Tetsunobu Yamane

The relationship between flow-mediated brachial artery vasodilation and coronary vasomotor responses to bradykinin: comparison with those to acetylcholine.

Flow-mediated dilation (FMD) of brachial artery provides a noninvasive assessment of coronary endothelial dysfunction. Acetylcholine (ACh) has been used as an agent for estimating coronary endothelial function. In contrast to ACh, there is no evidence for a relationship between FMD and coronary vasodilation to bradykinin (BK). The aim of this study was to compare the flow-mediated vasodilation of brachial artery with coronary vasomotor responses to intracoronary ACh or BK in patients with an angiographically normal left anterior descending coronary artery. Ninety-one patients underwent the cardiac catheterization examination with coronary endothelial function testing and the brachial ultrasound study. BK (0.2, 0.6, 2.0 μg/min) and ACh (3, 10, 30 μg/min) were administered into the left coronary artery in a stepwise manner. Coronary blood flow was evaluated by the Doppler flow velocity measurement. Coronary diameters were measured by the quantitative coronary angiography. The assessment of endothelial function in the brachial artery was made in response to reactive hyperemia with high-resolution ultrasound. Bradykinin induced dose-dependent increases in epicardial coronary diameter and blood flow. There was a significant positive correlation between FMD- and BK-induced vasodilations of epicardial coronary arteries (0.2 μg/min: r = 0.30; 0.6 μg/min: r = 0.42; 2.0 μg/min: r = 0.44, P < 0.01, respectively) and resistance coronary arteries (0.2 μg/min: r = 0.40; 0.6 μg/min: r = 0.56; 2.0 μg/min: r = 0.59, P < 0.0001, respectively). FMD correlated with ACh-induced vasomotions of resistance but not epicardial coronary arteries. No correlation was seen between nitroglycerin-induced brachial artery vasodilation and BK-induced coronary vasodilation. The endothelial dysfunction of peripheral arteries correlated well with that of the coronary arteries especially vasomotor responses to BK.

Association of the Plasma Platelet-Derived Microparticles to Platelet Count Ratio with Hospital Mortality and Disseminated Intravascular Coagulopathy in Critically Ill Patients

AIM The role of platelet-derived microparticles (PDMPs) in the crosstalk between coagulopathy and inflammation in critically ill patients remains unclear. The aim of this cohort observational study was to investigate the associations between the PDMP levels and hospital mortality or disseminated intravascular coagulopathy (DIC). METHODS This study included 119 patients who were admitted to the ICU. The PDMP levels were measured using an enzyme-linked immunosorbent assay three times a week, for a total of 372 samples. We calculated the maximum (max) PDMP value, max PDMP/platelet (PDMP/Plts) ratio (converted to the PDMP levels per 10(4) platelets) and nadir platelet count during the ICU stay. Baseline patient data and scores, including the Japanese Association for Acute Medicine (JAAM) DIC score, were collected, and potential predictors were analyzed for possible associations with hospital mortality. RESULTS The max PDMP/Plts ratio was significantly different comparing the survivors (n=98: median, 2.54) and non-survivors (n=21: median 17.59; p＜0.001). There was a weak but statistically significant negative correlation between the max PDMP level and nadir platelet count (r=-0.332, p＜0.001). The max PDMP level and max PDMP/Plts ratio were higher in the DIC group (81.48 and 9.27, respectively) than in the non-DIC group (34.88 and 2.35, p=0.001 and p＜0.001, respectively). The max PDMP/Plts ratio was the only variable found to be independently associated with hospital mortality according to a multivariate logistic regression analysis. CONCLUSIONS PDMPs are involved in the development of DIC but are not related to hospital mortality. There is a good association between the PDMP/Plts ratio and hospital mortality and/or DIC in critically ill patients.

Brachial Artery Flow-Mediated Vasodilation Is Correlated with Coronary Vasomotor and Fibrinolytic Responses Induced by Bradykinin

Endothelium plays a key role in the regulation of not only vascular tone but also thrombosis and fibrinolysis. Brachial flow-mediated vasodilation (FMD) provides a noninvasive method of assessing coronary endothelial dysfunction. However, no data are available on the relationship between brachial FMD and coronary fibrinolytic activity. Thus, we examined the relationship between brachial FMD and coronary vasomotor and fibrinolytic function. Brachial FMD by reactive hyperemia was defined as a change in diameter relative to the baseline as measured using high-resolution ultrasound. Coronary blood flow (CBF) responses to bradykinin (BK) were analyzed using Doppler flow velocity measurement. Coronary release of tissue-type plasminogen activator (tPA) antigen was determined as the transcardiac tPA gradient × {CBF × (100 − hematocrit)/100}. In 77 patients with normal coronary arteries, BK caused dose-dependent increases in CBF, transcardiac tPA gradient, and coronary tPA release. Among them, brachial FMD, the BK-induced CBF increase, and the coronary tPA release induced by BK in 14 diabetic subjects were lower than those in 63 non-diabetic subjects (p<0.05, respectively). Brachial FMD correlated with the CBF increase, transcardiac tPA gradient (0.2 μg/min: r=0.25; 0.6 μg/min: r=0.43; 2.0 μg/min: r=0.34; p<0.05, respectively), and coronary tPA release (0.2 μg/min: r=0.24; 0.6 μg/min: r=0.44; 2.0 μg/min: r=0.32; p<0.05, respectively) in response to BK. Brachial FMD correlated significantly with coronary endothelial function and fibrinolytic activity in response to BK. Type 2 diabetes impaired coronary and brachial endothelium-dependent vasodilation and coronary fibrinolytic activity.

Impact of Paraoxonase Polymorphism (Q192R) on Endothelial Function in Intact Coronary Circulation

Paraoxonase-1 (PON1) can protect endothelial function by preventing the oxidation of low-density lipoprotein (LDL) cholesterol and retarding the development of atherosclerosis. We examined whether PON1 polymorphism influences endothelium-dependent coronary vasomotor responses. Sixty-seven patients underwent diagnostic cardiac catheterization, but showed no significant coronary artery stenosis. In all patients, PON1 genotypes (Q/Q, Q/R and R/R) were determined, and provocative testing was performed by the intracoronary administration of graded doses of bradykinin (BK; 0.2, 0.6 and 2.0 μg/min) and acetylcholine (ACh; 3, 10 and 30 μg/min). Coronary blood flow (CBF) was evaluated by a Doppler guide wire. The patients were divided into 2 groups on the basis of ACh testing: one with coronary spastic angina (CSA) and one with non-CSA. The frequencies of the PON1 genotype in the CSA group did not differ significantly from those in the non-CSA group. In the non-CSA group, the patients were subdivided into 2 groups: a group with the Q/Q or Q/R genotypes and a group with the R/R genotype. The vasoconstrictive responses of the epicardial coronary artery to ACh were comparable between the Q/Q + Q/R and R/R groups. Also, the coronary vasodilations induced by BK in the R/R group were similar to those in the QR + QQ group. There were no significant differences in the CBF responses induced by BK or ACh between the Q/Q + Q/R and R/R groups. In conclusion, as estimated by BK and ACh testing, our findings suggest that PON1 genotypes may not play a critical role in the modulation of endothelial vasomotor function in the intact coronary circulation.

Angiotensin-Converting Enzyme Inhibition Augments Coronary Release of Tissue Plasminogen Activator in Women But Not in Men

The renin-angiotensin system regulates the vascular fibrinolytic balance. In the human forearm vasculature, angiotensin-converting enzyme (ACE) inhibitors (ACE-Is) increase the release of t-PA through endogenous bradykinin. We tested the hypothesis that ACE inhibition and sex modulate the endogenous coronary release of tissue plasminogen activator (t-PA) in hypertensive patients. Seventy-three patients underwent diagnostic coronary angiography and had normal coronary angiograms. Thirty-three patients (21 men and 12 women) were treated with imidapril (5 mg/day) for 4 weeks (ACE-I group), and 40 (23 men and 17 women) were not treated with ACE-I (non-ACE-I group). All of the women were postmenopausal. Coronary blood flow in the left anterior descending artery was evaluated by measuring Doppler flow velocity. Net coronary t-PA release was determined as (coronary sinus−aorta gradient of t-PA)×(coronary blood flow)×[(100−hematocrit)/100]. Age, arterial pressure, heart rate, lipid levels, coronary flow, and the plasma level of t-PA at either aorta or coronary sinus were comparable among the 4 groups. In women, net t-PA release in the ACE-I group was significantly higher than that in the other groups (P<0.05; man non-ACE-I group: 1.4±2.6 ng/mL; woman non-ACE-I group: 1.4±3.1 ng/mL; man ACE-I group: −1.8±2.8 ng/mL; woman ACE-I group: 14.8±3.6 ng/mL). Correction for smoking status gave similar results. There was a significant negative correlation between serum ACE activity and coronary t-PA release in women (r=−0.38; P<0.05) but not in men. ACE inhibition increases coronary release of t-PA in women but not in men.

Airway obstruction caused by rapid enlargement of cervical lymphangioma in a five‐month‐old boy

Cervical lymphangioma can cause airway obstruction secondary to enlargement following infection. Physicians should be aware that the airway obstruction can progress rapidly when patients with cervical lymphangioma have respiratory symptoms. Sclerotherapy for lymphangioma can cause both transient swelling and airway obstruction; thus, prophylactic and elective tracheostomy should be considered.