A Prospective Multicenter Study Using a Virtual 3 Fr Percutaneous Coronary Intervention System: The V3 Registry.

OBJECTIVES: To evaluate the safety and feasibility of virtual 3 Fr (V3), sheathless 5 Fr percutaneous coronary intervention (PCI). BACKGROUND: A small-diameter guiding catheter (GC) makes less-invasive PCI possible. The V3 is an extremely slender PCI system; however, the outcome of using this system has not yet been determined. METHODS: The V3 registry is a prospective, multicenter, non-randomized study that enrolled patients who underwent elective V3-PCI. The primary endpoint was clinical success rate, and the secondary endpoints were PCI success rate in all cases, major adverse cardiac and cerebrovascular event (MACCE) at 30 days, and access-site complications. RESULTS: A total of 260 patients with 321 lesions were enrolled. Of this group, 70% were male and the mean age was 70.8 ± 10.0 years. Type B2/C lesions comprised 50.7% of the total. The clinical success rate was 95.8%, and the PCI success rate was 99.2%. PCI failure was reported in 2 chronic total occlusion cases. No MACCE was reported. Although there was no major bleeding, hematoma occurred at the puncture site in 12.7% of cases. There was a single radial artery occlusion (0.4%) without symptoms. CONCLUSIONS: PCI with the V3 was safe and feasible. Radial artery occlusion and major bleeding complications were extremely low. However, access-site hematoma frequently complicated catheter exchange.

The impact of anti-inflammatory cytokines provoked by CD163 positive macrophages on ventricular functional recovery after myocardial infarction.

Present study aimed to investigate the impact of anti-inflammatory cytokines provoked by the hemoglobin scavenger receptor, CD163, on left ventricular (LV) functional recovery after successful reperfusion in patients with acute myocardial infarction (AMI). Intraplaque hemorrhage accelerates plaque destabilization. Extracellular hemoglobin is cleared by CD163, a macrophage scavenger receptor. This process provokes secretion of anti-inflammatory atheroprotective cytokine, interleukin (IL)-10. In 40 patients with the first AMI, coronary atherothrombotic debris was retrieved during percutaneous coronary intervention (PCI), stained with antibodies to CD163 and IL-10. LV function was determined by echocardiography before PCI and 6 months after PCI. %CD163 was defined as ratio of CD163 (+)-cells to whole cells. %IL-10 was expressed as the ratio of positively stained areas per total tissue. Patients were divided into two groups depending on the amount of CD163 (+)-cells: CD163 > 10 % (CD163high, n = 20) and CD163 ≤ 10 % (CD163low, n = 20). CD163high group had significantly higher %IL-10. Final thrombolysis in myocardial infarction (TIMI) flow grade was significantly lower in CD163high group. In subgroups with the final TIMI-3 flow (CD163high-Reflow, n = 15 and CD163low-Reflow, n = 20), the time to reperfusion, infarct size, LV dimensions and fractional shortening (%FS) before PCI were similar. Significant correlation was observed between %IL10 and changes in LV dimensions (diastole, r = -0.49, P = 0.01; systole, r = -0.65, P < 0.01) or %FS (r = 0.51, P < 0.01) at 6 months after PCI. Plaque with CD163(+)-macrophages could impair distal flow after primary PCI. However, CD163(+)-macrophages enhance the anti-inflammatory cytokine expression that aids in ventricular functional recovery if distal flow can be achieved by successful reperfusion.

Mechanism of laser-induced size-reduction of gold nanoparticles as studied by nanosecond transient absorption spectroscopy.

Gold nanoparticles with an average diameter of approximately 8 nm (Au approximately 15,000) were irradiated with a tightly focused pulse laser at 355 nm in an aqueous solution of sodium dodecyl sulfate (SDS). Transient absorption spectra of the solution were measured at 25-100 ns after the laser irradiation. The observed transient absorption around 720 nm is assignable to the 2p <-- 1s transition of solvated electrons produced via multiple ionization of the gold nanoparticles. The nascent charge state of the gold nanoparticles was estimated from the transient absorbance. The dependence of the charge state on the SDS concentration shows a gradual increase from approximately +60 to approximately +70 in the 2 x 10(-4) to 3 x 10(-4) M range and an abrupt increase up to approximately +710 at the critical micelle concentration (CMC) of SDS, 8 x 10(-3) M. TEM measurements after laser irradiation reveal that the gold nanoparticles fragment into Au(approximately 1000) at a SDS concentration of 3 x 10(-4) M, whereas they are significantly dissociated into Au(approximately 100) above the CMC. The observed correlation between the nascent charge states and the extent of size reduction of the gold nanoparticles after the laser treatment indicates that the size reduction is caused by the Coulomb explosion of the highly charged gold nanoparticles. The mechanism of laser-induced size reduction is quantitatively discussed based on the liquid drop model.

Central sympathetic inhibition augments sleep-related ultradian rhythm of parasympathetic tone in patients with chronic heart failure.

BACKGROUND: Abnormal sleep dynamics in patients with heart failure is one of the mechanisms for the relative predominance of central sympathetic outflow over parasympathetic tone. This study was designed to examine whether central sympathoinhibition could improve the sympathovagal imbalance related to rapid-eye-movement (REM)/non-REM ultradian sleep rhythm in these patients. METHODS AND RESULTS: Beat-by-beat RR intervals of overnight electrocardiogram were serially subject to power spectral analysis in 14 patients with chronic heart failure and 13 age-matched subjects with normal cardiac function. To assess autonomic sleep dynamics, the ultradian rhythm was extracted from all-night consecutive high-frequency (HF) components of heart rate variability (HRV) before and after administration of an (alpha2)-adrenergic agonist, guanfacine. Night-time HRV in heart failure was characterized by an attenuated ultradian rhythm of HF-components with a concomitant reduction in averaged HF power. Guanfacine reduced blood pressure, heart rate, and plasma norepinephrine concentrations by 7%, 8%, and 34% (p < 0.01), respectively. After guanfacine, HF power rose by 154% (p < 0.01) with a prominent augmentation of the all-night ultradian rhythm (+361%, p < 0.01). CONCLUSIONS: Central sympathoinhibition augments a sleep-related ultradian rhythm of parasympathetic tone, suggesting a potential benefit to autonomic balancing and sleep quality in patients with chronic heart failure.

Circadian dynamics of heart rate and physical activity in patients with heart failure.

The present study was designed to develop a method to continuously measure Holter electrocardiogram (ECG) and physical activity in terms of metabolic costs to examine circadian dynamics of RR intervals and physical activity in patients with heart failure. A total of 7 healthy subjects and 3 heart failure patients performed cardiopulmonary exercise test using four-stage graded treadmill walking at 0% grade to examine whether the acceleration signals in the vertical direction could reflect actual body energy expenditure during physical activity. Then, using this new method, 24-hr monitorings of ECG and physical activity were performed in 24 inpatients with heart failure while they were allowed to walk around freely. Our results showed the integral of rectified acceleration signals was closely correlated with actual metabolic cost in all subjects. Instantaneous changes in heart rate were quite concordant with physical activity. As compared with the asymptomatic patients (n = 12), the symptomatic patients (n = 12) had lower energy expenditure during 8-hr daytime periods but higher mean heart rate. Furthermore, a more prominent ultradian rhythm of circadian changes in heart rate and physical activity was found in 50% of all subjects studied. The simultaneous analysis of Holter ECG and physical activity as the same time series revealed that in patients with heart failure, sympathovagal balance shifted toward sympathotonic conditions and their physical activity could become subject to intrinsic ultradian dynamics of body's homeostasis.

Attenuated respiratory modulation of chemoreflex-mediated sympathoexcitation in patients with chronic heart failure.

BACKGROUND: Enhanced hypercapnic chemoreflex in chronic heart failure could modulate sympathetic nerve activity in a different manner depending on the severity of heart failure. This study was designed to evaluate the dynamic aspects of sympathoexcitation caused by central hypercapnic chemoreflex in patients with chronic heart failure. METHODS AND RESULTS: In 21 patients with chronic heart failure, wavelet analysis was applied to elucidate the spectral components of muscle sympathetic nerve activity (MSNA) and instantaneous ventilation during hypercapnic chemoreceptor stimulation. Hypercapnia increased MSNA (83+/-8 versus 29+/-9 %, P<.01) and ventilation (209+/-27 versus 190+/-21%, P<.05) more in 12 symptomatic patients than in 9 asymptomatic patients. This hypercapnic chemoreflex exerted a greater influence on the sympathetic limb than on the ventilatory limb in the symptomatic patients. The wavelet analysis revealed that the within-breath sympathoinhibition in the symptomatic patients was attenuated as compared with that in the asymptomatic patients (0.33+/-0.03 vs. 0.44+/-0.04, P<.05). CONCLUSIONS: The enhanced chemoreflex sympathetic drive and relative attenuation of ventilatory sympathoinhibition could contribute to exaggerated sympathoexcitation in patients with heart failure when they are exposed to carbon dioxide during exercise or sleep apnea.

Pulse-synchronous sympathetic burst power as a new index of sympathoexcitation in patients with heart failure.

The upper limit of incidence of muscle sympathetic neural bursts can lead to underestimation of sympathetic activity in patients with severe heart failure. This study aimed to evaluate the pulse-synchronous burst power of muscle sympathetic nerve activity (MSNA) as a more specific indicator that could discriminate sympathetic activity in patients with heart failure. In 54 patients with heart failure, the pulse-synchronous burst power at the mean heart rate was quantified by spectral analysis of MSNA. Thirteen patients received a central sympatholytic agent (guanfacine) for 5 days to validate the feasibility of this new index. Both burst incidence and plasma norepinephrine level showed no significant difference between patients in New York Heart Association functional class III (94 +/- 6 per 100 heartbeats and 477 +/- 219 pg/ml, respectively) and class II (79 +/- 14 per 100 heartbeats and 424 +/- 268 pg/ml, respectively). In contrast, the burst power was useful for discriminating patients in class III from those in class II (61 +/- 8% vs. 39 +/- 10%; P < 0.05). Inhibition of sympathetic nerve activity by guanfacine was more sensitively reflected by the change of burst power (-36 +/- 25%) than by that of burst incidence (-12 +/- 14%; P < 0.001). The sympathetic burst power reflects both burst frequency and amplitude independently of the absolute values and provides a sensitive new index for interindividual comparisons of sympathetic activity in patients with heart failure.

Role of central sympathoexcitation in enhanced hypercapnic chemosensitivity in patients with heart failure.

BACKGROUND: Enhanced central hypercapnic chemosensitivity is known to mediate excessive exercise ventilation and to indicate a poor prognosis in patients with chronic heart failure. The present study was designed to elucidate the role of central sympathetic activity in the enhancement of hypercapnic chemosensitivity. METHODS: Central hypercapnic chemosensitivity and plasma norepinephrine were measured in 99 patients with chronic heart failure. In 40 patients, the alpha index was derived from simultaneous analysis of R-R interval and systolic blood pressure variability. The effects of a central sympatholytic agent, guanfacine (0.25 mg/day), on hypercapnic chemosensitivity and exercise ventilatory response were studied in 20 of these patients. RESULTS: Hypercapnic chemosensitivity was enhanced in 76% of the patients and correlated significantly with plasma norepinephrine levels (r = 0.49, P < .01) at rest. There was a significant inverse relationship between central chemosensitivity and the alpha index (r = -0.41, P < .01). Guanfacine significantly reduced plasma norepinephrine levels by 29% (P < .01) and chemosensitivity by 31% (P < .01). The beneficial effect of central sympathoinhibition with guanfacine was observed specifically in patients who had enhanced chemosensitivity prior to drug administration. Similarly, the patients with excessive exercise ventilation showed a greater reduction in exercise ventilation with this agent. CONCLUSIONS: The present findings suggest that central sympathoexcitation could play an important role in the pathogenesis of enhanced hypercapnic chemosensitivity and a resultant increase in exercise ventilation in chronic heart failure.

Parametric system identification of arterial baroreflex with random perturbation of blood pressure in normal subjects.

The purpose of the study was to evaluate the dynamic nature of heart rate baroreflex under closed-loop conditions. We applied pressure perturbation with a random-interval cuff inflation to parametric system identification of the baroreflex. In 10 healthy men (six young, 27 +/- 3.9 years old, and four older, 50 +/- 3.8 years old), blood pressure variations were produced by a random-interval (0.06-0.50 Hz) cuff inflation around bilateral thighs to identify characteristics of the baroreflex with an autoregressive moving average model with exogenous input. The model faithfully described the dynamic relationship between mean blood pressure and RR interval. A theoretical 1 mmHg step input of mean blood pressure caused a rapid increase in RR intervals toward the steady state within 10 s in younger subjects. In older subjects, however, the step response showed a delayed and gradual increase in RR interval over 20 s. The steady-state gain obtained from the autoregressive moving average model with exogenous input was significantly greater than that determined from the slope of the pressure-RR relationship. The conclusion was that the dynamic baroreflex gain was quantified using a parametric system identification technique and blood pressure perturbation by means of a random-interval cuff inflation. This method would potentially be of great use in helping us gain insights into a closed-loop system of complex and dynamic cardiovascular regulation in humans.