Molecular biology of oncogenes and cardiovascular hypertrophy.

in Journal of hypertension (1992), 10(12), 1447-52

Isolierte Kardiomyozyten - ein Modell zur Aufklaerung der Pathophysiologie der hypertensiven Herzkrankheit - physiologische und erste molekularbiologische Ergebnisse

in Ganten, D (Ed.) Herz-Kreislaufregulation, Organprotektion und Organschaden (1991)

Isolated myocardial cells: a new tool for the investigation of hypertensive heart disease.

in Journal of Hypertension. Supplement) (1990), 8(4), 99-102

Cardiac hypertrophy is characterized by marked abnormalities in the contraction/relaxation pattern of the heart. For example, delayed relaxation is a prominent feature, impairing ventricular filling and ... [more ▼]

Cardiac hypertrophy is characterized by marked abnormalities in the contraction/relaxation pattern of the heart. For example, delayed relaxation is a prominent feature, impairing ventricular filling and coronary flow. In intact heart preparations the relative contribution of fibrosis and of the myocardial cell itself to these abnormalities cannot be correctly assessed. Biochemical studies on the mechanisms of impaired contraction and relaxation and hypertensive heart failure are hampered by the fact that 75% of all heart cells are non-myocytes. We therefore established the model of the isolated calcium-tolerant, adult rat cardiomyocyte as a new approach to the investigation of these problems. Contractility was measured using a videomicroscope system with high time resolution (1 ms). Angiotensin II induced a marked relaxation delay in the cardiomyocyte from normotensive rats and showed a moderate positive inotropic effect, whereas isoproterenol had a strong positive inotropic effect but accelerated relaxation. Therefore, angiotensin II is capable of inducing a relaxation delay even in the absence of coronary ischaemia or hypertension. These first results show that the isolated cardiomyocyte model may be a useful approach to investigating the mechanisms of hypertensive heart disease. [less ▲]

[Hypertensive heart disease. Pathophysiological foundation, diagnosis and therapy].

in Deutsche medizinische Wochenschrift (1946) (1990), 115(39), 1480-6

Impaired relaxation of the hypertrophied myocardium is potentiated by angiotensin II.

in Journal of Hypertension. Supplement) (1989), 7(6), 104-5

Relaxation delay is an important feature of hypertensive heart disease which impairs diastolic coronary flow and ventricular filling and therefore contributes to heart failure. We investigated the ... [more ▼]

Relaxation delay is an important feature of hypertensive heart disease which impairs diastolic coronary flow and ventricular filling and therefore contributes to heart failure. We investigated the hypothesis that impaired relaxation is a property of the myocardium, rather than the consequence of ischaemia or interstitial fibrosis. A new videomicroscope system was used to define the contraction-relaxation cycle of isolated cardiac myocytes from spontaneously hypertensive rats (SHR) and normotensive control (Wistar-Kyoto, WKY) rats. The SHR cells showed a marked relaxation delay. Angiotensin II (Ang II) increased the contraction maximum by about 35% in WKY rats and induced a relaxation delay. In SHR Ang II greatly potentiated this relaxation delay. Our results demonstrate that impairment of relaxation is a property of the single cardiomyocyte. Angiotensin II induces a relaxation delay that is independent of blood pressure. The combination of hypertrophy and high levels of Ang II potentiates relaxation impairment and may therefore contribute to hypertensive left ventricular failure. [less ▲]

[Increased atrial natriuretic peptide in essential hypertension--relation to right atrial pressure behavior].

in Klinische Wochenschrift (1989), 67(15), 756-61

The role of atrial natriuretic peptide (ANP) in the pathogenesis of essential hypertension has not yet entirely been clarified. We investigated whether the increase of ANP in essential hypertension may be ... [more ▼]

The role of atrial natriuretic peptide (ANP) in the pathogenesis of essential hypertension has not yet entirely been clarified. We investigated whether the increase of ANP in essential hypertension may be explained by elevated right atrial pressures and/or a different relationship between right atrial pressures and ANP secretion. Patients with stable essential hypertension undergoing right and left heart catheterization because of suspected coronary heart disease had significantly higher ANP levels than normotensives: 58.7 +/- 6.7 pg/ml in hypertensives versus 42.0 +/- 4.1 pg/ml in normotensives (p less than 0.01). Matching hypertensives with normotensives at identical levels of left ventricular enddiastolic pressure revealed significantly higher mean pulmonary artery pressures in hypertensives. Right atrial diastolic pressure (v-wave) after matching for LVEDP was 4.8 +/- 0.5 mm Hg in hypertensives and 3.1 +/- 0.2 mm Hg in normotensives (p less than 0.05). In addition, at any given mean right atrial pressure hypertensives showed higher ANP levels than normotensives. These results demonstrate that hypertensives exhibit raised pressures in the pulmonary artery independent of left ventricular pressure load. The elevation in right atrial pressures and the steeper relationship between these pressures and ANP are a suitable explanation for raised ANP levels in hypertension. ANP in essential hypertension may represent a counterregulation against elevated pulmonary resistance. [less ▲]

[Diagnostic and prognostic value of plasma ANP determination after myocardial infarction].

in Zeitschrift fur Kardiologie (1988), 77 Suppl 2

In the present study the prognostic value of ANP measurement was investigated in 52 patients undergoing coronary angiography. 22 normotensive and 30 hypertensive subjects were included. A significant ... [more ▼]

In the present study the prognostic value of ANP measurement was investigated in 52 patients undergoing coronary angiography. 22 normotensive and 30 hypertensive subjects were included. A significant inverse correlation between left ventricular ejection fraction (EF) and plasma ANP was found in normotensives, but not in hypertensives. In patients with chronic myocardial infarction, there was no difference in ANP levels compared to patients without infarction in either group, provided that EF was normal. However, hypertensives showed a 35% increase in ANP compared to normotensives. This was true for subjects with and without myocardial infarction. These results show that in normotensives ANP levels have a prognostic value on a statistical rather than an individual basis. This does not apply to hypertensives, whose ANP level is increased by factors other than impaired ejection fraction. [less ▲]

[Concentrations of amiodarone and flecainide in plasma and saliva--indications for the active transport of flecainide].

in Zeitschrift fur Kardiologie (1988), 77(2), 99-102

Only the free protein-unbound drug concentration in plasma is pharmacologically active. The concentration of some drugs in saliva is equal to the free drug level. We compared concentrations (in plasma ... [more ▼]

Only the free protein-unbound drug concentration in plasma is pharmacologically active. The concentration of some drugs in saliva is equal to the free drug level. We compared concentrations (in plasma before, 30 and 60 min after the morning dose, in saliva before, 30, 60, 90 and 120 min after the morning dose) of amiodarone (n = 8, 2 x 200 mg orally per day) and flecainide (n = 16, 2 x 100 mg) administered as chronic antiarrhythmic treatment. Drug levels were measured by "high performance liquid chromatography". Results: Just prior to the first morning dose, amiodarone concentrations in plasma were 1.0-2.9 (2.0 +/- 0.6) micrograms/ml, in saliva 0.02-0.25 micrograms/ml; flecainide in plasma 80-560 (316 +/- 163) ng/ml, in saliva 630-3700 (1749 +/- 963) ng/ml. After the morning dose we found maximal flecainide plasma levels of 462 +/- 203 and saliva levels of 3218 +/- 2857 ng/ml. The highest flecainide concentrations in the saliva (13,400 and 11,300 ng/ml) were found in two patients 30 and 60 min after the morning dose. Flecainide, but not amiodarone, is excreted actively in the saliva, probably indicating an enteroenteric circulation. This should be considered to reduce life-threatening flecainide intoxications by gastric and intestinal lavage and suction. The concentration of flecainide in the saliva does not represent the non-protein-bound free drug level in the plasma. [less ▲]

Inhibition of flecainide absorption by activated charcoal.

in The American journal of cardiology (1987), 60(8), 753

Einfluss von oraler Volumenbelastung, Herzfrequenz und Reserpin auf die Sekretion von atrialem natriuretischen Peptid beim Menschen

in Kreye, V; Bussmann, W (Eds.) Atriales natriurestisches Peptid und das kardiovaskulaere System (1987)