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Biomedical subjects

V Wiegand

Publications and source records attributed to V Wiegand.

81 records · Page 5Linked to original sources

Acute myocardial infarction: intracoronary application of nitroglycerin and streptokinase.

In five patients with acute myocardial infarction, the effects of both intracoronary nitroglycerin (NTG) and subsequent intracoronary streptokinase application were evaluated. In addition, transluminal recanalization was performed in one of these patients. Injection of NTG into the infarct-related coronary artery resulted in improved distal filling of the subtotally occluded left circumflex artery in one patient, and in transient patency of the completely occluded right coronary artery in a second patient. In a third patient patency of the totally occluded left anterior descending artery (LAD) was achieved by transluminal recanalization with a guide wire. In a forth patient with occulsion of the LAD, there was no response to intracoronary NTG and mechanical recanalization was not attempted. Subsequent intracoronary infusion of streptokinase (1,000--2,000 U/min for 15--60 min) resulted in a further and long-term reduction of narrowing at the site of acute occlusion in patients I-III and in opening of the completely occluded LAD in patient IV. Improvement of lumen was paralleled by alleviation of symptoms. In a fifth patient, in whom the LAD was subtotally occluded, the degree of coronary obstruction could not be changed by intracoronary application of NTG or by lysis. In this patient, symptoms and ECG changes improved with reduction of pathologically elevated blood pressure values. The findings suggest that myocardial infarction had been caused by thrombotic occulsion in four patients, and that spasm of the infarct vessel could have been an additional factor in two of these patients. In the fifth patient, an increase of afterload in the presence of a subtotal lesion might have caused the critical imbalance between oxgen supply and demand, resulting in cell death.

Cardiac Catheterization↗

Prophylaxis of ventricular fibrillation after acute experimental coronary occlusion by chronic beta-adrenoceptor blockade with atenolol.

Acute occlusions of the left circumflex coronary artery were performed in open-chest dogs. A control group (n = 19) was compared with three groups (total n = 17) pretreated once daily with different doses of the cardioselective beta-blocking drug atenolol (ICI 66 082) given by mouth for 5 days. Only animals without coronary collateral vessels were examined, having a mortality rate of 100% in the control group. Arrhythmias and ventricular fibrillation during the first 30 min after coronary occlusion showed a biphasic distribution in time (phase 1a and 1b). A lower degree of beta-adrenoceptor blockade reduced the incidence of arrhythmias and ventricular fibrillation in phase 1a, but fibrillation occurred in all animals during phase 1b. A higher dose of the beta-blocking drug protected the animals from ventricular fibrillation, and arrhythmias in phase 1a were greatly reduced. At all times the ventricular fibrillation threshold in the group pretreated with atenolol was significantly higher than in the control group. In both groups a significant decrease in ventricular fibrillation threshold was found only during phase 1a. The greater sensitivity of phase 1a arrhythmias to beta-blockade and the lack of a decrease in ventricular fibrillation threshold during phase 1b might indicate differences in the genesis of arrhythmias and fibrillation in phases 1a and 1b.

Animals↗

Extracellular potassium activity changes in the canine myocardium after acute coronary occlusion and the influence of beta-blockade.

Extracellular potassium activity before and after coronary occlusion was measured in the canine heart by means of potassium-selective surface electrodes. In the ischaemic myocardium potassium activity rapidly increased from a preocclusion value of 3.2 +/- 0.3 mmol.litre-1 to 10 +/- 0.6 mmol.litre-1 within the first 5 min and to about 11.3 +/- 0.5 mmol.litre-1 after 10 min of ischaemia (range from 9.5 to 14.5 mmol.litre-1). Following the initial 10 min of ischaemia no further increase was measured. In the non-ischaemic area potassium activity remained constant. Acute beta-blockade significantly attenuated the initial rate of increase in potassium activity; however, beta-blockade did not influence maximal values of extracellular potassium activity measured after occlusion. Lowering of heart rate by vagal stimulation did not modify the pattern of increase in potassium during acute ischaemia. Following ventricular fibrillation, a slow but continuous rise in potassium activity was found. These results demonstrate that extracellular potassium activity in the acutely ischaemic myocardium is considerably higher than indicated by the technique of coronary vein sampling and is in the range necessary for the development of re-entrant arrhythmias in the early phase after coronary occlusion.

Animals↗

Antiproliferative effects of a c-myc antisense oligonucleotide on human arterial smooth muscle cells.

The effects of a c-myc antisense phosphorothioate DNA oligonucleotide were assessed on the proliferation rate of human arterial smooth muscle cells (HSMCs). Compared to a control oligonucleotide the antisense oligonucleotide suppressed the proliferation of HSMCs in a concentration-dependent manner without a major cytotoxic effect. Outgrowth of HSMCs from media explants was significantly inhibited as well. Induction of c-myc expression by serum stimulation of cells was blunted by the antisense oligonucleotide, as shown by immunoblotting. These results demonstrate that c-myc expression is an essential factor for proliferation of HSMCs after growth stimulation, and they show the potential of antisense technology for modulating gene expression of HSMCs in vitro.

Base Sequence↗

Proliferative response of human and minipig smooth muscle cells after coronary angioplasty to growth factors and platelets.

OBJECTIVES: Platelets aggregating at the site of angioplasty, shown to be a potent proliferative stimulus for cultured smooth muscle cells (SMC), could contribute to proliferation after angioplasty. METHODS: SMC were cultivated from human aorta and restenosed coronary lesions as well as from minipig aorta and from normal and post angioplasty coronary artery segments (n = 6 per source). 3H-thymidine incorporation was used as a measure of proliferation. RESULTS: 3H-thymidine incorporation varied greatly after passage 7 in all cell lines, but was significantly higher in SMC from human coronary restenosed lesions compared to those from human aorta and minipig coronary post angioplasty segments in passage 2 (44 +/- 6.4 x 10(3) cpm/5000 SMC vs 20 +/- 3.9 and 12.1 +/- 2.1). However, all SMC exhibited a dramatic increase of 3H-incorporation after passage 7. Growth factors stimulated 3H-thymidine incorporation either dose dependently (PDGF-BB and bFGF) or only very modestly (PDGF-AA, EGF, IGF-1). The most potent stimulation was seen with PDGF-BB, 50 ng/ml, and was 17 +/- 6% (human restenosed) and 16 +/- 8% (minipig post angioplasty) of the values observed after stimulation with 10% fetal calf serum. The most effective combination of growth factors, PDGF-BB (50 ng/ml) + bFGF(20 ng/ml) + IGF-1 (50 ng/ml), produced a 3H-thymidine incorporation of 44 +/- 10% (human restenosed) and 42 +/- 11% (minipig post angioplasty) of FCS values. Stimulation by isolated platelets was dose dependent and significantly higher: 75 +/- 19% and 70 +/- 15% of FCS values for those SMC. CONCLUSIONS: 1) SMC from all sources studied exhibit significant changes of proliferation with increasing passages, excluding the comparability of data obtained with cells in different passages. 2) Data obtained with SMC from any source might not apply for SMC from human coronary restenosed lesions. 3) Currently tested growth factors do not fully account for the proliferative effect of platelets on cultured SMC.

Adult↗

Influence of the thyroid state on myocardial myosin in the adult pig heart.

The influence of hyper- and hypothyroidism on atrial and ventricular myosin structure and Ca2+-activated ATPase activity has been analyzed in adult mini-pigs. Whereas no difference could be demonstrated between hypo- and euthyroid ventricular myocardium, Ca2+-activated ATPase activity was significantly higher in the hyperthyroid than in the hypo- or euthyroid state. Using pyrophosphate electrophoresis and isoelectric focusing of subfragment 1 this could be ascribed to an additional ventricular myosin in the hyperthyroid myocardium. Atrial myosin ATPase activity and structure were not influenced by the thyroid state of the animals. These results present evidence that thyreotoxicosis induces an additional isomyosin in the pig ventricular myocardium, albeit to a lesser degree than in the rodent heart. The lacking difference between the hypothyroid and the euthyroid states indicates that a myosin with a lower enzymatic activity than the normal ventricular myosin is not synthesized in the heart of higher mammals.

Animals↗

Altered distribution of myosin isoenzymes in the cardiomyopathic Syrian hamster (BIO 8.262).

Myosin of the ventricular myocardium of the cardiomyopathic Syrian hamster and of control animals was analysed using non-dissociating pyrophosphate electrophoresis. Three different myosin isoenzymes exhibiting different Ca2+ activated ATPase activities were demonstrated in the ventricular myocardium of the Syrian hamster. As shown by peptide mapping, ventricular myosin isoenzymes differ in their heavy chain composition. In the cardiomyopathic hamster a shift to myosins of lower Ca2+-activated ATPase activities occurs in the stage of insufficiency (age 220 days), whereas no different isoenzyme pattern could be found at the age of 65 days compared to control animals. We conclude that this redistribution of myosin isoenzymes is the basis of reduced myosin ATPase activity in the ventricular myocardium of the cardiomyopathic Syrian hamster during the development of myocardial insufficiency.

Adenosine Triphosphatases↗

Hypothyroid-like effect of amiodarone in the ventricular myocardium of the rat.

Due to the similar electrophysiological effects of amiodarone and hypothyroidism in the myocardium, the induction of a local hypothyroid state has been proposed as the mechanism of action of amiodarone. To examine this hypothesis we have studied the influence of amiodarone on the distribution of ventricular isomyosins--a sensitive parameter of the thyroid state in the rat heart--and the effects of amiodarone on 3,5,3'-triiodothyronine (T3) myocardial nuclear receptor binding in vivo. Amiodarone induced a dosage-dependent redistribution of isomyosins similar to hypothyroidism, while simultaneously inducing a low T3 syndrome at the higher dose level. In hypothyroid rats, which were pretreated with amiodarone, substitution of T3 (2 micrograms/100 g) led to a complete reversal of the myosin pattern not differing from control hypothyroid rats which were only given T3; the effect of T3 (0.5 microgram/100 g) was however partially inhibited by amiodarone. Nuclear receptor binding of T3 determined in hypothyroid rats in vivo was unaffected by amiodarone. We conclude that amiodarone induces a hypothyroid-like state in the ventricular myocardium of rats by inhibiting the action of T3--an effect which cannot be attributed to an antagonism at the T3 nuclear receptor level.

Amiodarone↗