Enhancement of cardiac actions of ouabain and its binding to Na+, K+-adenosine triphosphatase by increased sodium influx in isolated guinea-pig heart

The rate of development of the positive inotropic action of ouabain is enhanced when the heart is stimulated at higher frequencies. A hypothesis that this enhancement is due to a stimulation of the glycoside binding to sarcolemmal Na+,K+-adenosine triphosphatase (ATPase) caused by an increase in intracellular Na+ available to the sodium pump was tested in isolated left atrial muscle preparations of guinea-pig heart, incubated at 30 degrees C and electrically stimulated at 0.5, 1 or 2 Hz. The rate of development of the positive inotropic action of ouabain was dependent on the frequency of stimulation. Each preparation was homogenized at a predetermined time and the fractional occupancy of Na+,K+-ATPase by ouabain was estimated from the decrease in the initial velocity of ATP-dependent [3H]ouabain binding reaction. A parallel relationship was observed between effects of stimulation frequency of the positive inotropic action and those on the occupancy of Na+,K+-ATPase by ouabain. In quiescent preparations, a sodium ionophore, monensin, enhanced the development of contracture caused by a toxic concentration of ouabain and also the glycoside binding to Na+,K+-ATPase. Similar effects on the ouabain-induced contracture and on the glycoside binding were observed with either grayanotoxin I or batrachotoxin, agents known to increase sodium influx, when muscle preparations were exposed to these agents under 1.5 Hz stimulation and were subsequently tested for the actions of ouabain in quiescence. When the exposure to ouabain and either grayanotoxin I or batrachotoxin was restricted to quiescent period, the development of ouabain-induced contracture and glycoside binding to Na+,K+-ATPase were not significantly altered. Monensin, grayanotoxin I or batrachotoxin failed to significantly affect [3H]ouabain binding to muscle homogenates when added to the medium for the labeled glycoside binding assay. These results indicate that intracellular sodium ions promote the ouabain binding to Na+,K+-ATPase and thereby enhance the development of glycoside actions in the isolated atrial muscle of guinea-pig heart. The "beat-dependent" onset of the glycoside action is at least partially explained from the effect of membrane depolarization to increase Na+ available to the sodium pump and to enhance the glycoside binding.     

The Relation Between Optical Coherence Tomography-Detected Layered Pattern and Acute Side Branch Occlusion after Provisional Stenting of Coronary Bifurcation Lesions

Background/purposeLayered pattern (presumed to be healed plaque after a thrombotic event) can be observed by optical coherence tomography (OCT). We sought to assess the ability of OCT-detected plaque composition to predict acute side branch (SB) occlusion after provisional bifurcation stenting.MethodsThis is a retrospective observational study using pre-intervention OCT in the main vessel to predict Thrombolysis in Myocardial Infarction (TIMI) flow grade ≤1 in a SB (diameter ≥ 1.5 mm) after provisional bifurcation stenting. OCT-detected layered pattern was defined as plaque with a superficial layer that had a different optical intensity and a clear demarcation from underlying tissue.ResultsOverall, 207 patients with stable coronary disease were included. SB occlusion occurred in 26/207 (12.6%) bifurcation lesions. Operators decided not to perform additional treatment, and TIMI flow did not improve to ≥2 in cases with SB occlusion. The prevalence of OCT-detected layered pattern was more common in lesions with versus without SB occlusion (88.5% versus 33.7%, p < 0.0001); OCT-detected layered pattern was more often located on the same side of the SB (73.9% versus 21.3%, p < 0.0001) circumferentially compared to lesions without SB occlusion. Multivariable analysis showed that OCT-detected layered pattern was an independent predictor of SB occlusion (odds ratio 18.8, 95% confidence interval 5.1–68.8, p < 0.0001) along with true bifurcation lesion and wider angiographic bifurcation angle.ConclusionsThe presence of an OCT-detected layered pattern near its ostium was a strong predictor of SB occlusion after provisional bifurcation stenting.     

The usefulness of an earphone-type infrared tympanic thermometer during cardiac surgery with cardiopulmonary bypass: clinical report

We evaluated the usefulness of a novel earphone-type infrared tympanic thermometer (IRT) during cardiac surgery with cardiopulmonary bypass. Tympanic membrane temperature (T _Tym) was monitored using the IRT inserted into the right ear canal of 12 adult patients (ASA III) who had been scheduled for elective cardiac surgery with cardiopulmonary bypass under general anesthesia. Rectum (T _Rec) and nasopharyngeal temperatures (T _Naso) were also monitored, and all temperatures were recorded at 5-min intervals during cardiopulmonary bypass. Operating room temperature was kept at 20°–27°C; a conductive warming/cooling system was used to control the patient’s body temperature. Of 265 measurements obtained, body temperature range was 31.6°–37.6°C. No complications were related to site of insertion of the monitoring probe. Significant correlations were seen between T _Tym and T _Naso (r = 0.971, P < 0.001), and T _Tym and T _Rec (r = 0.759, P < 0.001). A Bland–Altman plot showed that average temperature of T _Tym was 0.06°C above T _Naso (±0.66°C, 2 SD) and 0.12°C below T _Rec (±1.78°C, 2 SD). We conclude that an earphone-type IRT is noninvasive and hygienic and could continuously evaluate selective cerebral temperature during cardiopulmonary bypass in adults.     

Safe and Effective Ablation of Atrial Fibrillation: Importance of Esophageal Temperature Monitoring to Avoid Periesophageal Nerve Injury as a Complication of Pulmonary Vein Isolation

Introduction: Catheter ablation on the left atrial posterior wall has been reported to potentially damage the esophagus or periesophageal vagal nerve. The aim of this study was to evaluate the efficacy of esophageal temperature monitoring (ETM) in preventing esophageal or periesophageal vagal nerve injury in patients with atrial fibrillation (AF) undergoing pulmonary vein (PV) isolation.
Methods: This study included 359 patients with drug-refractory AF who underwent extensive PV isolation. The first 152 patients were treated without ETM (non-ETM) and the last 207 with ETM. In the ETM group, the esophageal temperature (ET) was measured with a deflectable temperature probe that was placed close to the ablation electrode, and the radiofrequency energy applications were stopped when the ET reached 42°C.
Results: In all patients in the ETM group, the ET increased to 42°C in at least one site by 28 ± 14 seconds, mostly along the right side of the left PVs, especially near the left inferior PV. Less energy (6.3 ± 1.9 × 10⁴ J) was required for PV isolation in the ETM group than that in the non-ETM (6.8 ± 1.9 ×10⁴ J, P = 0.03). Gastric hypomotility owing to periesophageal nerve damage was observed in three patients in the non-ETM group, but in none in the ETM (P = 0.02). The recurrence rates of AF did not differ between the two groups (non-ETM, 29%; ETM, 27%).
Conclusion: Titration of the duration of the ablation energy delivery while monitoring the ET could prevent periesophageal nerve injury due to the AF ablation, without decreasing the success rate of maintaining sinus rhythm.     

Diagnostic utility of flow cytometry in low-grade myelodysplastic syndromes: a prospective validation study

Background

The diagnosis of myelodysplastic syndromes is not always straightforward when patients lack specific diagnostic markers, such as blast excess, karyotype abnormality, and ringed sideroblasts.

Design and Methods

We designed a flow cytometry protocol applicable in many laboratories and verified its diagnostic utility in patients without those diagnostic markers. The cardinal parameters, analyzable from one cell aliquot, were myeloblasts (%), B-cell progenitors (%), myeloblast CD45 expression, and channel number of side scatter where the maximum number of granulocytes occurs. The adjunctive parameters were CD11b, CD15, and CD56 expression (%) on myeloblasts. Marrow samples from 106 control patients with cytopenia and 134 low-grade myelodysplastic syndromes patients, including 81 lacking both ringed sideroblasts and cytogenetic aberrations, were prospectively analyzed in Japan and Italy.

Results

Data outside the predetermined reference range in 2 or more parameters (multiple abnormalities) were common in myelodysplastic syndromes patients. In those lacking ringed sideroblasts and cytogenetic aberrations, multiple abnormalities were observed in 8/26 Japanese (30.8%) and 37/55 Italians (67.3%) when the cardinal parameters alone were considered, and in 17/26 Japanese (65.4%) and 42/47 Italians (89.4%) when all parameters were taken into account. Multiple abnormalities were rare in controls. When data from all parameters were used, the diagnostic sensitivities were 65% and 89%, specificities were 98% and 90%, and likelihood ratios were 28.1 and 8.5 for the Japanese and Italian cohorts, respectively.

Conclusions

This protocol can be used in the diagnostic work-up of low-grade myelodysplastic syndromes patients who lack specific diagnostic markers, although further improvement in diagnostic power is desirable.     

Relation of atherothrombosis burden and volume detected by intravascular ultrasound to angiographic no-reflow phenomenon during stent implantation in patients with acute myocardial infarction

This study investigated the mechanism of occurrence of the no-reflow phenomenon during stent implantation in patients with acute myocardial infarction (AMI) using intravascular ultrasound (IVUS) with volumetric analysis. Of 70 patients with AMI who underwent IVUS-guided stent implantation within 24 hours of symptom onset, 12 developed decreased Thrombolysis In Myocardial Infarction flow grade during stent implantation and without subsequent restoration to Thrombolysis In Myocardial Infarction flow grade before stenting. External elastic membrane cross-sectional area and maximum diameter at the culprit lesion as measured by IVUS before stent implantation were significantly larger in the no-reflow group (n = 12) than in the normal reflow group (n = 58; 20.1 +/- 6.5 vs 16.4 +/- 4.3 mm2, p = 0.015 for cross-sectional area and 5.2 +/- 0.9 vs 4.8 +/- 0.6 mm, p = 0.049 for maximum diameter). Plaque volume, volumetric plaque burden (plaque volume/external elastic membrane volume), and change in plaque volume during stent implantation (plaque volume after vs before) were significantly greater in the no-reflow group than in the normal reflow group (239 +/- 142 vs 178 +/- 72 mm3, p = 0.030; 0.76 +/- 0.07 vs 0.71 +/- 0.06, p = 0.010; and -46 +/- 63 vs -11 +/- 37 mm3, p = 0.013, respectively). In conclusion, high atherothrombotic burden and decreased plaque volume as detected by IVUS may be risk factors for development of the no-reflow phenomenon during stent implantation in patients with AMI.     

Sleep in spontaneous dwarf rats

Spontaneous dwarf rats (SDRs) display growth hormone (GH) deficiency due to a mutation in the GH gene. This study investigated sleep in SDRs and their somatotropic axis and compared to Sprague-Dawley rats. SDRs had almost undetectable levels of plasma GH. Hypothalamic GH-releasing hormone (GHRH) mRNA was increased, whereas GHRH-receptor (GHRH-R) and somatostatin mRNAs were decreased in SDRs. Hypothalamic GHRH and somatostatin peptide content decreased in SDRs. Quantitative immunohistochemistry for GHRH and GHRH-R corroborated and extended these findings. In the arcuate nucleus, the number of GHRH-positive cells was significantly higher, whereas GHRH-R-positive perikarya were diminished in SDRs. Cortical GHRH and GHRH-R measurements showed similar expression characteristics as those found in the hypothalamus. SDRs had less rapid eye movement sleep (REMS) and more non-REMS (NREMS) than the control rats during the light period. The electroencephalogram (EEG) delta and theta power decreased during NREMS in the SDRs. After 4-h of sleep deprivation, SDRs had a significantly reduced REMS rebound compared to the controls, whereas NREMS rebound was normal in SDRs. The enhancement in delta power was significantly less than in the control group during recovery sleep. Intracerebroventricular (icv) administration of GHRH promoted NREMS in both strains of rats; however, increased REMS and EEG delta activity was observed only in control rats. Icv injection of insulin-like growth factor 1 increased NREMS in control rats, but not in the SDRs. These results support the ideas that GHRH is involved in NREMS regulation and that GH is involved in the regulation of REMS and in EEG slow wave activity regulation during NREMS.     

Specialists Play a Vital Role in General Practitioners' Prescription Behavior: A Qualitative Study of Asthma Care in Japan

Background. The prevalence of obesity and asthma has been increasing during the last several decades. Obesity has been reported to be associated with asthma. Obesity, especially abdominal obesity, is the main component of the metabolic syndrome. Objectives. We thus hypothesized that metabolic syndrome is an important contributing factor for the development of asthma-like symptoms. Methods. The Korean Health and Genome Study started in 2001 as an ongoing population-based study of Korean adults 40 to 69 years of age. The prevalence of asthma-like symptoms in the previous 12 months was obtained by a questionnaire, and spirometric testing was conducted. Results. Among the 10,038 participants, the data from 9,942 individuals (4,716 men and 5,226 women) was available. Asthma-like symptoms (wheeze [p = 0.0006], resting dyspnea [p = 0.0062], and post-exercise dyspnea [p < 0.0001]) were increased in the subjects of the metabolic syndrome group. Subjects with asthma-like symptoms had a decreased lung function compared to subjects without asthma-like symptoms. Among the components of the metabolic syndrome, abdominal obesity and hypertension were the risk factors for asthma-like symptoms. Conclusions. Metabolic syndrome is associated with asthma-like symptoms. Among the components of metabolic syndrome, abdominal obesity and hypertension are the risk factors for asthma-like symptoms.