Factors associated with COVID-19 booster vaccine hesitancy: a nationwide, cross-sectional survey in Japan.

OBJECTIVES: COVID-19 vaccine hesitancy/fatigue is increasing as the pandemic enters the endemic phase. The present study aimed to explore current perceptions about COVID-19 booster vaccination among the Japanese public. STUDY DESIGN: This was a cross-sectional study. METHODS: This cross-sectional study used data from the Japan COVID-19 and Society Internet Survey conducted in September 2021 and September 2022. The public's perceptions of COVID-19 vaccination and factors associated with COVID-19 booster vaccine hesitancy were analyzed. RESULTS: In total, 56,735 respondents were included. In the Japan COVID-19 and Society Internet Survey 2021, 75.1% of the participants (21,126/28,118) had completed the primary vaccination series. In the 2022 survey, 74.1% of the respondents (21,216/28,617) completed the primary series of vaccination with booster doses. The proportion of fear toward COVID-19 and obtaining information about COVID-19 has decreased from 2021 to 2022. Factors independently associated with booster vaccine hesitancy were young age (range: 18-29 years; adjusted odds ratio [aOR]: 6.56), history of COVID-19 (aOR: 1.82), distrust of the Japanese government's COVID-19 prevention measures (aOR: 1.55), lack of confidence in COVID-19 vaccine efficacy (aOR: 1.30), lack of confidence in COVID-19 vaccine safety (aOR: 1.62), low reliance on the COVID-19 vaccine (aOR: 1.92), and belief in COVID-19 conspiracy theories (aOR: 1.77). CONCLUSIONS: Providing clear and trustworthy information is critically important, especially targeted and tailored messages for the young generation, to promoting COVID-19 booster vaccination. Policymakers should therefore develop consistent and transparent communication strategies and the ability to respond promptly and flexibly to mitigate the negative impact of COVID-19 on the public while preparing for the next pandemic.

Synovial mesenchymal stem cells promote healing after meniscal repair in microminipigs.

OBJECTIVE: The induction of synovial tissue to the meniscal lesion is crucial for meniscal healing. Synovial Mesenchymal stem cells (MSCs) are an attractive cell source because of their high proliferative and chondrogenic potentials. We examined whether transplantation of synovial MSCs promoted healing after meniscal repair of extended longitudinal tear of avascular area in a microminipig model. DESIGN: Longitudinal tear lesion was made in medial menisci and sutured in both knees, and then a synovial MSC suspension was administered for 10 min only in unilateral knee. The sutured meniscus was evaluated morphologically and biomechanically at 2, 4, and 12 weeks. The behavior of transplanted MSCs was also examined. RESULTS: The meniscal healing at 12 weeks was significantly better in the MSC group than in the control group; macroscopically, histologically and by T1rho mapping analysis. Transmission electron microscopic analysis demonstrated that the meniscus lesion was occupied by dense collagen fibrils only in the MSC group. Biomechanical analysis revealed that the tensile strength to failure of the meniscus higher in the MSC group than in the control group in each microminipig. Synovial tissue covered better along the superficial layer from the outer zone into the lesion of the meniscus in the MSC group at 2 and 4 weeks in each microminipig. Synovial MSCs labeled with ferucarbotran were detected in the meniscus lesion and adjacent synovium by MRI at 2 weeks. CONCLUSION: Transplantation of synovial MSCs promoted healing after meniscal repair with induction of synovium into the longitudinal tear in the avascular zone of meniscus in pigs.

Tobacco smoking and the risk of subsequent primary cancer among cancer survivors: a retrospective cohort study.

BACKGROUND: Smoking is a well-known risk factor for cancer; however, there is little evidence as to whether the smoking status of cancer survivors has any risk for subsequent primary cancer (SPC) incidence, regardless of the first cancer sites. PATIENTS AND METHODS: In total, 29,795 eligible patients with a first cancer between 1985 and 2004 were examined for SPC until the end of 2006, using a record linkage between hospital-based and population-based cancer registries. The association between smoking at the time of the first cancer diagnosis and three SPC groups (i.e. specific SPC, smoking-related SPCs, and all SPCs) was calculated by Poisson regression. RESULTS: Ever smokers had 59% and 102% higher risk for all SPCs and smoking-related SPCs, respectively, than never smokers. Cancer survivors who had recently stopped smoking had 18% and 26% less risk, respectively, for these SPCs than those who smoked at the diagnosis. We also found that, compared with those who had never smoked, cancer survivors who had ever smoked had a significantly elevated risk of oral/pharyngeal, esophageal, stomach, lung, and hematological SPCs, regardless of the first cancer sites. CONCLUSIONS: These findings indicate that smoking increases not only the first cancer but also a second or SPC. Moreover, the results from recent quitters versus current smokers suggest that smoking cessation may decrease the risk for SPC, especially for smoking-related SPCs in cancer survivors. Preventive measures are necessary to reduce not only SPC incidence but also tobacco use.

Dental Pain and Worsened Socioeconomic Conditions Due to the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has led to economic contraction and significant restrictions on society. The shock to the economy could lead to a deterioration of physical health outcomes, including dental health. The present study investigated the association between worsened socioeconomic conditions due to the COVID-19 pandemic and dental pain in Japan. The mediating effects of psychological distress and oral health-related behaviors were also evaluated. Cross-sectional data from the Japan COVID-19 and Society Internet Survey conducted from August to September 2020 (n = 25,482; age range, 15-79 y) were analyzed. Multivariable logistic regression models were fitted to evaluate the independent associations of household income reduction, work reduction, and job loss due to the COVID-19 pandemic with dental pain within a month. Dental pain was reported by 9.8%. Household income reduction, work reduction, and job loss were independently associated with dental pain after adjusting for confounders (odds ratios: 1.42 [95% confidence interval (CI), 1.28-1.57], 1.58 [95% CI, 1.41-1.76], 2.17 [95% CI, 1.64-2.88], respectively). The association related to household income reduction was mediated by psychological distress, postponing dental visits, toothbrushing behavior, and between-meals eating behavior by 21.3% (95% CI, 14.0-31.6), 12.4% (95% CI, 7.2-19.6), 1.5% (95% CI, -0.01 to 4.5), and 9.3% (95% CI, 5.4-15.2), respectively. Our findings showed that worsened socioeconomic conditions due to the COVID-19 pandemic deteriorated dental health. Policies that protect income and job loss may reduce dental health problems after the pandemic.

Characteristics of the serum pepsinogen (Pg) test, and the relationship between Pg test results and gastric cancer outcomes.

BACKGROUND AND AIMS: The serum pepsinogen (Pg) test is considered to be a high-risk marker for gastric cancer, so that it is intended that it will be gradually adopted for mass surveys in Japan. This manuscript examines the characteristics of the preoperative Pg test and the relationship between its results and the postoperative outcomes of gastric cancer cases in relation to the neutrophil/lymphocyte ratio (NLR) as a prognostic -marker. MATERIALS AND METHODS: Peripheral blood samples were taken within 1 week before gastrectomy for the Pg test and NLR. RESULTS: The Pg test identified 128 (+) cases (59.0%) and 89 (-) cases (41.0%). In three of all cases, cancer had not been detected by an upper gastrointestinal series (UGI) in the previous year (every case showed Pg (+)). Five-year survival was 80.5% in the Pg (+) group, 60.7% in the Pg (-) group, 85.6% in the NLR (<5.0) group, and 29.9% in the NLR (5.0) group, but 14.3% in the NLR (5.0) plus Pg (-) group, and 89.5% in the NLR (<5.0) plus Pg (+) group. The differences in the 5-year survivals were statistically significant. CONCLUSIONS: A mass survey using the Pg test alone is inadequate, but the Pg test may be an important adjunct to the conventional methods. Gastric cancer with Pg (-) may have a higher potential for malignancy than cancer with Pg (+).

Effect of atorvastatin on microRNA 221 / 222 expression in endothelial progenitor cells obtained from patients with coronary artery disease.

BACKGROUND: Endothelial progenitor cells (EPCs) play an important role in the maintenance of vascular integrity. Lipid lowering therapy (LLT) with statins may contribute to biologically relevant activities including the proliferation of endothelial cells. The physiological role of microRNA (miR)-221/222, a newly discovered class of small RNA, is closely linked to the proliferation of endothelial cells. We therefore investigated whether LLT with statins might affect miR-221/222 expression in EPCs obtained from patients with coronary artery disease (CAD). MATERIALS AND METHODS: This study included 44 patients with stable CAD and 22 subjects without CAD (non-CAD). Patients with CAD were randomized to 12 months of LLT with atorvastatin (10 mg day(-1)) or pravastatin (10 mg day(-1)). EPCs were obtained from peripheral blood at baseline and after 12 months of statin therapy. Levels of miR-221/222 in EPCs were measured by real-time RT-PCR. RESULTS: Levels of miR-221/222 were significantly higher in the CAD group than in the non-CAD group (P < 0.01). Levels of miR-221/222 were weakly negatively correlated with EPC number in the CAD group. After 12 months of therapy, changes in lipid profiles were greater in the atorvastatin group than in the pravastatin group. LLT with atorvastatin markedly increased EPC numbers and decreased miR-221/222 levels (all P < 0.05), whereas LLT with pravastatin did not change EPC numbers or miR-221/222 levels. CONCLUSIONS: This study demonstrates that LLT with atorvastatin increases EPC numbers and decreases miR-221/222 levels in patients with CAD, possibly contributing to the beneficial effects of LLT with atorvastatin in this disorder.

Lymphangiosarcoma in a cat.

This report describes a 5-year-old female cat with lymphangiosarcoma arising within the dermis and subcutis of the caudal mammary region. The mass presented as a large, poorly demarcated and fluctuant swelling with bruising of the overlying skin. Histopathologically, the dermis and subcutis in the affected region were diffusely oedematous, haemorrhagic, and infiltrated by plump spindle cells that formed irregular vascular clefts and cavernous channels. Neoplastic cells were aligned in one or more layers along oedematous collagenous trabeculae. The vascular clefts and channels contained only a few or no erythrocytes. The neoplastic cells had moderate to marked nuclear pleomorphism and prominent nucleoli. Lymphocytes and plasma cells were scattered throughout the neoplasm and the adjacent soft tissues. Immunohistochemical labelling revealed the neoplastic cells to express vimentin, factor VIII-related antigen and the lymphatic endothelial cell marker PROX-1, but the cells did not express cytokeratin. The nuclei of many neoplastic cells expressed the proliferation marker Ki67. These histopathological and immunohistochemical findings confirmed the diagnosis of lymphangiosarcoma. This is the first report describing the usefulness of expression of PROX-1 for differentiating between angiosarcoma of lymphatic and vascular origin in cats.

The Infundibular Recess Passes through the Entire Pituitary Stalk.

BACKGROUND AND PURPOSE: The infundibular recess (IR), commonly illustrated as a V-shaped hollow in the sagittal view, is recognized as a small extension of the third ventricle into the pituitary stalk. The precise morphology of the human IR is unknown. The present study sought to delineate the morphology of the IR using magnetic resonance imaging. MATERIALS AND METHODS: Subjects included 100 patients without acute cerebral infarcts, intracranial hemorrhage, intrasellar or suprasellar cysts, hydrocephalus, inflammatory disease, or brain tumors. Patients with symptoms of increased intracranial pressure, intracranial hypotension, or pituitary dysfunction were excluded. Thin-sliced, seamless T2-weighted sequences involving the optic chiasm, entire pituitary stalk, and pituitary gland were performed in axial and sagittal planes for each patient. The numbers of slices delineating the pituitary stalk and IR were recorded from the axial images and quantified as ratios. RESULTS: The pituitary stalk consistently appeared as a styloid- or cone-shaped structure with variable inclinations toward the third ventricle floor. The IR was delineated as a smoothly tapering, tubular extension of the third ventricle located in the central portion of the pituitary stalk. In 81 % of patients, the IR passed through the entire length of the pituitary stalk and reached the upper surface of the pituitary gland, which was identified in 40 % of the midsagittal images. CONCLUSIONS: The IR is a cerebrospinal fluid-filled canal passing through the center of the pituitary stalk and connects the third ventricle to the pituitary gland. It may function in conjunction with the pituitary gland.

Significance of late diastolic potential preceding Purkinje potential in verapamil-sensitive idiopathic left ventricular tachycardia.

BACKGROUND: Verapamil-sensitive idiopathic left ventricular tachycardia (VT) is due to reentry with an excitable gap. A late diastolic potential (LDP) is recorded during endocardial mapping of this VT, but its relation to the reentry circuit and significance in radiofrequency (RF) ablation remain to be elucidated. METHODS AND RESULTS: Sixteen consecutive patients with this specific VT were studied (12 men and 4 women; mean age, 32 years). In all patients, sustained VT was induced and during left ventricular endocardial mapping, LDP preceding Purkinje potential (PP) was recorded at the basal (11 patients), middle (3 patients), or apical septum (2 patients). The area with LDP recording was confined to a small region (0.5 to 1.0 cm2) in each patient and was included in the area where PP was recorded (2 to 3 cm2). The relative activation times of LDP, PP, and local ventricular potential (V) at the LDP recording site to the onset of QRS complex were -50.4+/-18.9, -15.2+/-9.6, and 3.0+/-13.3 ms, respectively. The earliest ventricular activation site during VT was identified at the posteroapical septum and was more apical in the septum than the region with LDP in every patient. In 9 patients, VT entrainment was done by pacing from the right ventricular outflow tract while recording LDP. During entrainment, LDP was orthodromically captured, and as the pacing rate was increased, the LDP-to-PP interval was prolonged, whereas stimulus-to-LDP and PP-to-V interval were constant. In 3 patients, the pressure applied to the catheter tip at the LDP region resulted in conduction block between LDP and PP and in VT termination. RF energy application at the LDP recording site successfully eliminated VT. CONCLUSIONS: LDP was suggested to represent the excitation at the entrance to the specialized area with a conduction delay in response to the increase in the rate within the critical slow conduction zone participating in the reentry circuit of this VT. LDP can be a useful marker for successful RF ablation for this VT.

[Penetrating right ventricular trauma by stab injury; report of a case].

A 52-year-old woman, who had attempted to commit suicide with a kitchen knife, was admitted. Upon arrival, conscious level was II-30 and blood pressure was 76/46 mmHg. The knife with a blade 20 cm long penetrated the thorax from the 7th left intercostal space beside sternum toward the heart and synchronously moved with pulsation of the heart. The chest X-ray showed the left hemothorax and a computed tomography (CT) revealed the tip of the knife reached the right ventricle. After draining the pleural effusion from the left thorax, the median sternotomy and pericardiotomy were made. The knife was shown to be stuck in right ventricle as it grazed the left anterior descending artery and the right posterior descending artery through pericardium from the apex. The ST segments in II, III, aVF and chests leads were elevated in the preoperative electrocardiography (ECG), but any damage was not recognized in coronary arteries. Under the total bypass on extracorporeal circulation, the knife was removed. The wound at the right ventricle reached about 12 cm length from the apex to the inferior wall. Fortunately, papillary muscles, chorda, septum in the right ventricle and also the left lung were not injured. The wound of the right ventricle was closed with reinforced using felt-strips. The postoperative course was uneventful. This case suggested that the most important factor for survival in cardiac trauma would be to make the hemodynamics stable with the urgent treatment just after arrival and to perform the surgical repair immediately.

Enhancement of myocardial reactive hyperemia with manganese-superoxide dismutase: role of endothelium-derived nitric oxide.

OBJECTIVE: To test the hypothesis that superoxide radicals generated during myocardial ischemia and reperfusion influence reactive hyperemia (RH) by reacting with endothelium-derived nitric oxide (EDNO), we examined the effect of manganese (Mn)-superoxide dismutase (SOD) on RH in anesthetized dogs. METHODS: Twelve dogs were pretreated with 8-phenyltheophylline (8PT) to block adenosine's effect. Five dogs were pretreated with 8PT and NG-nitro-L-arginine methyl ester (L-NAME) to block adenosine's and EDNO's effects. Following occlusion of the left circumflex artery (LCX) for 10 and 60 s, RH was observed before and after Mn-SOD. In another group of 6 dogs pretreated with 8PT, RH following 60-s LCX occlusion was observed before and after Mn-SOD and catalase. For comparison with the effect of Mn-SOD, that of copper, zinc (Cu,Zn)-SOD was also examined in another group of 5 dogs. RESULTS: In the dogs pretreated with 8PT, Mn-SOD significantly increased excess flow and repayment of flow debt during RH after 60-s LCX occlusion but did not affect RH after 10-s LCX occlusion. Mn-SOD-induced augmentation of RH following 60-s LCX occlusion was not affected by catalase, while it was completely abolished by L-NAME. In contrast to Mn-SOD, Cu,Zn-SOD showed no effect on RH following 60-s LCX occlusion in the dogs pretreated with 8PT. CONCLUSIONS: Superoxide radicals generated during ischemia for 60 s and reperfusion attenuates myocardial RH through inactivation of EDNO. Mn-SOD shows more beneficial effects on myocardial RH than Cu,Zn-SOD.

Measurements of free thyroxine: comparison of per cent of free thyroxine in diluted and undiluted sera.

The effect of dilution on values of the per cent of free T4 in serum (%FT4) measured by equilibrium dialysis, was determined by comparing the values for %FT4 in diluted and undiluted specimens. The specimens studied were sera obtained from 10 normal subjects, 10 patients with hyperthyroidism, 5 with hypothyroidism, and 9 women with normal pregnancy. The method of analysis employed was that described by Sterling and Brenner, except that the 125I-thyroxine used was predialyzed to remove non-thyroxine contaminants and that "corrected" values for %FT4 were calculated by dividing measured values by the numerical extent to which the serum had been diluted.

The upper turnover site in the reentry circuit of common atrial flutter.

The upper turnover site of the reentry circuit of common atrial flutter was examined with the uses of atrial activation mapping and extrastimulus techniques during atrial flutter. The findings suggest that it is anterior to the orifice of the superior vena cava, i.e., between the superior vena cava and tricuspid annulus.

Effects of angiotensin-converting enzyme inhibitor alacepril in patients with stable effort angina during chronic isosorbide dinitrate treatment.

Nitrate tolerance has been reported to be reversed by certain types of angiotensin-converting enzyme (ACE) inhibitors. We examined whether alacepril, a new long-acting oral ACE inhibitor, has beneficial effects against exercise-induced angina in patients with stable effort angina after substantial isosorbide dinitrate (ISDN) treatment. Thirteen men with stable effort angina were treated with oral ISDN (80 mg/d) for >3 weeks. After this period, efficacy of single oral administration of either alacepril (50 mg) or its placebo on exercise-induced angina and electrocardiographic changes was examined by treadmill exercise test in a double-blind crossover design. Alacepril significantly improved the exercise duration by 9.1% (p=0.03), the time to 1 mm ST-segment depression by 19% (p<0.01), and the maximal ST-segment depression by 33% (p=0.015) compared with placebo. Alacepril did not significantly alter the rate-pressure product, a marker of myocardial oxygen demand, during exercise test compared with placebo. Plasma renin activity was significantly increased (p<0.05) after administration of alacepril, indicating that alacepril significantly blocked ACE activity in our patients. In conclusion, a single oral administration of the ACE inhibitor alacepril (50mg) elicited beneficial effects against exercise-induced myocardial ischemia in patients with stable effort angina during chronic nitrate treatment. These effects may be mediated by increased coronary blood flow.

Characteristics of slow conduction zone demonstrated during entrainment of idiopathic ventricular tachycardia of left ventricular origin.

Idiopathic ventricular tachycardia (VT) with the right bundle branch block pattern and left-axis deviation has been shown to be due to reentry, but the property of the slow conduction zone within the reentry circuit is little understood. In 7 patients (mean VT cycle length [CL]: 361 +/- 49 ms), rapid pacing from the right ventricular outflow tract was performed during VT while recording electrograms at the early activation site in the left ventricle and at the right ventricular apex; also, conduction times from the pacing site to these recording sits (St-A and St-B intervals, respectively) were measured. Both constant fusion (except for the last paced beat) and progressive fusion were seen in all patients, indicating VT entrainment. The left ventricular site was captured orthodromically with an St-A of 394 +/- 57 ms at the pacing CL of 351 +/- 47 ms during entrainment, while the right ventricular apex was captured directly with an St-B interval of 63 +/- 19 ms. The St-A interval was gradually prolonged with the shortening of the pacing CL, whereas the St-B interval remained unchanged. VT was interrupted in all patients at the pacing CL of 279 +/- 39 ms. The effects of intravenous lidocaine (1 mg/kg) and verapamil (1 mg) were examined in 5 and 7 patients, respectively. Neither drug terminated VT but the VT-CL was increased to 369 +/- 57 ms after lidocaine (p <0.05) and to 413 +/- 69 ms after verapamil (p <0.05) (p <0.05 vs after lidocaine). The St-A interval was significantly increased after lidocaine (p <0.05) and after verapamil (p <0.05), while the St-B interval remained unchanged. A significant correlation between changes in St-A interval and VT-CL after verapamil was noted (p <0.001). In conclusion, the slow conduction zone of this VT shows tachycardia-dependent conduction delay, and the mechanism of this slow conduction involves mainly calcium channel-dependent conduction and partly depressed sodium channel-dependent conduction.

Multiple actin-related proteins of Saccharomyces cerevisiae are present in the nucleus.

An increasing number of actin-related proteins (Arps), which share the basal structure with skeletal actin but possess distinct functions, have been found in a wide variety of organisms. Individual Arps of Saccharomyces cerevisiae were classified into Arps 1-10 based on the relatedness of their sequences and functions, where Arp1 is the most similar to actin, and Arp10 is the least similar. While Arps 1-3 and their orthologs in other organisms are localized exclusively in the cytoplasm, Arp4 (also known as Act3) is localized in the nucleus and is involved in transcriptional regulation. Here we examined the more divergent Arps for possible nuclear functions. We show that Arps 5-9 are localized in the nucleus, but Arp10 is not. The nuclear export signals identified in actin are well conserved in the cytoplasmic Arps, Arps 1-3, but less conserved in the nuclear Arps. Gel filtration chromatography experiments show that the nuclear Arps are larger than monomer in size and thus are present in multi-protein complexes. Since nuclear protein complexes containing Arps are found to be responsible for histone acetylation and chromatin remodeling, it is suggested that most of the divergent Arps are involved in the !transcriptional regulation through chromatin modulation.

Antipyrine disposition in relation to lowered anticonvulsant plasma level during pregnancy.

The authors studied antipyrine disposition before and after delivery in 4 epileptic women whose anticonvulsant plasma level per dosage ratio was lowered during pregnancy, and compared the results to those found in nonpregnant women undergoing antiepileptic treatment (N = 6) and healthy women (N = 6). The antipyrine clearance at term (0.53 +/- 0.11 ml/min/kg, mean +/- SD) was lower than it was early during puerperium (0.70 +/- 0.14 ml/min/kg, P less than .05) and approximately 3 months after delivery (1.14 +/- 0.26 ml/min/kg, P less than .01). The antipyrine clearance in nonpregnant epileptics (1.17 +/- 0.44 ml/min/kg) was comparable to that found 3 months after delivery, whereas it was significantly (P less than .01) higher than that found in healthy women (0.47 +/- 0.02 ml/min/kg). These observations suggest that the fall during pregnancy of anticonvulsant plasma concentrations relative to dosage is not attributable to the enhanced oxidative process of hepatic drug metabolism.

Corticonuclear and corticovestibular projections from the uvula in the albino rat: differential projections from sublobuli of the uvula.

The organization of the corticonuclear and corticovestibular projections from the uvula was investigated in the albino rat by an autoradiographic method. The corticonuclear fibers from sublobule a of the uvula terminated in the caudoventral part of the medial cerebellar nucleus, and the caudomedial part of the posterior interpositus nucleus with mediolateral topography. The medial and lateral portions of the sublobule projected to the medial cerebellar and posterior interpositus nuclei, respectively. The corticovestibular fibers from sublobule a terminated in the dorsal and rostral parts of the superior vestibular nucleus, the dorsal part of the lateral vestibular nucleus, and the caudomedial part of the spinal vestibular nucleus. However, the corticonuclear fibers from sublobuli b and c of the uvula terminated additionally in the ventromedial part of the lateral cerebellar nucleus, while the corticovestibular fibers from these sublobuli terminated additionally in the subnucleus y of the vestibular complex, with probable termination in the medial vestibular nucleus. The cortical region which sent efferent projections to the ventromedial part of the lateral cerebellar nucleus and the subnucleus y was located laterally in sublobuli b and c of the uvula. These differential projection patterns from the dorsal and ventral sublobuli suggest the difference of the functional correlates between the sublobuli in the uvula.

Effects of pilsicainide and propafenone on vagally induced atrial fibrillation: role of suppressant effect in conductivity.

The effects of pilsicainide on vagally induced atrial fibrillation and on electrophysiological parameters were compared with those of propafenone in alpha-chloralose-anesthetized dogs. Conduction velocity, effective refractory period, wavelength, averaged atrial fibrillation cycle length and activation sequence in the right atrial free wall were determined before and after drug administration. Pilsicainide (2 mg/kg/5 min and 3 mg/kg/h)(n=10) or propafenone (2 mg/kg/15 min and 4 mg/kg/h)(n=10) was intravenously infused during stable atrial fibrillation sustaining > 30 min. Pilsicainide terminated atrial fibrillation in nine dogs, while propafenone did so in three (p < 0.01). After the drug, conduction velocity was suppressed more in the pilsicainide than in the propafenone group(p < 0.01). There was no difference in effective refractory period after drug between the two groups. Mean wavelength was prolonged from 46.0 to 70.4 mm in the pilsicainide group and from 45.0 to 110.8 mm in the propafenone (p < 0.01 vs. pilsicainide). Activation mapping during atrial fibrillation showed Type II or III atrial fibrillation as previously defined [Konings, K.T.S., Kirchhof, C.J.H.J., Smeets, J.R.L.M., Wellens, H.J.J., Penn, O.C., Allessie, M.A., 1994. High-density mapping of electrically induced atrial fibrillation in humans. Circulation. Vol. 89, pp. 511-521.] before the drug, and changed to Type I before atrial fibrillation termination. Thus, pilsicainide was more effective to terminate vagally induced atrial fibrillation than was propafenone despite a greater effect of propafenone than of pilsicainide on wavelength. In this canine atrial fibrillation model, the suppression of conduction velocity may play an important role in changing the activation pattern of atrial fibrillation and thus, terminating atrial fibrillation.

Vasodilator effect of carboxy-2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl in the coronary circulation: in vivo and in vitro studies.

2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO) derivatives, new radical forms of nitric oxide (NO) antagonists, are reported to react with NO and generate NO2 and 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl (PTI) derivatives. We found that carboxy-PTI, a water-soluble derivative of PTI, showed a potent vasodilator effect in the canine coronary artery system. In anesthetized dogs, intracoronary infusion of carboxy-PTI significantly increased the coronary flow in a dose-dependent manner without altering systemic hemodynamic variables. This coronary flow increasing effect of carboxy-PTI was not influenced by pretreatment with either NG-nitro-L-arginine methyl ester or 8-phenyltheophylline or autonomic blockade. However, the flow increasing effect of carboxy-PTI was abolished by reducing carboxy-PTI with ascorbic acid to a non-radical form of carboxy-PTI, indicating that carboxy-PTI shows its effect only in a radical form. In isolated canine coronary arterial rings, carboxy-PTI caused endothelium-independent relaxation. This relaxation response was significantly attenuated by pretreatment with methylene blue, an inhibitor of soluble guanylate cyclase. Thus, carboxy-PTI has an endothelium-independent coronary vasodilator effect in both large conduit arteries and small resistance vessels. The results of the in vitro experiment suggested that the activation of soluble guanylate cyclase of the vascular smooth muscle cell may be involved, at least in part, in the vasodilator mechanism of carboxy-PTI in large conduit arteries.