Left ventricular asynergy in patients with impending myocardial infarction: two-dimensional echocardiographic assessment

To determine the clinical significance of regional left ventricular asynergy in patients with impending myocardial infarction, we recorded two-dimensional echocardiograms (2DE) serially and performed coronary angiography immediately after the hospital admission in nine patients with initial impending infarction and their last anginal attacks were within 48 hours. Left ventricular asynergy on the first 2DE was observed in six of nine patients during symptom-free periods (Group A: LV asynergy group). Five of the six patients had significant coronary artery lesions (greater than or equal to 75% stenosis) in at least one major coronary artery. Intracoronary filling defects were detected in four of the five patients. Another three patients without asynergy (Group B) had significant fixed stenosis. Coronary artery spasm was observed in two patients during coronary angiography, but no patient had intracoronary filling defects. Intracoronary nitroglycerin (0.1-0.3 mg) reduced the severity of coronary artery narrowing in two patients. In addition, urokinase (240,000-480,000 IU) via the corresponding vessel (PTCR) in the remaining seven patients resulted in reduction in the severity of coronary artery stenosis in four patients, but not in the remaining three patients. Left ventricular wall movement in the asynergy group improved rapidly and no asynergy was observed by the seventh hospital day in five of the six patients. Successful PTCR treatment resulted in improvement of left ventricular wall movement. No asynergy was found in the non-asynergy group throughout their hospitalizations. These findings indicated that abnormal left ventricular wall movement is found in patients with impending myocardial infarction, even during symptom-free periods, but the wall movement gradually improves. The 2DE observations are useful for estimating the clinical status and for planning precise therapy for impending myocardial infarction.     

Immature dendritic cells (CD11c+ CD3- B220- cells) present in mouse peripheral blood

It is well known that dendritic cells (DCs) are developed from the peripheral blood of mice when peripheral blood mononuclear cells (PBMCs) are cultured with GM-CSF. We have previously found that immature DCs are present in the blood even in humans. In the present study, we show that CD11c+ CD3- B220- cells in the mouse peripheral blood are immature DCs. The percentage of CD11c+ CD3- B220- cells in the (PBMCs) of normal mice ranges from 0.5 to 2.5%. The CD11c+ CD3- B220- cells in the PBMCs show dendrites, similar in shape to the CD11c+ CD3- B220- cells in the spleen, which are thought to be DCs definitely. However, they have practically no capacity to stimulate the proliferation of allogeneic T cells, and show a lower expression of MHC class II, B7-1 and B7-2 than CD11c+ CD3- B220- cells in the spleen. When the CD11c+ CD3- B220- cells in the PBMCs are cultured with GM-CSF, they show not only the potent ability to stimulate the proliferation of allogeneic T cells but also a higher expression of MHC class II, B7-1 and B7-2. Moreover, they migrate into the spleen when they are injected intravenously. These results suggest that CD11c+ CD3- B220- cells in the PBMCs are immature DCs, and that they migrate into the spleen, where they mature.     

Intracerebroventricular injection of brain natriuretic peptide inhibits vasopressin secretion in conscious rats

The effect of intracerebroventricular (i.c.v.) injection of brain natriuretic peptide (BNP), a novel peptide purified from the porcine brain, on arginine vasopressin (AVP) secretion was studied in conscious, unrestrained rats and was compared with that of atrial natriuretic polypeptide (ANP). I.c.v. administration of BNP (0.01, 0.1 or 1 nmol) significantly inhibited basal AVP secretion and the effect of BNP was comparable to that of ANP. The AVP secretion induced by i.c.v. injection of angiotensin II (0.1 nmol) was significantly suppressed by the pretreatment with BNP (0.1 or 1 nmol). These results suggest that BNP is involved in the central control of AVP secretion either alone or in combination with brain ANP.     

Pravastatin restored the infarct size-limiting effect of ischemic preconditioning blunted by hypercholesterolemia in the rabbit model of myocardial infarction

OBJECTIVES

We tested to find out whether pravastatin restores the infarct size (IS)-limiting effect of ischemic preconditioning (IP) and if it has any effect on the IP-induced activation of adenosine producing enzyme ecto-5′-nucleotidase which plays a key role in the IP-induced cardioprotection.

BACKGROUND

The IS-limiting effect of IP is blunted by hypercholesterolemia. Recently, HMG-CoA reductase inhibitors are shown to have direct cytoprotective effects.

METHODS

Rabbits were fed with a normal or cholesterol (1%) added diet with or without pravastatin (5 mg/kg/day) treatment. Infarct size was measured after 30 min occlusion and 3 h reperfusion of circumflex coronary artery with or without the IP procedure (5 min occlusion and 10 min reperfusion). Additionally, ecto-5′-nucleotidase activities of ischemic and nonischemic myocardium were measured immediately after IP procedure.

RESULTS

This dose of pravastatin did not normalize the increased level of serum cholesterol. The IS-limiting effect of preceding IP (IS reduced from 36.7% to 9.6%, p < 0.001) was abolished by hypercholesterolemia (from 46.1% to 31.3%, p = NS) and restored by pravastatin treatment (from 35.2% to 9.4%, p < 0.001). Pravastatin treatment did not affect IS or the effect of IP under normocholesterolemia. The activation of ecto-5′-nucleotidase presented as the activity ratio of ischemic to nonischemic myocardium (3.1-fold in normocholesterolemia) was blunted by hypercholesterolemia (1.8-fold, p < 0.05) and restored by pravastatin treatment (2.9-fold).

CONCLUSIONS

Pravastatin, at the dose serum cholesterol was not normalized, restored the IS-limiting effect of IP and IP-induced ecto-5′-nucleotidase activation, which were both blunted by hypercholesterolemia. The activation of ecto-5′-nucleotidase may be worth further investigation as a possible mechanism for the hypercholesterolemia-induced retardation and pravastatin-mediated restoration of the cardioprotective effect of IP.     

Vascular endothelial growth factor receptor-1 regulates postnatal angiogenesis through inhibition of the excessive activation of Akt

Vascular endothelial growth factor (VEGF) binds both VEGF receptor-1 (VEGFR-1) and VEGF receptor-2 (VEGFR-2). Activation of VEGFR-2 is thought to play a major role in the regulation of endothelial function by VEGF. Recently, specific ligands for VEGFR-1 have been reported to have beneficial effects when used to treat ischemic diseases. However, the role of VEGFR-1 in angiogenesis is not fully understood. In this study, we showed that VEGFR-1 performs "fine tuning" of VEGF signaling to induce neovascularization. We examined the effects of retroviral vectors expressing a small interference RNA that targeted either the VEGFR-1 gene or the VEGFR-2 gene. Deletion of either VEGFR-1 or VEGFR-2 reduced the ability of endothelial cells to form capillaries. Deletion of VEGFR-1 markedly reduced endothelial cell proliferation and induced premature senescence of endothelial cells. In contrast, deletion of VEGFR-2 significantly impaired endothelial cell survival. When VEGFR-1 expression was blocked, VEGF constitutively activated Akt signals and thus induced endothelial cell senescence via a p53-dependent pathway. VEGFR-1(+/-) mice exhibited an increase of endothelial Akt activity and showed an impaired neovascularization in response to ischemia, and this impairment was ameliorated in VEGFR-1(+/-) Akt1(+/-) mice. These results suggest that VEGFR-1 plays a critical role in the maintenance of endothelial integrity by modulating the VEGF/Akt signaling pathway.     

Cardiac free wall rupture in acute myocardial infarction: ameliorative effect of coronary reperfusion.

To investigate the pathophysiology of cardiac free wall rupture (cardiac rupture) following acute myocardial infarction (AMI), and to clarify whether reperfusion therapy prevents cardiac rupture, 1,329 cases of AMI (conventional therapy group: 807 cases and reperfusion therapy group: 533 cases) were studied retrospectively. The overall incidence of cardiac rupture was 2.3% (2.7% in the conventional therapy group vs. 1.7% in the reperfusion therapy group). Patients with cardiac rupture were divided into two subgroups according to the time interval from the onset of AMI to cardiac rupture (early rupture less than or equal to 72 h and late rupture greater than or equal to 4 days). The indices of initial evolution of AMI was a significant risk of early cardiac rupture. The reperfusion therapy group showed significantly lower incidence of late rupture (0.4 vs. 1.5% in conventional therapy group; p less than 0.05). The incidence of cardiac rupture in the unsuccessful reperfusion therapy group was higher than that of the successful group (5.9% of 118 cases vs. 0.5% of 404 cases; p less than 0.05). It is concluded that the etiology of cardiac rupture following AMI cannot be explained by any single factor. Early rupture depends on the initial evolution of AMI, and early reperfusion and collateral flow prevent the late onset cardiac rupture.     

Triglyceride Deposit Cardiomyovasculopathy with Massive Myocardial Triglyceride which Was Proven Using Proton-magnetic Resonance Spectroscopy

The patient was a 73-year-old man with a history of hypertension, diabetes mellitus, dyslipidemia, rheumatoid arthritis, repeated percutaneous coronary intervention and percutaneous peripheral intervention procedures. He was frequently admitted to our hospital for congestive heart failure with orthopnea. The myocardial washout rate of iodine-123-β-methyl iodophenyl-pentadecanoic acid was defective on scintigraphy. He was diagnosed with triglyceride deposit cardiomyovasculopathy (TGCV). Proton magnetic resonance spectroscopy (¹H-MRS) indicated the level of myocardial triglyceride (TG) content to be extremely high (4.92%). This is the first report to confirm a massive accumulation of TG in the myocardium of a patient with TGCV using ¹H-MRS noninvasively.