P Gaudron

University of Wuerzburg, Würzburg, Bavaria, Germany

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Publications (66)503.6 Total impact

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    ABSTRACT: Changes in creatine kinase (CK) and lactate dehydrogenase (LDH) isoform expression occur in residual tissue after myocardial infarction. It is unknown how these changes correlate with cardiac remodeling, contractile performance and efficiency. Rats were subjected to left coronary artery ligation (MI) or sham operation (sham). Left ventricular end-diastolic pressure (EDP) was measured in vivo 8 weeks later. Hearts were isolated, buffer-perfused (Langendorff) at constant pressure and isovolumetric left ventricular (LV) pressure-volume (PV) curves were recorded. LV PV areas (PVA) were calculated and related to oxygen consumption. Biopsies of intact left ventricular tissue were taken for biochemical measurements. Correlations between in vivo EDP and biochemical parameters were found: Total CK activity (r = -.47, p = .022), CK isoenzyme percentage for BB (r = +.57, p = .004), MB (r = +.54, p = .006) and CK-mito (r = -.51, p = .012), total creatine content (r = -.61, p = .002) and the ratio of LDH5/LDH1 (r = .49, p = .016). Correlations were also detected for left ventricular volume and PVAs at in vivo EDP demonstrating that the extent of CK and LDH system alterations correlate with the extent of LV dilatation and mechanical energy requirements. The slope of the MVO(2)-PVA relation decreased significantly with increasing values of in vivo EDP (r = -.68, p = 0.0003) indicating increased contractile ef.ciency. Improved efficiency correlated with the increase in fetal CK isoenzyme expression. Thus, contractile efficiency increases parallel to the extent of left ventricular dilatation and dysfunction. CK and LDH system changes in residual intact myocardium also occur proportional to LV dysfunction.
    Archiv für Kreislaufforschung 04/2005; 100(2):171-8. DOI:10.1007/s00395-005-0507-2 · 5.96 Impact Factor
  • Kai Hu, Peter Gaudron, Georg Ertl
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    ABSTRACT: We examined the effect of high- (AHD) and low-dose (ALD) amiodarone on survival, hemodynamics, and left ventricular remodeling in rats with experimental myocardial infarction (MI). Thirty minutes after coronary artery ligation or sham operation, amiodarone (100 or 20 mg/kg/d) or placebo was given by gavages daily for 8 weeks. Eight weeks later, hemodynamic measurements were performed and left ventricular (LV) volume was determined after KCl-induced cardiac arrest. Early after MI, mortality was lower after both doses of amiodarone. However, excess mortality beginning 15 days after MI outweighed reduced early mortality in rats treated with AHD. Body weight and heart rate were reduced significantly and maximal stroke volume index improved by AHD. In rats with MI, AHD significantly shifted LV pressure-volume curves to the right and increased LV operating volume (2.84 +/- 0.10 versus 2.20 +/- 0.07 mL/kg, P < 0.05). In conclusion, high-dose amiodarone aggravated LV remodeling in rats with large experimental chronic MI probably by lowering heart rate. An early beneficial effect on mortality was probably also lost later by this mechanism. Low-dose amiodarone improved survival without effect on LV remodeling.
    Journal of Cardiovascular Pharmacology 12/2004; 44(6):627-30. DOI:10.1097/00005344-200412000-00001 · 2.11 Impact Factor
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    ABSTRACT: The importance of heart rate for left ventricular remodeling and prognosis after myocardial infarction is not known. We examined the contribution of heart rate reduction by zatebradine, a direct sinus node inhibitor without negative inotropic effects on left ventricular function and dilatation, on mortality, energy metabolism, and neurohormonal changes in rats with experimental myocardial infarction (MI). Thirty minutes after left coronary artery ligation or sham operation, the rats were randomized to receive either placebo or zatebradine (100 mg x kg(-1) x day(-1) per gavage) continued for 8 wk. Mortality during 8 wk was 33.3% in the placebo and 23.0% in the zatebradine group (P < 0.05); MI size was 36 +/- 2% and 30 +/- 1% (means +/- SE, P < 0.05), respectively. Zatebradine improved stroke volume index in all treated rats but increased left ventricular volume in rats with small MI (2.43 +/- 0.10 vs. 1.81 +/- 0.10 ml/kg, P < 0.05) but not in rats with large MI (2.34 +/- 0.09 vs. 2.35 +/- 0.11 ml/kg, not significant). Zatebradine reduced left and right ventricular norepinephrine and increased left and right ventricular 3,4-dihydroxyphenyl ethylene glycol-to-norepinephrine ratio suggesting aggravation of cardiac sympathetic activation by zatebradine after MI. Creatine kinase and lactate dehydrogenase isoenzymes in rats with MI remained unchanged by zatebradine. Lowering heart rate per se reduces mortality and MI size in this model but induces adverse effects on left ventricular remodeling in rats with small MI.
    AJP Heart and Circulatory Physiology 04/2004; 286(4):H1281-8. DOI:10.1152/ajpheart.00390.2003 · 4.01 Impact Factor
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    ABSTRACT: The effect of ACE inhibition after myocardial infarction (MI) on MI healing and remodeling in the presence of hypertension is not exactly known. Therefore, the effect of quinapril on scar formation, remodeling and hemodynamics was studied in spontaneously hypertensive rats (SHR). Nine weeks after moderate and large MI, left ventricular end-diastolic pressure (LVEDP) and passive pressure-volume relations were similar in 28-week-old hypertensive and normotensive rats. Chronic therapy with quinapril (6 mg/kg/day, started 30 min post-MI) reduced LVEDP and LV to body weight ratio, yet did not affect pressure-volume relations. Quinapril increased MI size and reduced the content and brightness of collagen fibers in the scar examined by polarized light microscopy. In conclusion, ventricular dilatation after MI was not accelerated in SHR, probably due to LV hypertrophy. Quinapril produced beneficial hemodynamic effects similar to that observed in the normotensive rat model. The significance and timing of ACE inhibitor-induced impairment of scar formation need further evaluation.
    Cardiovascular Pathology 03/2002; 11(2):88-93. DOI:10.1016/S1054-8807(01)00114-4 · 2.34 Impact Factor
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    ABSTRACT: We prospectively studied the relationship between left ventricular (LV) dilation, dysfunction, electrical instability and death in patients after a first myocardial infarction (MI) without symptoms of heart failure and ischemia. Mechanisms linking LV dysfunction and sudden death in patients after MI remained controversial. Left ventricular volumes, hemodynamics, electrocardiogram and 24-h Holter recordings were sequentially obtained between two days and seven years after MI. Left ventricular catheterization and coronary angiography were performed, and revascularization was performed if appropriate. Death occurred in 16 (12%) of the 134 patients included; it was of cardiac origin in 14 (88%) and sudden in origin in 12 (75%) patients. Of 37 (28%) patients with LV dilation, 12 died (32%); four patients (5.8%) died in the group without dilation. Left ventricular dilation was closely related to signs of electrical instability, as indicated by a significant correlation between end-diastolic LV volume index, Lown score (r = 0.98, p < 0.0001) and QTc prolongation (r = 0.998, p < 0.01), respectively. Patients with progressive remodeling are at increased risk of sudden death in chronic MI. Cardiac electrical instability is closely related to progressive LV dilation. Parameters of electrical instability and remodeling are predictors of sudden death. The findings suggest that remodeling might serve as a link between dysfunction, electrical instability of the heart and sudden death after MI.
    Journal of the American College of Cardiology 08/2001; 38(1):33-40. · 15.34 Impact Factor
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    ABSTRACT: OBJECTIVESWe prospectively studied the relationship between left ventricular (LV) dilation, dysfunction, electrical instability and death in patients after a first myocardial infarction (MI) without symptoms of heart failure and ischemia.BACKGROUNDMechanisms linking LV dysfunction and sudden death in patients after MI remained controversial.METHODSLeft ventricular volumes, hemodynamics, electrocardiogram and 24-h Holter recordings were sequentially obtained between two days and seven years after MI. Left ventricular catheterization and coronary angiography were performed, and revascularization was performed if appropriate.RESULTSDeath occurred in 16 (12%) of the 134 patients included; it was of cardiac origin in 14 (88%) and sudden in origin in 12 (75%) patients. Of 37 (28%) patients with LV dilation, 12 died (32%); four patients (5.8%) died in the group without dilation. Left ventricular dilation was closely related to signs of electrical instability, as indicated by a significant correlation between end-diastolic LV volume index, Lown score (r = 0.98, p < 0.0001) and QTc prolongation (r = 0.998, p < 0.01), respectively.CONCLUSIONSPatients with progressive remodeling are at increased risk of sudden death in chronic MI. Cardiac electrical instability is closely related to progressive LV dilation. Parameters of electrical instability and remodeling are predictors of sudden death. The findings suggest that remodeling might serve as a link between dysfunction, electrical instability of the heart and sudden death after MI.
    Journal of the American College of Cardiology 07/2001; 38(1-38):33-40. DOI:10.1016/S0735-1097(01)01319-5 · 15.34 Impact Factor
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    ABSTRACT: Alterations of the central nervous system may be important for imbalance of cardiovascular and fluid regulation in heart failure. The central renin-angiotensin and atrial natriuretic peptide (ANP) systems act as mutual antagonists. The effects of angiotensin converting enzyme (ACE) inhibition (quinapril, 6 mg/kg/day) and angiotensin II type 1 (AT1) receptor blockade (losartan, 10 mg/kg/day) on ANP levels in 18 selected, microdissected brain nuclei were determined in sham-operated rats and rats with left ventricular dysfunction 8 weeks after myocardial infarction (MI). Plasma ANP tended to increase in MI rats and was further increased by quinapril. ANP was decreased in 12 brain areas of MI rats. ANP concentration was also significantly decreased by quinapril in six brain nuclei including subfornical organ and organum vasculosum laminae terminalis (areas lacking blood-brain barrier), and by losartan in 16 brain nuclei outside and within the blood-brain barrier in sham operated rats. However, both quinapril and losartan prevented a further reduction of central ANP as a result of myocardial infarction. These data suggest that there are effects on central ANP that result from chronic left ventricular dysfunction as well as an ACE-inhibitor and AT1-antagonist. Mechanisms and consequences of central ANP depression remain unclear. They could, however, support systemic vasoconstriction and sodium and fluid retention.
    Archiv für Kreislaufforschung 04/2001; 96(3):258-66. DOI:10.1007/s003950170056 · 5.96 Impact Factor
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    ABSTRACT: Alterations of the central nervous system may be important for imbalance of cardiovascular and fluid regulation in heart failure. The central renin-angiotensin and atrial natriuretic peptide (ANP) systems act as mutual antagonists. The effects of angiotensin converting enzyme (ACE) inhibition (quinapril, 6 mg/kg/day) and angiotensin II type 1 (AT1) receptor blockade (losartan, 10 mg/kg/day) on ANP levels in 18 selected, microdissected brain nuclei were determined in sham-operated rats and rats with left ventricular dysfunction 8 weeks after myocardial infarction (MI). Plasma ANP tended to increase in MI rats and was further increased by quinapril. ANP was decreased in 12 brain areas of MI rats. ANP concentration was also significantly decreased by quinapril in six brain nuclei including subfornical organ and organum vasculosum laminae terminalis (areas lacking blood-brain barrier), and by losartan in 16 brain nuclei outside and within the blood-brain barrier in sham operated rats. However, both quinapril and losartan prevented a further reduction of central ANP as a result of myocardial infarction. These data suggest that there are effects on central ANP that result from chronic left ventricular dysfunction as well as an ACE-inhibitor and AT1-antagonist. Mechanisms and consequences of central ANP depression remain unclear. They could, however, support systemic vasoconstriction and sodium and fluid retention.
    Archiv für Kreislaufforschung 03/2001; 96(3):258-266. · 5.96 Impact Factor
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    ABSTRACT: Approximately 20% of patients with healed myocardial infarction develop asymptomatic progressive left ventricular (LV) dilation and remodeling and are at increased risk for progression to symptomatic congestive heart failure and premature death. It was the goal of this study to test whether quinapril may interrupt this process and to analyze potential mechanisms. Of 138 patients with an average infarct age of 56 months, 25 had asymptomatic progressive LV dilation and were randomized in a prospective, double-blind study to placebo or quinapril. At baseline (mean +/- SEM) ejection fraction was reduced (35 +/- 3% and 39 +/- 3%) and end-diastolic volume (gated single-photon emission computed tomography) increased (104 +/- 9 and 117 +/- 12 ml/m(2)) with placebo (n = 13) and quinapril (n = 12), respectively. Progressive dilation continued in patients taking placebo (6 months: 9.4 +/- 5.2 ml/m(2), 12 months 24.6 +/- 5. 4 ml/m(2); change from baseline: p <0.05 vs baseline; p <0.05 vs 6 months), but not with quinapril (6 months: -0.9 +/- 4.0 ml/m(2); 12 months: 4.1 +/- 5.2 ml/m(2) [p <0.05] vs placebo). Wedge pressure during bicycle exercise was similar at baseline, but at 12 months tended to be lower with quinapril (17 +/- 1 mm Hg) than with placebo (24 +/- 4 mm Hg, p = 0.1673). Thus, quinapril prevented further progression of asymptomatic LV dilation and remodeling after remote myocardial infarction, possibly due to attenuation of an exercise-induced increase in LV filling pressure.
    The American Journal of Cardiology 08/2000; 86(2):139-44. DOI:10.1016/S0002-9149(00)00849-3 · 3.43 Impact Factor
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    ABSTRACT: The plasma membrane calmodulin-dependent calcium ATPase (PMCA) is a calcium-extruding enzyme controlling Ca2+ homeostasis in nonexcitable cells. However, its function in the myocardium is unclear because of the presence of the Na+/Ca2+ exchanger. We approached the question of the physiological function of the calcium pump using a transgenic "gain of function" model. Transgenic rat lines carrying the human PMCA 4 cDNA under control of the ventricle-specific myosin light chain-2 promoter were established, and expression in the myocardium was ascertained at the mRNA, protein, and functional levels. In vivo hemodynamic measurements in adult homozygous animals showed no differences in baseline and increased cardiac performance recruited by volume overload compared with controls. No differences between transgenic and control cardiomyocytes were found in patch clamp voltage dependence, activation/inactivation behavior of the L-type Ca2+ current, or fast [Ca2+]i transients (assessed by the Fura-2 method). To test whether the PMCA might be involved in processes other than beat-to-beat regulation of contraction/relaxation, we compared growth processes of neonatal transgenic and control cardiomyocytes. A 1.6- and 2.3-fold higher synthesis rate of total protein was seen in cells from transgenic animals compared with controls on incubation with 2% FCS for 24 hours and 36 hours, respectively. An effect of similar magnitude was observed using 20 micromol/L phenylephrine. A 1.4-fold- and 2.0-fold-higher protein synthesis peak was seen in PMCA-overexpressing cardiomyocytes after stimulation with isoproterenol for 12 hours and 24 hours, respectively. Because pivotal parts of the alpha- and beta-adrenergic signal transduction pathways recently have been localized to caveolae, we tested the hypothesis that the PMCA might alter the amplitude of alpha- and beta-adrenergic growth signals by virtue of its localization in caveolae. Biochemical as well as immunocytochemical studies suggested that the PMCA in large part was colocalized with caveolin 3 in caveolae of cardiomyocytes. These results indicate that the sarcolemmal Ca2+-pump has little relevance for beat-to-beat regulation of contraction/relaxation in adult animals but likely plays a role in regulating myocardial growth, possibly through modulation of caveolar signal transduction.
    Circulation Research 12/1998; 83(9):877-88. DOI:10.1161/01.RES.83.9.877 · 11.09 Impact Factor
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    ABSTRACT: The plasma membrane calmodulin-dependent calcium ATPase (PMCA) is a calcium-extruding enzyme controlling Ca2+ homeostasis in nonexcitable cells. However, its function in the myocardium is unclear because of the presence of the Na+/Ca2+ exchanger. We approached the question of the physiological function of the calcium pump using a transgenic "gain of function" model. Transgenic rat lines carrying the human PMCA 4 cDNA under control of the ventricle-specific myosin light chain-2 promoter were established, and expression in the myocardium was ascertained at the mRNA, protein, and functional levels. In vivo hemodynamic measurements in adult homozygous animals showed no differences in baseline and increased cardiac performance recruited by volume overload compared with controls. No differences between transgenic and control cardiomyocytes were found in patch clamp voltage dependence, activation/inactivation behavior of the L-type Ca2+ current, or fast [Ca2+]i transients (assessed by the Fura-2 method). To test whether the PMCA might be involved in processes other than beat-to-beat regulation of contraction/relaxation, we compared growth processes of neonatal transgenic and control cardiomyocytes. A 1.6- and 2.3-fold higher synthesis rate of total protein was seen in cells from transgenic animals compared with controls on incubation with 2% FCS for 24 hours and 36 hours, respectively. An effect of similar magnitude was observed using 20 micromol/L phenylephrine. A 1.4-fold- and 2.0-fold-higher protein synthesis peak was seen in PMCA-overexpressing cardiomyocytes after stimulation with isoproterenol for 12 hours and 24 hours, respectively. Because pivotal parts of the alpha- and beta-adrenergic signal transduction pathways recently have been localized to caveolae, we tested the hypothesis that the PMCA might alter the amplitude of alpha- and beta-adrenergic growth signals by virtue of its localization in caveolae. Biochemical as well as immunocytochemical studies suggested that the PMCA in large part was colocalized with caveolin 3 in caveolae of cardiomyocytes. These results indicate that the sarcolemmal Ca2+-pump has little relevance for beat-to-beat regulation of contraction/relaxation in adult animals but likely plays a role in regulating myocardial growth, possibly through modulation of caveolar signal transduction.
    Circulation Research 11/1998; 83(9):877-88. · 11.09 Impact Factor
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    ABSTRACT: Myocardial ischemia results in myocardial dysfunction. Recovery may be delayed ("stunning"), or persistent if perfusion remains reduced ("hibernation") and ischemia may go on to necrosis, thus, contributing to chronic heart failure. In addition, myocardium not directly affected by ischemia may undergo adaptive processes like hypertrophy and dilatation, which may result in chronic left heart failure. This process is characterized by hemodynamic, neurohumoral, and progressive morphologic changes of the heart which are closely interrelated. Hemodynamic changes basically consist of an increase in left ventricular filling pressure and a decrease in global ejection fraction, and, in most cases years after myocardial infarction, in an increase in systemic vascular resistance and right atrial pressure. Neurohumoral changes consist of an increase in plasma catecholamines, atrial natriuretic factor and vasopressin, and in an activation of the renin-angiotensin-system. Plasma endothelin-1 was recently reported to be increased in patients with heart failure, and prognosis was related to endothelin levels. Diminished response of vessels to endothelium (EDRF/NO) dependent vasodilatation suggests impairment of vascular endothelium in heart failure. Local changes of cardiac neurohumoral systems could contribute to structural changes of the heart, e.g., systemic activation to hemodynamic changes. Structural changes of the heart are characterized by an increase in volume and thickness of surviving myocardium and an expansion of ischemic and necrotic myocardium. Molecular control of these processes which include various cell types, such as cardiomyocytes and cardiofibroblasts, are currently an issue of intense research and could result in specific therapeutic importance.
    Zeitschrift für Kardiologie 10/1998; 87(9):667-75. · 0.97 Impact Factor
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    ABSTRACT: The long-term effects and mechanisms of early started angiotensin converting enzyme (ACE) inhibition post myocardial infarction (MI) are not well understood. Chronic effects of early ACE inhibition on hemodynamics, left ventricular diastolic wall stress and remodeling were, therefore, compared to that of angiotensin AT1-receptor subtype blockade in rats with experimental myocardial infarction. The contribution of bradykinin potentiation to both ACE inhibitor and angiotensin AT1-receptor subtype blockade was assessed by cotreatment of rats with a bradykinin B2-receptor antagonist. MI was produced by coronary artery ligation in adult male Wistar rats. The ACE inhibitor, quinapril (6 mg/kg per day), or the angiotensin AT1-receptor subtype blocker, losartan (10 mg/kg per day), administered by gavage, and the bradykinin B2-receptor antagonist, Hoe-140 (500 micrograms/kg per day s.c.), administered either alone or in combination with quinapril or losartan, were started 30 min after MI and continued for eight weeks. Quinapril and losartan reduced left ventricular end-diastolic pressure and global left ventricular diastolic wall stress only in rats with large MI. Pressure volume curves showed a rightward shift in proportion to MI size that was not prevented by quinapril or losartan treatment. Only the ACE inhibitor reduced left ventricular weight and this effect was prevented by cotreatment with the bradykinin antagonist. Baseline and peak cardiac index and stroke volume index, as determined using an electromagnetic flowmeter before and after an acute intravenous volume load, were restored by quinapril, whereas losartan had no effects. Treatments starting 30 min after coronary artery ligation, with either quinapril or losartan, reduced preload only in rats with large MI. Despite this unloading of the heart, structural dilatation was not prevented by this early treatment. Only quinapril improved cardiac performance and reduced left ventricular weight and this effect was abolished by cotreatment with Hoe-140, suggesting an angiotensin II blockade-independent, but bradykinin potentiation-dependent, mechanism.
    Cardiovascular Research 09/1998; 39(2):401-12. DOI:10.1016/S0008-6363(98)00090-X · 5.81 Impact Factor
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    ABSTRACT: Myokardischämie führt zu Störungen der myokardialen Funktion, die sich als “Stunning” verzögert erholen, bei persistierend reduzierter Durchblutung als “Hibernation” persistieren oder in Nekrose münden können. Diese Störungen können im Rahmen einer Myokardischämie zur Herzinsuffizienz beitragen. Darüber hinaus kommt es jedoch bei nicht direkt von der Ischämie betroffenem Myokard zu Anpassungsvorgängen, insbesondere Hypertrophie und Dilatation, die zur chronischen Linksherzinsuffizienz führen können. Diese Entwicklung ist von hämodynamischen und neurohumoralen Veränderungen sowie progredienten morphologischen Veränderungen des Herzens charakterisiert, welche in enger Beziehung zueinander stehen. Die hämodynamischen Veränderungen bestehen im wesentlichen in einer Zunahme des linksventrikulären Füllungsdrucks und einer Abnahme der globalen Ejektionsfraktion, meist jedoch erst Jahre nach dem Infarkt, schließlich in einer Zunahme des systemischen Gefäßwiderstandes und rechten Vorhofdruckes. Die neurohumoralen Veränderungen bestehen in einer Zunahme von Plasmakatecholaminen, atrialem natriuretischem Faktor und Vasopressin, schließlich in einer Aktivierung des Renin-Angiotensin-Systems. Endothelin-1 wurde neuerdings bei Patienten mit Herzinsuffizienz erhöht gefunden mit einer prognostischen Bedeutung gesteigerter Endothelin-Plasmaspiegel. Ein vermindertes Ansprechen der Gefäße auf eine Endothel-(EDHF/NO-)abhängige Vasodilatation spricht für weitere Störungen des Gefäßendothels bei der Herzinsuffizienz. Lokale Veränderungen von kardialen neurohumoralen Systemen könnten an Strukturveränderungen des Herzens, systemische Aktivierung an hämodynamischen Veränderungen beteiligt sein. Die Strukturveränderungen des Herzens sind charakterisiert durch eine Volumenzunahme und Dickenzunahme des überlebenden Myokardes sowie eine Expansion des ischämischen und nekrotischen Myokards. Die molekulare Steuerung dieser Prozesse, die verschiedene Zelltypen, insbesondere die Kardiomyozyten und Kardiofibroblasten betrifft, ist zur Zeit Gegenstand intensiver Forschung und könnte eine besondere therapeutische Bedeutung erlangen. Myocardial ischemia results in myocardial dysfunction. Recovery may be delayed (“stunning”), or persistent if perfusion remains reduced (“hibernation”) and ischemia may go on to necrosis, thus, contributing to chronic heart failure. In addition, myocardium not directly affected by ischemia may undergo adaptive processes like hypertrophy and dilatation, which may result in chronic left heart failure. This process is characterized by hemodynamic, neurohumoral, and progressive morphologic changes of the heart which are closely interrelated. Hemodynamic changes basically consist of an increase in left ventricular filling pressure and a decrease in global ejection fraction, and, in most cases years after myocardial infarction, in an increase in systemic vascular resistance and right atrial pressure. Neurohumoral changes consist of an increase in plasma catecholamines, atrial natriuretic factor and vasopressin, and in an activation of the renin-angiotensin-system. Plasma endothelin-1 was recently reported to be increased in patients with heart failure, and prognosis was related to endothelin levels. Diminished response of vessels to endothelium (EDRF/NO) dependent vasodilatation suggests impairment of vascular endothelium in heart failure. Local changes of cardiac neurohumoral systems could contribute to structural changes of the heart, e.g., systemic activation to hemodynamic changes. Structural changes of the heart are characterized by an increase in volume and thickness of surviving myocardium and an expansion of ischemic and necrotic myocardium. Molecular control of these processes which include various cell types, such as cardiomyocytes and cardiofibroblasts, are currently an issue of intense research and could result in specific therapeutic importance. Schlüsselwörter Myokardischämie – Herzinusffizienz – neurohumorale Systeme – Hämodynamik – RemodellingKey words Myocardial ischemia – cardiac failure – neurohumoral systems – hemodynamics – remodeling
    Zeitschrift für Kardiologie 09/1998; 87(9):667-675. DOI:10.1007/s003920050225 · 0.97 Impact Factor
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    ABSTRACT: An endothelin (ET(A)) antagonist reduced mortality and an ET(A) + ET(B) antagonist prevented left ventricular dilatation in rats with large myocardial infarction. This study tested the hypothesis that long-term blockade of the ET(A) receptor would have beneficial effects on left ventricular function and remodeling. Three hours after coronary artery ligation or sham operation in rats, EMD94246 (100 mg/kg/day, n=62) or placebo (n=62) was given by gavage. Eight weeks later, left ventricular hemodynamic measurements were performed and left ventricular volume determined with a double-lumen catheter after KCl-induced cardiac arrest. EMD94246 treatment had no effects on mortality or hemodynamic parameters. In rats with large infarcts, EMD94246 significantly increased left ventricular volume (2.5+/-0.1 vs. 2.2+/-0.1 ml/kg; p < 0.05). The nonpeptide ET(A)-selective antagonist EMD94246 promoted chronic left ventricular dilatation in rats with large myocardial infarction.
    Journal of Cardiovascular Pharmacology 09/1998; 32(3):505-8. DOI:10.1097/00005344-199809000-00024 · 2.11 Impact Factor
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    ABSTRACT: It has been speculated that high pressure implantation may improve the results of coronary stenting. However, this method bears the risk of persistent dissection and may increase late lumen loss. Presently, there is no consensus about the optimal stent implantation technique with the regard to balloon size and pressure. To elucidate this question an experimental study was performed in a coronary stenosis model. 3.5 mm Multi-Link (ML) stents were implanted in 3.3 mm silicone rubber tubes containing 50% concentric narrowings. Three implantation techniques were applied: 1. The standard technique using the conventional ML delivery system with a compliant balloon (ML-ST). 2. A new deployment method with a high pressure delivery system (ML-HP). 3. "Focal postdilation" using the ARC catheter, which has a special balloon with an inner compliant and an outer non-compliant section (ML-ARC). For comparison, the Palmaz-Schatz stent was implanted by using a high pressure balloon. Stent expansion was imaged by magnification radiography. Minimal lumen diameter within the stent (MLD) and the lumen diameter outside the stent (BD) were measured after dilations with 6, 9, 12, 15, 18, and 21 atm. The relation of the BD to the MLD was used as an index of vessel trauma. The results lead to the following conclusions: 1. A complete apposition to the vessel wall for a balloon/vessel relation of 1.1:1 could not be reached with pressures below 9-15 atm. The increase of the pressure beyond 15 atm resulted only in a minimal additional lumen. 2. Compared to the Palmaz-Schatz stent the recoil of the ML stent was significantly lower. 3. For all three implantation techniques the ML-ARC showed the best results with the maximal dilation of the stenotic vessel-area and the minimal expansion of the vessel outside the stent.
    Zeitschrift für Kardiologie 06/1998; 87(5):344-52. · 0.97 Impact Factor
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    ABSTRACT: Die Hochdruckdilatationstechnik scheint geeignet, die Ergebnisse der Stentimplantation in Koronargefäßen zu verbessern. Trotzdem birgt diese Methode das Risiko einer Gefäßdissektion im Stentbereich und eines Anstiegs der Restenoserate. Gegenwärtig besteht kein Konsensus zur optimierten Stentimplantation hinsichtlich Ballongröße und -druck. Um diese Frage zu untersuchen, wurde eine experimentelle Studie anhand eines Koronarstenose-Modells durchgeführt. 3,5-mm-Multi-Link-(ML-)Stents wurden in 3,3 mm weite Silikon-Gummischläuche mit einer 50%igen konzentrischen Enge implantiert. Drei Implantationstechniken wurden verwendet: 1. Die Standardtechnik mit konventionellem ML-Träger-System und zugehörigem Ballon (ML-ST). 2. Ein neu entwickeltes Hochdruck-System (ML-HP). 3. Die “fokale” Implantationstechnik unter Verwendung des ARC-Katheters, dessen Ballon in der Mitte compliant und außen nichtcompliant ist (ML-ARC). Zu Vergleichszwecken wurde der Palmaz-Schatz-Stent untersucht. Die Stentexpansion wurde mit der hochauflösenden Vergrößerungsradiographie wiedergegeben. Der minimale Diameter innerhalb des Stents (MLD), am Randbereich des Stents (BRD) und der Ballondiameter außerhalb des Stents (BD) wurden nach Aufdehnung bei 6, 9, 12, 15, 18 und 21 atm gemessen. Das Verhältnis BD zu MLD diente als “Traumatisierungsindex” für das angrenzende Gerfäß. Zusammenfassend läßt sich sagen: 1. Eine komplette Apposition des Multi-Link-Stents wurde auch bei adäquater Größenwahl des Ballons (Ballon-Gefäß-Verhältnis 1,1:1) bei allen Systemen erst bei Drücken zwischen 9 und 15 atm erzielt. Eine Hochdruckdilatation mit Drücken oberhalb von 15 atm brachte nur einen geringen Lumengewinn und erscheint nur in Einzelfällen, insbesondere bei nicht komplett vordilatierten Stenosen, sinnvoll. 2. Der Multi-Link-Stent wies aufgrund seiner größeren radialen Kraft einen geringeren Recoil als der Palmaz-Schatz-Stent auf. 3. Unter den verglichenen Implantationstechniken zeigte das ML-ARC-System die besten Resultate mit maximal hoher Aufdehnung des stenotischen Bereiches (MLD) bei geringster Aufdehnung des angrenzenden Gefäßabschnitts (BD). It has been speculated that high pressure implantation may improve the results of coronary stenting. However, this method bears the risk of peristent dissection and may increase late lumen loss. Presently, there is no consensus about the optimal stent implantation technique with the regard to balloon size and pressure. To elucidate this question an experimental study was performed in a coronary stenosis model. 3.5 mm Multi-Link (ML) stents were implanted in 3.3 mm silicone rubber tubes containing 50% concentric narrowings. Three implantation techniques were applied: 1. The standard technique using the conventional ML delivery system with a compliant balloon (ML-ST). 2. A new deployment method with a high pressure delivery system (ML-HP). 3. “Focal postdilation” using the ARC catheter, which has a special balloon with an inner compliant and an outer non-compliant section (ML-ARC). For comparison, the Palmaz-Schatz stent was implanted by using a high pressure balloon. Stent expansion was imaged by magnification radiography. Minimal lumen diameter within the stent (MLD) and the lumen diameter outside the stent (BD) were measured after dilations with 6, 9, 12, 15, 18, and 21 atm. The relation of the BD to the MLD was used as an index of vessel trauma. The results lead to following conclusions: 1. A complete apposition to the vessel wall for a balloon/vessel relation of 1.1:1 could not be reached with pressures below 9–15 atm. The increase of the pressure beyond 15 atm resulted only in a minimal additional lumen. 2. Compared to the Palmaz-Schatz stent the recoil of the ML stent was significant lower. 3. For all three implantation techniques the ML-ARC showed the best results with the maximal dilatation of the stenotic vesselarea and the minimal expansion of the vessel outside the stent. Schlüsselwörter Multi-Link-Stent – Hochdruckdilatation – In-vitro-Gefäßmodell – Vergrößerungsradiographie – StentappositionKey words Multi-Link stent – high pressure dilatation – in vitro vessel model – magnification radiography – stent apposition
    Zeitschrift für Kardiologie 05/1998; 87(5):344-352. DOI:10.1007/s003920050190 · 0.97 Impact Factor
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    Kai Hu, Peter Gaudron, Georg Ertl
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    ABSTRACT: This study was designed to assess the long-term effects of a beta1-selective beta-adrenergic blocking agent on mortality, in vivo hemodynamic function, left ventricular volume and wall stress in post-myocardial infarction (MI) rats. Beta-blockers have shown beneficial results in clinical studies after MI. However, the underlying mechanism is not yet understood, and experimental studies have shown conflicting results. Bisoprolol (60 mg/kg body weight per day) was given 30 min or 14 days after MI or sham operation. The mortality rate was reduced only in early bisoprolol-treated rats (29% vs. 46% in untreated rats, p < 0.05). Heart rate was equally reduced in all treatment groups, and the maximal rate of rise of left ventricular systolic pressure (dP/dt(max)) decreased in sham rats and in rats with a small to moderate infarct size. Stroke volume index was unchanged in sham rats and in rats with a small to moderate infarct with early or late bisoprolol treatment and increased in rats with a large infarct in the late bisoprolol group. Left ventricular volume was increased by bisoprolol in sham rats and rats with a small infarct but not in rats with a large infarct. Treatments starting early (30 min) or late (14 days) after coronary artery ligation with bisoprolol increased left ventricular volume in sham rats and in rats with a small infarct but not in rats with a large infarct. Late bisoprolol treatment improved stroke volume index, and early bisoprolol treatment reduced diastolic wall stress, in rats with a large myocardial infarct. Thus, bisoprolol effects on remodeling and cardiac performance after myocardial infarction strongly depend on infarct size and timing of treatment. This finding may explain previous controversial results that did not consider infarct size and timing of treatment.
    Journal of the American College of Cardiology 03/1998; 31(3):692-700. DOI:10.1016/S0735-1097(97)00527-5 · 15.34 Impact Factor
  • P. Gaudron, K. Hu, P. Ganß, G. Erti
    Journal of the American College of Cardiology 02/1998; 31(2):408. DOI:10.1016/S0735-1097(98)80121-6 · 15.34 Impact Factor
  • Journal of the American College of Cardiology 02/1998; 31(2):311-311. DOI:10.1016/S0735-1097(98)81998-0 · 15.34 Impact Factor

Publication Stats

1k Citations
503.60 Total Impact Points

Institutions

  • 1989–2004
    • University of Wuerzburg
      • • Department of Nuclear Medicine
      • • Department of Internal Medicine II
      Würzburg, Bavaria, Germany
  • 1996–2001
    • Universität Heidelberg
      • • Medical University Clinic and Polyclinic
      • • II. Medical Clinic
      Heidelberg, Baden-Wuerttemberg, Germany
  • 1996–1998
    • Universität Mannheim
      Mannheim, Baden-Württemberg, Germany