Kunihiko Imai

A Na+–H+ exchange inhibitor (SM-20550) protects from microvascular deterioration and myocardial injury after reperfusion

Na+-H+ exchange inhibitors may reduce myocardial damage after reperfusion. However, their effects on microvascular deterioration are not known. We examined the potency of a novel Na+-H+ exchange inhibitor, SM-20550 [ N-(Aminoiminomethyl)-1,4-dimethyl-1H-indole-2-carboxamide methanesulfonate], and its effects on microvascular damage after reperfusion. In an in vitro study, the Na+-H+ exchange inhibiting activity of SM-20550 was about 10 times greater than that of ethylisopropyl amiloride. In in vivo experiments, we occluded the left circumflex coronary artery in 29 dogs for 2 h and then reperfused for 5 h. SM-20550 was administered either before ischemia (n = 11) or before reperfusion (n = 7). Another 11 dogs served as controls. We found that SM-20550 not only improved coronary vasodilator responses to acetylcholine and adenosine after reperfusion, but also reduced infarct size (P < 0.01). Intramyocardial bleeding, which should reflect microvascular damage, was not found in dogs with SM-20550 treatment. Infarct size was correlated inversely with collateral blood flow in control (both, P < 0.01) but not in SM-20550-treated animals. Furthermore, SM-20550 significantly suppressed ventricular fibrillation during both ischemia and reperfusion. These results suggest that protective effects of Na+-H+ exchange inhibitors on reperfused myocardium are due at least in part to microvascular protection.

Myocarditis, hepatitis, and pancreatitis in a patient with coxsackievirus A4 infection: a case report

Viral myocarditis presents with various symptoms, including fatal arrhythmia and cardiogenic shock, and may develop chronic myocarditis and dilated cardiomyopathy in some patients. We report here a case of viral myocarditis with liver dysfunction and pancreatitis. A 63-year-old man was admitted to our hospital with dyspnea. The initial investigation showed pulmonary congestion, complete atrioventricular block, left ventricular dysfunction, elevated serum troponin I, and elevated liver enzyme levels. He developed pancreatitis five days after admission. Further investigation revealed a high antibody titer against coxsackievirus A4. The patient’s left ventricular dysfunction, pancreatitis, and liver dysfunction had resolved by day 14, but his troponin I levels remained high, and an endomyocardial biopsy showed T-lymphocyte infiltration of the myocardium, confirming acute myocarditis. The patient underwent radical low anterior resection five weeks after admission for advanced rectal cancer found incidentally. His serum troponin I and plasma brain natriuretic peptide levels normalized six months after admission. He has now been followed-up for two years, and his left ventricular ejection fraction is stable.This is the first report of an adult with myocarditis and pancreatitis attributed to coxsackievirus A4. Combined myocarditis and pancreatitis arising from coxsackievirus infection is rare. This patient’s clinical course suggests that changes in his immune response associated with his rectal cancer contributed to the amelioration of his viral myocarditis.

Two Patients with Ruptured Posterior Inferior Pancreaticoduodenal Artery Aneurysms Associated with Compression of the Celiac Axis by the Median Arcuate Ligament

Patients with compression of the celiac axis by the median arcuate ligament may develop aneurysms in the pancreaticoduodenal arcades. We experienced two cases of ruptured pancreaticoduodenal artery aneurysm associated with this condition. Both patients presented with abdominal pain and shock, and abdominal contrast-enhanced computed tomography showed retroperitoneal hematoma and compression of the celiac axis by the median arcuate ligament. Both patients were successfully treated by coil embolization. Patients with celiac axis compression or stenosis may develop recurrent aneurysms unless revascularization of the celiac axis is performed. Long-term follow-up is required because aneurysms may develop after 10 years or longer.

A Risk Score with Additional Four Independent Factors to Predict the Incidence and Recovery from Metabolic Syndrome: Development and Validation in Large Japanese Cohorts

Background Although many risk factors for Metabolic syndrome (MetS) have been reported, there is no clinical score that predicts its incidence. The purposes of this study were to create and validate a risk score for predicting both incidence and recovery from MetS in a large cohort. Methods Subjects without MetS at enrollment (n = 13,634) were randomly divided into 2 groups and followed to record incidence of MetS. We also examined recovery from it in rest 2,743 individuals with prevalent MetS. Results During median follow-up of 3.0 years, 878 subjects in the derivation and 757 in validation cohorts developed MetS. Multiple logistic regression analysis identified 12 independent variables from the derivation cohort and initial score for subsequent MetS was created, which showed good discrimination both in the derivation (c-statistics 0.82) and validation cohorts (0.83). The predictability of the initial score for recovery from MetS was tested in the 2,743 MetS population (906 subjects recovered from MetS), where nine variables (including age, sex, γ-glutamyl transpeptidase, uric acid and five MetS diagnostic criteria constituents.) remained significant. Then, the final score was created using the nine variables. This score significantly predicted both the recovery from MetS (c-statistics 0.70, p<0.001, 78% sensitivity and 54% specificity) and incident MetS (c-statistics 0.80) with an incremental discriminative ability over the model derived from five factors used in the diagnosis of MetS (continuous net reclassification improvement: 0.35, p < 0.001 and integrated discrimination improvement: 0.01, p<0.001). Conclusions We identified four additional independent risk factors associated with subsequent MetS, developed and validated a risk score to predict both incident and recovery from MetS.

Three Cases of Spontaneous Isolated Dissection of the Superior Mesenteric Artery

BACKGROUND Spontaneous isolated superior mesenteric artery dissection is a rare disease that may cause bowel ischemia or aneurysm rupture and subsequent death. Thus, the establishment of a correct diagnosis in the early stage is quite important. OBJECTIVE To describe the presentation of 3 patients diagnosed with spontaneous isolated supramesenteric artery dissection and briefly summarize the diagnostic procedure, treatment, and clinical course. CASE REPORTS We experienced three cases of isolated mesenteric artery dissection in the past 5 years. A definitive diagnosis was obtained by abdominal spiral computed tomography in two cases and angiography in one case. All patients were provided anticoagulation therapy. CONCLUSION One patient died of bowel ischemia, 2 were discharged within 21 days without complications, and one was able to discontinue anticoagulation therapy 12 months after discharge. The remaining patient has continued warfarin, making it difficult to determine the end point of anticoagulation.

The Effect of N,N,N-Trimethylsphingosine on Reperfusion Injury

The paradoxical phenomenon of the exacerbation of myocardial injury after reintroduction of blood into the ischemic tissue of the heart is well known. It has been reported that in the relatively short time from 15 to 30 min of reperfusion, a supply of neutropenic blood reduced myocardial infarct size in ischemia-reperfusion canine models. The neutrophils play a major role in the exacerbation of myocardial injury[1][2], N, N,N-Trimethylsphingosine(TMS) derived from sphingosine strongly inhibits oxidative burst and phagokinetic migration of neutrophils, due to its inhibitory effect on protein kinase C (Kimura S, Hakomori S, Igarashi Y, et al., submitted). Based on this finding, the possible protective effect of TMS on reperfusion injury in dog heart was studied.

Simultaneous occurrence of myocardial infarction and duodenal perforation

An 81-year-old woman with no cardiovascular risk factors, but with a family history of thrombosis (her brother died from pulmonary thromboembolism), was admitted after experiencing tarry stools for the previous month. She had also experienced sudden onset severe abdominal pain. Physical examination showed pallor of the face and severe abdominal tenderness. Computed tomography indicated ascites and abdominal free air, suggesting gastrointestinal perforation (Fig. 1a). Laboratory data showed severe anemia (Hb 4.6 g/dl), low antithrombin activity (51%), normal disseminated intravascular coagulation (DIC) score (4 points), and normal troponin-I and creatine kinase level, suggesting an antithrombin deficiency irrelevant to DIC. Although she reported no chest pain, an electrocardiogram was performed, which showed normal sinus rhythm and ST segment elevation in the inferior and lateral leads (Fig. 1b). Echocardiography showed inferior, posterior, and apical hypokinesis with an ejection fraction of 40%, suggesting acute myocardial infarction. An emergency coronary angiography was performed, and a normal right coronary artery and multiple left coronary thromboses were identified (Fig. 1c); atherosclerosis was not detected by intravascular ultrasound. A thrombectomy was performed and coronary flow was improved. After the thrombectomy, laboratory data showed elevated cardiac enzymes (troponin-I 50 ng/mL and creatine kinase: 1800 U/L), suggesting an acute phase of myocardial infarction. Because of unstable hemodynamics, the gastrointestinal perforation was treated conservatively. She died 19 days later of multiple organ failure. An autopsy revealed colon carcinoma, in addition to duodenal perforation (Fig. 1d), and inferior and posterior myocardial infarction. Duodenal perforation was not ischemic, but digestive. No other condition that would lead to coronary thrombosis, such as left atrial thrombosis or right-left shunt, was detected. We discovered two important clinical issues in this case. First, myocardial infarction can occur by multiple coronary thromboses due to duodenal perforation. Co-occurrence of myocardial infarction and duodenal perforation is rare [1], and to our knowledge, this may be the first case of confirmed concomitant multiple coronary thromboses. Although the possibility of embolism remains, no evidence of embolism was determined at autopsy. Duodenal perforation might trigger thrombosis due to the effects of carcinoma and antithrombin deficiency on coagulation [2, 3]. Second, patients with myocardial infarction complicated by gastrointestinal perforation may find it difficult to feel chest pain. Chest pain from myocardial infarction might be masked by the severe abdominal pain from the gastrointestinal perforation. Unreported, hidden myocardial infarction can exist in patients with gastrointestinal perforation. In patients with duodenal perforation, we should consider the possible complications that follow myocardial infarction, even without reported chest pain. & Toshihiro Suga ss2200@hotmail.co.jp

Spontaneous coronary artery dissection with a collateral vessel

A 54-year-old woman with no cardiovascular risk factors except a history of smoking, and without a history of oral contraceptive use or signs of apparent fibromuscular dysplasia, was admitted following sudden-onset morning chest pain. Physical examination revealed no abnormalities; vital signs and hemodynamics were stable. Electrocardiography indicated normal sinus rhythm and ST segment elevation in the anterior leads. Echocardiography showed anterior mild hypokinesis with an ejection fraction of 50%. Laboratory data showed slightly elevated cardiac enzymes (troponin-I 0.07 ng/ml, creatine kinase 220 IU/l), suggesting acute myocardial infarction (AMI). Emergency coronary angiography revealed no stenosis in the right coronary artery (RCA) and left circumflex and total occlusion of segment 7 in the left anterior descending artery (LAD). The occlusion appeared to be caused by compression as opposed to typical atherosclerosis-induced AMI (Fig. 1a). An RCA-LAD-connecting collateral vessel was observed (Fig. 1b). Percutaneous coronary intervention (PCI) was performed: the wire could only pass to segment 10 and not to segment 8. Intravascular ultrasound showed no atherosclerosis (Fig. 1a ) but intramural hematoma and intimal tear in segment 7 (Fig. 1a`), with the true lumen compressed by the intramural hematoma (Fig. 1a ́), suggesting spontaneous coronary artery dissection (SCAD)-induced AMI. Because antegrade wiring was difficult, retrograde wiring was performed using the collateral vessel. The kissing-wire technique was effective, enabling the antegrade wire to pass to segment 8 (Fig. 1c). A drug-eluting stent was implanted, improving coronary flow (Fig. 1d). Post-PCI laboratory tests showed creatine kinase elevation up to 800 IU/l. The patient was discharged from the hospital 14 days later with no complications. This case revealed two important clinically relevant issues. First, SCAD can be accompanied by a collateral vessel. Although SCAD accompanied by collateral vessels caused by chronic atherosclerosis has been reported, to our knowledge, SCAD accompanied by collateral vessels not attributable to atherosclerosis, as observed in this case, has not been previously reported. SCAD is rare and its etiology is not entirely clear. Coronary artery spasm, which is related to smoking and the occurrence of SCAD [1], is also associated with the formation of collateral vessels [2]. Considering the smoking history of this patient, spasm might have caused the SCAD with a collateral vessel. Second, retrograde wiring, which has been reported to be effective in chronic total occlusion [3], may be effective in patients with SCAD-induced AMI if a collateral vessel exists. SCAD-induced AMI is & Toshihiro Suga ss2200@hotmail.co.jp

Cross-Sectional Study of Patients With Onset of Acute Coronary Syndrome During Statin Therapy

Background Although statin therapy significantly reduces cardiovascular morbidity and mortality, atherosclerotic plaque progresses in some patients taking statins. This study investigated the factors associated with onset of acute coronary syndrome (ACS) early after the initiation of statin therapy. Methods Consecutive patients taking statins who presented with ACS (n = 64) were divided into < 1-year and > 1-year groups based on the duration of statin therapy. Patient characteristics, coronary risk factors, lesion locations, and percutaneous intervention procedures were compared between groups. Results The < 1-year group was significantly younger (57.6 ± 11.9 years vs. 76.6 ± 9.1 years, P < 0.01), had significantly higher body mass index (27.22 ± 4.20 kg/m2 vs. 24.60 ± 4.65 kg/m2, P < 0.05), higher proportion of males (94% vs. 70%, P < 0.05), higher proportion of current smokers (61% vs. 17%, P < 0.01), and lower proportions taking aspirin and calcium antagonists (both 17% vs. 57%, P < 0.05) than the > 1-year group. In the < 1-year group, there were significant correlations between the low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels (r = 0.649, P = 0.004) and between the TG and hemoglobin (Hb)A1c levels (r = 0.552, P = 0.018), but these correlations were not observed a year before admission. TG level was the only parameter associated with LDL-C and HbA1c levels. Conclusions A linear correlation between the LDL-C and TG levels, obesity, older age, male sex, and smoking may be associated with increased risk of onset of ACS early after the initiation of statin therapy. Prospective cohort studies are needed to further explore these interactions.