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H Köppel

Publications and source records attributed to H Köppel.

At least 37 records · Page 2Linked to original sources
PubMed1998

First description of the effect of a non-sulfonylurea compound, tetramethylpyrazine, on coronary response to desoxyglucose-induced ischemia.

The compound 2,3,5,6-Tetramethylpyrazine (TMP; Ligustrazine), a flavouring component and sweetness enhancer for beverages constitutes a commonly used food additive. Now we studied the effect of TMP on coronary artery dilation during ischemia: In our experiments we used isolated, Langendorff-perfused guinea pig hearts, arrested with K(+)-rich Normal Tyrode solution (in mM: NaCl 129.5, KCl 15, MgCl2 0.8, CaCl2 1.0, glucose 10), buffered with 10 mM HEPES to pH 7.4 at 37 degrees C, equilibrated with 100% O2. Ischemia was simulated by equimolar replacement of glucose by 2-deoxyglucose (DOG), an inhibitor of oxydative phosphorylation. We found that coronary perfusion pressure (CPP) decreased by 20 +/- 1.2 cm H2O (from initially 90 cm H2O; n = 6, +/- SEM) within 15 min from the onset of DOG. In the presence of 1 mM TMP the decrease in CPP was largely attenuated and CPP declined by 1.4 +/- 1.0 cm H2O (n = 6, +/- SEM; p < 0.01). In 2 out of the 6 TMP experiments even as light increase in CPP (< 2 cm H2O) could be seen. We conclude that TMP, a blocker of ATP-dependent K(+)-channels in pancreatic beta-cells and possibly in arterial smooth muscle cells, prevents coronary dilation in response to ischemia. The possible suppression of this vital mobilization of coronary reserve during ischemia in patients with coronary artery disease certainly merits further attention and may question the use of this compound as a food additive.

Adenosine Triphosphate↗
PubMed1998

[Protection against myocardial ischemia by nisoldipine--an experimental study with valinomycin K-sensitive microelectrodes].

It has been shown that dihydropyridines exert a cardioprotective effect during experimental ischemia. This effect is reflected in a reduced K-efflux from the ischemic tissue. Recently we have shown that ischemic K-efflux is largely mediated by ATP-dependent K-channels. Using K-selective microelectrodes we studied the effect of nisoldipine on K-efflux during simulated ischemia (guinea pig papillary muscle immersed in paraffin oil; normal Tyrode solution, HEPES buffered, 100% O2-equilibrated, 37 degrees C). While ischemic K-efflux was Ca-dependent in stimulated preparations, it was independent of extracellular Ca in resting preparations. Our results show that nisoldipine leads to an inhibition of ischemic K-efflux during simulated ischemia. In resting preparations this inhibition is not a direct Ca-antagonistic effect, since withdrawal of extracellular Ca does not inhibit ischemic K-efflux but nisoldipine does. We suggest a direct effect of nisoldipine on the KATP channel which is mainly responsible for ischemic K-loss.

Animals↗
PubMed1997

[Contractile force and myocardial ischemia--electrical and ionic mechanisms].

In early myocardial ischemia we find several characteristic electrical and ionic alterations, like action potential shortening K(+)-accumulation or contractile failure. Trautwein and Dudel were 1954 the first to discuss action potential shortening as an important characteristic of myocardial ischemia. They already demonstrated that the action potential shortening is due to an enhanced outward current, while recently KATP-channels have been found to play an important role in the context. It has been suggested that contractile failure due to myocardial ischemia is caused by the shortening of action potential duration, reduced cytoplasmic free calcium levels, intracellular acidification, and a rise in inorganic phosphate and Mg. All of these phenomena may be related to the opening of KATP-channels. The different ionic and molecular mechanisms of contractile failure in myocardial ischemia will be discussed in this paper.

Animals↗
PubMed1996

KATP channel opening does not contribute significantly to the vasodilatory effect of SH-group-containing ACE inhibitors.

Angiotensin-converting enzyme (ACE) inhibitors are widely used in the management of hypertension, heart failure, and nephropathy. It has been suggested that ACE inhibitors containing the sulfhydryl group (SH) have an additional effect on KATP channels. To prove this hypothesis, we studied the effects of the SH-containing ACE inhibitors, captopril and zofenopril, on KATP channel opening of bovine coronary arteries and guinea pig thoracic aortas. Bovine coronary arteries were precontracted with the thromboxane A2 analogue, U46619, and guinea pig thoracic aortas were precontracted with phenylephrine and then relaxed with either captopril or zofenopril (n = 8). Inhibition of KATP channel opening with glibenclamide moderately attenuated the zofenopril-induced relaxation of guinea pig thoracic aorta. However, in the bovine coronary arteries, the relaxing effect of both captopril and zofenopril remained uneffected by glibenclamide. In experiments with enalapril (a non SH-containing ACE inhibitor; n = 6) on guinea pig thoracic aortas, no effect on KATP channels could be seen. From our experiments, we conclude that the postulated opening of KATP channels by SH-group-containing ACE inhibitors contributes little to the vasodilation of guinea pig thoracic aortas caused by ACE inhibitors, and that SH groups have no influence upon KATP channels of bovine coronary arteries.

Adenosine Triphosphate↗
PubMed1996

[ACE inhibitors with SH groups have no effect of ATP-dependent K channels--a dissertation].

ACE-inhibitors are used in the treatment of hypertension, and ischemic heart disease, chronic heart failure, cardiomyopathy and diabetic nephropathy. The effect of the ACE inhibitors is mainly due to the inhibition of the angiotensin converting-enzyme, but they also potentiate the effect of bradykinine. Sargent et al. have indicated, that SH-containing ACE-inhibitors show an effect on KATP-channel open probability in vascular smooth muscle. In our experiments, we used isolated bovine coronary arteries and guinea pig aortas, which were cut transversally and brought into Normal-Tyrode-solution. The vessels were precontracted with phenylephrine or U 46619, and after that a cumulative dose of the SH-containing ACE-inhibitors Captopril or Zofenopril was added to obtain a relaxation curve. In a second series we blocked the KATP-channels with glibenclamide to see if the relaxation could be attenuated. In bovine coronary arteries the relaxing effect of Captopril could not be attenuated by glibenclamide, a specific blocker of KATP-channels of vascular smooth muscle. In the guinea pig aorta, the relaxing effect of Zofenopril was also not effected by glibenclamide. The concentrations of Zofenopril were between 10(-7) and 10(-4) mol/l; the maximal effect could be seen at a concentration of 10(-5) mol/l. Experiments with the non SH-containing ACE-inhibitor Enalapril did also not show any statistically significant difference between the 2 groups of series. We conclude, that, in contrast to Sargent's conclusions, there is little or no effect on KATP-channels due to the presence of SH-groups.

Adenosine Triphosphate↗
PubMed1995

[Recent molecular and pharmacologic aspects of ACE inhibitors].

ACE-Inhibitors are well established in the treatment of hypertension and heart failure. Other indications, that are under discussion, are coronary artery disease, renal failure and diabetes mellitus. The mechanism of action of ACE-Inhibitors is not only the reduction of angiotensin II and accumulation of bradykinin but also an increase of the action potential of the heart muscle, increase in glucose uptake in skeletal muscle, inhibition of platelet aggregation and opening of the K-ATP-channels.

Angiotensin II↗
PubMed1995

Cyclic phenomena in early myocardial infarction.

It has been shown by a number of authors that early myocardial infarction constitutes a dynamic process of cyclic oscillation between coronary occlusion and spontaneous coronary reopening. Infarct-markers, such as ST-segment elevation, serum-creatine kinase isoenzyme MB, the atrionatriuretic peptide (ANP) and serum-myoglobin (Mb) exhibit cyclic behaviour pattern during early AMI and thus reflect episodes of intermittent, spontaneous reperfusion. The latter have recently been verified by angiography. The mechanism underlying the phenomena seen in early myocardial infarction is likely to be based on a constant vasoconstrictive stimulus, deriving from aggregating platelets. The vasoconstriction subsequent to platelet aggregation produces an initial episode of myocardial ischemia. This episode is followed by a hypoxia of the artery wall. Reactive coronary dilation secondary to ischemia is than promoted by the release of vasoactive by-products of anaerobic glycolysis as well as changes in the open propability of certain transmembrane ion channels. Thereafter, the initial coronary occlusion is interrupted by transient vasodilation. A wave of reperfusion follows and leads to reoxygenation and wash-out of ischemia-induced vasodilative components as well as biochemical markers. The vasoconstrictive forces then take over again. This results in repeated waves of reperfusion. A number of arguments in favour of this concepts are discussed in this paper.

Atrial Natriuretic Factor↗