Demand dynamic bio-girdling in heart failure: improved efficacy of dynamic cardiomyoplasty by LD contraction during aortic out-flow

PURPOSE: The value of dynamic cardiomyoplasty has been brought into question by the disappointing results produced by slow contraction-relaxation cycle and possibly degeneration of the latissimus dorsi muscle (LD) secondary to temporary tenotomy and chronic daily electrical stimulation. Objective of our study is to determine whether daily periods of rest introduced by demand stimulation in the continuous contraction protocol produce systolic assistance and improve clinical results. METHODS: Twelve dynamic cardiomyoplasty patients (mean age 58.2 +/- 5.8 years, M/F=11/1, sinus rhythm/atrial fibrillation=11/1) with dilated myocardiopathy were enrolled in an unrandomized trial of Demand Dynamic Heart Bio-Girdling in a public regional teaching hospital. Periods of LD inactivity, each lasting several hours, were introduced daily on a heart rate-based demand regime. To avoid full transformation of LD, fewer impulses per day were delivered, daily providing the LD with long periods of rest (Demand light stimulation). The contractile properties were measured by transcutaneous non-invasive LD tensiomyogram interrogation (LD tensiomyogram). Bio-Girdle activation was synchronized to heart beat by combining tensiomyogram and echocardiography. Clinical, echocardiographic and hemodynamic records, as well as aortic flow measurements by Doppler aortic flow wire were taken during the follow-up. MAIN FINDINGS: Mean duration of the demand stimulation follow-up was 40.2+13.8 months. At five years, "Demand stimulation" shows: 1) no operative death; 2) 83% actuarial survival; 3) highly significant 47.4% decrease of the NYHA class (from 3.17 +/- 0.38 to 1.67 +/- 0.77, p=0.0001); 4) 41.6% improvement of LVEF (from 22.6 +/- 4.38 to 32.0 +/- 7.0, p=0.001); 5) 7.5 +/- 3.0% increase in aortic flow velocity peak in assisted vs. unassisted beats, and 6) preservation of LD from slowness (TFF value 33 +/- 7.86 at follow-up versus 15.8 +/- 11.1 Hz just before switching from continuous to demand stimulation, p=0.0001) and muscle degenerative atrophy. CONCLUSIONS: In dynamic cardiomyoplasty the demand light stimulation maintains LD contraction properties over time, produces effective systolic assistance, and improves clinical results. Demand dynamic bio-girdling is a safe and effective treatment for end-stage heart failure in selected patients.     

Provocation of ventricular ectopy by cheyne-stokes respiration in patients with heart failure

STUDY OBJECTIVES: Previous reports have suggested an association between Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) and ventricular ectopy, but there has been relatively little evidence of a cause-effect relationship. The objective of this study was to determine whether CSR-CSA directly provokes ventricular ectopy and, if so, whether it is associated with any particular phase of the CSR-CSA breathing cycle. DESIGN: We compared the frequency of ventricular premature beats (1) between the apneic and hyperpneic phases of CSR-CSA, (2) between periods of CSR-CSA and periods of regular breathing during sleep, and (3) in response to the elimination of CSR-CSA by administration of a low concentration of inhaled CO2. SETTING: Hospital-based cardiopulmonary sleep laboratory. PATIENTS: Twenty-three patients with heart failure and CSR-CSA. MEASUREMENTS AND RESULTS: Ventricular premature beats were found to occur 40% more frequently during the hyperpneic phase than the apneic phase of CSR-CSA (mean+/-SD, 7.0+/-7.4 versus 4.9+/-5.7 ventricular premature beats per minute, P = .003). Ventricular premature beat frequency was also found to be higher during periods of CSR-CSA than during periods of regular breathing occurring either spontaneously (median [25th, 75th percentile], 2.2 [1.2, 6.5] versus 1.1 [0.8, 2.0] ventricular premature beats per minute, P = .027), or induced through inhalation of CO2 (from 4.7+/-3.8 to 3.3+/-4.0 ventricular premature beats per minute, P = .048). CONCLUSIONS: CSR-CSA provokes ventricular ectopy that is most pronounced during the hyperpneic phase. Such an increase in ventricular premature beats might contribute to the higher mortality rates reported in heart failure patients with CSR-CSA.     

Histopathological findings in skeletal muscle used in human dynamic cardiomyoplasty

Patients submitted to dynamic cardiomyoplasty had an initial clinical improvement followed by a decrease in cardiac failure indices. A histopathological study of the skeletal muscle was undertaken to explain this. Latissimus dorsi fragments from 15 patients submitted to dynamic cardiomyoplasty in a 1:1 (heart beat:muscle stimulation) conditioning were analysed by light microscopy. The interval between surgery and obtaining the specimens (13 from necropsies, two from heart transplants) ranged from 37 days to 6 years. Nuclear clumps and internalization, the presence of round fibres, inflammation, and fibrosis were analysed semi-quantitatively; the thickness of muscle fibres and the percentage of tissue fat were measured by image analysis. The quantitative data were also compared, in 12 cases, with gender- and age-matched necropsy controls. The mean thickness of muscle fibres in cases and controls was 27.21+/-5.33 and 40.84+/-9.42 microm, respectively (p=0.001). The percentage of tissue fat in cases and controls was 12.04+/-12.66% and 0.93+/-0.91%, respectively (p=0.008). The duration of grafts correlated positively with the quantity of nuclear clumps (R=0.80, p<0.001) and round fibres (R=0.53, p=0.04), as well as with the percentage of tissue fat (R=0.68, p=0.005). Accordingly, a negative correlation was found between the duration of grafts and the mean diameter of fibres, characterizing muscle atrophy (R=-0.66, p=0.01). The longer the post-surgical period, the more intense the degenerative lesions. This study shows that skeletal muscle used in human dynamic cardiomyoplasty may atrophy and be replaced by fat when stimulation is synchronized to every cardiac beat. These findings could play a role in explaining the long-term results of this surgical procedure.     

Effects of intra-aortic counterpulsation on aortic wall energetics and damping: in vivo experiments

Intra-aortic balloon pumping (IABP) could modify the arterial biomechanics; however, its effects on arterial wall properties have not been fully explored. This dynamical study was designed to characterize the pressure-dependent and smooth muscle-dependent effects of IABP on aortic wall energetics in an in vivo animal model. Intra-aortic balloon pumping (1:2) was performed in six anesthetized sheep in which aortic pressure and diameter signals were measured in basal, augmented (during balloon inflation), and assisted (postaugmented) beats. Energy dissipation values in augmented and assisted beats were significantly higher than those observed in basal state (p < 0.05). Assisted beats showed a significant increase of wall damping with respect to basal and augmented beats (p < 0.05). Intra-aortic balloon pumping resulted in a significant increase of pulse wave velocity (p < 0.05) in augmented beats with respect to basal state (6.3 +/- 0.8 vs. 5.2 +/- 0.5 m x s(-1)); whereas values observed in assisted beats were significantly (p < 0.05) lower than those observed in augmented beats (4.9 +/- 0.5 vs. 6.3 +/- 0.8 m x s(-1)). Our findings show that IABP determined the pressure and smooth muscle-dependent changes in arterial wall energetics and damping properties in this animal model.     

Predictability of O2 consumption from contractility and mechanical energy of absolute arrhythmic beats in canine heart

Left ventricular (LV) O2 consumption (V(O2)) per minute is measurable for both regular and arrhythmic beats. LV V(O2) per beat can then be obtained as V(O2) per minute minute divided by heart rate per minute minute for regular beats, but not for arrhythmic beats. We have established that V(O2) of a regular stable beat is predictable by V(O2) = a PVA + b E(max) + c, where PVA is the systolic pressure-volume area as a measure of the total mechanical energy of an individual contraction and E(max) is the end-systolic maximum elastance as an index of ventricular contractility of the contraction. Furthermore, a is the O2 cost of PVA, b is the O2 cost of E(max), and c is the basal metabolic V(O2) per beat. We considered it theoretically reasonable to expect that the same formula could also predict LV V(O2) of individual arrhythmic beats from their respective PVA and E(max) with the same a, b, and c. We therefore applied this formula to the PVA - Emax data of individual arrhythmic beats under electrically induced atrial fibrillation (AF) in six canine in situ hearts. We found that the predicted V(O2) of individual arrhythmic beats highly correlated linearly with either their V(O2) (r = 0.96 +/- 0.01) or E(max) (0.97 +/- 0.03) while both also highly correlated linearly with each other (0.88 +/- 0.04). This suggests that the above formula may be used to predict LV Vo2 of absolute arrhythmic beats from their Emax and PVA under AF.     

Baseline hemodynamic and echocardiographic indices in anesthetized calves

The experimental calf model is used to assess mechanical circulatory support devices and prosthetic heart valves. Baseline indices of cardiac function have been established for the normal awake calf but not for the anesthetized calf. Therefore, we gathered hemodynamic and echocardiographic data from 16 healthy anesthetized calves (mean age, 189.0 +/- 87.0 days; mean body weight, 106.9 +/- 32.3 kg) by cardiac catheterization and noninvasive echocardiography, respectively. Baseline hemodynamic data included heart rate (65 +/- 12 beats per minute), mean aortic pressure (113.5 +/- 17.4 mm Hg), left ventricular end-diastolic pressure (16.3 +/- 38.9 mm Hg), and mean pulmonary artery pressure (21.7 +/- 8.3 mm Hg). Baseline two-dimensional echocardiographic data included left ventricular systolic dimension (3.5 +/- 0.7 cm), left ventricular diastolic dimension (5.6 +/- 0.8 cm), end-systolic intraventricular septal thickness (1.7 +/- 0.2 cm), end-diastolic intraventricular septal thickness (1.2 +/- 0.2 cm), ejection fraction (63 +/- 10%), and fractional shortening (37 +/- 10%). Doppler echocardiography revealed a maximum aortic valve velocity of 0.9 +/- 0.5 m/s and a cardiac index of 3.7 +/- 1.1 L/minute/m2. The collected baseline data will be useful in assessing prosthetic heart valves, cardiac assist pumps, new cannulation techniques, and robotics applications in the anesthetized calf model and in developing calf models of various cardiovascular diseases.     

Heart-rate-proportional oxygen consumption for constant cardiac work in dog heart

We studied whether there is an optimal heart rate (HR) that would minimize myocardial oxygen consumption (MVO2) per min for a constant minute cardiac work. We measured minute MVO2 (ml O2/min) of the left ventricle paced at increasing rates (100-200 beats/min) in 10 right-heart-bypassed dogs. In each experiment, cardiac output was kept constant with a constant-flow bypass pump, and mean aortic pressure was also kept constant by inflation or deflation of an intra-aortic balloon. Minute cardiac work was thus kept constant. Minute MVO2 was obtained as the product of mean coronary arteriovenous O2 difference and mean coronary blood flow drained from the collapsed right ventricle. Both left ventricular Emax (contractility index defined as the slope of the left ventricular end-systolic pressure-volume relation) and PVA (pressure-volume area as a measure of total mechanical energy of contraction) were obtained by an abrupt aortic occlusion method. The obtained-minute MVO2-HR relationship showed a good linear positive correlation (r = 0.824-0.995) in every heart. We accounted for this relationship by the changes in PVA and Emax that we had proposed as primary determinants of MVO2. We conclude that minute MVO2 for a constant minute cardiac work increased monotonically with increases in HR from 100 to 200 beats/min, being minimum at the lowest HR, and that this relation was ascribable to the HR-proportional increase in the MVO2 component for the excitation-contraction coupling.     

An experimental evaluation of the use of an ensemble average for the calculation of turbulence in pulsatile flow

A comparison was made between turbulence calculated by subtracting an ensemble average from the instantaneous velocity and calculations made with a high pass digital filter. Velocity was measured with a laser Doppler anemometer in vitro in the region of a normal porcine aortic valve and in patients with a hot film anemometer in the region of normal aortic valves. From the velocity obtained in patients, the absolute turbulence intensity calculated using an ensemble average of 50 beats was nearly twice the turbulence intensity calculated using a digital filter. Individual beats sometimes showed differences of 150% compared to calculations based upon the use of a digital filter. Inspection showed that the ensemble average varied widely from the actual nonfluctuating velocity. Studies in vitro showed less beat to beat variation than occurred in patients. The absolute turbulence intensity measured in vitro, when calculated using an ensemble average, was only 20% greater than calculations using a digital filter. The differences were due primarily to beat-to-beat variations of the nonfluctuating velocity, but these beat-to-beat variations were less prominent than occurred in patients. These observations suggest that ensemble averaging may not be appropriate for the calculation of turbulence, particularly in patients.     

Non-invasive evaluation of the conduit function and the buffering function of large arteries in man.

The purpose of this study was to validate a two-dimensional (2D) echography coupled range-gated Doppler system for the non-invasive measurement of internal diameter, blood flow velocity, and pulse wave velocity of peripheral arteries, such as the common carotid artery (CCA), femoral artery (FA), and brachial artery (BA) in man. The array of the ultrasonic system and the Doppler probe were attached and formed a fixed angle (38 degrees 30'). The artery was firstly visualized using the echo-graphic array probe in order to position the Doppler beam. Then, the range-gated Doppler system was used to measure both internal diameter and blood flow velocity with the sample volume position covering the internal diameter. Using a hydraulic device, there was an obvious correlation between the calculated and the measured velocities (r = 0.98). Normal values of diameter, blood flow velocity and blood flow were measured in 18 healthy volunteers. The means (+/- 1 standard deviation) was as follows: diameter, CCA = 0.636 +/- 0.027 cm, FA = 0.843 +/- 0.074 cm, BA = 0.302 +/- 0.052 cm; flow velocity, CCA = 19.5 +/- 2.1 cm s-1, FA = 11.4 +/- 1.2 cm s-1, BA = 6.7 +/- 1.0 cm s-1. Blood flows were as follows: CCA, 370.6 +/- 42.5 ml mn-1, FA 387.0 +/- 75.0 ml mn-1 and BA (wrist occlusion) 29.8 +/- 12.5 ml mn-1. The intra-observer reproducibilities for CCA, FA and BA were respectively: for diameter, 4.9%, 4.12% and 14.8%; for velocity, 8.9%, 10.6% and 10.2%. The inter-observer reproducibilities were respectively: for diameter, 5.6%, 5.4% and 11.3% for velocity, 6.5%, 5.7% and 6.3%. Simultaneous determinations of pulse wave velocity from blood flow velocity recording allowed estimations of the distensibility of these arteries. Finally, the coupled echo and range-gated Doppler system permitted non-invasive evaluation of blood flow calculated as the product of the vessel cross-sectional area and measured blood velocity and also of arterial compliance as the ratio of the cross-sectional area and the square of pulse wave velocity. Such estimations of the conduit and buffering functions of peripheral large arteries in man were shown to be more accurate for the common carotid and the femoral arteries than for the brachial artery.     

Cardiomyoplasty: long-term results in ischemic cardiomyopathy

INTRODUCTION: Cardiomyoplasty was introduced into clinical practice in 1985 by Alain Carpentier. Since then, the procedure has been performed on more than 400 patients worldwide. The latissimus dorsi muscle is prepared maintaining the vascular supply, then the muscle flap is wrapped around the heart and connected to a cardiomyostimulator. The muscle is later stimulated synchronously with ventricular systole to augment the cardiac contractility. METHODS: To evaluate the long-term outcome of cardiomyoplasty, we investigated 3 patients electively undergoing this procedure in our hospital. All of these patients (2 male, 1 female) had severe chronic heart failure which did not respond to optimal medical treatment. The mean follow-up time was 42 months (range 24 - 60). All patients showed symptoms corresponding to NYHA class III, and one patient intermittently showed class IV despite conventional medical therapy. Patients were evaluated at 6-month intervals for 2 years with right heart catheterization, radionuclide scans, echocardiography, as well as questionnaires for assessing quality of life. RESULTS: There was no operative mortality. One patient experienced sudden death 2 years after operation. There were no significant changes in hemodynamic variables at 6, 12 or 24 months after surgery, respectively. Left ventricular ejection fraction increased from 20.0 ( 9.2 to 40.0 +/- 7.1 % (p = 0.05) 1 year after operation. Considerable improvement of symptoms was seen in all, and 1 patient returned to work. NYHA-class decreased from 3.1 to 2.0 (p = 0.02). CONCLUSIONS: Following cardiomyoplasty, patients may exhibit impressive clinical improvement with less striking changes of objective hemodynamic parameters. Thus, in our patients, dynamic cardiomyoplasty improves quality of life. We do not consider this treatment to be an alternative to heart transplantation. It does, however, provide a therapeutic option for patients for whom transplantation is contraindicated.     

Quantification of aortic regurgitation by Doppler echocardiography: a new method evaluated in pigs

We have developed a method to quantify aortic regurgitant orifice and volume, based on measurements of the velocity of the regurgitant jet, aortic systolic flow, the systolic and diastolic arterial pressures, a Windkessel arterial model, and a parameter estimation technique. In six pigs we produced aortic regurgitant flows between 2·1 and 17·8 ml per beat, i.e. regurgitant fractions from 0·06 to 0·58. Pulmonary and aortic flows were measured with electromagnetic flow probes, aortic pressure was measured invasively, and the regurgitant jet velocity was obtained with continuous-wave Doppler. The parameter estimation procedure was based on the Kalman filter principle, resulting primarily in an estimate of the regurgitant orifice area. The area was multiplied by the velocity integral of the regurgitant jet to estimate regurgitant volume. A strong correlation was found between the regurgitant volumes obtained by parameter estimation and the electromagnetic flow measurement. These results from our study in pigs suggest that it may be possible to quantify regurgitant orifice and volume in patients completely noninvasively from Doppler and blood pressure measurements.     

Omnicarbon 21 mm aortic valve prosthesis: in vitro hydrodynamic and echo-Doppler study

The aim of this study was to perform combined hydrodynamic and Doppler echocardiographic tests of the Omnicarbon 21 mm cardiac valve in aortic position in our Pulse Duplicator System for simultaneous assessment of valve performance and valve leakage data. During forward flow conditions, measured mean pressure gradients are between 4.5 and 20.2 mmHg (11.9 +/- 4.4 mmHg) for cardiac outputs between 3.6 and 5.3 /min (4.5 +/- 0.4 /min). Doppler-derived mean pressure gradients are between 2.0 and 170 mmHg (9.3 +/- 3.9 mmHg) for the same flow conditions. Effective Orifice area is 1.31 +/- 0.08 cm2 and the performance index is 0.74 +/- 0.04, using the actual geometric orifice area, and 0.38 +/- 0.02, using the tissue annulus diameter, for a cardiac output of 4.5 +/- 0.4 l/min. Regurgitation volumes are below 3 ml. There is a trend to an effect of valve orientation on hemodynamics.     

Investigating the effects of random balloon pulsation on gas exchange in a respiratory assist catheter

We are developing an intravenous respiratory assist catheter, which uses hollow-fiber membranes wrapped around a pulsating balloon that increases oxygenation and CO2 removal with increased balloon pulsation. Our current pulsation system operates with a constant rate of pulsation and delivered balloon volume. This study examined the hypothesis that random balloon pulsation would disrupt fluid entrainment within the fiber bundle and increase our overall gas exchange. We implemented two different modes for random (rates and delivered volume) versus constant pulsation. The impact on gas exchange was measured in a 3 l/min water flow loop at 37 degrees C. CO2 gas exchange for randomized beat rate mode was comparable to its corresponding average constant pulsation (e.g., constant 286 beats/min versus randomized 200-400 beats/min was 299.5+/-0.9 and 302.2+/-1.4 ml/min/m, respectively). Random volume mode CO2 exchange was also comparable to constant delivered balloon volume (100% inflation and deflation) (e.g., 294.3+/-0.6 and 301.1+/-1.7 ml/min/m, random 50-100% inflation and constant, respectively). Greater active mixing was seen with constant pulsation as compared with randomly changing the parameters of balloon pulsation.     

Heart rate changes evoked by hypoxia in the anaesthetized, artificially ventilated cat.

Reflex changes in heart rate evoked by hypoxia were investigated in cats anesthetized with chloralose and ventilated by positive pressure during administration of vecuronium or gallamine. In five cats receiving vecuronium and with aortic pressure stabilized, systemic hypoxia (arterial O2 pressure (Pa, O2) 34.9 mmHg) reduced heart rate by 55.8 +/- 7.5 beats min-1 (mean +/- S.E.M.). After administration of atropine, hypoxia (Pa, O2 32.1 mmHg) increased heart rate by 28.2 +/- 3.4 beats min-1. After subsequent bilateral ablation of carotid sinus and vagus nerves, hypoxia (Pa, O2 31.9 mmHg) increased heart rate by 7.1 +/- 1.8 beats min-1. The cardiac accelerator response to hypoxia was further examined in groups of cats treated with gallamine and atropine. In four vagotomized cats, local perfusion of both carotid sinuses with hypoxic blood (Pa, O2 37.7 mmHg) increased heart rate by 15.5 +/- 2.3 beats min-1. In the same cats, systemic hypoxia (Pa, O2 38.3 mmHg) increased heart rate by 16.4 +/- 2.3 beats min-1. The heart rate increment in cats which had undergone either bilateral adrenalectomy or cardiac sympathectomy was similar to the increment in unoperated cats. The increment was significantly less in cats which had both adrenal glands and cardiac sympathetic nerves ablated. It is concluded that stimulation of the carotid bodies in the cat excites both parasympathetic and sympathetic cardiac nerves simultaneously.     

The reflex bradycardia during brain ischemia in the rabbit.

We examined the responses of whole aortic nerve activity, aortic baroreceptor activity, heart rate (HR), and arterial pressure (AP) to brain ischemia sustained for approximately 30 s in anesthetized spontaneously breathing rabbits. The minimum values of HR observed during brain ischemia were 76 +/- 11 beats/min (mean +/- S.E., n = 14) before sectioning the bilateral aortic nerve (BAN), and 161 +/- 12 beats/min after sectioning the left aortic nerve (LAN), and 225 +/- 11 beats/min after sectioning the LAN and right aortic nerve (RAN). Averages for reflex fall in HR during BAN, LAN, and RAN activation were 140 +/- 9, 78 +/- 7, and 62 +/- 7 beats/min, respectively, by subtracting the HR fall responses to brain ischemia in the absence of aortic baroreceptor afferents from their control values. The heights of the integrated whole left and right aortic nerve activities in systole slightly increased during brain ischemia, whereas the brain ischemia remarkably increased those activities during the diastolic phases. The brain ischemia induced a hysteresis in the mean AP-aortic barorecept or activity relationship. These results suggest that the total activity of aortic nerve fibers would determine the bradycardia evoked by brain ischemia and that the difference between the relative contributions of LAN and RAN on the brain ischemia-induced reflex bradycardia would reflect the total impulse frequency of aortic myelinated and non-myelinated fibers.     

冠脉造影数字跟踪技术测量冠脉血流速度的临床研究

本研究通过对冠脉生理学分析,结合流体力学原理,利用冠脉造影配套硬件和软件开发,建立血管造影计算机辅助分析系统。应用数字跟踪技术测定冠脉血流速度,并与“金标准”Doppler血流导丝和TIMI氏血流作相关分析和初步临床应用研究80例,结果表明:冠脉造影跟踪法测定LAD的平均流速(17．98±5．66)与Doppler测得的LAD近中断的APV(17．70±5．77)呈正相关(r=0．75,P<0．001),与TIMI氏血流呈负相关(18．58±6．46 cm／s对28±7．5帧,r=-0．51,P<0．05)。研究结果和临床应用表明:该方法所提取的冠脉血流动力学指标具有科学性和实用性,有助于提高常规冠脉造影解剖形态与生理功能相结合的诊断能力,且方法简便易行,节约成本。     

Assessment of coronary flow reserve with transthoracic Doppler echocardiography: comparison with intracoronary Doppler method

To evaluate the feasibility and usefulness of transthoracic Doppler echocardiography (TTDE) as a non-invasive method in recording distal anterior descending (LAD) coronary flow velocity, we compared coronary flow reserve (CFR) measured by TTDE with measurements by intracoronary Doppler wire (ICDW). Twenty-one patients without LAD stenosis were studied. ICDW performed at baseline and after intracoronary injection of 18 microg adenosine. TTDE was performed at baseline and after intravenous adenosine (140 microg/kgmin for 2 min). Adequate Doppler recordings of coronary flow velocities during systole were obtained in 14 of 21 study patients (67%) and during diastole in 17 (81%) patients. Baseline and hyperemic peak diastolic flow velocities measured by TTDE were significantly smaller than those obtained by ICDW (p<0.05). However, diminishing trends of diastolic and systolic velocity ratio after hyperemia were similarly observed in both methods. CFR obtained by TTDE (3.0+/-0.5), was higher than the value calculated by ICDW (2.5+/-0.4). There were significant correlations between the values obtained by the two methods (r=0.72, p<0.01). It is concluded that TTDE is a feasible method in measuring coronary flow velocity and appears to be a promising non-invasive method in evaluating CFR.     

Chemoreflex sympathoexcitation was not altered by the antagonism of glutamate receptors in the commissural nucleus tractus solitarii in the working heart-brainstem preparation of rats

The changes in thoracic sympathetic nerve activity, heart rate and frequency of phrenic nerve discharge in response to chemoreflex activation before and after bilateral microinjections of glutamate receptor antagonists into the comissural nucleus tractus solitarii (cNTS) were evaluated in the working heart-brainstem preparation of rats. Microinjections of kynurenic acid (KYN, 250 mM), (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG, 100 mM), or KYN plus MCPG into the cNTS were performed in three different groups. These microinjections into the cNTS did not affect the increase in the thoracic sympathetic nerve activity elicited by chemoreflex activation (KYN, 54 +/- 3 versus 51 +/- 2%, n = 11; MCPG, 48 +/- 5 versus 54 +/- 5%, n = 7; and KYN plus MCPG, 57 +/- 6 versus 55 +/- 3%, n = 5). The increase in the frequency of the phrenic nerve discharge in response to chemoreflex activation was also not affected by KYN (0.28 +/- 0.02 versus 0.30 +/- 0.04 Hz), MCPG (0.27 +/- 0.03 versus 0.27 +/- 0.04 Hz), or KYN plus MCPG (0.30 +/- 0.04 versus 0.20 +/- 0.03 Hz). The bradycardic response to chemoreflex activation was significantly reduced after microinjection of KYN at 2 (-220 +/- 16 versus -50 +/- 6 beats min(-1)) and 10 min (-220 +/- 16 versus -65 +/- 9 beats min(-1)) and after microinjection of KYN plus MCPG into the NTS it was abolished at 2 (-192 +/- 14 versus -2 +/- 1 beats min(-1)) and 10 min (-192 +/- 14 versus -4 +/- 2 beats min(-1)). These data support the hypothesis that the neurotransmission of the sympathoexcitatory and respiratory components of the chemoreflex in the cNTS involves neurotransmitters other than L-glutamate and also the concept that the parasympathetic component of this reflex is mediated by L-glutamate.     

Frequency distribution,variance, and moving average of left ventricular rhythm and contractility during atrial fibrillation in dog

Mean levels of left ventricular rhythm and contractility averaged over arrhythmic beats would characterize the average cardiac performance during atrial fibrillation (AF). However, no consensus exists on the minimal number of beats for their reliable mean values. We analyzed their basic statistics to find out such a minimal beat number in canine hearts. We produced AF by electrically stimulating the atrium and measured left ventricular arrhythmic beat interval (RR) and peak isovolumic pressure (LVP). From these, we calculated instantaneous heart rate (HR = 60,000/RR), contractility (E(max) = LVP/isovolumic volume above unstressed volume), and beat interval ratio (RR1/RR2). We found that all their frequency distributions during AF were variably nonnormal with skewness and kurtosis. Their means +/- standard deviations alone cannot represent their nonnormal distributions. A 90% reduction of variances of E(max) and RR1/RR2 required a moving average of 15 and 24, respectively, arrhythmic beats on the average, whereas that of RR and HR required 60 beats on the average. These results indicate that a statistical characterization of arrhythmic cardiodynamic variables facilitates better understanding of cardiac performance during AF.     

Twenty-four-hour pattern of circulation by radiotelemetry in the unrestrained dog.

Eight dogs with indwelling transducers for continuous radiotelemetry of the hemodynamic function were acclimatized in an unisolated room under 12:12 LD photoperiods, in phase with the solar day cycle, and constant temperature (20 +/- 1 degrees C). Light was turned on at 0600 and off at 1800. Mean aortic blood flow (ABF), mean aortic blood pressure (ABP), heart rate (HR), respiratory rate (RR), and cardiac work (CW) were maximal at about 1800 and minimal at time 0600. Total peripheral resistance (TPR) was highest and stroke volume (SV) lowest at about 1200. The 24-h mean was for HR 77 beats/min, SV 28 ml/beat, RR 11 breaths/min, ABF 177 ml/min per kg body wt, ABP 102 Torr, TPR 3,960 dyn . s . cm-5, and CW 218 Torr . 1/min. The range of amplitude fluctuations for daytime means was about 6% for ABP and SV and 11-17% for all others. It is suggested that the homeostatic balance and timing of circulation is circadian time dependent.