Increased expression of biglycan mRNA in pressure-overloaded rat heart.

Biglycan mRNA expression in rat myocardium after abdominal aortic banding with renal ischemia was examined. The Northern blot analysis demonstrated that expression of biglycan mRNA in the pressure-overloaded hearts on days 2, 7, 14 and 28 was 2.88 +/- 0.89, 2.32 +/- 0.49, 2.17 +/- 0.57 and 1.81 +/- 0.46-fold higher, respectively, than that in the sham-operated hearts. In situ hybridization showed an increased density of biglycan mRNA signal-positive cells in the pressure-overloaded hearts. The cells with positive signals were spindle-shaped mesenchymal cells in the myocardial interstitium. A marked increase in biglycan mRNA signal expression was also observed in endothelial cells and smooth muscle cells of the thickened myocardial capillary wall. These results demonstrated an increase in biglycan mRNA in the pressure-overloaded heart in mesenchymal cells in the myocardial interstitium, and in endothelial and smooth muscle cells of the capillaries, indicating that biglycan contributes to the ventricular and vascular remodeling in response to pressure overload.

Establishment of a long-surviving murine model of myocardial infarction: qualitative and quantitative conventional microscopic findings during pathological evolution.

Ongoing basic molecular analyses are being performed in mice, and a simple long-surviving murine model of myocardial infarction (MI) would be very useful in this regard. Although a few studies have induced MI in mice by coronary artery ligation, the induction involves a complex technique and has a relatively high mortality rate. In addition, the identification of the basic pathological sequence is essential to the interpretation of experimental results. We developed a simple technique for the induction of MI in mice and examined qualitative and quantitative conventional microscopic findings during the pathological evolution over a 28-day observation period. Male BALB/c mice weighing approximately 25-30 g were anesthetized and then ventilated with a positive pressure ventilator. The heart was exposed by thoracotomy. Left coronary artery occlusion was performed by thermocoagulation using a thermocoagulation knife at the level of the tip of the left atrium. After establishing this surgical method, we used it to induce MI in 71 mice. The operative and postoperative mortality rates of this model were 5.6% (4/71) and 12.6% (9/71), respectively. In 3 (5.2%) of the 58 surviving mice, the area of infarct was not sufficient. The infarct area in the remaining 55 mice was 40 +/- 9% of the entire perimeter of the left ventricle. Conventional microscopic examinations with hematoxylin-eosin and Masson-trichrome staining disclosed that all of the characteristic histopathological features of MI occurred 1-2 days earlier than those in rats. Our surgical technique provides a sufficient infarct area, with an acceptable mortality rate. The present study clarified the histopathological sequence in this long surviving murine MI model.

Volume of infarction and blood flow in cerebral embolism.

The value of measuring asymmetry of cerebral perfusion semiquantitatively by single-photon emission computed tomography (SPECT) correlated with measuring the volume of infarction on computed tomography (CT) was evaluated in cerebral embolism. Eighteen patients with acute cerebral embolism (mean age: sixty-nine years) were evaluated. Ten were diagnosed as having middle cerebral artery (MCA) occlusion, 3 as having MCA branch occlusion, and 4 as having unilateral and 1 as having bilateral internal carotid occlusion. The infarct volume was measured, summing up the area of infarction on CT, at 8.5 days, mean time after onset. Outcomes of the patients were classified into three groups: good, fair, or dead, judged by the consequences one month after onset. Regional cerebral blood flow (rCBF) was measured in 9 of 10 surviving patients at one month, mean time after onset, by 123[iodine N-isopropyl-p-iodoamphetamine (IMP) SPECT. Semiquantitative rCBF index of asymmetry (AI) was evaluated from four regions of brain cortex. Eleven patients with < 300 mL infarct and 7 with > or = 300 mL infarct showed a significant difference of outcome with infarct volumes (P < 0.01). The mean AI value in patients with < 150 mL infarct was 31% while it was 52% with > or = 150 mL infarct (P < 0.039). There were significant linear correlations between mean AI values and the volumes of infarction or infarct/brain volume ratios (P < 0.034 or P < 0.018). The significant correlations of the AI values with the volumes of infarction suggest that the measured asymmetry of perfusion evaluated by SPECT could reflect the ultimate tissue damage and residual intact brain volume after cerebral embolism.

Cerebellar diaschisis in pontine infarctions: a report of five cases.

We evaluate regional cerebral and cerebellar perfusion to prove the occurrence and follow the persistence of crossed cerebellar diaschisis in infratentorial pontine infarction. Six consecutive patients exhibiting mild hemiparetic symptoms or a heavy feeling in the head (mean age 65 years; four women, two men) and diagnosed as having pontine infarction by magnetic resonance imaging were subjected to evaluation. Lesions due to infarction were located at the upper basis pontis in five patients and the upper tegmentum pontis in one, and medially at the paramedian portion in four and laterally in two. Regional cerebral and cerebellar perfusion was evaluated semiquantitatively by iodine-123 N-isopropyl-p-iodoamphetamine (IMP) single-photon emission tomography (SPET); this was done during the acute stage in five cases (mean time after onset: 0.7 months) and during the chronic stage in three (mean time after onset: 14.8 months). Four patients had two examinations during their clinical courses. For semiquantitative evaluation of perfusion, an asymmetry index was calculated for each region of interest, set symmetrically in regions of the cerebral cortex and cerebellum in both hemispheres. Significant asymmetry (P < 0.01) in cerebellar perfusion, which was reduced in the contralateral (n = 4) or ipsilateral (n = 1) cerebellar hemisphere, was demonstrated semiquantitatively in four cases during the acute stage and in one during the chronic stage, as compared with normal controls (n = 5, mean age 61 years). This asymmetry continued to the chronic stage (6.5 and 33.0 months) in two cases, while no patient showed any significant asymmetries in cerebral perfusion in any region of interest in either SPET study.(ABSTRACT TRUNCATED AT 250 WORDS)

Cortical blood flow and cognition after extracranial-intracranial bypass in a patient with severe carotid occlusive lesions. A three-year follow-up study.

The long-term effect of extra-intracranial arterial bypass on cerebral circulation was examined. Cortical blood flow and cognitive ability were evaluated pre- and up to 3 years post-bypass in a 58-years-old man with severe carotid occlusive lesions, who presented with 3 transient cerebral ischaemic attacks which resulted in mental deterioration over 3 years. Regional cerebral blood flow (rCBF) was evaluated pre- and up to 33 months post-bypass by 123Iodine N-isopropyl-p-iodoamphetamine (IMP) single-photon emission CT (SPECT). Mental abilities were evaluated before and up to 33 months after surgery by the Hasegawa's dementia rating scale (HDRS). Pre-operatively, cerebral angiography showed left carotid siphon occlusion and hypoplastic stenosis of left anterior cerebral artery with collaterals from the anterior communicating artery. CT and MRI showed left temporo-parietal borderzone infarction and an enhanced T 1 lesion by gadolinium-DTPA at left periventriculum. rCBF showed extensive hypoperfusion in left anterior-parieto-temporal-cortex. HDRS scores deteriorated apparently on days 3, 5, which recovered gradually on days 8, 10, 75 after onset of mental deterioration. A bypass was performed 4 months after onset. rCBF showed gradual recovery in the left anterior-parietal cortex up to 33 months after bypass. Semiquantitative rCBF showed gradual decreases of regional asymmetry after the bypass. HDRS scores returned to their maximum up to 37 months after onset. Three-year follow-up shows improved cortical rCBF and cognition after the bypass.

Effect of medication with pravastatin sodium on hemorheological parameters in patients with hyperlipoproteinemia.

Pravastatin sodium, a newly developed potent synthesis inhibitor of HMG-CoA (beta-hydroxy-beta-methylglutaryl-cocarboxylase-A) reductase (Sankyo Co., Ltd., Japan) was medicated, 10 approximately 15 mg/day (mean: 11.1 mg/day) for 10.2 weeks in mean, in 14 patients with primary hyperlipoproteinemia of more than 230 mg/dl of serum cholesterol levels (mean age: 56.9 y.o.). The values of serum cholesterol decreased (from 242 +/- 12 to 207 +/- 22; mg/dl), and of high density lipoprotein (HDL) increased (from 42.3 +/- 8.8 to 45.3 +/- 9.2; mg/dl) significantly (p < 0.05, respectively) 10.2 weeks in mean after medication with pravastatin sodium. The whole blood viscosity, at every shear rate examined, corrected blood viscosity, for the standard hematocrit level of 45%, and plasma fibrinogen decreased significantly (p < 0.05, respectively) at the same time, without showing significant differences any more 10.2 weeks in mean after medication with those in 14 elderly normal subjects (mean age: 56.7 y.o.), which suggested that the hemorheological parameters in patients with primary hyperlipoproteinemia had improved significantly by medication with pravastatin sodium.

Semiquantitative regional cerebral blood flow evaluation using 123I-IMP SPECT in a case showing transient ischemic attack caused by putaminal hemorrhage.

A 69-year-old woman presented a transient cerebral ischemic attack, showing left arm weakness and slurred speech which recovered within 4 h of onset, while computed tomography indicated a putaminal hemorrhage. The regional cerebral blood flow distribution, measured semiquantitatively by use of 123I amphetamine emission tomography, was disturbed, which persisted more than one month up to a maximum of 4.5 months from the onset of symptoms. This case illustrates a variety of putaminal hemorrhage of good functional and vital prognosis, and provides an example in which the regional cerebral blood flow disturbances might persist for more than one month up to 4.5 months after the occurrence of a transient ischemic attack caused by a putaminal hemorrhage.