Transoesophageal echocardiography in patients with acute stroke with sinus rhythm and no cardiac disease history.

BACKGROUND: Transoesophageal echocardiography (TOE) is the gold standard for detecting potential cardiac sources of embolism (PCSE). However, the role of TOE in patients with ischaemic stroke with normal sinus rhythm (NSR) and no cardiac disease remains uncertain. METHODS: The authors retrospectively analysed 1833 consecutive patients with ischaemic stroke with NSR and no history of cardiac disease who were examined by TOE. The authors investigated the frequency of PCSE and aortic plaques detected in these patients. Determination of high- and medium-risk PCSE was based on the Trial of ORG 10172 in the Acute Stroke Treatment classification. The authors also determined how the proportions of stroke subtypes and treatment strategies based on current guidelines have been changed after TOE. RESULTS: PCSE and/or aortic plaques were detected in 753 (41.1%) of 1833 patients. After TOE, a total of 355 PCSE (45 high-risk PCSE and 310 medium-risk PCSE) were found in 323 patients (17.6%). Aortic plaques were found in 502 patients (27.4%). Among these, complex aortic plaques, which are significant sources of embolism, were found in 157 patients (8.5%). Changes in treatment strategies for secondary prevention based on the current guidelines would have been necessary in 63 patients (3.4 %) after TOE examination. CONCLUSION: Potential embolic sources from the heart and aorta can be detected by TOE examination in many patients with stroke with NSR and no cardiac disease, which enables a better determination of stroke mechanisms.

Allopurinol modulates reactive oxygen species generation and Ca2+ overload in ischemia-reperfused heart and hypoxia-reoxygenated cardiomyocytes.

Myocardial oxidative stress and Ca2+ overload induced by ischemia-reperfusion may be involved in the development and progression of myocardial dysfunction in heart failure. Xanthine oxidase, which is capable of producing reactive oxygen species, is considered as a culprit regarding ischemia-reperfusion injury of cardiomyocytes. Even though inhibition of xanthine oxidase by allopurinol in failing hearts improves cardiac performance, the regulatory mechanisms are not known in detail. We therefore hypothesized that allopurinol may prevent the xanthine oxidase-induced reactive oxygen species production and Ca2+ overload, leading to decreased calcium-responsive signaling in myocardial dysfunction. Allopurinol reversed the increased xanthine oxidase activity in ischemia-reperfusion injury of neonatal rat hearts. Hypoxia-reoxygenation injury, which simulates ischemia-reperfusion injury, of neonatal rat cardiomyocytes resulted in activation of xanthine oxidase relative to that of the control, indicating that intracellular xanthine oxidase exists in neonatal rat cardiomyocytes and that hypoxia-reoxygenation induces xanthine oxidase activity. Allopurinol (10 microM) treatment suppressed xanthine oxidase activity induced by hypoxia-reoxygenation injury and the production of reactive oxygen species. Allopurinol also decreased the concentration of intracellular Ca2+ increased by enhanced xanthine oxidase activity. Enhanced xanthine oxidase activity resulted in decreased expression of protein kinase C and sarcoendoplasmic reticulum calcium ATPase and increased the phosphorylation of extracellular signal-regulated protein kinase and p38 kinase. Xanthine oxidase activity was increased in both ischemia-reperfusion-injured rat hearts and hypoxia-reoxygenation-injured cardiomyocytes, leading to reactive oxygen species production and intracellular Ca2+ overload through mechanisms involving p38 kinase and extracellular signal-regulated protein kinase (ERK) via sarcoendoplasmic reticulum calcium ATPase (SERCA) and protein kinase C (PKC). Xanthine oxidase inhibition with allopurinol modulates reactive oxygen species production and intracellular Ca2+ overload in hypoxia-reoxygenation-injured neonatal rat cardiomyocytes.

Transfection of mesenchymal stem cells with the FGF-2 gene improves their survival under hypoxic conditions.

Bone marrow mesenchymal stem cells (MSCs) have shown potential for cardiac repair following myocardial injury, but this approach is limited by their poor viability after transplantation. To reduce cell loss after transplantation, we introduced the fibroblast growth factor-2 (FGF-2) gene ex vivo before transplantation. The isolated MSCs produced colonies with a fibroblast-like morphology in 2 weeks; over 95% expressed CD71, and 28% expressed the cardiomyocyte-specific transcription factor, Nkx2.5, as well as a-skeletal actin, Nkx2.5, and GATA4. In hypoxic culture, the FGF-2-transfected MSCs (FGF-2-MSCs) secreted increased levels of FGF-2 and displayed a threefold increase in viability, as well as increased expression of the anti-apoptotic gene, Bcl2, and reduced DNA laddering. They had functional adrenergic receptors, like cardiomyocytes, and exposure to norepinephrine led to phosphorylation of ERK1/2. Viable cells persisted 4 weeks after implantation of 5.0 yen 105 FGF-2-MSCs into infarcted myocardia. Expression of cardiac troponin T (CTn T) and a voltage-gated Ca2+ channel (CaV2.1) increased, and new blood vessels formed. These data suggest that genetic modification of MSCs before transplantation could be useful for treating myocardial infarction and end-stage cardiac failure.

The impact of the preoperative severity of target-vessel stenosis on the short-term patency of radial artery grafts.

The fate of a grafted radial artery remains unknown. The purpose of this study was to determine whether the preoperative severity of stenosis of the target vessel influence short-term patency of radial artery (RA) grafts used as coronary artery bypass conduits. In 54 patients who had coronary artery bypass grafting (CABG) with RA grafts, RA patency was determined with multi-slice computed tomography (MSCT) 1 year after CABG. These patients were divided into three groups on the basis of the percentage of the target vessel stenosis: mild (< 60%, n=17), moderate (60% to 79%, n=19), and severe (>/= 80%, n=18). MSCT was also performed 1 week later to exclude early occlusion of RA grafts. In 3 patients, the MSCT failed to adequately discriminate the status of the RA graft due to poor image resolution. The overall incidence of RA occlusion was 23.5% (12 of 51) at 1 year in the entire population. The mild stenosis, moderate stenosis and severe stenosis group showed an occlusion rate of 50% (8 of 16), 23.5% (4 of 17) and 0% (0 of 18), respectively. The severe stenosis group had significantly lower rate of RA graft occlusion compared to the mild stenosis group (p < 0.001) and moderate stenosis group (p < 0.05). No difference in occlusion between grafts used for the different coronary artery branches could be demonstrated. Preoperative severity of the target coronary artery significantly affected the short-term RA grafts patency. Correct indication is the key factor for short-term RA patency.

Direct myocardial depressant effect of naloxone: mechanical and electrophysiological actions in vitro.

BACKGROUND: Naloxone, an opioid antagonist, has a cardiovascular pressor effect and has been used in various types of shock states. The aim was to determine the non-opioid effect on direct cardiac muscle contractility and explore the mechanism using guinea pig right ventricular papillary muscles. METHODS: With institutional approval, isometric contractile force was measured in modified normal and 26 mM K+ Tyrode solution at various stimulation rates. The effects of naloxone on sarcoplasmic recticulum function were evaluated by measuring rested-state contraction in low Na+ (25 mM) Tyrode solution and rapid cooling contracture in modified normal Tyrode solution. Normal and slow action potentials (APs) were measured using conventional microelectrode technique. Patch clamp study was performed to examine the direct effect on Ca2+ current in cardiac ventricular myocytes. RESULTS: Naloxone (50, 100, and 200 microM) caused a concentration-dependent depression of peak force and maximal rate of force development. Modest depression, approximately 20%, was shown in rested-state contraction in low Na+ Tyrode solution. Naloxone (100 microM) modestly depressed the rapid cooling contracture to 80 +/- 3% of baseline, accompanied by prolongation of time to peak contracture by approximately 37%. In 26 mM K+ Tyrode solution, naloxone (100 microM) markedly and selectively depressed the late force development. While naloxone (100 microM) did not alter the amplitude and dV/dt-max in normal and slow APs at 0.25 Hz, AP duration was prolonged significantly. In patch clamp experiment, naloxone (50 microM) depressed Ca2+ current by approximately 50%. CONCLUSIONS: The direct myocardial depressant effect of naloxone appeared to be in part caused by depression of Ca2+ influx through cardiac membrane. Sarcoplasmic reticulum function appeared to be modestly depressed.

Multiple coronary artery-left ventricular microfistulae in a patient with apical hypertrophic cardiomyopathy: a demonstration by transthoracic color Doppler echocardiography.

Among the congenital coronary artery fistulae, multiple coronary artery microfistulae arising from the left and right coronary artery and emptying into the left ventricle are very rare and little is known of their anatomic and clinical features, especially in apical hypertrophic cardiomyopathy. A 67-year- old woman was referred for the evaluation of chest pain at exertion, and shortness of breath. Electrocardiographic and echocardiographic findings were typical of apical hypertrophic cardiomyopathy. Coronary arteriography showed normal epicardial coronary arteries, but multiple coronary artery-left ventricular microfistulae arising from the left and right coronary arteries. Transthoracic color Doppler echocardiography, using a high frequency transducer with a low Nyquist limit, demonstrated multiple coronary artery-left ventricular microfistulae just beneath the apical impulse window.

Assessment of coronary artery bypass graft patency by multislice computed tomography.

The recently developed multislice computed tomography (MSCT) is capable of rapid imaging of cardiac structures, including coronary arteries, during a single breath-hold. We evaluated coronary artery bypass graft (CABG) patency by comparing MSCT results to those of contrast angiography. MSCT and contrast angiography were performed in 39 patients (10 women, 29 men and mean age 60.0 +/- 7.8 years) with a total of 115 bypass grafts including 36 left internal mammary arteries, 4 right internal mammary arteries, 19 radial arteries, 2 gastroepiploic arteries and 54 vein grafts. Patients were investigated for an average of 14 +/- 27 months (range 1 - 108 months) after CABG surgery. Contrast angiography showed a patency rate of 87.0% (100/115). Ninety-nine of these 100 patent grafts by contrast angiography and 14 of the remaining 15 occluded grafts were correctly classified by MSCT (93.3% sensitivity and 99.0% specificity for bypass graft occlusion). The positive and negative predictive values for bypass graft occlusion were 93.3% and 99%, respectively, with an overall diagnostic accuracy of 98.3% (97.2% for left internal mammary artery, 100% for radial artery, 98.1% for vein graft and 100% for other grafts). In conclusion, MSCT is a useful and accurate diagnostic tool for the evaluation of bypass graft patency.

Development and evaluation of a new apparatus for continuous perfusion of isolated perfused pig heart.

To develop a better model of isolated perfused heart, a new apparatus of coronary artery cannula- fixed-in-aortic tube was developed for continuous normothermic perfusion and compared to the Casalis apparatus with cold ischemia. Eight mongrel pigs with the body weight of 18 to 24 kg were divided half into two groups. All the continuous perfusion experimental hearts resumed a spontaneous heart beat and stabilized earlier than the control hearts without the need of defibrillator or pacemaker, indicating no reperfusion injury on the heart. All the experimental hearts did not show fibrillation nor stopped beating during the entire experiment, whereas the control hearts fibrillated. Two control hearts stopped beating, and only one of the two survived with the help of pacemaker.The coronary systolic, diastolic, and mean pressures were more stable with low variation in the experimental hearts than the cold ischemic control hearts. The experimental hearts consumed more oxygen than the control hearts, indicating more cardiac output. According to these results, the continuous normothermic perfusion method by the new cannula, even though with a short-period of hypothermic perfusion, provided better myocardial protection than the cold ischemia.