Hemodynamic performance of mitroflow aortic pericardial bioprosthesis - optimizing management for the small aortic annulus.

BACKGROUND: Documentation of the hemodynamics of the Mitroflow aortic pericardial bioprosthesis has been incomplete. The aim of the study was to provide reference effective orifice areas for the implant calculation of effective orifice area indexes to avoid prosthesis-patient mismatch. METHODS: Echocardiograms were evaluated in 55 patients (39 females, 16 males), mean age 77.0 +/- 6.9 years (range 51-90 years). The mean time of the studies was 11.0 months. The prosthesis sizes and numbers evaluated were 19 mm (n = 13), 21 mm (n = 19), 23 mm (n = 13) and 25 mm (n = 10). RESULTS: Peak aortic velocities averaged from 2.2 to 2.7 m/sec, mean gradients from 10.6 to 15.1 mmHg, peak gradients from 20.7 to 29.7 mmHg, and effective orifice area (EOA) from 1.4 to 1.8 cm (2). When accounting for the subaortic velocity, mean gradients averaged from 7.5 to 10.0 mmHg, and peak gradients averaged 15.1 to 23.5 mmHg. The effective orifice area indexes ranged from 0.8 to 1.0 cm (2)/m (2). The mean postoperative left ventricular mass index was 101.6 gm/m (2). CONCLUSIONS: The IN VIVO effective orifice areas by valve size of the Mitroflow aortic pericardial bioprosthesis provide the opportunity of avoiding obstructive characteristics for all valve sizes, including optimizing the management of the small aortic annulus.

Oxazoline N-oxide mediated [2 + 3] cycloadditions. Application to a formal synthesis of (+)-carpetimycin A.

[formula: see text] Cycloaddition between gamma,delta-unsaturated beta-enamino ester 9 and camphor-derived oxazoline N-oxide 8 afforded a single adduct, 14. Dipolarophile 9 proved to be very reactive despite the substitution on the double bond. Stereoselective sodium cyanoborohydride reduction of the imminium intermediate 14a gave rise stereoselectively to beta-amino ester derivative 15a. Oxidative acidic hydrolysis, oxidation of the resulting aldehyde 18, deprotection, and cyclization afforded the beta-lactam 23, a direct precursor of (+)-carpetimycin A.

Mitral stenosis obscuring the diagnosis of plexogenic pulmonary arteriopathy and familial pulmonary hypertension.

A patient who died after surgery for critical mitral stenosis was found to have underlying unrecognised plexogenic pulmonary arteriopathy and familial pulmonary hypertension. The importance of recognising familial pulmonary hypertension is discussed, together with the contribution of genetic and other risk factors to plexogenic pulmonary arteriopathy.

Oxazoline N-oxide-mediated [2+3] cycloadditions. Application to a synthesis of (-)-tetrahydrolipstatin.

[reaction: see text] A [2+3] cycloaddition of camphor-derived oxazoline N-oxide to alpha,beta-unsaturated ester afforded adduct 8. Tetrahydrolipstatin 1 was prepared from this compound in a nine-step sequence of reactions.

Correlation of desensitisation of platelet activating factor (PAF) receptors with intensity of inflammation and intestinal PAF content during experimental ileitis in guinea pig.

AIM: To determine the kinetics of platelet activating factor (PAF) and prostaglandin E2 (PGE2) receptor desensitisation during intestinal inflammation induced by trinitrobenzenesulphonic acid (TNB) instillation and to study the relation between receptor regulation, inflammatory lesions, and PAF content of the gut wall. METHODS: Receptor desensitisation was assessed on isolated smooth muscle cells from the circular layer. PAF content of the intestinal wall was determined by thin layer chromatography and radioimmunoassay. RESULTS: After an acute inflammatory phase on day 1, subacute changes appeared in TNB instilled ileum, with a maximal intensity on day 6. In control animals, PAF 10 nM and PGE2 10 nM provoked a maximal contraction in the range of 24% of cell shortening. On days 1 and 3 after intestinal instillation of TNB, PAF induced contraction was not altered whereas the effect of PGE2 was progressively desensitised (2 logM rightward shift of its concentration-response curve: Cmax = 1 microM; p < 0.01). Between days 4 and 6, the concentration-response curve of PGE2 shifted by only 1 logM (p < 0.05) whereas the curve of PAF induced contraction shifted by 2 logM (Cmax = 1 microM; p < 0.01). The PAF content of the ileal wall was maximal between days 3 and 5 (300 ng/mg tissue). On days 10 and 15, PAF and PGE2 induced contractions were similar to those observed on day 1, and PAF content returned to basal. CONCLUSION: Inflammation induced by TNB instillation triggers PAF and PGE2 receptor desensitisation; this is dependent on the duration of inflammation and correlates with PAF content in the ileum. This receptor desensitisation may play a protective role by preventing overstimulation of intestinal smooth muscle cells.

Outcome of asymptomatic patients with carotid disease. Asymptomatic Cervical Bruit Study Group.

Asymptomatic cervical atherosclerosis carries a variable risk of vascular events. We sought to identify patients with asymptomatic cervical bruits who may be at increased risk of developing ischemic events. We conducted a prospective multicenter cohort study of neurologically asymptomatic patients presenting a cervical bruit. Patients had biannual neurologic and carotid duplex evaluation. Association between ultrasonographic findings and vascular events, adjusting for common risk factors, was evaluated. Seven hundred fifteen patients were followed on average for 3.6 years. Mean age was 65 years. At initial visit, 357 subjects had a > or = 50% stenosis. Overall, 237 events occurred in 177 patients. Annual rate of all primary vascular events in patients with > or = 50% stenosis was 11.0% versus 4.2% in those with < 50% stenosis (p < 0.001). Annual rate of stroke and vascular death was 5.5% in the > or = 50% group compared with 1.9% in the < 50% group (p < 0.001). Yearly rate of unheralded ischemic stroke was 4.2% in subjects with > or = 80% stenosis and 1.4% in those with stenosis < 80% (p < 0.001). A stroke or TIA was ipsilateral to a > or = 80% stenosis in 66% of patients. Progression of carotid stenosis particularly to more than 80% was associated both with a higher rate of ipsilateral neurologic events and overall combined vascular events. Our data suggest that severity of carotid stenosis is the main risk factor predicting occurrence of neurologic and other vascular events. Yearly rate of ipsilateral stroke with > or = 50% carotid stenosis is low (1.4%) and most are nondisabling. Progression to > or = 80% or occlusion is associated with worse outcome.

Lack of effect of aspirin in asymptomatic patients with carotid bruits and substantial carotid narrowing. The Asymptomatic Cervical Bruit Study Group.

OBJECTIVE: To determine the effectiveness of aspirin in preventing ischemic events in patients with asymptomatic carotid stenosis. DESIGN: Double-blind, placebo-controlled trial. SETTING: University-affiliated hospitals. PATIENTS: 372 neurologically asymptomatic patients with carotid stenosis of 50% or more in at least one artery as determined by luminal diameter reduction on duplex ultrasonography. INTERVENTION: Patients were randomly assigned to receive either enteric coated aspirin, 325 mg/d, or identically appearing placebo. Duration of therapy was 2.0 years for the aspirin recipients and 1.9 years for the placebo recipients. OUTCOME MEASURES: Patients were scheduled for a clinical examination every 6 months for assessment of the occurrence of any clinical event in the composite end point, which consisted of transient ischemic attack, stroke, myocardial infarction, unstable angina, or death. RESULTS: At baseline, the 188 patients receiving aspirin and the 184 patients receiving placebo had similar demographic, ultrasonographic, and laboratory characteristics. The median duration of follow-up was 2.3 years. The annual rate of all ischemic events and death from any cause was 12.3% for the placebo group and 11.0% for the aspirin group (P = 0.61). The Cox proportional hazards analysis yielded an adjusted hazard ratio (aspirin-placebo) of 0.99 (95% CI, 0.67 to 1.46; P = 0.95). The annual rates for vascular events only were 11% for the placebo group and 10.7% for the aspirin group (P = 0.99). The multivariate analysis yielded a hazard ratio of 1.08 (CI, 0.72 to 1.62; P = 0.71). CONCLUSION: Aspirin did not have a significant long-term protective effect in asymptomatic patients with high-grade (> or = 50%) carotid stenosis.

Cardiorespiratory effects of hemic versus nonhemic prime during and immediately following mitral valve replacement in dogs.

In order to limit the hemodilution effect during cardiopulmonary bypass (CPB) in low weight animal patients, blood is often used as a component of the prime solution. This study was undertaken to evaluate the effects of the addition of blood to the prime solution on the hemodynamic and respiratory parameters during and following mitral valve replacement in dogs. Ten dogs were randomly assigned to receive either a hemic (HP), 75% blood component, or a nonhemic prime (NP) solution. The hemodilution was 5 +/- 4% and 25 +/- 10% for the HP and NP groups, respectively. Cardiopulmonary measurements were taken 20 minutes before initiating CPB, during CPB, and 20 min after termination. The hematocrit level, the hemoglobin concentration, and the arterial oxygen content were significantly lower in the NP group during and following CPB. However, the systemic oxygen transport index was not significantly different between the NP group (355 +/- 87 mL/min/m2) and the HP group (546 +/- 155 mL/min/m2) following CPB. Our study indicates that, in normal dogs undergoing hemodilution from a nonhemic prime solution, the cardiovascular function is able to maintain the systemic oxygen transport in the period immediately following mitral valve replacement.

Receptor imaging with atrial natriuretic peptide. Part 1: High specific activity iodine-123-atrial natriuretic peptide.

METHODS: Atrial natriuretic peptide (ANP) was labeled in high specific activity using 123I (p,2n). The biodistribution of 123I-ANP was studied in green vervet monkeys by gamma scintigraphy and in rats by dissection and gamma counting. Iodine-125-ANP was also studied in monkeys by in vitro autoradiography. RESULTS: Iodine-123-ANP showed rapid blood clearance with localization to ANP receptors in the kidneys and lungs, which accounted for 35% of total uptake. In vivo competition imaging studies using cold ANP99-126 and C-ANP102-121 proved that uptake is receptor mediated and allowed imaging of the differential biodistribution of A/B and C-ANP receptor families. Thus, it was possible through the use of selective receptor occupation to prevent uptake in certain organs and to effectively steer the labeled ANP to others. The observed biodistribution patterns were confirmed by an in vitro study using 125I-ANP in the same monkeys, which correlated the scintigraphic images with receptor distribution. An in vivo biodistribution study in rats showed a profound effect of specific activity on biodistribution, with a cutoff for receptor uptake at less than 3000 Ci/mmole. CONCLUSION: Gamma scintigraphy with 123I-ANP permits the imaging of ANP receptors in vivo. In contrast to receptor imaging with either organic molecules or antibodies, ANP provides rapid first-pass uptake and substantial accumulation (%dose/organ approximately 20% or greater) in receptors. The key to receptor imaging with peptides is high specific activity. Labeled ANP offers potential as a diagnostic tool for diabetic nephropathy, particularly for quantifying the involvement of glomerular disease.

Limitations of ultrasonic duplex scanning for diagnosing lower limb arterial stenoses in the presence of adjacent segment disease.

PURPOSE: The purpose of this study was to provide a quantitative evaluation of the effect of adjacent segment lesions on disease classification in lower limb arteries by ultrasonic duplex scanning. METHODS: Lower limb arterial duplex scanning from the distal aorta to the popliteal artery was performed in 55 patients. Arterial lesions evaluated by visual interpretation of Doppler spectra were compared blindly with those measured by angiography. RESULTS: To recognize severe stenoses (50% to 100% diameter reduction) in any arterial segment, duplex scanning had sensitivity and specificity rates of 74% and 96%, respectively. However, sensitivity and specificity rates increased to 80% and 98%, respectively, when there was no 50% to 100% diameter-reducing lesion in adjacent segments, whereas they decreased to 66% and 94%, respectively, when there was at least one 50% to 100% diameter-reducing lesion in adjacent segments. Moreover, among the 48 duplex misclassifications underestimating or overestimating the degree of arterial stenoses, 30 (62.5%) involved a segment with at least one 50% to 100% lesion in adjacent segments. The segments mostly affected by proximal and distal arterial lesions were the popliteal arteries and the common and deep femoral arteries, where it was found that 86% (24/28) of the misclassifications involved the presence of either proximal or distal severe stenoses. CONCLUSION: The results demonstrated that the presence of multiple stenoses was an important limitation of duplex scanning for the detection and quantification of lower limb arterial disease.

Cardiac Doppler blood-flow signal analysis. Part 1. Evaluation of the normality and stationarity of the temporal signal.

The normality (Gaussian property) and stationarity of the cardiac Doppler blood-flow signal were evaluated on short-time segments distributed over the cardiac cycle. The basic approaches used to perform statistical tests on the nonstationary and quasiperiodic cardiac Doppler signal are presented. The results obtained from the data of ten patients having a normal aortic valve and ten patients having a stenotic valve indicate that a complex Gaussian random process is an acceptable approximation for the clinical cardiac Doppler signal. For segments of 10 ms or less, 82 per cent of them were accepted to be stationary with a significance level of 0.05, whereas for durations greater than 40 ms, the percentage of stationary segments was less than 75 per cent. It was concluded that the 10 ms window generally used in practice is a good choice for Doppler spectrogram estimation, but a shorter time interval would be preferable.

Cardiac Doppler blood-flow signal analysis. Part 2. Time/frequency representation based on autoregressive modelling.

Doppler spectrograms obtained by using autoregressive (AR) modelling based on the Yule-Walker equations were investigated. A complex AR model using the in-phase and the quadrature components of the Doppler signal was used to provide blood-flow directions. The effect of model orders on the spectrogram estimation was studied using cardiac Doppler blood flow signals taken from 20 patients. The 'final prediction error' (FPE) and the 'Akaike's information criterion' (AIC) provided almost identical results in model-order selection. An index, the spectral envelope area (SEA), was used to evaluate the effect of window duration and sampling frequency on AR Doppler spectrogram estimation. The statistical analysis revealed that the SEA obtained from AR modelling was not sensitive to window duration and sampling frequency. This result verified the consistency of the AR Doppler spectrogram. The white-noise characteristics of the AR modelling error signal indicated that the Doppler blood-flow signal can be adequately modelled as a complex AR process. With appropriate model orders, AR modelling provided better Doppler spectrogram estimates than the periodogram.

In vivo measurement of atrial natriuretic peptide receptors using nuclear imaging.

We have successfully visualized atrial natriuretic peptide (ANP) receptors in vivo using nuclear imaging. 123I-Labelled ANP, injected in green vervet monkeys, was rapidly bound to ANP receptors in the kidneys and lungs. That the observed uptake was receptor mediated was demonstrated with competition studies using simultaneous injection of unlabelled ANP 99-126. It was possible to distinguish between the ANP receptor subtypes by the use of selective antagonists. Thus coinjection of ANP 102-121-des[Gln, Ser, Gly, Leu, Gly] (C-ANP), an ANP analog that selectively binds to the ANP C-receptor, decreased uptake in the kidneys by 50% but increased relative uptake in the lungs and soft tissues. This method permits for the first time, the dynamic in vivo analysis of ANP receptors and their interaction with endogenous ligand. Differences and changes in local ANP receptor concentrations and occupancy could be detected. Since ANP receptor density and affinity are influenced by various physiological and pathological conditions, clinical and diagnostic applications seem possible.

Optimal time-window duration for computing time/frequency representations of normal phonocardiograms in dogs.

The optimal duration of the time-window used to compute the time-frequency representation (spectrogram) of the phonocardiogram was studied in four dogs by using intracardiac and thoracic measurements of the PCG. The power and cross-spectrograms of the intracardiac and thoracic PCGs were computed using a fast Fourier transform algorithm and a sine-cosine window with 10 per cent decaying functions. A coherence spectrogram was also computed for each dog to study the linear relationship between the two signals and determine the optimal time-window duration. Results show that the optimal range of the time-window duration is between 16 and 32 ms. A time-window shorter than 16 ms spreads out low-frequency components into the higher frequencies and generates a spectrographic representation with poor frequency resolution (> or = 62.5 Hz). A window larger than 32 ms increases the frequency resolution but smears the spectrographic representation of the signal in the time domain and thus cannot correctly reflect the time-varying properties of the signal. In both cases, the amplitude of the coherence function computed between the left ventricular and the thoracic phonocardiograms is overestimated.

Effect of ensemble averaging on amplitude and feature variabilities of Doppler spectrograms recorded in the lower limb arteries.

The objective of the present study was to analyse the effect of averaging Doppler blood flow signals in lower limb arteries on amplitude and feature variabilities. Doppler signals recorded in 41 iliac and 35 superficial femoral arteries having different categories of stenosis were averaged over 1-15 cardiac cycles. Based on the relative decreasing rate of an index of variability, results indicated that amplitude variability of the spectrograms was exponentially reduced to 30, 6 and 1 per cent when averaging five, ten and 15 cardiac cycles, respectively. Nine diagnostic features were extracted from Doppler spectrograms and their variations from one cardiac cycle to the next quantified. Based on the relative decreasing rate of these variations, results indicated that feature variability was exponentially reduced to 30, 4 and 1 per cent when averaging five, ten and 15 cardiac cycles, respectively. The effect of averaging on the discriminant power of the features to separate the different categories of stenosis was also investigated by performing t-test analyses. Results showed that averaging between five and ten cardiac cycles provided the better discriminant power for most cases, whereas averaging over more than ten cardiac cycles was of little benefit. Based on the spectral analysis technique used in the present study, we conclude that averaging over ten cardiac cycles is sufficient for the analysis of Doppler spectrograms recorded in the lower limbs.

Interaction between the aortic valve leaflets and a Millar dual-micromanometer catheter during recording of the aortic component of the second heart sound in dogs.

The influence of the closure of the aortic valve leaflets on a dual-micromanometer Millar catheter is investigated with respect to the power spectrum of the aortic component (A2) of the second heart sound in dogs. The catheter inserted through the aortic valve is used to simultaneously record A2 in the left ventricle and in the aorta and to study the transmission of A2 up to the body surface. Results indicate that the interaction of the valve leaflets with the Millar dual-micromanometer catheter during the closure and vibration of the aortic valve does not produce a clapping artefact. The main effect is a change in the natural modes of vibration (resonant frequencies) of the aortic valve resulting from a modification of the vibrating structure (combined structure composed of the catheter, the aortic valve and the surrounding blood and tissues) because of the tight mechanical coupling between the aortic valve leaflets and the catheter. In addition, this modification of the natural modes of resonance does not invalidate the estimation of the frequency response of the transfer function between the aortic root and the thoracic recording site, even if the mean gain of the transfer function is affected and the phase slightly increased with frequency. On the contrary, the interaction of the aortic valve leaflets with the catheter seems to slightly increase the spectral contribution (coherence) of the intra-aortic A2 to the thoracic A2.

Acoustic transmission of the aortic component of the second heart sound within the ascending aorta of dogs.

The spectral characteristics of the acoustic transmission of the aortic component of the second heart sound within the ascending aorta was studied using a Millar dual-micromanometer catheter. The tip micromanometer was located close to the aortic valve leaflets while the second micromanometer was located 3 cm above the aortic valve. The frequency response of the transmission properties (amplitude and phase) of the blood and the aortic wall was modelled by an equivalent acoustic transmission system. The signal recorded by the tip micromanometer located near the aortic valve was considered to be the input signal of the equivalent system and the signal recorded by the second micromanometer was used as the output signal. Results of the spectral analysis of the input and output signals show that the acoustic transmissibility of blood in the ascending aorta is high at 20 Hz (the attenuation is negligible). Between 20 and 60 Hz, the transmissibility decreases at a rate of -3 dB per octave while between 60 and 120 Hz it decreases at a rate of -14 dB per octave. Above 120 Hz the transmissibility is low and the resulting attenuation is greater than 20 dB. The phase of the transfer function is shifted by -60 degrees at 20 Hz and decreases at a mean rate of -2.0 degrees Hz-1 between 20 and 100 Hz and -0.75 degrees Hz-1 up to 400 Hz. The phase velocity of the sound transmission is relatively constant (5.5 ms-1) between 40 and 100 Hz and increases up to 9 ms-1 at 300 Hz.

Change in amplitude distributions of Doppler spectrograms recorded below the aortic valve in patients with a valvular aortic stenosis.

Amplitude distributions of Doppler spectrograms were characterized in a group of 22 patients having no aortic pressure gradient and another group of 26 patients having a stenotic aortic valve. Specifically, for each patient, the ratios of the mean amplitude in three normalized frequency bands (low, middle and high) to the mean amplitude of the Doppler spectrogram computed in selected portions of the systolic period were considered. Pulsed-wave Doppler spectrograms were recorded by positioning the sample volume in the left ventricular outflow tract, approximately 1 cm below the aortic valve. Statistically significant differences were found between the middle (p = 0.041) and high (p = 0.028) frequency bands of Doppler signals recorded from the two groups of patients. The differences observed are believed to be attributed to blood flow eddies generated below the stenotic aortic heart valve and to changes in blood flow orientation.

Computer analysis and pattern recognition of Doppler blood flow spectra for disease classification in the lower limb arteries.

In the present study, a computer processing method was developed to objectively classify disease in the lower limb arteries evaluated by noninvasive ultrasonic duplex scanning. This method analyzes Doppler blood flow signals, extracts diagnostic features from Doppler spectrograms and classifies the severity of the disease into three categories of diameter reduction (0-19%, 20-49% and 50-99%). The features investigated were based on frequency features obtained at peak systole, spectral broadening indices and normalized amplitudes of the power spectrogram computed in various positive and negative frequency bands. A total of 379 arterial segments studied from the aorta to the popliteal artery were classified using a pattern recognition method based on the Bayes model. Two classification schemes using a two-node decision rule were tested. Both schemes gave similar results, the first one provided an overall accuracy of 83% (Kappa = 0.42) and the second an overall accuracy of 81% (Kappa = 0.35) when compared with conventional biplane contrast arteriography. These performances, especially for the 0 to 19% lesion category, are better than the one obtained by the technologist (accuracy = 76% and Kappa = 0.33), based on visual interpretation of the Doppler spectrograms. To recognize hemodynamically significant stenoses (50-99% lesions), the pattern recognition system has a sensitivity and a specificity of 50% and 99%, respectively, using classification scheme I. With classification scheme II, the sensitivity and the specificity are 50% and 98%, respectively. Visual interpretation of the Doppler spectrograms leads to a sensitivity and a specificity of 50% and 98%, respectively. These results are the first to be obtained by a pattern recognition system in classifying lower limb arterial stenoses.