Transient oxygen uptake response to exercise characterizes functional capacity of the cardiocirculatory system in patients with chronic heart failure: a random stimulus approach.

The transient response of oxygen uptake (VO2) to submaximal exercise, known to be abnormal in patients with cardiovascular disorders, can be useful in assessing the functional status of the cardiocirculatory system, however, a method for evaluating it accurately has not yet been established. As an alternative approach to the conventional test at constant exercise intensity, we applied a random stimulus technique that has been shown to provide relatively noise immune responses of system being investigated. In 27 patients with heart failure and 24 age-matched control subjects, we imposed cycle exercise at 50 W intermittently according to a pseudo-random binary (exercise-rest) sequence, while measuring breath-by-breath VO2.

Regional cerebral blood flow during rewarming of cardiopulmonary bypass correlates with posthypothermic regional glucose use.

Background And Objectives: Although global measurements of cerebral blood flow and metabolism during and after profoundly hypothermic cardiopulmonary bypass have been performed both in experimental animals and in human beings, little is known about their regional changes. The purpose of this study was to investigate the changes in regional cerebral blood flow during profoundly hypothermic cardiopulmonary bypass and regional cerebral glucose use after cardiopulmonary bypass.

Methods: We measured regional cerebral blood flow with positron emission tomography during both the cooling (n=5) and rewarming (n=5) of hypothermic cardiopulmonary bypass in anesthetized dogs by continuously infusing 15O-labeled water.

The brain is a possible target for an angiotensin-converting enzyme inhibitor in the treatment of chronic heart failure.

Background: Although many lines of evidence have shown beneficial effects of angiotensin-converting enzyme (ACE) inhibitors on patients with chronic heart failure (CHF) after myocardial infarction (MI), the target of ACE inhibitors still remains unclear. The objectives of the present study were to evaluate the dipsogenic response to centrally administered angiotensin and to examine the effect of central administration of an ACE inhibitor on cardiac remodeling in rats with CHF after large MI.

Methods And Results: The drinking responses to intracerebroventricular (i.

Cholinesterase affects dynamic transduction properties from vagal stimulation to heart rate.

Recent investigations in our laboratory using a Gaussian white noise technique showed that the transfer function representing the dynamic properties of transduction from vagus nerve activity to heart rate had characteristics of a first-order low-pass filter. However, the physiological determinants of those characteristics remain to be elucidated. In this study, we stimulated the vagus nerve according to a Gaussian white noise pattern to estimate the transfer function from vagal stimulation to the heart rate response in anesthetized rabbits and examined how changes in acetylcholine kinetics affected the transfer function.

Accumulation of cAMP augments dynamic vagal control of heart rate.

Recent investigations in our laboratory using a Gaussian white noise perturbation technique have shown that simultaneous sympathetic stimulation augmented the gain of the transfer function from vagal stimulation frequency to heart rate response. However, the mechanism of that augmentation remains to be elucidated. In this study, we examined in anesthetized rabbits how three pharmacological interventions known to cause intracellular accumulation of cAMP affected the transfer function.

Dynamic sympathetic regulation of left ventricular contractility studied in the isolated canine heart.

We investigated the dynamic sympathetic regulation of left ventricular end-systolic elastance (Ees) using an isolated canine ventricular preparation with functioning sympathetic nerves intact. We estimated the transfer function from both stellate ganglion stimulation to Ees and ganglion stimulation to heart rate (HR) for both left and right ganglia by means of the white noise approach and transformed those transfer functions into corresponding step responses. The HR response was much larger with right sympathetic stimulation than with left sympathetic stimulation (4.

Preload and incident angle independent index of left ventricular contractility determined by continuous wave Doppler echocardiography.

Although left ventricular dP/dtmax can be accurately assessed using Doppler echocardiography, the fact that Doppler-derived dP/dtmax depends both on preload and Doppler incident angle limits its clinical value. We investigated the clinical usefulness of Doppler-derived (dP/dtmax)/IP (IP, isovolumic pressure), which is known to be relatively insensitive to preload and theoretically independent of the incident angle in 9 subjects. We conclude that Doppler-derived (dP/dtmax)/IP is relatively insensitive to both the incident angle and preload.

Norepinephrine efflux evoked by potassium chloride in cat sympathetic nerves: dual mechanism of action.

Using a dialysis technique, prominent efflux of norepinephrine (NE) from cardiac sympathetic nerve endings was observed under local administration of potassium chloride (KCl, 100 mM). KCl induced NE efflux was suppressed by omega-conotoxin GVIA or desipramine but residual efflux of NE was still detectable. In the presence of omega-conotoxin GVIA, KCl induced efflux of NE was augmented by pretreatment with reserpine, indicating that this efflux of NE was derived from axoplasma with neurotransporter.

ESPVR of in situ rat left ventricle shows contractility-dependent curvilinearity.

We developed a miniaturized conductance catheter for in situ rat left ventricular (LV) volumetry. After the validation study of the conductance volumetry in 11 rats, we characterized the end-systolic pressure-volume relationship (ESPVR) in 24 sinoaortic-denervated, vagotomized and urethan-anesthetized rats. Stroke volume (SV) measured with the conductance catheter correlated closely with that measured by electromagnetic flowmetry (r > 0.

Noninvasive differential diagnosis between chronic pulmonary thromboembolism and primary pulmonary hypertension by means of Doppler ultrasound measurement.

Objectives: The purpose of this investigation was to differentiate chronic pulmonary thromboembolism (CPTE) from primary pulmonary hypertension (PPH) by using noninvasive Doppler ultrasound techniques.

Background: A recent investigation in our laboratory has indicated that the pulmonary artery (PA) pressure waveform conveys significant information that can be used to differentiate CPTE from PPH. Pulse pressure was markedly larger in CPTE than in PPH, indicating that the major occlusive site is central in CPTE and peripheral in PPH.

A new method to measure regional myocardial time-varying elastance using minute vibration.

We developed a new technique to evaluate regional myocardial elastance using minute vibration. In 13 isolated cross-circulated canine hearts, we applied small sinusoidal vibrations of displacement to the left ventricular surface at various frequencies (50-100 Hz). Using the measured displacement and force between the vibrator head and myocardium, we derived myocardial elastance on the basis of the equation of motion for a given moment of the cardiac cycle.

Experimental myelitis caused by herpes simplex virus type 2 in C57BL/6N and BALB/cN mice.

Intraperitoneal and intracranial inoculation of herpes simplex virus type 2 (HSV 2) into BALB/cN and C57BL/6N mice was carried out to induce experimental myelitis. The myelitis was clearly observed in C57BL/6N mice following intraperitoneal inoculation. Within 24 hours before death, the mice showed urinary and rectal incontinence and paraplegia of the hind legs.

Estimation of arterial mechanical properties from aortic and tonometric arterial pressure waveforms.

Although arterial mechanical properties have been evaluated using arterial input impedance, the relative difficulty in accurate flow measurement made the value of impedance somewhat limited. To develop an alternative method to evaluate arterial mechanical properties, we analyzed the aortic pressure (AoP)-radial arterial pressure (RAP) relationship because of relative ease in obtaining peripheral pressure waveform by tonometry. In 8 patients we simultaneously recorded aortic root and radial arterial pressure waveforms.

Dynamic transduction properties of in situ baroreceptors of rabbit aortic depressor nerve.

We developed a new method for isolating in situ baroreceptor regions of the rabbit aortic depressor nerve (ADN) and estimated the transfer function from pressure to afferent nerve activity in the frequency range of 0.01-5 Hz by a white noise technique. Complete isolation of the baroreceptor area of the right ADN was made in situ by ligation of the innominate artery and the right subclavian and common carotid arteries.

Negative inotropic effect of basic fibroblast growth factor on adult rat cardiac myocyte.

Background: Basic fibroblast growth factor (bFGF) is highly expressed in the myocardium in some cardiac disorders, such as ischemia-reperfusion and cardiac allograft rejection. However, whether bFGF has any effects on myocardial contraction is unknown.

Methods And Results: We examined the effects of bFGF on myocardial contractility using isolated adult rat cardiac myocyte preparations.

Interstitial norepinephrine level by cardiac microdialysis correlates with ventricular contractility.

Although a cardiac microdialysis technique has made it possible to estimate myocardial interstitial norepinephrine (NE) levels, whether such levels reflect the local NE concentration that would regulate ventricular contractility remains unknown. If such levels indicate locally regulating NE concentration, then ventricular contractility should be a unique function of the interstitial NE level regardless of how the latter is altered. To examine this hypothesis, we altered the interstitial NE level endogenously by stimulating the cardiac sympathetic nerves at 1 and 2 Hz while monitoring ventricular contractility.

Closed-loop identification of carotid sinus baroreflex open-loop transfer characteristics in rabbits.

In the circulatory system, a change in blood pressure operates through the baroreflex to alter sympathetic efferent nerve activity, which in turn affects blood pressure. Existence of this closed feedback loop makes it difficult to identify the baroreflex open-loop transfer characteristics by means of conventional frequency domain approaches. Although several investigators have demonstrated the advantages of the time domain approach using parametric models such as the autoregressive moving average model, specification of the model structure critically affects their results.

Vagal stimulation decreases left ventricular contractility mainly through negative chronotropic effect.

Although an increase in vagal tone is known to slow heart rate (HR), whether it also depresses left ventricular contractility through mechanisms independent of the bradycardic effect remains unknown. The chief aim of this investigation, therefore, was the separation of the observed vagally mediated depression of ventricular contractility into direct and indirect vagal effects, the latter resulting via negative chronotropism. In 12 anesthetized, sympathectomized open-chest rabbits, we measured left ventricular contractility through determination of the end-systolic elastance (Ees).

Inhibition of NO synthesis does not potentiate dynamic cardiovascular response to sympathetic nerve activity.

We examined whether the inhibition of nitric oxide (NO) synthesis potentiates the dynamic sympathetic regulation of the cardiovascular system through the baroreflex. In anesthetized rabbits, we imposed random pressure perturbations on the isolated carotid sinuses to evoke random changes in sympathetic nerve activity (SNA). We estimated the transfer functions from SNA to both aortic pressure (AoP) and heart rate (HR).

omega-Conotoxin GVIA and desipramine insensitive norepinephrine efflux from cardiac sympathetic nerve terminal.

Using dialysis technique, prominent accumulation of norepinephrine (NE) in the myocardial interstitial space was observed under local administration of a monoamine oxidase inhibitor (pargyline, 10 mM), and a vesicle uptake inhibitor (reserpine, 10 microM). Accumulation of NE in the myocardial interstitial space was associated with a reduction of dihydroxyphenylglycol levels. Pretreatment with omega-conotoxin GVIA (10 microM) or desipramine (10 microM) did not suppress this response.

Vasodilator effects of adrenomedullin on small pulmonary arteries and veins in anaesthetized cats.

1. This study was conducted to determine adrenomedullin (AM) action sites in the pulmonary vascular bed and the relation between its vasodilator effects and vascular tone. Moreover, an examination was made into whether calcitonin gene-related peptide (CGRP) receptors mediate pulmonary vasodilatations induced by AM.

Inhibition of NO synthesis minimally affects the dynamic baroreflex regulation of sympathetic nerve activity.

The purpose of this investigation was to examine the role of nitric oxide (NO) in the dynamic baroreflex regulation of cardiac sympathetic nerve activity. In anesthetized rabbits, we imposed random pressure perturbations on the isolated carotid sinuses before and after the intravenous administration of NG-monomethyl-L-arginine. We characterized the dynamic properties relating carotid sinus pressure input to sympathetic nerve activity by means of a transfer function analysis.

Dynamic vagosympathetic interaction augments heart rate response irrespective of stimulation patterns.

We previously demonstrated that tonic stimulation of either the sympathetic or the vagal nervous system augmented the dynamic heart rate response to the other of the two systems. We characterized the phenomenon as bidirectional augmentation of heart rate regulation. The question remained unanswered, however, as to whether such augmentation could occur under simultaneous dynamic stimulation of the two systems.

Characteristics of pulmonary artery pressure waveform for differential diagnosis of chronic pulmonary thromboembolism and primary pulmonary hypertension.

Objectives: The accurate diagnosis of chronic pulmonary thromboembolism (CPTE) is a prerequisite for life-saving surgical interventions. To help in the differential diagnosis of CPTE and primary pulmonary hypertension (PPH), we characterized the configuration of the pulmonary artery pressure waveform.

Background: Because CPTE predominantly involves the proximal arteries, whereas PPH involves the peripheral arteries, we hypothesized that patients with CPTE would have stiff or high resistance proximal arteries, whereas those affected by PPH would have high resistance peripheral arteries.

A new, concise dialysis approach to assessment of cardiac sympathetic nerve terminal abnormalities.

We applied a dialysis technique to the hearts of anesthetized cats and examined whether the concentration of dialysate norepinephrine (NE) reflected NE disposition at the cardiac sympathetic nerve terminals. Dialysis probes were implanted in the left ventricular wall, and dialysate NE concentrations were measured as an index of myocardial interstitial NE levels. Stimulation of stellate ganglia significantly increased dialysate NE responses that were suppressed by local administration of an NE-releasing inhibitor (omega-conotoxin GVIA, 10 microM).