Impaired coronary flow reserve as a marker of microvascular dysfunction to predict long-term cardiovascular outcomes, acute coronary syndrome and the development of heart failure.

BACKGROUND: In the absence of obstructive coronary narrowing, impaired coronary flow reserve (CFR) represents coronary microvascular dysfunction. Transthoracic Doppler echocardiography (TTDE) allows non-invasive measurement of CFR in the left anterior descending (LAD) artery. This study aimed to assess the prognostic value of TTDE-derived CFR (as a marker of microvascular function) in predicting long-term cardiovascular events, acute coronary syndrome (ACS) events, and the development of heart failure (HF). METHODS AND RESULTS: This study consisted of 272 patients with coronary artery disease not involving obstructive narrowing (≥50%) in the LAD. Patients underwent TTDE examination for CFR measurement in the LAD. During the follow-up period of 4.0±1.9 years, 32 patients (12%) had cardiovascular events. Cox proportional hazard analysis identified lower CFR as an independent risk factor of cardiovascular events (P<0.001), ACS events (P=0.008), and HF development (P=0.003). A CFR less than 2.4 was the best cut-off value for predicting all events (area under the curve=0.82). CFR excellently predicted the development of HF (area under the curve=0.95), but not ACS events (area under the curve=0.67). CONCLUSIONS: This TTDE study demonstrated that CFR was a significant and independent determinant of long-term cardiovascular events, ACS events and HF in patients with coronary artery disease. A CFR greater than 2.0 was not suitable to predict a favorable long-term outcome, even in the absence of obstructive coronary narrowing.

"Passive exercise" using whole body periodic acceleration: effects on coronary microcirculation.

BACKGROUND: The whole body periodic acceleration (WBPA) system has recently been developed as a "passive exercise" device by providing increased pulsatile shear stress for improvement of endothelial function. This study aimed to investigate the short-term effect of WBPA on coronary flow reserve (CFR) through transthoracic Doppler echocardiography (TTDE) in healthy subjects and patients with coronary artery disease (CAD). METHODS: This study consisted of 15 healthy subjects and 20 patients with CAD who underwent CFR examination before and immediately after WBPA. The flow velocity in the distal portion of the left anterior descending coronary artery (LAD) was measured with TTDE at baseline and during adenosine infusion. Coronary flow reserve was calculated as the ratio of hyperemic to basal mean diastolic flow velocity. RESULTS: The WBPA treatment was completed in all 35 subjects without complications. There were no significant differences in heart rate and systolic blood pressure before and after WBPA. Whole body periodic acceleration increased CFR from 3.3 +/- 1.0 to 3.7 +/- 1.1 in the 35 subjects (P < .001). Coronary angiography showed significant LAD narrowing in 8 of the 20 CAD patients, but WBPA increased CFR from 2.4 +/- 0.4 to 2.7 +/- 0.5 in them as well (P < .01). CONCLUSIONS: This study demonstrates that WBPA improves CFR in healthy subjects and patients with CAD.

Circadian variation in coronary flow velocity reserve and its relation to α1-sympathetic activity in humans.

BACKGROUND: The circadian change in coronary microvascular function has not been directly assessed in human beings. Recent advances in transthoracic Doppler echocardiography (TTDE) provide noninvasive, physiological assessment of coronary flow velocity reserve (CFVR). METHODS: This study consisted of 20 young healthy subjects (24 ± 2 years, 20 men) who underwent CFVR examinations at 3 different times; early morning (6AM), late morning (11AM) and late evening (10PM). The flow velocity in the distal portion of the left anterior descending coronary artery was measured with TTDE at baseline and during adenosine infusion to calculate CFVR. These examinations were repeated with the intake of α1-blocker (prazosin 1mg) on the other day. RESULTS: CFVR showed a circadian variation with an increase from the early morning to the late morning, following a decrease to the late evening thereafter (4.4 ± 0.9 at 6AM; 5.2 ± 1.3 at 11AM; 4.2 ± 1.1 at 10PM, p<0.001). In the study with α1-blocker, CFVR was comparable between the early morning and the late morning, whereas CFVR in the late evening was lower than those in other 2 time points (5.0 ± 1.1 at 6AM; 4.9 ± 0.9 at 11AM; 4.3 ± 0.9 at 10PM, p<0.001). CONCLUSIONS: This study demonstrates that CFVR has a circadian variation in humans, with an increase from the late evening to the late morning. Adding α1-blocker ameliorated CFVR only in the early morning, indicating that α1-sympathetic activity plays a heterogeneous and important role in the circadian change of CFVR in humans.

Aromatherapy alleviates endothelial dysfunction of medical staff after night-shift work: preliminary observations.

Night-shift work causes mental stress and lifestyle changes, and is recognized as a risk of cardiovascular diseases associated with impaired endothelial function. Aromatherapy is becoming popular as a complementary therapy that is beneficial for mental relaxation. The purpose of this study was to investigate the effect of aromatherapy on the endothelial function of medical staff after night-shift work. This study consisted of 19 healthy medical personnel (19 men, mean age 32 ± 7 years), including 11 physicians and 8 technicians. Aromatherapy was performed for 30 min by inhalation of the essential oil of lavender. Flow-mediated dilation (FMD) of the brachial artery was measured three times in each subject: on a regular workday, and after night-shift work before and immediately after aromatherapy. A control study was performed to assess the effect of a 30-min rest without aromatherapy. The mean value of sleep time during night-shift work was 3.3 ± 1.3 h. FMD after night-shift work was lower than on a regular workday (10.4 ± 1.8 vs. 12.5 ± 1.7%, P<0.001), which improved after aromatherapy (11.8 ± 2.5%, P=0.02 vs. before aromatherapy). FMD was stable in the control study (10.1 ± 1.9 vs. 10.1 ± 2.2%, P=0.9). This study demonstrated that night-shift work impaired endothelial function in medical staff, an effect that was alleviated by short-term aromatherapy.

Comparison of coronary microcirculation in female nurses after day-time versus night-time shifts.

Nightshift work, which is known to cause mental stress and disrupt normal biological diurnal rhythms, leads to endothelial dysfunction resulting in increased risk for cardiovascular disease. This study aimed to investigate the acute effect of night-shift work on coronary microcirculation through assessment of coronary flow reserve (CFR) by transthoracic Doppler echocardiography. This study consisted of 36 women nurses who underwent transthoracic Doppler echocardiographic examinations after working a nightshift and on a regular day without previous nightshift work. Flow velocity in the distal portion of the left anterior descending coronary artery was measured at baseline and during adenosine infusion. CFR was calculated as the ratio of hyperemic to basal mean diastolic flow velocity. CFR after night work was lower than that on a regular workday (3.8 ± 0.6 vs 4.1 ± 0.6, p <0.001). Degree of decreases in CFR after night work was correlated to Framingham risk score (r = 0.35, p = 0.036). In conclusion, this study demonstrated that coronary microcirculation was impaired after nightshift work in women nurses.

Pocket-sized transthoracic echocardiography device for the measurement of cardiac chamber size and function.

BACKGROUND: A pocket-sized portable transthoracic echocardiographic (pTTE) imaging device is commercially available, but its feasibility and accuracy in the assessment of cardiac chamber size and function has not been fully compared with the results of standard TTE (sTTE) examination. METHODS AND RESULTS: The target population comprised 125 unselected patients who underwent sTTE and pTTE examinations. The left ventricular (LV) diastolic and systolic dimensions, fractional shortening (FS), the thickness of the interventricular septum (IVS) and of the LV posterior wall (PWT), left atrial (LA) dimension, and ascending aorta diameter were measured. Echocardiographic measurements were completed for both pTTE and sTTE in all patients (feasibility 100%). LV dimensions, FS, IVS, PWT, LA dimension, and aorta diameter obtained by pTTE showed excellent correlation and agreement with sTTE (r=0.87-0.98, all P<0.001). Observer variabilities for these measurements were similar between pTTE and sTTE. CONCLUSIONS: In the present study, pTTE with the Acuson P10 was feasible and accurate for assessing cardiac chamber size and function.

Direct measurement of wall stiffness for carotid arteries by ultrasound strain imaging.

OBJECTIVE: The elastic properties of the carotid arterial wall have not been directly characterized in the clinical setting. Strain rate (SR) imaging is a newly developed echocardiographic method developed for imaging the tissue motion of the myocardium. The purpose of this study was to directly estimate the elastic properties of the carotid artery by using SR imaging in patients with coronary artery disease (CAD). METHODS: A total of 135 patients with CAD, 15 age-matched controls, and 35 young healthy subjects had a carotid ultrasound examination for measuring the values of SR and strain of the carotid artery. The intima-media thickness and distensibility coefficient of the carotid artery were estimated. RESULTS: Age and Framingham risk score were significantly related to SR and strain, respectively (r = 0.62-0.67, all P < .001). These strain measurements were significantly correlated with distensibility coefficient and intima-media thickness, respectively (r = 0.30-0.56, all P < .001). Similar values of the areas under the receiver operating characteristic curves were obtained among Framingham risk score (0.70 +/- 0.05), SR (0.67 +/- 0.05), and strain (0.73 +/- 0.05). CONCLUSION: This study demonstrated that the elastic properties of the carotid artery wall were directly characterized by using SR imaging in patients with CAD.

Transnasal transesophageal echocardiography in the detection of left atrial thrombus.

BACKGROUND: The widespread use of transesophageal echocardiography (TEE) is limited by disadvantages, including patient intolerance and increased medical costs. We aimed to investigate the feasibility and safety of transnasal TEE in the detection of possible embolic sources in patients with atrial fibrillation (AF) and/or stroke, using an ultrathin TEE probe. METHODS: Sixty-two patients with AF and/or stroke underwent transnasal TEE without conscious sedation. The presence or the absence of the following parameters was evaluated: left atrial (LA) thrombus; LA spontaneous echocardiographic contrast; intraatrial shunts; and aortic plaque. RESULTS: The insertion of a TEE probe was successful in 52 (84%) patients. TEE found LA thrombus in 10 (19%) patients and other embolic sources in 4 (8%) patients. Two (4%) patients had mild epistaxis. CONCLUSIONS: This study demonstrated that the use of transnasal TEE was feasible and safe in the detection of LA thrombus in patients with AF and/or stroke.

Microbiological safety of bottled mineral water in patients susceptible to infections.

We evaluated the microbiological safety of bottled mineral water products commercially available in Japan. Of 10 bottled mineral water products manufactured in Japan, no bacteria or fungi were detected in 9 (90%), but 1 (10%) contained 1.8x10(3) colony-forming units (cfu)/mL. Of 12 bottled mineral water products manufactured in the EU, 11 (91.7%) contained 23-3.5x10(4) cfu/mL. On the other hand, of 5 bottled mineral water products manufactured in North America, 2 (40%) contained 2.3x10(2)-2.5x10(3) cfu/mL. The detected microorganisms were glucose-nonfermentative Gram-negative bacilli such as Brevundimonas vesicularis, Moraxella spp., and Burkholderia cepacia, but Pseudomonas aeruginosa was not detected in any product. For immunocompromised host patients being managed in ultra-clean rooms, the examined bottled mineral water products manufactured in Japan, except 1, were microbiologically safe.

Antimicrobial effects of drugs against multidrug-resistant Pseudomonas aeruginosa.

We evaluated the effects of antimicrobial drugs on four strains of Pseudomonas aeruginosa that are resistant to eight widely used antipseudomonal drugs (piperacillin, piperacillin-tazobactam, imipenem, meropenem, ceftazidime, aztreonam, amikacin, ciprofloxacin) and colistin. In the killing test, colistin (2 microg/ml) was the most effective, followed by aztreonam (48 microg/ml), piperacillin-tazobactam (192-4 microg/ml), piperacillin (192 microg/ml), and a three drug combination of azetreonam (16 microg/ml), ceftazidime (16 microg/ml), and amikacin (4 microg/ml). Six hours after drug addition, colistin (2 microg/ml), aztreonam (48 microg/ml), piperacillin-tazobactam (192-4 microg/ml), piperacillin (192 microg/ml), and the above three drug combination had bacteriostatic effects on all four strains. Colistin, three time breakpoint of aztreonam, piperacillin, or piperacillin-tazobactam, and the three drug combination of aztreonam, ceftazidime, and amikacin were effective in vitro.

Microbial contamination of fruit and vegetables and their disinfection.

We evaluated the microbial contamination of 17 types of vegetable and 10 types of fruit after 30-s washing with tap water with and without subsequent disinfection by 10-min immersion in 0.01% (100 ppm) sodium hypochlorite. The mean microbial contamination level of 9 types of leafy vegetable was 2.8 x 10(5) colony-forming units (CFU)/g after washing with water and 3.4 x 10(4) CFU/g after washing followed by disinfection. The mean microbial contamination level of 8 types of nonleafy vegetable was 3.4 x 10(4) CFU/g after washing with water and 1.0 x 10(4) CFU/g after washing followed by disinfection. The mean microbial contamination level of 10 types of unpeeled fleshy fruit was 9.3 x 10(3) CFU/g after washing with water and 1.3 x 10(3) CFU/g after washing followed by disinfection. The contaminants in vegetables and unpeeled fruit were similar after washing and after washing followed by disinfection, including Pseudomonas fluorescens and Pseudomonas aeruginosa. The contamination did not markedly decrease even after disinfection with sodium hypochlorite. However, the flesh of each type of peeled fruit showed no or only low levels of contamination (

Genetic approach to study the relationship between penicillin-binding protein 3 mutations and Haemophilus influenzae beta-lactam resistance by using site-directed mutagenesis and gene recombinants.

To clarify the relationship between mutations commonly found for penicillin-binding protein 3 (PBP 3) of beta-lactamase-nonproducing ampicillin-resistant (BLNAR) Haemophilus influenzae isolates and beta-lactam resistance, single and multiple amino acid mutations at positions 377, 385, 389, 517, and 526 were introduced into PBP 3 of a beta-lactam-susceptible Rd strain by site-directed mutagenesis. Twelve isogenic recombinant strains were challenged with nine beta-lactam antibiotics. Replacement of the asparagine at position 526 with lysine (N526K) increased the resistance to imipenem eightfold and increased the resistance to various cephalosporins two- to eightfold. Substitution of threonine for serine at position 385 (S385T) and/or substitution of phenylalanine for leucine at position 389 (L389F), in addition to the N526K mutation, led to two- to fourfold additional increases in cephalosporin resistance. An isoleucine-to-methionine substitution at position 377 did not change the antibiotic sensitivity of any of the recombinant strains also carrying other PBP 3 mutations tested. Thirty-six clinical isolates carrying a PBP 3 gene (ftsI) with the S385T, L389F, R517H, and/or N526K mutation were chosen from among 279 clinical isolates collected in Japan, and the isolates were grouped into six classes on the basis of the patterns of the four mutations in PBP 3. Rd recombinants were made with each of the ftsI genes. The levels of resistance to beta-lactams varied between recombinants of different classes but were comparable for those of the same class. The levels of resistance to cephalosporins of these recombinants were similar to those of the parent clinical isolates, while those to ampicillin and carbapenems were lower. These results indicate that resistance to beta-lactams, at least to cephalosporins, depends in large part on the PBP 3 mutations R517H, N526K, S385T, and L389F.

Comparison of activities of beta-lactam antibiotics against Streptococcus pneumoniae with recombinant penicillin-binding protein genes from a penicillin-resistant strain.

We investigated the antibacterial activities of 19 beta-lactams against three recombinant bacterial strains, in which three penicillin-binding protein genes, pbp2x, pbp1a, and pbp2b, from penicillin-resistant Streptococcus pneumoniae (PRSP), were transformed to a penicillin-susceptible strain. By the acquisition of the pbp2x gene from PRSP, the minimum inhibitory concentrations (MICs) of third-generation cephalosporins were increased more than eight fold. When the strain acquired the PRSP pbp1a gene in addition to pbp2x, the MICs of all tested beta-lactams increased 2- to 16-fold. When the strain acquired the PRSP pbp2b gene in addition to pbp2x and pbp1a, the MICs of penicillins and carbapenems increased 4- to 16-fold. However, two novel carbapenems, ME1036 and L-036, showed excellent antibacterial activities against these recombinant strains, as well as against the parent PRSP.