Yoshinobu Murasato

Effects of systemic hypoxia on R-R interval and blood pressure variabilities in conscious rats

The effects of systemic hypoxia with different levels of CO2 on R-R interval (RRI) and systolic blood pressure (SBP) variabilities were investigated in conscious rats. Wistar rats chronically instrumented for the measurement of blood pressure, electrocardiogram, and renal sympathetic nerve activity (RSNA) were exposed to hypocapnic (Hypo), isocapnic (Iso), and hypercapnic (Hyper) hypoxia. On another day, the rats were treated with atropine and exposed to the same type of hypoxia. Sinoaortic denervation (SAD)-treated rats were exposed to Iso and Hyper, and RRI and SBP variabilities before and during hypoxia were analyzed using the maximum-entropy method with high resolution. With regard to RRI variability, very low frequency (VLF), low frequency (LF), and high frequency (HF) powers all decreased during Hypo, increased during Hyper, and did not change during Iso in intact rats. Changes during Hypo were attenuated by atropine, and those during Hyper were abolished by either atropine or SAD. The ratio of LF power to HF power decreased independently of increases in RSNA during each type of hypoxia. On the other hand, there were no changes in VLF, LF, or HF power in SBP variability during each type of hypoxia in intact rats. In atropine-treated rats, LF power increased during Iso and Hyper and HF power increased during each type of hypoxia. There was no difference in respiratory frequency among the three kinds of hypoxia in both intact and atropine-treated rats. The results suggest that arterial[Formula: see text] level rather than respiration frequency produces changes in powers of RRI variability through changes in parasympathetic nerve activity and that with regard to SBP variability, parasympathetic nerve activity masks changes in LF power that reflect an increase in RSNA and those in HF power that reflect a mechanical consequence of respiration.

Impact of three-dimensional characteristics of the left main coronary artery bifurcation on outcome of crush stenting

Background: Crush stenting with drug‐eluting stents is used to treat left main coronary artery (LMCA) bifurcations. However, the rate of restenosis at the left circumflex (LCX) artery ostium is high. The impact of the three‐dimensional (3D) structure of LMCA bifurcation on the outcome of crush stenting with respect to restenosis has not been described. Objectives: This study examined the stent expansion, deformity, overlapping, and apposition after crush stenting of LMCA bifurcations. Methods: Bare metal stents were crushed at LMCA bifurcations in a 3D model that reproduced actual angles, such that the stent deployed from the LMCA to the left anterior descending (LAD) artery crushed the stent deployed from the LMCA to the LCX, followed by kissing balloon inflation. The stents were inspected under fluoroscopy and endoscopy. The effect of the bifurcation angle on stent expansion was also examined. Results: In the 3D model, one stent overlapped the other in the distal LMCA, in contrast to the nearly parallel position of the stents observed in a separate two‐dimensional model. When the LAD stent overlapped the LCX stent, the latter was crushed on the myocardial side of the vessel, and an unstented segment was observed on the nonmyocardial side, at the LCX ostium. When the overlap was reversed, the LCX stent was crushed on the nonmyocardial side and an unstented segment was observed on the myocardial side. A narrow LMCA–LCX angle was associated with less expansion of the LCX stent at the ostium than more distally, and with a higher likelihood of incomplete stent apposition. Conclusions: Overlap of the LAD stent over, as opposed to under, the LCX stent was associated with close apposition of the stent to the vessel on the myocardial side, at the ostium of the LCX artery, where atherosclerotic plaques are likely to be present. The spatial plaque burden and bifurcation angle should be closely examined before crush stenting, and segments should not be left unstented over large plaques.

Examination of Stent Deformation and Gap Formation after Complex Stenting of Left Main Coronary Artery Bifurcations Using Microfocus Computed Tomography

BACKGROUND Fluoroscopy and intravascular ultrasound (IVUS) lack sufficient resolution for assessing the results of complex stenting in true bifurcation lesions. OBJECTIVES After diverse bifurcation stenting at the left main coronary artery (LM) bifurcation model, the results were examined using microfocus computed tomography (MFCT). METHODS The strut distribution of three kinds of stents deployed on a straight vessel segment was investigated. Classical crush, double kissing (DK)-double crush, and culotte stenting were performed on a three-dimensional (3D) LM model. The results were assessed using cross-sectional, longitudinal, and 3D reconstruction views of MFCT. RESULTS Nonuniform strut distribution was observed in a corrugated stent design deployed on a straight vessel segment. Following classical crush stenting, a relatively large gap at the nonmyocardial site was observed in the corrugated stents. When the guidewire recrossed outside the ostium of the crushed side branch stent, kissing balloon inflation caused further crushing of the stent at the more distal segment. The dilated strut rose up from the main vessel bed after the first kissing balloon inflation in DK crush stenting; the advantage of DK would be cancelled after main vessel stenting due to recrushing the raised strut. The culotte stenting with closed-cell stents showed the restriction of the expansion at the branch ostium when it was dilated with a 3.5-mm balloon. The culotte stenting with open-cell-based stents showed a good stent apposition except for a tiny gap and small metallic carina at the distal bifurcation. CONCLUSION MFCT analysis in the 3D phantom model is useful to assess the structural deformation of the stents and gap on vessel wall coverage after complex stenting at the LM bifurcation.

Three‐dimensional modeling of double‐stent techniques at the left main coronary artery bifurcation using micro‐focus X‐ray computed tomography

Various double‐stent techniques using drug‐eluting stents have been proposed to treat the left main coronary artery (LMCA) bifurcation. However, use of these techniques is frequently associated with focal restenosis at the ostium of the left circumflex coronary artery (LCX).

Effect of Magnesium Deficiency on Autonomic Circulatory Regulation in Conscious Rats

A close relationship between magnesium and cardiovascular function has been reported; however, the effect of magnesium deficiency on autonomic cardiovascular regulation has not been clarified. We investigated the effect of magnesium deficiency on the autonomic regulation of oscillations of the R-R interval, arterial blood pressure (BP), and renal sympathetic nerve activity (RSNA) by using the maximum entropy method in conscious rats. Its effect on baroreflex control of RSNA and heart rate were also investigated with a logistic function curve. Mean BP in magnesium-deficient rats was higher than that in control rats (mean+/-SE, 114.0+/-4.3 versus 101.6+/-3.4 mm Hg; P<0.05), and urinary excretion of catecholamine was increased by 2.4-fold. The fraction of low-frequency oscillation of RSNA was reduced (31.7+/-0.9% versus 36.2+/-1.5%, P<0.05) and the correlation between low-frequency oscillations of BP and RSNA was weakened in magnesium-deficient rats. There was no difference in high-frequency oscillation of the R-R interval, which is related to vagal tone, whereas sympathetic tone became dominant (square root of low-frequency/high-frequency ratio of R-R interval, 1.00+/-0.05 versus 0.67+/-0.05, P<0.0001) in magnesium-deficient rats. The maximal gain in the BP-RSNA relation tended to be reduced in magnesium-deficient rats (-7.7+/-1.1% versus -12.2+/-1.9%/mm Hg, P=0. 07); however, that in the BP-heart rate relation was increased (-8. 1+/-0.7 versus -4.5+/-0.5 bpm/mm Hg, P<0.01). These results suggest that magnesium deficiency induces sympathetic excitation, which results in hypertension but attenuates the baroreflex-related response of sympathetic nerves, whereas magnesium deficiency enhances the sensitivity of the sinus node to autonomic regulation.

Vascular endoscopic and macroscopic observations after crush stenting of coronary artery bifurcations in pigs

The crush stent technique has recently been proposed to limit the development of restenosis between drug‐eluting stents implanted at coronary artery bifurcations. We studied the stent expansion, apposition to the vessel, and aspect of the overlapping stents after in vivo crush stent implantation. Crush stent implantation was performed at coronary bifurcations in anesthetized swines. The treated sites were examined using intravascular ultrasound and a vascular endoscope. The stents removed from the vessel were analyzed macroscopically. After final kissing balloon inflation, an adequate apposition of the stent to the vessel wall was confirmed by vascular endoscopy and visual inspection. However, the side‐branch stent was narrowed at the site of stent overlap, and the overlapping stents in the main branch created a metal mass, which could promote the development of thrombosis. The technique of crush stent implantation with additional kissing balloon inflation is feasible and promising. However, it may be limited by thrombosis and restenosis at the carina because of stent overlapping and potential incomplete apposition. Additional studies are needed to confirm the safety and long‐term clinical results of this technique.

Brainstem mechanisms of autonomic dysfunction in encephalopathy‐associated Shiga toxin 2 intoxication

Acute encephalopathy is the major determinant of death in an early stage of Shiga toxin (Stx)‐producing Escherichia coli infection. Rapid progress toward refractory hypotension and dysfunction of breathing implies autonomic center dysfunction of patients. To clarify whether autonomic dysfunction becomes an ultimate cause of death in Shiga toxemia, we injected purified Stx2 (20 μg/kg) intravenously into rabbits, and monitored changes in cardiovascular and respiratory function together with renal sympathetic nerve activity (RSNA) in the conscious state. After an approximately 24‐hour silent (lag) period, all rabbits given Stx2 developed hemorrhagic diarrhea (25.7 ± 1.1 hours) and limb paralysis (31.2 ± 1.3 hours). This limb paralysis was observed initially in the hind legs, and then it gradually extended to the forelegs. After 23.2 ± 2.3 hours, RSNA increased gradually, and arterial blood pressure was maintained within normal limits together with an increase in the maximum gain of baroreflex response. Severe hypotension developed within 34.8 ± 2.2 hours, without any increase in heart rate; RSNA significantly increased by 39.5 ± 0.9 hours. In the final stage, RSNA decreased concurrently with decreases in arterial blood pressure, heart rate, and baroreflex response, suggesting dysfunction of the baroreflex control system. Thereafter, all rabbits died within 47.8 ± 1.2 hours after the intravenous Stx2 injection. Magnetic resonance imagings of the central nervous system (T2‐weighted images) showed high‐intensity areas in the dorsal two‐thirds of the cervical spinal cord and brainstem 48 hours after Stx2 administration. These results show that the cause of death is circulatory failure caused by impairment of the cardiovascular center in the medulla. We believe that this animal model helps to clarify the mechanism of rapid progress to death of patients with Shiga toxin–producing E coli infection. Ann Neurol 1999;45:716–723

Natural history of side branches jailed by drug-eluting stents.

BACKGROUND  Stent deployment across side branch (SB) ostium is common in daily practice. The present study investigated the natural history of SBs jailed by drug-eluting stents (DES). METHODS  The thrombolysis in myocardial infarction (TIMI) flow grades of 271 consecutive SBs jailed by DES in 196 patients was assessed immediately after the procedure and at 9 months of follow-up. Patients receiving any SB intervention were excluded. RESULTS Of 271 jailed SBs, occlusion occurred in 6.27% and deterioration of flow occurred in 6.27% immediately after stenting. In patients with these SB changes, periprocedural myocardial infarction was more likely than in those without (10.0% vs. 1.8%, P = 0.017), while there was no increase of cardiac death or life-threatening complications such as stent thrombosis and Q-wave myocardial infarction (Q MI) during follow-up. At 9 months, angiography showed that one-third of the initially obstructed SBs were still occluded. In contrast, flow was maintained in almost all (98.6%) SBs with early TIMI flow grade 3 and there was no delayed occlusion of these branches. Multiple regression analysis showed that lesion complexity (Medina bifurcation class, calcification, and preprocedural TIMI grade 2 flow in the SB) and technical factors (jailing by overlapping stents) were related to SB occlusion or flow deterioration. CONCLUSIONS  Jailed SBs showing good flow after stenting had a favorable angiographic and clinical outcome after 9 months of follow-up. However, preprocedural lesion complexity and technical factors should be considered to avoid SB occlusion/flow deterioration associated with periprocedural myocardial infarction.

Impact of final kissing balloon inflation on vessel healing following drug-eluting stent implantation: Insight from the optical coherence tomography sub-study of the J-REVERSE trial

BACKGROUND We sought to clarify the impact of final kissing inflation (FKI) after single stenting of bifurcation lesions on vessel healing. METHODS From the J-REVERSE registry enrolling 303 bifurcation lesions treated with provisional single stenting using sirolimus- (SES) or everolimus-eluting stent (EES), 65 lesions treated with (n=30) and without (n=35) FKI underwent 9-month follow-up optical coherence tomography. Average stent eccentricity index (SEI: minimum/maximum stent diameter) and neointimal unevenness score (NUS: maximum/average neointimal thickness of the same cross-section) for the proximal, bifurcation, and distal segments were compared between FKI and non-FKI groups. RESULTS At the proximal segment, the FKI group demonstrated significantly larger average stent area with greater asymmetric stent expansion, and average lumen area remained significantly larger at 9-month follow-up despite a tendency toward greater neointimal proliferation. Jailed strut and thrombus incidence were also significantly lower at the side branch orifice, and NUS was significantly smaller at the bifurcation and proximal segments in the FKI group. CONCLUSIONS Nine months after SES and EES treatment of bifurcation lesions, FKI reduced proximal-segment luminal narrowing. Considering its homogeneous neointimal distribution and fewer jailed struts, FKI may be beneficial for treating bifurcation lesions.

Efficacy of kissing balloon inflation after provisional stenting in bifurcation lesions guided by intravascular ultrasound: short and midterm results of the J-REVERSE registry

AIMS Our aim was to investigate the efficacy of the kissing balloon technique (KBT) in the provisional stenting of bifurcation lesions guided by intravascular ultrasound. METHODS AND RESULTS In the J-REVERSE registry, 300 non-left main bifurcation lesions in 299 patients were divided into two groups, KBT (n=163) and non-KBT (n=137). Patient and lesion characteristics were similar except for a higher prevalence of diabetic patients in the non-KBT group. The major adverse cardiac events (MACE) incidence at nine-month follow-up, including target lesion revascularisation, myocardial infarction, stent thrombosis, and death, was 6.3% in the KBT group versus 9.1% in the non-KBT group (p=0.47). Regardless of more SB dissection (10.5% vs. 1.5%, p=0.001), the KBT group obtained a greater luminal volume in the proximal main vessel (MV) (7.8±2.3 vs. 7.0±2.0 mm3/mm, p=0.006), maintained larger minimal lumen diameter at follow-up (2.73±0.43 vs. 2.63±0.39 mm, p=0.04), and demonstrated less binary side branch (SB) restenosis (9.7% vs. 21.0%, p=0.0004), which was beneficial for both true and non-true bifurcation lesions. Multivariate analysis showed the efficacy of KBT on SB restenosis (OR 0.28, 95% CI: 0.12-0.62, p=0.002). CONCLUSIONS Although the KBT increased SB dissection, it provided greater luminal gain in the proximal MV and SB with a similar MACE rate to non-KBT treatment up to nine-month follow-up.