reference and display of specific component loops of a cardiac cycle. The system is in use for recording VCG at rest and during stress tests involving exercise and hypoxia at simulated altitude. Its performance has been found satisfactory and the system highly reliable.     

心脏收缩时间间期与冠状动脉狭窄程度或范围的相关性研究

心脏收缩时间间期(STI)通过单笔心电图机叠加记录ECG、心音图和颈动脉图后测得。对83例患者进行了STI均值与选择性冠状动脉造影(CAG)及左室造影的相关研究。患者除陈旧性心肌梗塞及室壁瘤外,根据冠状动脉(CA)狭窄程度而分组。STI随CA狭窄程度及范围的增加而显著异常,提示心功能随心肌缺血程度加重而进行性恶化。左室射血分数(LVEF)的降低也支持这一点。CA狭窄程度、范围与射血前时间/左室射血时间(PEP/LVET)呈正相关。在决定左室功能的异常方面,PEP/LVET和LVEF的临床意义完全相同。提示STI在评价冠心病心功能上是有用的。排除影响STI的某些因素后,PEP/LVET≥0.38可作为判断冠心病左心功能减退的标志。但轻度CA狭窄患者的STI可正常,这可能与静息时尚有足够的CA贮备力有关。     

Electrotropic acetylcholine action on the mammalian auricle by means of the "phase plane" trajectories of the action potential

A single sucrose gap techniques has been used to study action potentials and phase plane trajectories of them in atrial trabeculae of the rabbit. Using polynomial representations of current-voltage relationships a model of membrane action potential of atrial myocardial fibres is described and allows an interpretation of recording data from the phase plane trajectories. Our findings show: 1. Increasing extracellular calcium concentration increases a potassium conductivity of the atrial membrane. 2. An anomalous rectification concerning repolarizing currents in atrial fibres decreases with increasing extracellular calcium. 3. Acetylcholine (3.10(-4) g.cm-3) abolishes the anomalous rectification. These results are discussed in relation to previous electrophysiological studies of negative electrotropic effects of acetylcholine in cardiac muscle.     

Effect of temporary hypovolemia on the early central pooling of the blood circulation following resuscitation and the survival of animals experiencing clinical death

The experiments were conducted on cats under pentobarbitone sodium anesthesia (40 mg/kg). The effect of 30-min hypovolemia (Wiggerse's model, 13.3 kPa or 100 mm Hg) on the cardiac output, its main fractions and the survival of animals recovered after clinical death (5 min) were studied. Hypovolemia was induced after cardiac contractions were recovered. In experimental (19 cats) and control (23 cats) studies clinical death was caused by arterial blood loss. The animals had been previously subject to hemorrhagic hypotension (according to Wiggerse, 6.7 kPa or 50 mm Hg, for 30 minutes). Temporary exclusion of part of blood volume from the circulation was found to abolish the phase of cardiac output increase in the postresuscitation period, attenuate the reaction of blood circulation centralization, improve the course of reparative processes and increase the survival of animals recovered after clinical death.     

Change of salinity of medium as a function loading in estimating functional state of the crayfish Astacus leptodactylus

Benthic invertebrates are widely used in toxicological research and in automated biomonitoring systems for assessing water quality. However, development of criteria of physiological performance is still required for identification of candidate animals. Assessment of an organism’s performance proposed in the paper is based on standard test treatments of different magnitude and exposure time. With freshwater crustaceans, such a treatment (functional stress) may be performed by changing water salinity by 1‰ through addition of sodium chloride. A non-invasive cardiac rhythm recording method has been used to reveal the response of the cardiovascular system of crayfish to this treatment.     

Analysis of the timing parameters of blood flow in the carotid basin arteries of hypertensive patients

Vascular duplex ultrasound study with simultaneous ECG recording was performed to estimate the timing parameters of blood flow in the common carotid, internal carotid, and middle cerebral arteries in patients with grades 1 and 2 arterial hypertension. There was an increase in the blood flow acceleration phase index in the common carotid and middle cerebral arteries and a reduction in the systolic phase index in the internal carotid arteries. There were correlations of phasic blood flow parameters in the extra- and intracranial arteries with age and lipidogram readings.     

Effect of cimetidine on the heart conduction system]

An effect of cimetidine on ECG records has been investigated in a group of 40 patients with gastric or duodenal ulcers and coexisting circulatory disorders. For this purpose ECG has been recorded with Holter's technique (Medilog 2000) together with ECG-recording using high amplifying technique. An intravenous injection of 200 mg of cimetidine produced in some of patients inhibition of the sinus rhythm atrio-ventricular conduction disturbances as well as changes in the end phase of ECG ventricular image. The authors suggest, that intravenous administration of cimetidine to patients with cardiac diseases should be monitored with ECG recording.     

Pulse wave analysis as an experimental tool to clinical application: past and present (review)

Pulse examination by palpation of a peripheral artery against a bony prominence is the most commonly used and widely accepted method. However this is subjective and thus prone to errors. Although pulse waveform was recorded in the 19th century, it did not gain popularity because of inconvenience in using the recording instruments and the absence of a sound theory to explain the wave forms recorded. Sphygmomanometry for recording blood pressure gained popularity as it was easy to record and had a sound theoretical background. Sphygmomanometry provides two extreme values of blood pressure but does not give a true representation of the blood pressure changes occurring in the entire cardiac cycle. Recently there has been resurgence in the analysis of the graphical recording of the pulse wave. Photoplethysmography is becoming a widely accepted technique in assessing the volume pulse. The whole review is about historical background, non-invasive methods of pulse recording, relation of the digital volume pulse to the pressure pulse and the advantages of recording the pressure pulse.     

The Effects of Involuntary Respiratory Contractions on Cerebral Blood Flow during Maximal Apnoea in Trained Divers

The effects of involuntary respiratory contractions on the cerebral blood flow response to maximal apnoea is presently unclear. We hypothesised that while respiratory contractions may augment left ventricular stroke volume, cardiac output and ultimately cerebral blood flow during the struggle phase, these contractions would simultaneously cause marked ‘respiratory’ variability in blood flow to the brain. Respiratory, cardiovascular and cerebrovascular parameters were measured in ten trained, male apnoea divers during maximal ‘dry’ breath holding. Intrathoracic pressure was estimated via oesophageal pressure. Left ventricular stroke volume, cardiac output and mean arterial pressure were monitored using finger photoplethysmography, and cerebral blood flow velocity was obtained using transcranial ultrasound. The increasingly negative inspiratory intrathoracic pressure swings of the struggle phase significantly influenced the rise in left ventricular stroke volume (R ² = 0.63, P<0.05), thereby contributing to the increase in cerebral blood flow velocity throughout this phase of apnoea. However, these contractions also caused marked respiratory variability in left ventricular stroke volume, cardiac output, mean arterial pressure and cerebral blood flow velocity during the struggle phase (R ² = 0.99, P<0.05). Interestingly, the magnitude of respiratory variability in cerebral blood flow velocity was inversely correlated with struggle phase duration (R ² = 0.71, P<0.05). This study confirms the hypothesis that, on the one hand, involuntary respiratory contractions facilitate cerebral haemodynamics during the struggle phase while, on the other, these contractions produce marked respiratory variability in blood flow to the brain. In addition, our findings indicate that such variability in cerebral blood flow negatively impacts on struggle phase duration, and thus impairs breath holding performance.     

EEG alpha indices depending on the menstrual cycle phase and salivary progesterone level

The effects of neurohumoral status on the EEG α activity were studied in 78 women (18–27 years old) during one or two menstrual cycles using a within-subjects design. The psychometric and electroencephalographic (EEG) indices of α waves, basal body temperature, and salivary progesterone level were monitored every two or three days. The menstrual and follicular recording sessions occurred before the basal temperature rise caused by ovulation, the luteal recording session occurred after the increase in progesterone level by more than 20% compared to the day before, and the premenstrual recording sessions occurred after the decrease in progesterone level by more than 20% compared to the day before. The EEG, electromyographic (EMG) and electrocardiographic (ECG) characteristics of cognitive efficiency and psycho-emotional tension were recorded at rest and during task performance. The experiments were started in the menstrual phase in half the subjects and in the luteal phase in the other half. Psychometric characteristics, EEG α activity, EMG and ECG indices were compared for all the five phases at rest and in response to cognitive task performance. The results have shown that all psychometric and α EEG indices are menstrual-cycle-dependent. The maximum cognitive fluency, α peak frequency, α band width, and power in the α₂ frequency band are observed in the luteal phase, while the maximum power in the low-frequency α₁ band, as well as visual and cognitive activation calculated from α power reduction, are observed in the follicular phase of the menstrual cycle. The hypothesis that EEG α activity depends on the neurohumoral status is supported by the positive correlation of salivary progesterone level with the α peak frequency and the power in the α₂ band and its negative correlation with the power in the α₁ band. It is concluded that psycho-physiological recording sessions in women must be carried out with due consideration of the menstrual cycle phase.     

Role of oxidative stress in alterations of mitochondrial function in ischemic-reperfused hearts

To study the mechanisms of mitochondrial dysfunction due to ischemia-reperfusion (I/R) injury, rat hearts were subjected to 20 or 30 min of global ischemia followed by 30 min of reperfusion. After recording both left ventricular developed pressure (LVDP) and end-diastolic pressure (LVEDP) to monitor the status of cardiac performance, mitochondria from these hearts were isolated to determine respiratory and oxidative phosphorylation activities. Although hearts subjected to 20 min of ischemia failed to generate LVDP and showed a marked increase in LVEDP, no changes in mitochondrial respiration and phosphorylation were observed. Reperfusion of 20-min ischemic hearts depressed mitochondrial function significantly but recovered LVDP completely and lowered the elevated LVEDP. On the other hand, depressed LVDP and elevated LVEDP in 30-min ischemic hearts were associated with depressions in both mitochondrial respiration and oxidative phosphorylation. Reperfusion of 30-min ischemic hearts elevated LVEDP, attenuated LVDP, and decreased mitochondrial state 3 and uncoupled respiration, respiratory control index, ADP-to-O ratio, as well as oxidative phosphorylation rate. Alterations of cardiac performance and mitochondrial function in I/R hearts were attenuated or prevented by pretreatment with oxyradical scavenging mixture (superoxide dismutase and catalase) or antioxidants [N-acetyl-L-cysteine or N-(2-mercaptopropionyl)-glycine]. Furthermore, alterations in cardiac performance and mitochondrial function due to I/R were simulated by an oxyradical-generating system (xanthine plus xanthine oxidase) and an oxidant (H(2)O(2)) either upon perfusing the heart or upon incubation with mitochondria. These results support the view that oxidative stress plays an important role in inducing changes in cardiac performance and mitochondrial function due to I/R.     

Active regulation of respiration and circulation in pupae of the codling moth (Cydia pomonella)

Regulation of autonomic physiological functions has been investigated by means of multisensor electronic methods, including electrocardiographic recording of heartbeat, strain-gauge recording of extracardiac hemocoelic pulsations (EHPs), anemometric recording of air passage through spiracles and respirographic recording of O(2) consumption and CO(2) output. Pupae of Cydia exhibit continuous respiration without remarkable bursts of CO(2). The dorsal vessel of these pupae exhibited regular heartbeat reversals characterized by shorter intervals of faster (forward oriented or anterograde) pulsations and longer intervals of slower (backward oriented or retrograde) peristaltic waves. The periodically repeated EHPs were present during the whole pupal interecdysial period. The internal physiological mechanisms regulating the cardiac (heartbeat) and extracardiac (EHP) pulsations were completely independent for most of the pupal instar. Simultaneous multisensor analysis revealed that the anterograde heartbeat of the dorsal vessel had similar but not identical frequency with EHPs. During advanced pharate adult development, frequency of cardiac and extracardiac pulsation periods profoundly increased until almost uninterrupted pulsation activity towards adult eclosion. At this time, the cardiac and extracardiac pulsations occasionally performed in concert, which enhanced considerably the efficacy of hemolymph circulation in pharate adults with high metabolic rates. The fastest hemolymph flow through the main body cavity was always associated with EHPs and with anterograde heartbeat. Simple physical diffusion of O(2) and CO(2) through spiracles (diffusion theory of insect respiration) does not play a significant role in pupal respiration. Instead, several kinds of regulated, mechanical ventilations of the tracheal system, including EHPs are responsible for effective tracheal ventilation.     

一套研究机械电反馈的心室压力钳系统

在心脏机械电反馈的研究中准确控制机械刺激是非常重要的。本研究室构建了一套适用于离体家兔心脏的心室压力钳系统。该系统通过计算机控制压力钳,不仅能模拟正常生理条件下左心室的压力波形,还能在心室活动周期的特定时相、以适当波形对心室施加机械刺激。该系统集心脏灌流与起搏、表面心电图记录、单相动作电位记录、心室压力钳制与测定等多种功能于一体,特别适用于器官水平上观察机械电反馈现象并探讨其机制。     

Significance of biological parameters of human blood levels of CoQ10

Ninety-one men and 143 women who were so-called normal subjects were tested for cardiac performance at rest and their blood levels of co-enzyme Q10 (CoQ10) were determined. In males, a negative relationship between progression of age and cardiac performance, and a positive relationship between progression of age and blood levels of CoQ10 were revealed. In females, a positive relationship between age and blood levels of CoQ10 was found. The mean CoQ10 blood level for both sexes was the same (0.79 +/- 0.20 micrograms/ml for males and 0.79 +/- 0.23 for females). Cardiac performance declines with age in the male population. A decreased biosynthesis and/or incorporation of CoQ10 into mitochondrial structures of muscle cells may occur with age in a normal population.