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Biomedical subjects

D A Kass

Publications and source records attributed to D A Kass.

At least 19 recordsLinked to original sources
PubMed1999

Improved left ventricular mechanics from acute VDD pacing in patients with dilated cardiomyopathy and ventricular conduction delay.

BACKGROUND: Ventricular pacing can improve hemodynamics in heart failure patients, but direct effects on left ventricular (LV) function from varying pacing site and atrioventricular (AV) delay remain unknown. We hypothesized that the magnitude and location of basal intraventricular conduction delay critically influences pacing responses and that single-site pacing in the delay-activated region yields similar or better responses to biventricular pacing. METHODS AND RESULTS: Aortic and LV pressures were measured in 18 heart failure patients (mean+/-SD: LV ejection fraction, 19+/-7%; LV end-diastolic pressure, 25+/-8 mm Hg; QRS duration, 157+/-36 ms). Data under normal sinus rhythm were compared with ventricular pacing (VDD) at varying sites and AV delays (randomized order). Right ventricular (RV) apical or midseptal pacing had negligible contractile/systolic effects. However, LV free-wall pacing raised dP/dtmax by 23.7+/-19.0% and pulse-pressure by 18.0+/-18.4% (P<0.01). Biventricular pacing yielded less change (+12.8+/-9.3% in dP/dtmax, P<0.05 versus LV). Pressure-volume analysis performed in 11 patients consistently revealed minimal changes with RV pacing but increased stroke work and lower end-systolic volumes with LV pacing. Optimal AV intervals averaged 125+/-49 ms, and within this range, AV delay had less influence on LV function than pacing site. Basal QRS duration positively correlated with %DeltadP/dtmax (P<0.005), but pacing efficacy was not associated with QRS narrowing. Conduction delay pattern generally predicted pacing sites with most effect. CONCLUSIONS: VDD pacing acutely enhances contractile function in heart failure patients with intraventricular conduction delay. Single-site pacing at the site of greatest delay achieves similar or greater benefits to biventricular pacing in such patients. These data clarify pacing-effect mechanisms and should help in candidate identification for future studies.

Adult↗
PubMed1999

Mechanisms of altered excitation-contraction coupling in canine tachycardia-induced heart failure, I: experimental studies.

Pacing-induced heart failure in the dog recapitulates many of the electrophysiological and hemodynamic abnormalities of the human disease; however, the mechanisms underlying altered Ca2+ handling have not been investigated in this model. We now show that left ventricular midmyocardial myocytes isolated from dogs subjected to 3 to 4 weeks of rapid pacing have prolonged action potentials and Ca2+ transients with reduced peaks, but durations approximately 3-fold longer than controls. To discriminate between action potential effects on Ca2+ kinetics and direct changes in Ca2+ regulatory processes, voltage-clamp steps were used to examine the time constant for cytosolic Ca2+ removal (tauCa). tauCa was prolonged by just 35% in myocytes from failing hearts after fixed voltage steps in physiological solutions (tauCa control, 216+/-25 ms, n=17; tauCa failing, 292+/-23 ms, n=22; P<0.05), but this difference was markedly accentuated when Na+/Ca2+ exchange was eliminated (tauCa control, 282+/-30 ms, n=13; tauCa failing, 576+/-83 ms, n=11; P<0. 005). Impaired sarcoplasmic reticular (SR) Ca2+ uptake and a greater dependence on Na+/Ca2+ exchange for cytosolic Ca2+ removal was confirmed by inhibiting SR Ca2+ ATPase with cyclopiazonic acid, which slowed Ca2+ removal more in control than in failing myocytes. beta-Adrenergic stimulation of SR Ca2+ uptake in cells from failing hearts sufficed only to accelerate tauCa to the range of unstimulated controls. Protein levels of SERCA2a, phospholamban, and Na+/Ca2+ exchanger revealed a pattern of changes qualitatively similar to the functional measurements; SERCA2a and phospholamban were both reduced in failing hearts by 28%, and Na+/Ca2+ exchange protein was increased 104% relative to controls. Thus, SR Ca2+ uptake is markedly downregulated in failing hearts, but this defect is partially compensated by enhanced Na+/Ca2+ exchange. The alterations are similar to those reported in human heart failure, which reinforces the utility of the pacing-induced dog model as a surrogate for the human disease.

Action Potentials↗
PubMed1999

The pathogenesis of familial hypertrophic cardiomyopathy: early and evolving effects from an alpha-cardiac myosin heavy chain missense mutation.

Familial hypertrophic cardiomyopathy (FHC) is a genetic disorder resulting from mutations in genes encoding sarcomeric proteins. This typically induces hyperdynamic ejection, impaired relaxation, delayed early filling, myocyte disarray and fibrosis, and increased chamber end-systolic stiffness. To better understand the disease pathogenesis, early (primary) abnormalities must be distinguished from evolving responses to the genetic defect. We did in vivo analysis using a mouse model of FHC with an Arg403Gln alpha-cardiac myosin heavy chain missense mutation, and used newly developed methods for assessing in situ pressure-volume relations. Hearts of young mutant mice (6 weeks old), which show no chamber morphologic or gross histologic abnormalities, had altered contraction kinetics, with considerably delayed pressure relaxation and chamber filling, yet accelerated systolic pressure rise. Older mutant mice (20 weeks old), which develop fiber disarray and fibrosis, had diastolic and systolic kinetic changes similar to if not slightly less than those of younger mice. However, the hearts of older mutant mice also showed hyperdynamic contraction, with increased end-systolic chamber stiffness, outflow tract pressure gradients and a lower cardiac index due to reduced chamber filling; all 'hallmarks' of human disease. These data provide new insights into the temporal evolution of FHC. Such data may help direct new therapeutic strategies to diminish disease progression.

Aging↗
PubMed1999

Preservation of canine myocardial high-energy phosphates during low-flow ischemia with modification of hemoglobin-oxygen affinity.

Conventional approaches for the treatment of myocardial ischemia increase coronary blood flow or reduce myocardial demand. To determine whether a rightward shift in the hemoglobin-oxygen saturation curve would reduce the metabolic and contractile effects of a myocardial oxygen-supply imbalance, we studied the impact of a potent synthetic allosteric modifier of hemoglobin-oxygen affinity, a 2-[4-[[(3,5-disubstituted anilino)carbonyl]methyl] phenoxy] -2-methylproprionic acid derivative (RSR13), during low-flow ischemia. Changes in myocardial high-energy phosphate levels and pH were studied by 31P nuclear magnetic resonance (NMR) spectroscopy in 12 open-chest dogs randomized to receive RSR13 or vehicle control during a reversible reduction of left anterior descending (LAD) coronary artery blood flow. Changes in cardiac metabolites and regional ventricular function studied by pressure segment-length relations were also investigated in additional animals before and after RSR13 administration during low-flow LAD ischemia. The intravenous administration of RSR13 before ischemia resulted in a substantial increase in the mean hemoglobin p50 and attenuated the decline in cardiac creatine phosphate/adenosine triphosphate (PCr/ATP), percent PCr, and pH during ischemia without a change in regional myocardial blood flow, heart rate, or systolic blood pressure. RSR13 given after the onset of low-flow ischemia also improved cardiac PCr/ATP ratios and regional function as measured by fractional shortening and regional work. Thus, synthetic allosteric reduction in hemoglobin-oxygen affinity may be a new and important therapeutic strategy to ameliorate the metabolic and functional consequences of cardiac ischemia.

Aniline Compounds↗
PubMed1998

Mechanism of acute mechanical benefit from VDD pacing in hypertrophied heart: similarity of responses in hypertrophic cardiomyopathy and hypertensive heart disease.

BACKGROUND: Dual-chamber pacing can improve symptoms in hypertrophic cardiomyopathy (HCM), but the mechanism remains unclear. We hypothesized that pacing generates discoordinate contraction and a rightward shift of the end-systolic pressure-volume relation (ESPVR) and that benefits from this mechanism do not depend on the presence of resting outflow pressure gradients or obstruction. METHODS AND RESULTS: Eleven patients with NYHA class III symptoms, 5 with HCM, and 6 with hypertensive hypertrophy and cavity obliteration, were studied by invasive conductance catheter methods. No patient had coronary artery or primary valvular disease. Pressure-volume relations were recorded before and during VDD pacing by use of a short (75-millisecond) PR interval to achieve preexcitation. Left ventricular cavity pressure was simultaneously recorded at basal and apical sites, with pressure at the basal site used to generate the ESPVRs. VDD pacing shifted the ESPVR rightward, increasing end-systolic volume by 45% (range, 17% to 151%; P=0.002). Resting and provokable gradients declined by 20% (range, -56% to +3%) and 30% (range, -65% to -12%), respectively (P<0.05). Preload declined by 3% to 10% because of the short PR interval. Preload-corrected contractility indexes and myocardial workload declined by approximately 10% (P<0.001). Diastolic compliance and relaxation time were unchanged. Pacing made apical pressure-volume loops discoordinate, limiting cavity obliteration and reducing distal systolic pressures. Results in both patient groups were similar. CONCLUSIONS: VDD pacing shifts the ESPVR rightward in HCM patients with cavity obliteration with or without obstruction, increasing end-systolic volumes and reducing apical cavity compression and cardiac work. These effects likely contribute to reduced metabolic demand and improved symptoms.

Adult↗
PubMed1998

Pertussis toxin-sensitive G proteins influence nitric oxide synthase III activity and protein levels in rat heart.

Inhibitory G protein activity (Gi) and nitric oxide (NO) modulate muscarinic-cholinergic (MC) inhibition of cardiac beta-adrenergic inotropic responses. We hypothesized that Gi mediates MC-NO synthase (NOS) signal transduction. Isoproterenol (0.2-0.8 microg/min) and acetylcholine (1 microM) were administered to isolated perfused rat hearts pretreated with saline (controls; n = 8) or pertussis toxin (PT; 30 microg/kg intraperitoneally 3 d before study; n = 20). PT abrogated in vitro ADP-ribosylation of Gi protein alpha subunit(s) indicating near-total decrease in Gi protein function. Isoproterenol increased peak +dP/dt in both control (peak isoproterenol effect: +2, 589+/-293 mmHg/s, P < 0.0001) and PT hearts (+3,879+/-474 mmHg/s, P < 0.0001). Acetylcholine reversed isoproterenol inotropy in controls (108+/-21% reduction of +dP/dt response, P = 0.001), but had no effect in PT hearts. In controls, NG-monomethyl-L-arginine (100 microM) reduced basal +dP/dt, augmented isoproterenol +dP/dt (peak effect: +4,634+/-690 mmHg/s, P < 0.0001), and reduced the MC inhibitory effect to 69+/-8% (P < 0.03 vs. baseline). L-arginine (100 M) had no effect in controls but in PT hearts decreased basal +dP/dt by 1, 426+/-456 mmHg/s (P < 0.005), downward-shifted the isoproterenol concentration-effect curve, and produced a small MC inhibitory effect (27+/-4% reduction, P < 0.05). This enhanced response to NO substrate was associated with increased NOS III protein abundance, and a three- to fivefold increase in in vitro calcium-dependent NOS activity. Neomycin (1 microM) inhibition of phospholipase C did not reverse L-arginine enhancement of MC inhibitory effects. These data support a primary role for Gi in MC receptor signal transduction with NOS in rat heart, and demonstrate regulatory linkage between Gi and NOS III protein levels.

Acetylcholine↗
PubMed1998

Synergistic exacerbation of diastolic stiffness from short-term tachycardia-induced cardiodepression and angiotensin II.

Synergistic interaction between angiotensin II (Ang II) and evolving cardiodepression may play an important role in worsening chamber function, particularly in diastole. To test this hypothesis, Ang II was infused at 10 or 17 ng.kg(-1).min(-1) in 18 conscious dogs 4 days before and during induction of subacute cardiodepression by 48-hour tachypacing. The lower dose yielded negligible systemic pressure changes. Twelve additional animals served as paced-only controls. Pressure-dimension relations were recorded, and serial endocardial biopsies were obtained to assess histological and metalloproteinase (MMP) changes. Forty-eight-hour pacing alone depressed systolic function but had little effect on diastolic stiffness. Ang II alone only modestly raised diastolic stiffness at both doses and enhanced contractility at the higher dose. These changes recovered toward baseline after a 7-day infusion. However, Ang II (at either dose) combined with 48-hour pacing markedly increased ventricular stiffness (110+/-26% over baseline) and end-diastolic pressure (22+/-1.7 mm Hg). In contrast, pacing-induced inotropic and relaxation abnormalities were not exacerbated by Ang II. Zymography revealed MMP activation (72- and 92-kD gelatinases and 52-kDa caseinase) after a 4-day Ang II infusion (at both doses), which persisted during pacing. Tachypacing initiated 24 hours after cessation of a 7-day Ang II infusion also resulted in diastolic stiffening and corresponded with MMP reactivation. Ang II also induced myocyte necrosis, inflammation, and subsequent interstitial fibrosis, but these changes correlated less with chamber mechanics. Thus, Ang II amplifies and accelerates diastolic dysfunction when combined with evolving cardiodepression. This phenomenon may also underlie Ang II influences in late-stage cardiomyopathy, when chamber distensibility declines.

Angiotensin I↗
PubMed1998

Force-frequency relation in patients with left ventricular hypertrophy and failure.

Our study demonstrated a loss of normal systolic contractile enhancement with increasing heart rate in patients with ventricular hypertrophy and symptoms of congestive heart failure. This decline in systolic reserve was not accompanied by worsening of diastolic function, and would therefore not seem to reflect underlying ischemia. Rather, it was more likely related to abnormalities of excitation-contraction coupling, particularly in light of findings of both increased post-rest potentiation and a reduced recirculation fraction. In contrast, mechanical restitution was unchanged, suggesting that alterations in Ca2+ release from the SR did not play a major role. Finally, we showed that increasing heart rate adversely affects the efficiency of ventriculo-vascular coupling in LVH hearts. This suggested another explanation of how dysfunction of cardiac force-frequency behavior can lead to limited cardiovascular reserve and contribute to clinical symptoms of exertional intolerance. Future efforts aimed at enhancing the force-frequency response, perhaps by enhancing the SR-ATPase, or manipulating its regulation, should prove helpful in ameliorating the limitations of LVH patients associated with rapid heart rate.

Adult↗
PubMed1998

Coupled systolic-ventricular and vascular stiffening with age: implications for pressure regulation and cardiac reserve in the elderly.

OBJECTIVES: We tested the hypothesis that age-related arterial stiffening is matched by ventricular systolic stiffening, and that both enhance systolic pressure sensitivity to altered cardiac preload. BACKGROUND: Arterial rigidity with age likely enhances blood pressure sensitivity to ventricular filling volume shifts. Tandem increases in ventricular systolic stiffness may also occur and could potentially enhance this sensitivity. METHODS: Invasive left ventricular pressure-volume relations were measured by conductance catheter in 57 adults aged 19 to 93 years. Patients had normal heart function and no cardiac hypertrophy and were referred for catheterization to evaluate chest pain. Twenty-eight subjects had normal coronary angiography and hemodynamics, and the remaining had either systolic hypertension or coronary artery disease without infarction. Data recorded at rest and during transient preload reduction by inferior vena caval obstruction yielded systolic and diastolic left ventricular chamber and effective arterial stiffness and pulse pressure. RESULTS: Left ventricular volumes, ejection fraction and heart rate were unaltered by age, whereas vascular load and stiffening increased (p < 0.008). Arterial stiffening (Ea) was matched by increased ventricular systolic stiffness (Ees): Ees=0.91 x Ea + 0.53, (r=0.50, p < 0.0001), maintaining arterial-heart interaction (Ea/Ees ratio) age-independent. Ventricular systolic and diastolic stiffnesses correlated (r=0.51, p < 0.0001) and increased with age (p < 0.03). Both ventricular and vascular stiffening significantly increased systolic pressure sensitivity to cardiac preload (p < 0.006). CONCLUSIONS: Arterial stiffening with age is matched by ventricular systolic stiffening even without hypertrophy. The two effects contribute to elevating systolic pressure sensitivity to altered chamber filling. In addition to recognized baroreflex and autonomic dysfunction with age, combined stiffening could further enhance pressure lability with diuretics and postural shifts in the elderly.

Adult↗
PubMed1998

Surgical approaches to arresting or reversing chronic remodeling of the failing heart.

Chronic ventricular remodeling is a central feature of heart failure that strongly correlates with a poor prognosis. Several recent surgical treatments for heart failure may derive benefit by their ability to arrest or substantially reverse this remodeling process. Dynamic cardiomyoplasty involves wrapping the heart with the latissimus dorsi muscle and stimulating the muscle to assist contraction. The wrap itself may provide a constraint helping to limit progressive cardiac dilation and/or assist in reversing this process. Left ventricular assist devices almost completely unload the heart and augment systemic circulation, thereby reducing neurohumoral activation. These combined effects seem to alter the chamber and cellular phenotype, and reversal of some molecular changes are associated with failure. Lastly, the partial ventriculectomy procedure directly reverses remodeling by acute removal of a portion of the lateral wall. Only preliminary nonrandomized trial data are currently available for each of these therapies with larger trials under way. However, early results are intriguing and are yielding insights into these mechanisms.

Cardiomyoplasty↗
PubMed1998

Optimal preload adjustment of maximal ventricular power index varies with cardiac chamber size.

BACKGROUND: Maximal left ventricular power (PWRmax) can index contractile function and reserve; however, its marked preload dependence mandates load adjustment to yield a more cardiac-specific measurement. Prior studies have used varying methods, but supporting data have generally been lacking. We hypothesized that the optimal approach for preload adjustment varies with ventricular volume (particularly end-systolic volume) and is significantly different for dilated hearts with reduced left ventricular function compared with small to normal-sized hearts with normal systolic function. METHODS: Left ventricular pressure-volume relations were measured by the conductance catheter method in 36 patients, with preload altered by inferior vena cava obstruction. Patients with normal ventricles (n = 16), hypertrophy or mitral stenosis (n = 12), and dilated cardiomyopathy (n = 8) were divided into three groups based on resting end-diastolic volume: group 1, 66.3 +/- 12; group 2, 118.1 +/- 20; and group 3, 218.2 +/- 48 ml. PWRmax was the maximal product of simultaneous left ventricular pressure and rate of volume change. PWRmax end-diastolic volume (EDV) data were fit to a power function, PWRmax = alphaEDVbeta (where alpha is a scaling factor and beta is the power coefficient), and the preload sensitivity of beta and PWRmax/EDVbeta ratios (beta = 1, 2, or best fit) were compared. RESULTS: Beta varied directly with chamber size: 0 = 0.004 x (EDV + 0.56), r = 0.65, p < 0.0001. However, it was equally well approximated by 1.0 in groups 1 and 2 (ESV <75 ml, EF >40%), whereas beta = 2 was more appropriate in group 3. CONCLUSION: PWRmax/EDV provides adequate preload independence in all but dilated hearts with reduced LV function, whereas PWRmax/EDV2 is required in the latter. These data should help clinical application of a noninvasive PWRmax index for assessing chamber contractility and contractile reserve in human beings.

Adult↗
PubMed1998

In vivo murine left ventricular pressure-volume relations by miniaturized conductance micromanometry.

The mouse is the species of choice for creating genetically engineered models of human disease. To study detailed systolic and diastolic left ventricular (LV) chamber mechanics in mice in vivo, we developed a miniaturized conductance-manometer system. alpha-Chloralose-urethan-anesthetized animals were instrumented with a two-electrode pressure-volume catheter advanced via the LV apex to the aortic root. Custom electronics provided time-varying conductances related to cavity volume. Baseline hemodynamics were similar to values in conscious animals: 634 +/- 14 beats/min, 112 +/- 4 mmHg, 5.3 +/- 0.8 mmHg, and 11,777 +/- 732 mmHg/s for heart rate, end-systolic and end-diastolic pressures, and maximum first derivative of ventricular pressure with respect to time (dP/dtmax), respectively. Catheter stroke volume during preload reduction by inferior vena caval occlusion correlated with that by ultrasound aortic flow probe (r2 = 0.98). This maneuver yielded end-systolic elastances of 79 +/- 21 mmHg/microliter, preload-recruitable stroke work of 82 +/- 5.6 mmHg, and slope of dP/dtmax-end-diastolic volume relation of 699 +/- 100 mmHg.s-1.microliter-1, and these relations varied predictably with acute inotropic interventions. The control normalized time-varying elastance curve was similar to human data, further supporting comparable chamber mechanics between species. This novel approach should greatly help assess cardiovascular function in the blood-perfused murine heart.

Animals↗
PubMed1997

Effect of altering filling pattern on diastolic pressure-volume curve.

BACKGROUND: The early-to-late ventricular filling ratio (E:A) is widely used to index diastolic function. While filling patterns reflect diastolic properties, they can also modulate chamber pressures due to myocardial viscoelasticity. We hypothesized that such feedback can potentially temper effects of delayed relaxation and/or volume loading on diastolic pressures. METHODS AND RESULTS: Six isolated blood-perfused canine left ventricles were studied with ejection and filling controlled by an intracavitary volume servo-pump. Diastolic filling was determined by a simulated atrial pressure source that was either constant or varied to yield dual-phase filling at a specified E:A ratio. E:A ratio was randomly set to 3:1, 1:3, or 1:1, and data were recorded at each ratio at three different preloads. With principally early filling (E:A=3:1), diastolic pressure rise from viscosity increased in proportion with the relaxation time constant (r=.91, P<.0001). However, this dependence was lost as E:A ratio declined (eg, P=.63 for E:A 1:3). Furthermore, E:A=3:1 yielded 37% to 50% lower end-diastolic pressures at similar volumes (versus E:A=1:3) as initial viscous forces decayed. Offsetting early and late filling effects led to little net change in mean diastolic pressure independent of E:A ratio or preload. CONCLUSIONS: Diastolic filling pattern itself influences chamber pressures early and late in diastole due to viscoelasticity, with larger net effects on end-diastolic pressure. Since E:A ratio normally falls with delayed relaxation but rises with higher preload or reduced compliance, the present results suggest that changes in filling pattern may modulate direct effects of such factors on elevating diastolic pressure.

Animals↗
PubMed1997

Comparison of continuous left ventricular volumes by transthoracic two-dimensional digital echo quantification with simultaneous conductance catheter measurements in patients with cardiac diseases.

Automated border detection enables real-time tracking of left ventricular (LV) volume by 2-dimensional transthoracic echocardiography. This technique has not been previously compared with simultaneously measured continuous LV volumes at rest or during transients in humans. We performed 18 studies in 16 patients (age 50 +/- 15 years, range 22 to 70; ejection fraction 63 +/- 20%, range 15% to 85%) in which continuous LV volumes acquired by digital echo quantification (DEQ) were compared with simultaneous conductance catheter volume obtained by cardiac catheterization. Both volume signals were calibrated by thermodilution-derived cardiac output and ventriculogram-derived ejection fraction. Volume traces acquired at rest were averaged to generate a comparison cycle. The averaged volume waveforms acquired by DEQ and by conductance catheter were similar during all phases of the cardiac cycle and significantly correlated (conductance catheter = slope. DEQ + intercept, slope = 0.94 +/- 0.09, intercept = 5 +/- 8 ml, r2 = 0.86 +/- 0.12, all p <0.0001). Steady-state hemodynamic parameters calculated using either averaged volume signal were significantly correlated. Transient obstruction of the inferior vena cava yielded a 45 +/- 13% decrease in end-diastolic volume. Successful recordings of DEQ volume during preload reduction were obtained in only 50% of studies. End-diastolic volumes from the 2 methods were significantly correlated (mean slope 0.88 +/- 0.31, mean intercept 14 +/- 37 ml, average r2 = 0.89 +/- 0.11, all p <0.01), as were end-systolic volumes: mean slope 0.80 +/- 0.43, intercept = -20 +/- 26 ml, r2 = 0.67 +/- 0.18, all p <0.05). We conclude that automated border detection technique by DEQ is reliable for noninvasive, transthoracic, continuous tracking of LV volumes at steady state, but has limitations in use during preload reduction maneuvers in humans.

Adult↗
PubMed1997

Estimation of central aortic pressure waveform by mathematical transformation of radial tonometry pressure. Validation of generalized transfer function.

BACKGROUND: Central aortic pressures and waveform convey important information about cardiovascular status, but direct measurements are invasive. Peripheral pressures can be measured noninvasively, and although they often differ substantially from central pressures, they may be mathematically transformed to approximate the latter. We tested this approach, examining intersubject and intrasubject variability and the validity of using a single averaged transformation, which would enhance its applicability. METHODS AND RESULTS: Invasive central aortic pressure by micromanometer and radial pressure by automated tonometry were measured in 20 patients at steady state and during hemodynamic transients (Valsalva maneuver, abdominal compression, nitroglycerin, or vena caval obstruction). For each patient, transfer functions (TFs) between aortic and radial pressures were calculated by parametric model and results averaged to yield individual TFs. A generalized TF was the average of individual functions. TFs varied among patients, with coefficients of variation for peak amplitude and frequency at peak amplitude of 24.9% and 16.9%, respectively. Intrapatient TF variance with altered loading (> 20% variation in peak amplitude) was observed in 28.5% of patients. Despite this, the generalized TF estimated central arterial pressures to < or = 0.2 +/- 3.8 mm Hg error, arterial compliance to 6 +/- 7% accuracy, and augmentation index to within -7% points (30 +/- 45% accuracy). Individual TFs were only marginally superior to the generalized TF for reconstructing central pressures. CONCLUSIONS: Central aortic pressures can be accurately estimated from radial tonometry with the use of a generalized TF. The reconstructed waveform can provide arterial compliance estimates but may underestimate the augmentation index because the latter requires greater fidelity reproduction of the wave contour.

Abdomen↗
PubMed1997

Comparison of heart rate variability in patients with chronic fatigue syndrome and controls.

Recent studies have reported a close association between chronic fatigue syndrome and neurally mediated hypotension. We hypothesized that this association may result from an abnormality in autonomic function among patients with chronic fatigue syndrome, which may be detectable using an analysis of heart rate variability. We prospectively studied 19 patients who fulfilled the Centers for Disease Control criteria for chronic fatigue syndrome and 11 controls. Each subject underwent a two-stage tilt-table test while wearing a Holter monitor. Heart rate variability was assessed in the supine baseline position and during upright tilt using frequency domain parameters. In the baseline supine position, high frequency (HF) power, low frequency (LF) power, and the ratio of low frequency power to high frequency power (LF/HF ratio) were similar. In both patient groups, upright tilt resulted in a similar decrease in HF power, increase in LF power, and increase in the LH/HF ratio. In conclusion, autonomic function, as assessed using an analysis of heart rate variability, does not differ in the baseline supine state, nor in response to upright tilt among patients with chronic fatigue syndrome and healthy controls.

Adult↗
PubMed1997

Repolarization abnormalities, arrhythmia and sudden death in canine tachycardia-induced cardiomyopathy.

OBJECTIVES: This study sought to determine whether the canine model of tachycardia-induced heart failure (HF) is an effective model for sudden cardiac death (SCD) in HF. BACKGROUND: Such a well established HF model that also exhibits arrhythmias and SCD, along with repolarization abnormalities that could trigger them, may facilitate the study of SCD in HF, which still eludes effective treatment. METHODS: Twenty-five dogs were VVI-paced at 250 beats/min for 3 to 5 weeks. Electrocardiograms were obtained, and left ventricular endocardial monophasic action potentials (MAPs) were recorded at six sites at baseline and after HF. Weekly Holter recordings were made with pacing suspended for 24 h. RESULTS: Six animals (24%) died suddenly, one with Holter-documented polymorphic ventricular tachycardia (VT). Holter recordings revealed an increased incidence of VT as HF progressed. Repolarization was significantly (p < 0.05) prolonged, as indexed by a corrected QT interval (mean [+/-SD] 311 +/- 25 to 338 +/- 25 ms) and MAP duration measured at 90% repolarization (MAPD90) (181 +/- 19 to 209 +/- 28 ms), and spatial MAPD90 dispersion rose by 40%. We further tested whether CsCl inhibition of repolarizing K+ currents, which are reportedly downregulated in HF, might preferentially prolong the MAPD90 in HF. With 1 mEq/kg body weight of CsCl, MAPD90 rose by 86 +/- 100 ms in dogs with HF versus only 28 +/- 16 ms in control animals (p = 0.002). Similar disparities in CsCl sensitivity were observed in myocytes isolated from normal and failing hearts. CONCLUSIONS: Tachycardia-induced HF exhibits malignant arrhythmia and SCD, along with prolonged, heterogeneous repolarization and heightened sensitivity to CsCl at chamber and cellular levels. Thus, it appears to be a useful model for studying mechanisms and therapy of SCD in HF.

Animals↗