Echocardiography in acute and remote myocardial infarction

Two dimensional echocardiography is just beginning to be used to characterize cardiac damage in patients with acute myocardial infarction. The two dimensional approach allows for a more comprehensive evaluation of cardiac anatomy and is able to detect with high sensitivity changes in regional wall motion that previously were sometimes missed or only found with difficulty using M mode echocardiography. Two dimensional echocardiography appears to offer a basis for quantifying the extent of myocardial damage in acute myocardial infarction and thus may permit objective assessment of therapeutic modalities and prognosis. In addition, the technique facilitates recognition of specific complications in acute myocardial infarction. In particular, the technique offers the ability to distinguish true from false ventricular aneurysm, postinfarction ventricular septal defect from papillary muscle dysfunction and rupture, and right ventricular infarction from cardiac tamponade.     

The electrocardiogram in acute pulmonary embolism

Electrocardiograms of 90 patients with arteriographically documented acute submassive or massive pulmonary embolism and no associated cardiac or pulmonary disease were studied. Patients were derived from the Urokinase-Pulmonary Embolism Trial National Cooperative Study. In massive embolism, the electrocardiogram was normal in 6% (3 of 50) of patients. With submassive embolism, 23% of patients (9 of 40) had a normal electrocardiogram. Since one or more of the traditional manifestations of acute cor pulmonale (S₁Q₃T₃, right bundle branch block, P pulmonale, or right axis deviation) occurred in only 26% of patients, one could not rely exclusively upon these electrocardiographic abnormalities for the diagnosis of pulmonary embolism. The most common electrocardiographic abnormalities were nonspecific T wave changes which occurred in 42% of patients and nonspecific abnormalities (elevation or depression) of the RST segment which occurred in 41% of patients. Left axis deviation occurring in 7% of the patients was as frequent as right axis deviation. Low voltage QRS complexes, previously undescribed in pulmonary embolism, occurred in 6% of patients. None of the patients had atrial flutter or atrial fibrillation, which appears to occur more typically in patients with pulmonary embolism who have preexistent cardiac disease. All of the varieties of electrocardiographic abnormalities disappeared in some of the patients by 2 wk. Inversion of the T wave was the most persistent abnormality. Larger defects on the lung scan or pulmonary arteriogram occurred in patients with various abnormalities on the electrocardiogram than in patients with normal electrocardiograms. The pulmonary arterial mean pressure and/or right ventricular end-diastolic pressure was significantly higher in patients with several varieties of abnormal electrocardiograms, although the partial pressure of oxygen in arterial blood, in general, did not differ from that in patients with normal electrocardiograms. These hemodynamic correlations, made for the first time in patients, suggest that acute ventricular dilatation, possibly in combination with hypoxemia, is a causative factor of the electrocardiographic changes in acute massive or submassive pulmonary embolism.     

Successful Directional Atherectomy of De Novo Coronary Lesions Assessed With Three-Dimensional Intravascular Ultrasound and Angiographic Follow-Up

Recent histopathologic and intravascular ultrasound (IVUS) data indicate that inadequate compensatory enlargement of atherosclerotic lesions contributes to the development of significant arterial stenoses. Such lesions may contain less plaque, which may have implications for atheroablative interventions. In this study, we compared lesions with (group A, n = 16) and without inadequate compensatory enlargement (group B, n = 30) as determined by IVUS. The acute results and the follow-up lumen dimensions of angiographically successful directional coronary atherectomy procedures were compared. Inadequate compensatory enlargement was considered present when the preintervention arterial cross-sectional area at the target lesion site was smaller than that at the (distal) reference site. Three-dimensional IVUS analysis and quantitative angiography were performed in 46 patients before and after intervention. IVUS measurements included the arterial, lumen, and plaque (arterial minus lumen) cross-sectional areas at the target lesion site (i.e., smallest lumen site) and the (distal) reference site. Angiographic follow-up was performed in 42 patients. Preintervention and postintervention angiographic measurements and IVUS lumen cross-sectional area measurements were similar in both groups. However, at follow-up, the angiographic minimum lumen and reference diameters were significantly smaller in group A compared with group B (1.71 ± 0.47 mm vs 2.14 ± 0.73 mm, p <0.03, and 2.97 ± 0.29 mm vs 3.39 ± 0.76 mm, p <0.02; group A vs B). The data of this observational study suggest that lesions with inadequate compensatory enlargement, as determined by IVUS before intervention, may have less favorable long-term lumen dimensions after directional coronary atherectomy procedures.     

Intravenous dopexamine in the treatment of acute congestive heart failure: Results of a multicenter,double-blind,placebo-controlled withdrawal study

Summary Acute hemodynamic effects of intravenous infusion of dopexamine were evaluated by a placebo-controlled withdrawal study in patients with acute congestive heart failure. Twenty patients were enrolled at 10 centers in Japan. All patients had a pulmonary capillary or diastolic pressure of 15 mmHg or greater and a cardiac index of 2.5 l/min/m² or less.Phase I: Intravenous dopexamine was introduced in a single-blind, uncontrolled fashion at the rate of 0.5 µg/kg/min and was titrated up to achieve a 30% or more increase in the cardiac index. Two patients withdrew from the study due to sinus tachycardia and ventricular ectopy or exacerbation of heart failure.Phase II: The remaining 18 responders who were free of limiting side effects were randomized in double-blind fashion to continue dopexamine or to switch to placebo for an additional 60 minutes. At the end of phase II, the hemodynamic improvement obtained in phase I of the study disappeared completely after substitution of placebo but was maintained in dopexamine-treated patients. Our findings suggest that dopexamine, when given in appropriate doses to selected patients, shows balanced vasodilator action suitable for the treatment of acute congestive heart failure.See Appendix 1 for complete list of participating centers and principal investigators     

Approach to the patient with venous thromboembolism. Treatment with thrombolytic agents.

This article reviews the different thrombolytic agents currently available and the different mechanisms by which they activate the body's fibrinolytic system. The discussion is confined to the approach to the patient with venous thromboembolism using the different thrombolytic agents. Data are presented supporting the use of thrombolytic therapy and its long-term benefits, especially in patients with pulmonary embolism. A substantial portion of this article is devoted to practical considerations involved in the administration of thrombolytic therapy.     

PDGF Receptor β Is a Potent Regulator of Mesenchymal Stromal Cell Function

Mesenchymal stromal cells (MSCs) in bone marrow are important for bone homeostasis. Although platelet‐derived growth factor (PDGF) has been reported to be involved in osteogenic differentiation of MSCs, the role remains controversial and the network of PDGF signaling for MSCs has not been clarified. To clarify the underlying regulatory mechanism of MSC functions mediated by PDGF, we deleted the PDGF receptor (PDGFR)β gene by Cre‐loxP strategy and examined the role of PDGF in osteogenic differentiation of MSCs and fracture repair. In cultured MSCs, the mRNA expression of PDGF‐A, ‐B, ‐C, and ‐D as well as PDGFRα and β was detected. Depletion of PDGFRβ in MSCs decreased the mitogenic and migratory responses and enhanced osteogenic differentiation as evaluated by increased alkaline phosphatase (ALP) activity and mRNA levels of ALP, osteocalcin (OCN), bone morphogenetic protein (BMP) 2, Runx2, and osterix in quantitative RT‐PCR. PDGF‐BB, but not PDGF‐AA, inhibited osteogenic differentiation accompanied by decreased ALP activity and mRNA levels, except for BMP2. These effects of PDGF‐BB were eliminated by depletion of PDGFRβ in MSCs except that PDGF‐BB still suppressed osterix expression in PDGFRβ‐depleted MSCs. Depletion of PDGFRβ significantly increased the ratio of woven bone to callus after fracture. From the combined analyses of PDGF stimulation and specific PDGFRβ gene deletion, we showed that PDGFRβ signaling distinctively induces proliferative and migratory responses but strongly inhibits osteogenic differentiation of MSCs. The effects of PDGFRα on the osteogenic differentiation were very subtle. PDGFRβ could represent an important target for guided tissue regeneration or tissue engineering of bone.     

Dosage form design for improvement of bioavailability of levodopa VI: formulation of effervescent enteric-coated tablets

A new dosage form of levodopa, which has the characteristics of loading high concentrations of levodopa at the upper part of the intestine, has been developed to improve its bioavailability. It is shown that an effervescent tablet formulation, coated with hydroxypropyl methylcellulose phthalate (carboxybenzoyl radical content: 20-24%) as the enteric material, is suitable for the purpose of dissolution. This was confirmed from animal experiments, which showed that tablets of this composition disintegrate instantly on reaching the upper part of the intestine. This tablet was considered appropriate for the bioavailability tests described in this paper.     

Cerebral aneurysms and variations in the circle of Willis

In order to obtain information about the relationship between variations in the circle of Willis and aneurysms, 44 complete circles of Willis with aneurysm were studied macroscopically. The incidence of variations was significantly higher in the aneurysm series than in the control circles without aneurysm. There was a definite correlation between asymmetric proximal segments of the anterior cerebral artery and aneurysms of the anterior communicating artery, and a tendency to correlation was found in the case of asymmetric posterior communicating arteries and aneurysms on the internal carotid artery-posterior communicating artery junction. In the light of these findings it seems likely that through hemodynamic changes variation in the circle of Willis plays some role in the development of cerebral aneurysms.