Worsening of coronary spasm during the perioperative period: A case report.

We present the case of a 65-year-old male with vasospastic angina (VSA) whose condition worsened during the perioperative period. He had been diagnosed with VSA 10 years prior. He was treated with two types of vasodilators and had not experienced any chest symptoms for 5 years. At this juncture, he underwent surgery for relapsed maxillary sublingual carcinoma. He had taken two vasodilators one day prior to surgery. Intravenous infusion of nitroglycerin (NTG) was initiated immediately before the surgery and continued the following day. Instead of stopping NTG, a dermal isosorbide dinitrate tape was applied on post-operative day 1. Two days later, a complete atrioventricular block with pulseless electrical activity appeared. After cardiopulmonary resuscitation, emergent coronary angiography showed severe coronary spasm in both the left and right coronary arteries. Intracoronary infusion of nitroglycerin and epinephrine with percutaneous cardiopulmonary support relieved the coronary spasm. During the perioperative period, several factors can trigger coronary vasospasm, including the discontinuation of vasodilators. Thus, surgeons, anesthetists, and cardiologists should watch for coronary vasospasm during this period and for worsening coronary spasm when discontinuing vasodilators in patients at risk for VSA.

Deep echo attenuation without calcification increases the risk of periprocedural myonecrosis after elective percutaneous coronary intervention in patients with coronary artery disease.

OBJECTIVE: To investigate the clinical factors, including intravascular ultrasound (IVUS) findings, associated with percutaneous coronary intervention (PCI)-related periprocedural myonecrosis (PM) in patients with stable coronary artery disease (CAD). METHODS: The study included 46 patients (mean age 65±2 y, 37 men) with stable CAD who underwent elective PCI using IVUS and a Doppler flow guidewire. In addition to routine IVUS measurements, the presence of deep echo attenuation (DEA) without calcification was assessed. The sum of all high-intensity transient signals (HITS) after a balloon deflation procedure was calculated using a Doppler flow guidewire. PM was defined as an elevation in troponin T to >0.03 ng/mL 24-hour after PCI. Patients were divided into 2 groups on the basis of the presence or absence of PM. RESULTS: PM was identified in 17 patients (37%). Estimated glomerular filtration ratio was lower in the PM group (p=0.021). Target vessel distribution was different between the groups (p=0.004). Positive remodeling and DEA, as observed on IVUS, were more common in the PM group (p=0.03 and p<0.0001, respectively). The total number of HITS was higher in the PM group (p=0.003). Logistic regression analysis demonstrated that the presence of DEA (p=0.003) was the sole factor associated with the occurrence of PM. CONCLUSION: These results demonstrated that DEA is an important factor associated with PM in patients who underwent an elective PCI. Therefore, IVUS to determine the presence of DEA should be performed before PCI.

Rho-associated kinase activity, endothelial function, and cardiovascular risk factors.

OBJECTIVE: Cardiovascular diseases are associated with chronic activation of Rho-associated kinases (ROCKs) and endothelial dysfunction. Both increased ROCK activity and endothelial dysfunction are thought to be closely associated with conventional cardiovascular risk factors. The purpose of this study was to determine the relationships between ROCK activity, endothelial function, and cardiovascular risk factors. METHODS AND RESULTS: We evaluated ROCK activity in peripheral leukocytes by Western blot analysis and flow-mediated vasodilation by ultrasonography in 242 men who had no cardiovascular or cerebrovascular diseases (mean age, 40±10 years; range, 20 to 73 years). ROCK activity was defined as the ratio of phospho myosin-binding subunit on myosin light chain phosphatase to total myosin-binding subunit. Univariate regression analysis revealed that leukocyte ROCK activity significantly correlated with body mass index (r=0.29, P=0.003); systolic blood pressure (r=0.25, P=0.01); low-density lipoprotein cholesterol level (r=0.21, P=0.04); and Framingham risk factor score, a cumulative cardiovascular risk index for heart attack (r=0.31, P<0.001), and that flow-mediated vasodilation significantly correlated with age (r=-0.23, P=0.02), body mass index (r=0.19, P=0.05), systolic blood pressure (r=-0.22, P=0.03), total cholesterol level (r=-0.21, P=0.04), low-density lipoprotein cholesterol level (r=-0.22, P=0.04), glucose level (r=-0.20, P=0.04), and Framingham risk factor score (r=-0.37, P<0.001). There was a significant correlation between leukocyte ROCK activity and flow-mediated vasodilation (r=-0.41, P<0.001). Multivariate analysis revealed that flow-mediated vasodilation was an independent predictor of leukocyte ROCK activity. CONCLUSIONS: These findings suggest that cumulative cardiovascular risk may enhance ROCK activity and endothelial dysfunction, leading to progression of cardiovascular diseases and outcomes.

Autologous bone-marrow mononuclear cell implantation reduces long-term major amputation risk in patients with critical limb ischemia: a comparison of atherosclerotic peripheral arterial disease and Buerger disease.

BACKGROUND: Bone-marrow mononuclear cell (BM-MNC) implantation improves ischemic symptoms in patients with critical limb ischemia (CLI). The purpose of this study was to evaluate long-term clinical outcomes after autologous BM-MNC implantation in patients with CLI. METHODS AND RESULTS: We assessed long-term clinical outcomes after BM-MNC implantation in 51 patients with CLI, including 25 patients with peripheral arterial disease (PAD) and 26 patients with Buerger disease. Forty-six CLI patients who had no BM-MNC implantation served as control subjects. Median follow-up period was 4.8 years. The 4-year amputation-free rates after BM-MNC implantation were 48% in PAD patients and 95% in Buerger disease, and they were 0% in control PAD patients and 6% in control Buerger disease. The 4-year overall survival rates after BM-MNC implantation were 76% in PAD patients and 100% in Buerger disease, and they were 67% in control PAD patients and 100% in control Buerger disease. Multivariable Cox proportional hazards analysis revealed that BM-MNC implantation correlated with prevention of major amputation and that hemodialysis and diabetes mellitus correlated with major amputation. In Buerger disease, ankle brachial pressure index and transcutaneous oxygen pressure were significantly increased after 1 month and remained high during 3-year follow-up. However, in patients with PAD, ankle brachial pressure index and transcutaneous oxygen pressure significantly increased after 1 month and gradually decreased during 3-year follow-up and returned to baseline levels. CONCLUSIONS: These findings suggest that BM-MNC implantation is safe and effective in patients with CLI, especially in patients with Buerger disease. Clinical Trial Registration- URL: http://home.hiroshima-u.ac.jp/angio/. Unique identifier: 001769.

Measurement of Rho-associated kinase (ROCK) activity in humans: validity of leukocyte p-MBS/t-MBS in comparison with vascular response to fasudil.

BACKGROUND: Rho-associated kinases (ROCKs) have been shown to be involved in the pathogenesis of atherosclerosis. It is clinically important to estimate the degree of ROCK activity in humans. The purpose of this study was to confirm the validity of a leukocyte ROCK parameter as an index of ROCK activity in comparison with vascular response to a ROCK inhibitor. METHODS AND RESULTS: We evaluated the ratio of phospho myosin-binding subunit (p-MBS) on myosin light-chain phosphatase to total MBS in peripheral leukocytes by Western blot analysis and forearm blood flow (FBF) response to the ROCK inhibitor fasudil using strain-gauge plethysmography in 36 healthy subjects and 39 patients with cardiovascular diseases. Fasudil (3, 10, 30µg/min) was infused intra-arterially for 5min at each dose. Leukocyte p-MBS/total-MBS was higher in cardiovascular diseases than in healthy subjects (0.97±0.37 vs. 0.51±0.14; P=0.002). Fasudil increased FBF from 4.9±1.2 to 14.5±5.7mL/min/100mL tissue (P<0.0001) in patients with cardiovascular diseases, while fasudil did not alter FBF in healthy subjects. There was a significant relationship between leukocyte p-MBS/total-MBS and maximal FBF response to fasudil in all subjects (r=0.72, P<0.0001). There was also a significant correlation between p-MBS/total-MBS and maximal FBF response to fasudil in patients with cardiovascular diseases (r=0.59, P<0.0001). In healthy subjects, there was no significant correlation between the two parameters. CONCLUSIONS: These findings suggest that assessment of leukocyte ROCK activity is minimally invasive and does not require pharmacologic intervention using ROCK inhibitors. Leukocyte p-MBS/total-MBS may be useful for evaluating ROCK activity in a clinical setting.

Vascular function and circulating progenitor cells in thromboangitis obliterans (Buerger's disease) and atherosclerosis obliterans.

Thromboangitis obliterans (TAO; Buerger's disease) and atherosclerosis obliterans (ASO) are associated with endothelial dysfunction. The purpose of this study was to evaluate the role of circulating progenitor cells (CPCs) in endothelial function in patients with TAO and ASO. We measured flow-mediated vasodilation (FMD), nitroglycerine-induced vasodilation, and circulating CPCs in 30 patients with TAO and 30 age- and sex-matched healthy subjects and in 40 patients with ASO. FMD was smaller in both the TAO group and ASO group than in the control group (6.6 ± 2.7%, 5.7 ± 3.3% versus 9.5 ± 3.1%, P<0.0001, respectively). There was no significant difference in FMD between the TAO group and ASO group. Nitroglycerine-induced vasodilation was similar in the 3 groups. The number of and migration of circulating CPCs were similar in the TAO group and control group, whereas the number of and migration of circulating CPCs were significantly lower in the ASO group than in other groups (ASO 553 ± 297/mL versus TAO 963 ± 543/mL; control 1063 ± 426/mL and ASO 36 ± 18/hpf versus TAO 62 ± 23/hpf; control 68 ± 18/hpf, P<0.0001, respectively). There was a significant relationship between the number of and migration of CPCs and FMD (r = 0.43 and r = 0.40, P<0.0001, respectively). FMD was impaired in patients with TAO as well as in patients with ASO compared to that in normal control subjects, and the number of and function of circulating CPCs were not decreased in patients with TAO. These findings may partially explain why there are differences in cardiovascular morbidity and mortality rates between patients with TAO and patients with ASO.

Calcium channel blocker and Rho-associated kinase activity in patients with hypertension.

BACKGROUND: Rho-associated kinases (ROCKs) play an important role in Ca sensitization and vascular resistance. Activation of ROCKs is associated with hypertension. The purpose of this study was to evaluate the effect of the calcium channel blocker amlodipine on ROCKs activity in patients with hypertension. METHODS: We evaluated ROCK activity in peripheral leukocytes by Western blot analysis in 651 patients with hypertension treated with antihypertensive agents, 28 untreated hypertensive patients and 28 healthy individuals, and the effects of treatment with amlodipine or losartan for 12 weeks on ROCK activity in 28 untreated hypertensive patients who were randomly divided into an amlodipine group (n = 14) and a losartan group (n = 14). ROCK activity was defined as the ratio of phospho myosin-binding subunit (MBS) on myosin light-chain phosphatase to total MBS. RESULTS: Leukocyte ROCK activity was greater in untreated patients with essential hypertension than in the healthy individuals (0.84 ± 0.24 vs. 0.61 ± 0.18, P = 0.03). In 651 patients with hypertension treated with antihypertensive agents, ROCK activity was significantly lower in the calcium channel blocker-treated group than in the groups treated with renin-angiotensin system inhibitors, diuretics, and ß-blockers (0.70 ± 0.24 vs. 0.85 ± 0.29, 0.83 ± 0.24, and 0.86 ± 0.31, P < 0.05, respectively). ROCK activity after 4 and 12 weeks of treatment was significantly decreased in the amlodipine group (0 weeks: 0.85 ± 0.25, 4 weeks: 0.66 ± 0.16, 12 weeks: 0.64 ± 0.15, P < 0.05, respectively) but not in the losartan group, whereas the antihypertensive effects were similar in the two groups. CONCLUSION: These findings suggest that calcium channel blocker amlodipine inhibits ROCK activity in patients with hypertension.

Classification of corkscrew collaterals in thromboangiitis obliterans (Buerger's disease): relationship between corkscrew type and prevalence of ischemic ulcers.

BACKGROUND: A corkscrew collateral appearance on angiography is one of the diagnostic criteria for Buerger's disease. The purpose of the present study was to classify the angiographic findings of corkscrew collaterals and to evaluate the relationship between corkscrew collateral type and the severity of Buerger's disease. METHODS AND RESULTS: Corkscrew collaterals were assessed on digital subtraction angiography in lower extremities of 28 patients with Buerger's disease (55 limbs). The corkscrew sign was classified into 4 types by size and pattern as follows: type I, artery diameter >2 mm, large helical sign; type II, diameter >1.5 mm and or=1 mm and

Increased leukocyte rho kinase (ROCK) activity and endothelial dysfunction in cigarette smokers.

Rho-associated kinases (ROCKs) have been shown to be involved in the pathogenesis of atherosclerosis. Although smoking is associated with endothelial dysfunction and ROCK inhibitors improve endothelial function in smokers, it is not known whether ROCK activity is increased in smokers and whether this correlates with endothelial dysfunction. The purpose of this study was to evaluate the relationship between ROCK activity and endothelial function in smokers. We evaluated flow-mediated vasodilatation (FMD) using ultrasonography and ROCK activity in peripheral leukocytes using western blot analysis in 14 male smokers (28.1+/-3.9 years) and 15 healthy male non-smokers (28.3+/-3.6 years). ROCK activity was defined as the ratio of phospho-myosin-binding subunit (MBS) on myosin light-chain phosphatase to total MBS. FMD was significantly less in smokers than in non-smokers (4.7+/-3.1 vs. 9.0+/-3.8%, P=0.005). Nitroglycerine-induced vasodilation was similar in the two groups. ROCK activity was greater in smokers than in non-smokers (0.78+/-0.27 vs. 0.54+/-018, P=0.012). The expression of total MBS, ROCK1 and ROCK2 were similar in the two groups. ROCK activity correlated with systolic blood pressure (r=0.42, P=0.039). Multiple regression analysis revealed that smoking is an independent predictor of ROCK activity. There was a significant correlation between FMD and ROCK activity (r=-0.42, P=0.035). No other variable was correlated with FMD. These findings suggest that ROCK activity is enhanced by smoking and is a predictor of endothelial function.

Pioglitazone improves endothelium-dependent vasodilation in hypertensive patients with impaired glucose tolerance in part through a decrease in oxidative stress.

BACKGROUND: The aim of this study was to determine pioglitazone treatment restores endothelial function in hypertensive patients with impaired glucose tolerance (IGT). METHODS AND RESULTS: We evaluated the effects of pioglitazone treatment for 12 weeks on forearm blood flow (FBF) responses to acetylcholine and sodium nitroprusside in 34 hypertensive patients with IGT who were randomly divided into a pioglitazone group (n=17) and an amlodipine monotherapy group (n=17) and in 34 healthy subjects. Pioglitazone, but not amlodipine, increased the FBF response to acetylcholine and decreased urinary excretion of 8-hydroxy-2'-deoxyguanosine. Pioglitazone did not alter sodium nitroprusside-stimulated vasodilation. NG-monomethyl-L-arginine abolished the augmentation of FBF response to acetylcholine after pioglitazone treatment. The increase in maximal FBF response to acetylcholine correlated with the decrease in urinary excretion of 8-hydroxy-2'-deoxyguanosine. CONCLUSION: Pioglitazone improved endothelial function in hypertensive patients with IGT through an increase in nitric oxide bioavailability by, in part, a decrease in oxidative stress.

Oral infection-inflammatory pathway, periodontitis, is a risk factor for endothelial dysfunction in patients with coronary artery disease.

OBJECTIVE: Several studies have shown that periodontitis is a risk factor for cardiovascular diseases. There is an association between inflammation and endothelial dysfunction. The purpose of this study was to evaluate endothelial function in patients with coronary artery disease (CAD) who had periodontitis. METHODS AND RESULTS: We evaluated forearm blood flow (FBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and to sodium nitroprusside (SNP), an endothelium-independent vasodilator, in 101 CAD patients with periodontitis (37 men and 11 women, 63+/-12 yr) and without periodontitis (36 men and 17 women, 62+/-13 yr). FBF was measured by using strain-gauge plethysmography. Circulating levels of C-reactive protein and interleukin-6 were significantly higher in the periodontitis group than in the non-periodontitis group. FBF response to ACh was significantly smaller in the periodontitis group than in the non-periodontitis group. SNP-stimulated vasodilation was similar in the two groups. Periodontal therapy reduced serum concentrations of C-reactive protein from 2.7+/-1.9 to 1.8+/-0.9mg/L (P<0.05) and interleukin-6 from 2.6+/-3.4 to 1.6+/-2.6ng/L (P<0.05) and augmented ACh-induced vasodilation from 14.7+/-5.2 to 20.1+/-6.1mL/(min100mL) tissue (P<0.05) in patients with periodontitis. The SNP-stimulated vasodilation was similar before and after treatment. After administration of N(G)-monomethyl-l-arginine, a nitric oxide synthase inhibitor, FBF response to ACh was similar before and after treatment. CONCLUSION: These findings suggest that periodontitis is associated with endothelial dysfunction in patients with CAD through a decrease in nitric oxide bioavailability. Systemic inflammation may be, at least in part, a cause and predictor of progression of endothelial dysfunction.

Right bundle-branch block in anterior acute myocardial infarction in the coronary intervention era: acute angiographic findings and prognosis.

BACKGROUND: Previous studies in the prethrombolytic or thrombolytic era have reported that right bundle-branch block (RBBB) is associated with poor clinical outcome in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: The purpose of this study was to examine the relations between RBBB and angiographic findings or clinical outcomes in patients with AMI in the coronary intervention era. A total of 430 patients with a first anterior AMI who underwent coronary angiography within 12 h after the onset were enrolled in this study. Seventy-one patients (17%) had RBBB documented during their hospital stay. RBBB was documented on admission in 35 patients. Patients with RBBB were older (p<0.01) and had prodromal angina less frequently (p=0.03) than those without. On the initial angiograms, patients with RBBB had an occluded left anterior descending artery (p<0.01) and multivessel disease (p=0.01) more frequently than those without. Thirty-day mortality rate was significantly higher in patients with RBBB than in those without (14.0% vs 1.9%, p<0.01). Multiple logistic-regression analysis demonstrated that RBBB (odds ratio 5.89, p<0.01) and multivessel disease (odds ratio 4.36, p=0.01) were independent predictors of 30-day mortality. CONCLUSIONS: Our data suggested that RBBB was still associated with poor clinical outcome in patients with anterior AMI even in the coronary intervention era.

Documentation of dynamic electrocardiographic changes shortly after the onset of tako-tsubo cardiomyopathy.

A 76-year-old female with atrial fibrillation and prior cerebral infarction had chest discomfort during rehabilitation for left hemiparesis, and visited the nearby hospital. Her ECG, which was obtained 10 min after the onset, showed marked ST-segment elevation in leads I, II, III, aV(F) and V(2-6), and she was referred to our hospital for cardiac examination. On admission, her ECG, which was obtained 50 min after the onset, showed poor R wave progression and mild ST-segment elevation in leads V(5-6). During only 10 min after the admission, the ST-segment level increased dynamically, and it decreased spontaneously again. Left ventriculography showed akinesia of the mid-to-distal portion and hyperkinesia of the basal portion of the left ventricular chamber, and coronary angiography showed no significant coronary artery disease despite of significant ST-segment elevation. We diagnosed her as having tako-tsubo cardiomyopathy. She was discharged well 10 days later.

Is admission hyperglycaemia in non-diabetic patients with acute myocardial infarction a surrogate for previously undiagnosed abnormal glucose tolerance?

AIMS: To investigate whether admission hyperglycaemia in non-diabetic patients with acute myocardial infarction (AMI) is a surrogate for previously undiagnosed abnormal glucose tolerance. METHODS AND RESULTS: Two hundred non-diabetic patients with AMI were divided into three groups: 81 patients with admission glucose < 7.8 mmol/L (group 1), 83 patients with admission glucose > or = 7.8 mmol/L and < 11.1 mmol/L (group 2), and 36 patients with admission glucose > or = 11.1 mmol/L (group 3). Abnormal glucose tolerance, diabetes, or impaired glucose tolerance (IGT) was diagnosed by oral glucose tolerance test (OGTT). OGTT identified diabetes in 53 patients (27%) and IGT in 78 patients (39%). When the fasting glucose criteria were applied, however, only 14 patients (7%) were diagnosed as having diabetes. The prevalence of abnormal glucose tolerance was similar among the three groups: 67% in group 1, 63% in group 2, and 69% in group 3 (P = 0.74). The relation of fasting glucose (r2 = 0.50, P < 0.001) and HbA1c (r2 = 0.34, P < 0.001) to 2-h post-load glucose was significant, but the relation of admission glucose to 2-h post-load glucose was not significant (r2 = 0.02, P = 0.08). Multivariable analysis showed that fasting glucose and HbA1c were independent predictors of abnormal glucose tolerance, but admission glucose was not. CONCLUSION: Admission hyperglycaemia in non-diabetic patients with AMI does not represent previously undiagnosed abnormal glucose tolerance. Fasting glucose and HbA1c, rather than admission glucose, may be useful to predict abnormal glucose tolerance. However, these parameters lacked sensitivity. OGTT should be considered in all non-diabetic patients with AMI.

Right atrial thrombosis as a complication of arrhythmogenic right ventricular cardiomyopathy.

A 65-year-old woman was admitted to our hospital due to palpitation. Electrocardiogram (ECG) showed ventricular tachycardia originating from the right ventricle, and transthoracic echocardiography revealed dilatations of the right atrium and ventricle. The diagnosis of arrhythmogenic right ventricular cardiomyopathy was made. Eleven months later, echocardiography revealed a solid thrombus (36x32 mm) attached to the free wall of the right atrium, and it was surgically resected. Four months after the operation, a solid thrombus (48x30 mm) appeared again at the same site despite anticoagulant treatment. The patient died of both left and right heart failure 33 months after the operation.

Persistent left ventricular dysfunction in takotsubo cardiomyopathy after pacemaker implantation.

Two cases of takotsubo cardiomyopathy occurred after pacemaker implantation, both in elderly women who received a dual-chamber pacemaker for complete atrioventricular block. They had persistent left ventricular dysfunction even during their convalescence.