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Biomedical subjects

J Metz

Publications and source records attributed to J Metz.

At least 73 records · Page 4Linked to original sources
PubMed1993

Suppression of neointimal thickening and smooth muscle cell proliferation after arterial injury in the rat by inhibitors of Na(+)-H+ exchange.

Replication of vascular smooth muscle cells is a key event in the pathogenesis of restenosis following angioplasty. Little is known about early biochemical events involved in the proliferation of smooth muscle cells following arterial injury. In the present study, the effect of Na(+)-H+ exchange inhibitors on neointima formation after balloon injury of the rat carotid artery was investigated. Neointima formation was quantified 14 days after injury by morphometric measurement of cross-sectional neointimal area and by fluorometric determination of DNA content. The specific Na(+)-H+ exchange inhibitor 3-methylsulfonyl-4-piperidino-benzoyl guanidine mesylate (Hoe 694) dose-dependently reduced neointimal area and DNA content, the latter finding indicating a true antiproliferative effect. The structurally different Na(+)-H+ exchange blocker 5-(N-ethyl-N-isopropyl)amiloride hydrochloride had comparable inhibitory effects on neointimal area and DNA content, whereas 5-methylsulfonyl-2-piperidino-benzoyl guanidine hydrochloride, a position isomer of Hoe 694 lacking Na(+)-H+ exchange blocking properties, did not suppress neointima formation. The effect of Na(+)-H+ exchange blockers on neointima formation depended on the duration of drug application. Maximal suppression was achieved only when Hoe 694 was applied throughout the entire experiment for 14 days. This inhibitory effect of Na(+)-H+ exchange blocker application for the first 2 weeks following injury lasted for 2 months. In conclusion, the results of the present study reveal a potential role of Na(+)-H+ exchange for smooth muscle cell proliferation in vascular disease.

Amiloride↗
PubMed1993

[Contrast echocardiography in the evaluation of myocardial flow reserve].

In order to determine whether changes in myocardial perfusion can be assessed by myocardial contrast echocardiography, intracoronary injections of 2 ml of sonicated iopromid were performed before and 30 to 45 s after application of papaverine in 31 patients (mean age 58 years). 13 patients showed coronary artery disease (KHE), 6 patients hypertensive heart disease (HHE), and 12 patients had no proven heart disease (KTR). Contrast decay-halftime (T/2), maximal video-intensity (Imax) and area under the curve (Area) were derived by computer-assisted videodensitometry. After papaverine KTR showed a significant increase of T/2 (from 5.1 +/- 1.5 to 6.8 +/- 3.2 s, p < 0.05), of Imax (from 36 +/- 13 to 52 +/- 16 E, p < 0.002) and of Area (from 203 +/- 95 to 379 +/- 188 E*s, p < 0.002) compared to baseline values. In this group the ratios of hyperemia to baseline flow conditions were 1.5 +/- 0.4 (from 1.0 to 2.4) for Imax and 1.9 +/- 0.9 (from 1.1 to 3.9) for Area. In HHE and KHE, hyperemia induced no significant changes of T/2, Imax and Area. Heart rate was increased by 4.3% and mean aortic pressure was decreased by 6.2% in all groups after papaverine. Double-product was not altered significantly in any group. Myocardial contrast echocardiography revealed a significant increase in variables of contrast wash-out curves only in patients without proven heart disease. In contrast, no relevant changes of T/2, Imax and Area on average were observed in patients with coronary and hypertensive heart disease. Thus, myocardial contrast echocardiography seems to be suitable to document a reduced papaverine vasodilator response in these patients.

Adult↗
PubMed1992

[Myocardial contrast echocardiography for the follow-up after percutaneous transluminal coronary angioplasty].

Myocardial contrast echocardiography was performed, before and after successful elective percutaneous transluminal angioplasty (PTCA) of a main coronary artery, in 35 patients (31 men, 4 women; mean age 56 +/- 6 years). After intracoronary injection of microbubbles-containing 2 ml iopromide, contrast half-life (t/2) and maximal echo-intensity (Imax) in the myocardial region supplied by the target vessel were measured. While t/2 decreased from 8.3 +/- 5.4 s to 5.7 +/- 3.3 s (P less than 0.0002), mean Imax remained unchanged (27.4 +/- 10.7 vs 26.1 +/- 10.1 grey value units). Repeat cardiac catheterization with contrast echocardiography was performed a mean of 37 weeks (7-53) later in 13 of 35 patients with optimal echo image quality. Re-stenosis of at least 75% was demonstrated in six patients, while in seven vessel diameter had decreased by less than 30%. In all patients with re-stenosis t/2 had increased by about 20 to 100% of the initial value. It was always over 5 s (mean 6.2 +/- 1.6 s before, 4.7 +/- 1.7 after PTCA, and 6.2 +/- 1.2 s at the end of the follow-up). In one patient a prolonged t/2 persisted due to vessel dissection. Mean t/2 remained unchanged in patients without re-stenosis (5.6 +/- 2.1 s before, 3.5 +/- 1.15 s immediately after PTCA, and 3.6 +/- 1.25 s at the follow-up examination). These data suggest that contrast half-life is suitable for demonstrating changes in myocardial perfusion after PTCA.

Angina Pectoris↗
PubMed1992

Effects of daltroban, a thromboxane (TX) A2 receptor antagonist, on lipid metabolism and atherosclerosis.

In rat hepatocyte cultures daltroban reduced 14C-acetate incorporation stronger into cholesterol (CH) esters than into free CH. Further data suggest that the reduction of cellular sterols by daltroban is independent from its TXA2 receptor antagonistic activity and caused by reduced capacity of ACAT depending CH esterification. In rabbits fed CH-enriched diet treatment with daltroban led to an inhibition of platelet aggregation and to a significant reduction of progression of atherosclerosis. Both reduced CH esterification and TXA2 receptor antagonism may contribute to the diminution of progression of atherosclerosis by daltroban.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Cobalamin deficiency and the pathogenesis of nervous system disease.

Neuropathy commonly complicates cobalamin (Cb1) deficiency in humans, monkeys, fruit bats, and pigs. The neuropathy is characterized by demyelination of the posterolateral columns of the spinal cord (subacute combined degeneration). The lesion was thought to arise primarily from impairment of the adenosylcobalamin-dependent methylmalonyl CoA mutase reaction, leading to the formation of abnormal odd-chain and branched-chain fatty acids and their incorporation into myelin with resultant demyelination. Data from recently developed animal models of the Cb1 neuropathy induced by exposure to nitrous oxide do not substantiate this hypothesis, but rather identify impairment of the methylcobalamin-dependent methionine synthetase reaction as the more important basic defect. The key evidence for this hypothesis is the ability of methionine to delay the onset of Cb1 neuropathy in experimental Cb1 deficiency. In the Cb1-deficient pig, adenosylhomocysteine accumulates in neural tissue, presumably owing to the inability to recycle homocysteine via the defective methionine synthetase reaction. Accumulation of adenosylhomocysteine results in a fall in the adenosylmethionine:adenosylhomocysteine methylation ratio, and this change is believed to cause defective methylation and demyelination in the nervous system. However, in the Cb1 neuropathy in the fruit bat, adenosylhomocysteine does not accumulate in the nervous system, the methylation ratio does not change, and no defect can be demonstrated in the methylation of myelin lipid or basic protein. Although a central role for methionine in the pathogenesis of the Cb1 neuropathy has been established, defective methylation attendant upon impairment of the methionine synthetase reaction may not be the universal defect underlying the Cb1 neuropathy. This would suggest that the methionine effect could be mediated via its role in formate metabolism or polyamine synthesis, or by some as yet unidentified pathway.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1991

Methylmalonic acid metabolism and nervous-system fatty acids in cobalamin-deficient fruit bats receiving supplements of methionine, valine and isoleucine.

Cobalamin neuropathy was produced in Cape fruit bats (Rousettus aegyptiacus) by a cobalamin-free diet combined with intermittent exposure to nitrous oxide, which inactivates cobalamin. Cobalamin-deficient bats had low hepatic methylmalonyl-CoA mutase holoenzyme activity, with elevated plasma and urinary methylmalonic acid levels. No significant changes could be demonstrated in the concentration of odd- or branched-chain fatty acids in the nervous system. Supplementation of the cobalamin-free diet with methionine, valine or isoleucine delayed the onset of neuropathy, despite persistence of methylmalonic acid accumulation. Supplementation with any of the three amino acids was associated with elevation of hepatic methionine concentration. The action of valine and isoleucine in delaying the onset of neuropathy can be explained by their methionine-sparing effect. These results emphasize the central role of methionine in the cobalamin neuropathy and do not support the hypothesis that the neuropathy is related to an effect of cobalamin deficiency on the propionic acid pathway.

Amino Acids↗
PubMed1991

Atherosclerosis in the aorta of hypercholesterolemic rabbits and the influence of daltroban.

These studies have examined aortic atherogenesis in cholesterol-fed rabbits and have correlated the effects of daltroban to the pathomechanism of the vessel wall lesions. After feeding a 0.5% cholesterol-enriched diet for 96 d atherosclerotic alterations were seen, which exhibited a proximo-distal pattern, to which the branching of the aorta contributed considerably. Depending on their localization and size a varying cellular constitution of the plaques was obvious. Large plaques, which were mainly seen in the aortic arch and the proximal descending thoracic aorta, consisted of numerous proliferating cells, masses of fibrillar ground substance, clusters of foam cells, and rarely contained cholesterol crystals and necroses. Emerging plaques mainly found in distal thoracic and abdominal aorta imposed as fatty streaks. Daltroban treatment, used in a clinically relevant doses of 10 mg/kg b. wt. per day, reduced extension and protrusional area of plaques to about 40%, which was evaluated using a newly developed computerized morphormetric method, in association with significant reductions in free cholesterol content within the aorta. The results suggest that daltroban inhibits the progression of atherosclerosis in cholesterol-fed rabbits. This effect may be related to its antagonistic interaction with the thromboxane A2 receptor and also to an inhibition of the cholesterol metabolism.

Animals↗
PubMed1991

Characteristics of endocardial monophasic action potentials recorded from areas with fractionated bipolar electrograms in infarcted canine ventricular myocardium.

STUDY OBJECTIVE: The aim was to characterise monophasic action potentials recorded from subacutely infarcted myocardial regions, where fractionated bipolar electrograms could be obtained. DESIGN: Dogs underwent ligation of the left anterior descending coronary artery. Before and 8-12 d after ligation, monophasic action potentials and local electrograms were recorded endocardially from the apex of the left ventricle. EXPERIMENTAL MATERIAL: 15 anaesthetised mongrel dogs (30 mg pentobarbitone.kg-1) were used. MEASUREMENTS AND MAIN RESULTS: Multiphasic fractionated bipolar electrograms could be recorded from infarcted sites of the left ventricle with a mean duration of 69(SD 10) ms and a mean amplitude of 3.7(1.6) mV, compared to control values of 42(7) ms (p less than 0.05) and 9.4(2.2) mV (p less than 0.05), respectively. Endocardial monophasic action potentials recorded from these areas were similar to action potentials obtained from non-infarcted sites before coronary ligation. The fractionated extracellular potentials were superimposed on the monophasic action potential upstroke. MAP90 was 189(31) ms, MAP30 138(12) ms, versus control values of 182(27) ms and 139(10) ms (NS). Monophasic action potential amplitude was significantly reduced at infarcted sites compared to control, at 26(7) mV v 38(6) mV. Histological specimens were taken to confirm that measurements were obtained from infarcted tissue. CONCLUSIONS: It is possible to record monophasic action potential in subacutely infarcted canine ventricular myocardium; this technique might help in further studies to characterise electrophysiological mechanisms of ventricular arrhythmias in chronic myocardial infarction in man.

Action Potentials↗
PubMed1991

Effects of diazepam on cerebral metabolism and mood in normal volunteers.

The effects of diazepam on regional cerebral metabolism were examined in eight healthy volunteers using positron emission tomography with 18-fluorodeoxyglucose as the tracer. Each subject was tested three times, at 1-week intervals, with placebo, a low oral dose of diazepam (0.07 mg/kg), and a moderate dose of diazepam (0.14 mg/kg). Subjects completed mood questionnaires before and at regular intervals after taking the drug, and performed a vigilance task during the 60-minute period of tracer uptake. The effects of the drug on cerebral metabolism were examined alone and in relation to the subjective and behavioral effects of the drug. Both doses of diazepam decreased global (whole brain) metabolic rate but did not affect specific regions differentially. Subjects experienced sedative like effects during all three scans (placebo as well as drug). Compared to placebo, both doses of diazepam decreased anxiety, and neither dose produced significant impairment of task performance. Neither the subjective nor behavioral drug effects were correlated with the changes in metabolic rate. Thus, diazepam decreased whole brain metabolic rate at doses that produced only modest subjective or behavioral effects. The changes in metabolic rate were not clearly related to other observable drug effects.

Adult↗
PubMed1991

[Diagnosis and evaluation of mitral endocarditis complicating obstructive cardiomyopathy using cardiac echo-Doppler].

The authors report a case of mitral endocarditis diagnosed by cardiac echo-Doppler and complicating an obstructive cardiomyopathy (OCM) in a 37-year-old woman. Despite the high degree of sub-aortic obstruction and the existence of an apparently severe mitral leak by Doppler analysis, the patient remained totally asymptomatic and the outcome was favourable with appropriate antibiotics. A review of the literature revealed 11 cases of endocarditis in a context of OCM, documented by echocardiography. Echo-Doppler enables precise evaluation of this grave and often poorly tolerated complication of OCM.

Adult↗
PubMed1990

Cobalamin neuropathy. Is S-adenosylhomocysteine toxicity a factor?

Cobalamin neuropathy was produced in cape fruit bats (Rousettus aegyptiacus) by a cobalamin-free diet combined with intermittent exposure to nitrous oxide, which inactivates cobalamin. There were no significant differences in S-adenosylmethionine/S-adenosylhomocysteine ratios in the central nervous system of cobalamin-deficient and cobalamin-replete bats. Taken with other data there are no grounds of support for a hypothesis that cobalamin neuropathy is the result of impaired methylation, however produced.

Animals↗
PubMed1990

Demyelinisation in the spinal cord of vitamin B12 deficient fruit bats.

1. Vitamin B12 deficiency induced in the fruit bat by a combination of dietary deprivation and exposure to nitrous oxide (N2O) is accompanied by profound neurological impairment, thus providing an experimental model for the study of vitamin B12 neuropathy. 2. Electron microscopy of the spinal cord of vitamin B12 deficient bats shows marked changes in the myelin of the posterior columns in the form of distension, separation and vacuolation of myelin lamellae similar to the changes described in the dietary induced B12 deficient monkey model. 3. No equivalent change occurred in bats exposed to N2O and supplemented with vitamin B12.

Animals↗