Association between resilience and advance care planning during the COVID-19 pandemic in Japan: a nationwide cross-sectional study.

Advance care planning (ACP) is essential for end-of-life care, especially during the novel coronavirus disease 2019 (COVID-19) pandemic, and resilience is critical to deal with pandemic-related stressors. Therefore, we investigated the association between resilience ability and ACP discussions during the COVID-19 pandemic. A nationwide web-based survey was conducted in July 2021 in Japan. We analyzed the respondents' ability to bounce back from stress (bouncing-back ability), positive stress coping (e.g., "seeking social support", "planning"), and negative stress coping (e.g., "avoidance", "alcohol and drug use") in relation to ACP discussions using multivariable logistic regression models. In total, 2000 responses (86% participation rate) were received (mean age: 51.8 ± 16.7). Normal and high bouncing-back ability (adjusted odds ratio [AOR]: 1.69, 95% CI: 1.03-2.79; AOR: 2.07, 95% CI: 1.18-3.65, respectively) were significantly associated with the occurrence of ACP discussions. Seeking social support and planning were significantly associated with ACP discussions, whereas avoidance and alcohol and drug use were not. Both bouncing-back ability and positive stress coping were significantly associated with the occurrence of ACP discussions during the COVID-19 pandemic in Japan. These findings could be useful for aiding health-care providers involved in ACP discussions during the COVID-19 pandemic.

Usefulness of a mobile phone application for respiratory rate measurement in adult patients.

AIMS: Respiratory rate measurement is one of the core nursing skills for early detection of deterioration of a patient's condition. Nevertheless, it is sometimes bothersome to visually measure respiratory rate over 1 min. Respiratory rate measurement using a mobile phone application "RRate" has been reported to be accurate and completed in a short time. However, it has only been investigated in children. The aim of this study was to validate the "RRate" compared with the 1-min method in adult patients. METHODS: This was a cross-sectional study in the setting of a nursing school. Videos of the movement of the thorax during respiration of adult patients were made. Nursing students watched these videos and measured respiratory rate with each method. Bland-Altman analysis was used to calculate bias and limits of agreement. The times taken for the measurements were compared using a t test. RESULTS: A total of 59 nursing students participated. When compared to the reference measurement, the one measured using "RRate" and the one measured over 1 min showed a bias of 0.40 breaths per minute and 0.65 breaths per minute, limits of agreement of -2.86 to 3.67 breaths per minute and -2.11 to 3.41 breaths per minute, respectively. The mean measurement time for "RRate" was 22.8 s (95% CI 13.9-36.6), which was significantly shorter than the 65.8 s (95% CI 61.0-73.2) for the measurement over 1 min (p < .001). CONCLUSIONS: Respiratory rate can be measured accurately in a shorter time using a mobile phone application in adult patients.

Giant right atrial diverticulum with thrombus formation.

A 28-year-old man was referred to our hospital with a giant right atrial diverticulum. The mass of the right atrial diverticulum compressed the right atrium and right ventricle, and thrombus formation was suspected. The diverticulum was surgically excised and the patient remained asymptomatic a year later.

Management strategy of isolated spontaneous dissection of the superior mesenteric artery.

OBJECTIVE: Isolated spontaneous dissection of the superior mesenteric artery (SMA) is very rare among of the visceral artery dissection and its treatment is not established. In this paper we present our experiences and consider the treatment of isolated SMA dissection. METHODS: A retrospective review of our cases from 2005 was performed. Clinical symptoms, radiologic findings and results were evaluated. There were 14 cases of visceral artery dissection, in which all cases were with SMA dissection. There were 12 males and 2 females with a mean age of 57 years (range 41-78 years). RESULTS: We categorized SMA dissection into the six types according to the Sakamoto's and Zerbib's classification. One patient with type VI underwent emergent endovascular surgery with stent. One patient with type VI received thrombectomy and intimectomy with open surgery. One patient with type II underwent aneurysmectomy due to enlarged dissected SMA 3 months later from onset. The other eleven patients were managed conservatively. At follow-up, the diameter of SMA did not enlarged and the length of the dissection significantly decreased to 20.7 ± 15.7 mm from 38.0 ± 15.1 mm at onset (p <0.01). After treatment, imaging indicated the following changes in classification: type I, one patient; type II, 4 patients; type IV, 4 patients; complete remodeling, one patient, all without any event during the follow-up period of 5-82 months. CONCLUSION: Most patients with isolated visceral artery dissection occurred in superior mesenteric artery and can be treated conservatively; however, endovascular or surgical procedures including laparotomy are indicated when there is suspicion of severe mesenteric ischemia. Because the dissection configuration will change, long term follow-up is necessary. (English translation of Jpn J Vasc Surg 2013; 22: 695-701).

Start and initial results of the Fukushima Prefecture acute myocardial infarction registration survey.

Acute myocardial infarction (AMI) remains one of the most serious heart diseases and elucidation of its pathogenesis and advances in treatment strategies have been desired. In 2009, to understand the status of AMI in Fukushima Prefecture for improving treatment outcomes, a new AMI registration survey system was conducted throughout the prefecture. A total of 1,556 cases were registered in the initial 2 years from 2009 to 2010. The hospital-based overall incidence of AMI in Fukushima Prefecture was 37.9 people per population of 100,000 per year. Mortality from AMI within 30 days of onset was 10.2%. We report herein the actual situation of AMI onset and treatment in Fukushima Prefecture based on the initial results of the survey.

Vasoconstrictive response in the vascular beds of the non-exercising forearm during leg exercise in patients with mild chronic heart failure.

BACKGROUND: Reduced exercise capacity may be related to decreased redistribution of blood flow from the non-exercising tissues to the exercising skeletal muscle in patients with mild chronic heart failure (CHF). METHODS AND RESULTS: In the present study 14 patients with mild CHF and 10 healthy subjects (N) underwent symptom-limited multistage-ergometer exercise, during which forearm vascular resistance (FVR), cardiac index (CI), systemic vascular resistance index (SVRI), and oxygen uptake (VO(2)) were measured non-invasively using the plethysmograph, impedance, and respiratory gas analysis methods, respectively. The VO(2) and CI at peak exercise were lower (p<0.01 each), and SVRI and FVR at both rest and peak exercise were higher in the CHF group than in N. However, both the percent increase in FVR and percent decrease in SVRI from the resting state to peak exercise were lower in CHF than N, and both of them correlated with not only peak VO(2), but also the corresponding resting value of FVR and SVRI (p<0.01 each). CONCLUSIONS: Redistribution of blood flow from the non-exercising tissues to the working skeletal muscles, which may participate in exercise capacity, can be blunted in CHF. The decreased vasoconstrictive response in the non-exercising tissues is intimately related to the increased resting vascular tone in CHF.

Comprehensive analyses of arrhythmogenic substrates and vulnerability to ventricular tachycardia in left ventricular hypertrophy in salt-sensitive hypertensive rats.

BACKGROUND: The contribution of conduction disturbances to susceptibility to ventricular tachycardia (VT) has not been directly examined in the process of left ventricular hypertrophy (LVH). METHODS AND RESULTS: Dahl salt-sensitive (S) and -resistant rats were raised on a high-salt diet. After echocardiography, a fractionation study was conducted using wavelet transform analysis, which reflects conduction disturbances, recording of monophasic action potential (MAP), measurement of conduction velocity, and programmed extrastimuli for the induction of VT, as well as patch-clamp analysis at 10, 13 and 16 weeks (W) (n=7, each). Systolic blood pressure, wall thickness and MAP duration significantly increased at 10W in S rats, whereas conduction velocity decreased and MAP duration and the power of wavelet transform increased at 13W and 16W. Paired extrastimuli induced polymorphic VT only at 13W and 16W in S rats. VT frequency correlated inversely with conduction velocity and positively with MAP duration. Power of wavelet transform correlated negatively with conduction velocity and positively with VT vulnerability. The patch-clamp study revealed that the action potential duration significantly increased in S rats with aging, and correlated with MAP duration. CONCLUSIONS: Latently progressing slow and inhomogeneous conduction, as well as a repolarization abnormality, may contribute to VT vulnerability in hypertensive LVH.

Attenuated cardioprotection by ischemic preconditioning in coronary stenosed heart and its restoration by carvedilol.

OBJECTIVE: Infarct size (IS) reduction by ischemic preconditioning (IPC) has been assessed in the heart in which coronary stenosis (CS)-induced chronic ischemia was not present. The aim of this study is to assess whether and how IS reduction by IPC is modified in the heart in which CS has occurred, and how further therapeutics, if any, modify it. METHODS: We assessed the IS produced by a 30-minute acute coronary occlusion and a 24-hour reperfusion (COR) in rat hearts in which CS had developed for 1-12 weeks. Modifications of IS by IPC and the mitochondrial KATP channel (mitoKATP) opener and blocker, and the effects of daily beta-blocker treatment with carvedilol on them, were also assessed. Myocardial protein kinase C (PKC)-epsilon activities in the risk areas were measured by Western blotting. RESULTS: One to 4 weeks after CS induction, myocardial PKC-epsilon was activated in the risk area of CS even without IPC, but such CS-induced PKC activation as well as that by IPC was attenuated 8-12 weeks after CS. The IS reductions by the mitoKATP opener as well as by IPC were attenuated 8-12 and 4-12 weeks after CS, respectively. Daily carvedilol treatment after inducing CS restored the malfunctioning PKC-mitoKATP signal cascade and the attenuated IPC and mitoKATP effect on IS. CONCLUSION: CS activates the PKC-mitoKATP signal cascade, mimicking the IPC effect, whereas this cardioprotective effect is attenuated late after CS via their downregulation. Restoration of these changes may be a novel mechanism for cardioprotection by carvedilol in the CS-induced ischemic heart.

Effects of angiotensin-converting enzyme inhibitors or an angiotensin receptor blocker in combination with aspirin and cilostazol on in-stent restenosis.

It remains to be determined whether adding an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) to antiplatelet therapy has a therapeutic benefit on in-stent restenosis. After successful coronary stenting, 165 patients (167 lesions) were randomly assigned to a basal (aspirin 162 mg + cilostazol 200 mg/day), ACEI (basal treatment + quinapril 10 mg or perindopril 4 mg/day), or ARB (basal treatment + losartan 50 mg/day) treatment group. Quantitative coronary angiography was performed before, immediately following, and 6 months after stenting. Follow-up coronary angiography was completed in 126 patients (128 lesions). Restenosis rates tended to be higher (12, 26, and 12% for the basal, ACEI, and ARB groups, respectively), and target lesion revascularization rates were higher in the ACEI group than in the other groups (9, 23,* and 5%, respectively, *P < 0.05 versus basal group). Moreover, late lumen loss was higher in the ACEI group than in the basal group (0.60 +/- 0.55, 0.98 +/- 0.61* and 0.73 +/- 0.64 mm in the basal, ACEI, and ARB groups, respectively). The combinations of an ACEI or ARB with aspirin and cilostazol are ineffective for the prevention of in-stent restenosis, and an ACEI may even promote intimal proliferation after stent implantation.

Specificity of vascular reactivity and remodeling after repeated endothelial injury in a swine model.

We investigated the difference in vascular responses and remodeling between coronary and iliac arteries after repeated endothelial denudation. Endothelial denudation of the left anterior descending coronary artery (LAD) and the right common iliac artery (RIA) was repeated 4 times twice a month using a Fogarty catheter in 21 pigs. Vascular responses to vasoactive drugs were evaluated as % luminal diameter changes on contrast angiography 2 weeks after the last denudation. Corresponding nondenuded sites, ie, the left circumflex coronary artery (LCX) and the left common iliac artery (LIA), were used as references. Acetylcholine (1 microg/kg) did not constrict the LCX (0 +/- 1%) and the LAD (1 +/- 1%, P < 0.05), whereas it constricted the RIA (20 +/- 6%) but not the LIA (-3 +/- 3%, P < 0.01). Alternatively, serotonin (10 microg/kg) constricted the LAD strikingly (88 +/- 5%, P < 0.01 versus LCX and RIA), as well as the RIA (35 +/- 10%, P < 0.05 versus LIA). Vasodilator responses to substance P and isosorbide dinitrate were not different after injury in both arteries. The intima-to-media ratio and adventitia-to-media ratio of the relevant site in cross section of tissue sample from LAD were greater than those from LCX, and were more prominent than those from RIA. The results show that vascular tone regulation after the endothelial injury and vascular remodeling might be altered in a vessel-specific manner.

Left ventricular dysfunction and remodeling in streptozotocin-induced diabetic rats.

BACKGROUND: It is not fully clarified how diabetes mellitus (DM)-induced cardiac dysfunction is associated with histopathological changes of the heart in a long lasting period of DM. METHODS AND RESULTS: Eighteen weeks after a streptozotocin injection was given to Wistar - Kyoto rats (D rats), echocardiography and hemodynamic studies including the dobutamine infusion test were performed. After perfusion fixation, immunofluorescent staining and histopathology of the heart were analyzed, and analysis with electron microscopy was also conducted. Systolic blood pressure in the conscious state and left ventricular (LV) ejection fraction by 2-dimensional echocardiography were reduced in D rats. LV mechanical responses to dobutamine assessed by maximal LV pressure derivative (+LVdP/dt) also decreased with higher dobutamine doses in D rats. Although LV and right ventricular (RV) wall thickness were smaller in D rats, there were increased RV volumes, indicating LV and RV dilatational remodeling in D rats. The cardiomyocyte transverse diameter and actin staining in cardiomyocytes in both the LV and RV were significantly reduced, and capillary tortuosity and type IV collagen were increased, indicating microangiopathy in D rats. CONCLUSIONS: Advanced insulin-dependent DM incurred not only RV remodeling but also overt resting LV systolic dysfunction and decreased LV responsiveness to beta adrenergic stimulation with dilatational remodeling, accompanied by pathological changes of capillaries and cardiomyocytes including actin filaments.

Estimation of microinhomogeneity of conduction impairment by wavelet analysis during early phase of myocardial ischemia in pigs.

Ventricular fibrillation (VF) is most frequent in the very early phase in acute coronary occlusion, and is triggered by the re-entrant mechanism in this phase. An inhomogeneous conduction in the ischemic myocardium would be substrates for re-entry. The aim of this study was to examine the relationship between the severity of irregularities of the QRS complex and VF. Eleven pigs were analyzed, and the heart was fixed in the pericardial cradle. Ag-AgCl bipolar electrodes were fixed on the epicardium in ischemic and non-ischemic regions. The proximal portion of the left anterior descending coronary artery was occluded for one hour. Electrocardiograms (ECGs) were continuously recorded on a magnetic tape, and wavelet analysis was performed on signal-averaged ECG (25 beats) every 60 sec after the experiment. The number of local maxima (N) and the duration between the first and the last local maximum (D) were automatically measured. N and D significantly increased in the ischemic area, but not in the non-ischemic area. N and D increased approximately twofold just before the occurrence of VF in 8 fibrillated pigs (p<0.01, each). There were significant positive linear relationships between the rate of increase in N and D to VF and basal heart rate before coronary occlusion (r=0.90, p <0.01 in N, r=0.84, p <0.01 in D at 160 Hz). These results suggest that there would be a threshold inhomogeneous conduction for the occurrence of VF and an increase in heart rate would accelerate the inhomogeneous conduction in acute myocardial ischemia.

Different effects of a high-cholesterol diet on ischemic cardiac dysfunction and remodeling induced by coronary stenosis and coronary occlusion.

OBJECTIVES: The aim of the study was to assess whether and how the high-cholesterol diet (HCD)-related worsening of heart failure differs between coronary stenosis (CS)-induced myocardial ischemia and coronary occlusion-induced myocardial infarction (MI). BACKGROUND: An HCD, a risk factor for coronary artery disease, also worsens ischemic heart failure. Although accelerated coronary plaque formation may be a cause of this, other mechanism(s), such as its effects through the coronary microcirculation, remain to be clarified. METHODS: In rats fed a normal chow diet or HCD, CS or MI was created surgically, and we assessed left ventricular (LV) function by echocardiography and myocardial inflammation by histopathology. In the CS groups, CS severity by histopathology, myocardial perfusion by microspheres, myocardial protein kinase C (PKC) translocation by Western blotting, and myocardial endothelial nitric oxide (NO) function were also investigated by the in vitro myocardial oxygen consumption method. RESULTS: Coronary stenosis impaired myocardial endothelial NO function and reduced coronary flow reserve, evoking myocardial ischemia, as shown by PKC- activation, myocardial inflammation, fibrosis, cardiac dysfunction, and remodeling. By itself, HCD greatly augmented such CS-induced myocardial abnormalities without modulating the CS severity. Such detrimental effects of HCD were ameliorated by supplying a cofactor of endothelial NO synthase-tetrahydrobiopterin. In contrast, MI-induced heart failure was not aggravated by HCD. CONCLUSIONS: The CS-induced ischemic myocardium seems to be more susceptible to the pro-inflammatory effect of HCD than infarcted myocardium, leading to aggravation of LV dysfunction and remodeling via modification of the coronary circulation downstream of the epicardial CS site, partly through impairment of endothelial NO.

Alterations of alpha-adrenergic modulations of coronary microvascular tone in dogs with heart failure.

BACKGROUND: It remains unclear whether coronary microvascular response to alpha-adrenergic activation alters in chronic heart failure (CHF). METHODS AND RESULTS: We investigated the alpha-adrenergic receptor-mediated effects on coronary pressure-flow relationship (CPFR) in a tachycardia-induced canine heart failure model. The dogs studied were male (29 of 31) and the drugs were given intracoronary. The slope of CPFR during long diastole was evaluated as an index of coronary vascular resistance, during alpha1- or alpha2-adrenergic stimulation or inhibition under anesthesia in the baseline and failing state after 3 weeks of rapid ventricular pacing. Resting coronary blood flow and CPFR did not change in the failing state from the baseline state. Neither alpha1 nor alpha2 stimulation changed the slope of CPFR in the baseline state. However, in the failing state, alpha1 stimulation decreased the slope of CPFR by 23 +/- 5% (P < .05), whereas alpha2 stimulation increased it by 73 +/- 10% (P < .05), which was nearly abolished by pretreatment with NG-nitro-L-arginine methyl ester. CONCLUSION: Alpha2-mediated vasodilatory action, presumably via endothelium-derived nitric oxide release, would be enhanced in the coronary microvascular bed, which may antagonize enhanced alpha1-induced vasoconstriction in CHF.

A case of recurrent chest pain with reversible left ventricular dysfunction and ST segment elevation on electrocardiogram.

There is a syndrome consisting of acute infarction-like symptoms and ECG findings, and transient left ventricular apical ballooning without epicardial coronary artery obstruction. A 67-year-old female admitted to our hospital because of severe anterior chest pain was diagnosed as having this syndrome. Since stenotic, spastic, or occlusive sites were not found in epicardial coronary arteries by emergency cardiac catheterization, we speculated coronary microvasculature involvement in the pathophysiology of the event. Four weeks later in a drug-free condition, there was no significant epicardial coronary vasospasm by intracoronary acetylcholine administration (IC-ACh). The average peak flow velocity (APFV) of the left coronary artery (LCA) was measured using the Doppler flow wire method. Under maximal dilatation of the epicardial LCA by intracoronary nitroglycerin administration, IC-ACh was again performed taking into consideration that the change in APFV in response to IC-ACh reflects a coronary microvascular response to it. In the nonischemic control subjects, basal APFV increased to 296+/-29% (n = 24) of the basal value after IC-ACh. In this patient, although IC-ACh did not cause vasospasm in epicardial LCA, APFV was decreased to 54% of its basal value. After administration of a Ca antagonist and KATP opener, she had no chest symptoms and was discharged from the hospital. In 2003, she forgot to take her medication for 3 days and then experienced a sudden recurrence of the same type of attack. She started her medication again and her symptoms disappeared. Three weeks later, she underwent an assessment of the coronary microvascular response to ACh with medicine. Her APFV after ACh increased to 177% of the basal value.

Different therapeutic responses to treadmill exercise of heart failure due to ischemia and infarction in rats.

OBJECTIVE: The effects of exercise, a therapeutic tool in ischemic heart disease (IHD), may differ in ischemic and infarcted hearts. METHODS AND RESULTS: To assess this, we created coronary stenosis (CS), which reduced coronary flow reserve (CFR), or coronary occlusion to induce myocardial infarction (MI) in rats, and subjected them to treadmill exercise for either 5 (5-min Ex) or 15 min/day (15-min Ex) for 12 weeks. Left ventricular (LV) diameters were increased and ejection fractions decreased by echocardiography, and myocardial nitric oxide (NO) activity, measured by the in vitro MVO2 method, was reduced in both CS and MI rats compared with the sham. In CS rats, myocardial wall thickening fractions were not affected at 5 min of exercise, whereas they were reduced at 15 min of exercise, suggesting exercise-induced ischemia. Despite no changes in CS severity, the 5-min Ex increased CFR, ameliorated myocardial NO activity, attenuated left ventricular (LV) dysfunction and remodeling, reduced serum brain natriuretic peptide (BNP) levels, and improved survival, whereas the 15-min Ex aggravated LV dysfunction and remodeling. In contrast, neither of the exercise protocols improved these parameters in MI rats. CONCLUSIONS: Therapeutic responses to exercise differed in ischemic and infarcted hearts, partly via circulatory modulation downstream of the epicardial CS in relation to exercise-induced ischemia. When employing exercise for IHD, the causes of IHD, as well as the exercise protocols, need to be considered to achieve optimal effects.

Transient improvement of left ventricular function after peripheral blood stem cell transplantation in a patient with myelodysplastic syndrome and dilated cardiomyopathy.

A patient who had myelodysplastic syndrome (MDS) and dilated cardiomyopathy (DCM) had a transient improvement of cardiac function after peripheral blood stem cell transplantation (PBSCT). When he was admitted to hospital for PBSCT, a chest X ray showed cardiomegaly, and Tc-99m quantitative gated single photon emission computed tomography (QGS) showed increases in left ventricular (LV) volumes and a decrease in LV ejection fraction (LVEF). A coronary angiogram showed no evidence of coronary artery disease. Left ventriculography showed similar findings as QGS, and the findings from a myocardial biopsy were compatible with DCM. Three months after a successful allo-PBSCT with his brother as the donor, the cardiomegaly had been attenuated, the LV volumes decreased and LVEF increased on the QGS images. However, 10 months later, his cardiac function had deteriorated. The changes in cardiac function did not correlate with the hematological changes, such as the hemoglobin level.

Altered effects of angiotensin ii type 1 and type 2 receptor blockers on cardiac norepinephrine release and inotropic responses during cardiac sympathetic nerve stimulation in aorto-caval shunt rats.

BACKGROUND: Inhibition of the sympathetic nervous and renin - angiotensin systems has become an important strategy in the treatment of chronic heart failure. However, direct evidence of how inhibition of the renin - angiotensin system alters sympathetic activity in a diseased heart is lacking. METHODS AND RESULTS: Four weeks after abdominal aorto-caval (AV) shunting or sham operation in rats, the hearts were retrogradely perfused in vivo and the left ventricles contracted isovolumetrically at 300 beats/min. Sympathetic nerve stimulation (SNS) was performed in the baseline state and repeated with an infusion of the angiotensin II (A-II) type 1 receptor (AT(1)-R) blocker, losartan, the A-II type 2 receptor (AT(2)-R) blocker, PD123319, or A-II. Norepinephrine (NE) overflow and left ventricular (LV) inotropic responses during baseline SNS were lower in the AV shunt rats. Losartan did not change the NE overflow or the LV inotropic responses to SNS in the sham rats, but did increase them in the AV shunt rats. PD123319 changed neither parameter in the sham rats, but decreased both in the AV shunt rats. A-II enhanced the NE overflow but attenuated the LV inotropic responses to SNS in the sham rats, but attenuated both in the AV shunt rats. CONCLUSIONS: The effects of A-II via the AT(1)-R and AT(2)-R on the adrenergic drive in the heart were altered significantly in volume overload hypertrophy induced by AV shunting.

Effects of antioxidants on coronary microvascular spasm induced by epicardial coronary artery endothelial injury in pigs.

OBJECTIVES: The effect of oxidative stress on coronary microvascular disease is unknown. We investigated whether chronic administration of ascorbic acid (ASC) or glutathione (GSH) prevents microvascular dysfunction and remodeling induced by upstream repeated coronary artery endothelial injury. METHODS: Balloon endothelial injury was repeated at the left anterior descending coronary artery (LAD), just distal to an implanted flow meter, every 2 weeks for 6 weeks in pigs. Changes in LAD blood flow induced by acetylcholine (ACh) and 5-hydroxytryptamine were assessed before each endothelial injury and at 8 weeks after the first endothelial injury in pigs without treatment (endothelial injury group, n = 12) and in pigs treated with oral ASC (3 g/day) (ASC group, n = 12) and ASC (3 g/day) plus GSH (1 g/day) (ASC + GSH group, n = 12). RESULTS: In the endothelial injury group, reduced blood flow in response to ACh was augmented from a decrease of 18 +/- 17% to a decrease of 100% (that is, zero flow, 8 weeks, P < 0.01), accompanied by an increase of ascorbyl free radicals (AFRs) in coronary sinus blood. In contrast, in the ASC + GSH group, blood flow response to ACh was altered to a decrease of 45 +/- 17% (8 weeks, P < 0.01 compared with the endothelial injury group), coronary sinus blood AFRs did not change (8 weeks, 21.4 +/- 12.5 signal intensities, P < 0.01 compared with the endothelial injury group) and the rate of platelet aggregation induced by adenosine diphosphate was small (8 weeks, 56 +/- 17%, P < 0.01 compared with the endothelial injury group). CONCLUSIONS: Chronic administration of antioxidants suppressed microvascular hypercontraction, suggesting that it may be a promising therapeutic strategy for treating coronary microvessel disorders, including microvascular angina.

Repeated epicardial coronary artery endothelial injuries lead to a global spontaneous coronary artery spasm.

OBJECTIVES: This study was conducted to develop a spontaneous coronary spasm model. MATERIALS AND METHODS: Balloon endothelial denudation was carried out in the epicardial left anterior descending coronary artery (LAD) every 2 weeks, for a total of four times, in 12 pigs. Changes in the denuded site diameter and LAD blood flow caused by acetylcholine or serotonin were assessed before each denudation and at week 8. Blood pressure, electrocardiogram (ECG) from the LAD area and LAD blood flow were monitored continuously in conscious and unrestrained pigs. RESULTS: Spontaneous ECG ST depression with a decrease in LAD blood flow appeared at around 2 weeks. In accordance with this, 0.5 microg/kg acetylcholine induced similar ECG and LAD blood flow changes without denuded site narrowing, suggesting microvascular spasm. Thereafter, ECG ST depression or elevation by serotonin via a denuded site spasm was found after 6 weeks and spontaneous ECG ST changes due to epicardial coronary artery spasm were observed. CONCLUSION: Epicardial coronary artery endothelial injury may induce spontaneous vasospasticity in the downstream coronary microvessels as well as in the denuded portion, suggesting functional abnormality through the entire coronary arterial tree.