t Mfinchen * Supported by research grants 86.015.1 and 86.015.2 of the Wilhelm Sander Foundation ... more t Mfinchen * Supported by research grants 86.015.1 and 86.015.2 of the Wilhelm Sander Foundation and grant DFG Ge-399/3-3 of the Deutsche Forschungsgemeinschaft in resting and particularly exercise hemodynamics during antihypertensive therapy.
, admissions to paediatric departments for Bordetella pertussis complications were reported to a ... more , admissions to paediatric departments for Bordetella pertussis complications were reported to a nationwide, hospitalbased active surveillance system. The case definition included pertussis complicated by pneumonia, apnoea requiring assisted ventilation, seizures, encephalopathy or a combination of these. Two hundred sixteen cases of pertussis complications were registered. 57.4% of them were in infants, 50.9% of them less than 6 months old. There were five deaths, three previously healthy children died. At the time of hospital admission, 106 cases would have been eligible for at least three doses of pertussis vaccine, only four (3.8%) had received the recommended number of immunisations. From the second quarter of 1995, the reported number of cases declined. The decrease coincides with an improvement of pertussis vaccination coverage between 1992 and 1995 due to an increased use of acellular vaccines. The reduction of complicated pertussis was observed even in age-groups too young for the recommended vaccinations. The observed decrease could be due to the increase in vaccination coverage with interuption of the chain of transmission to the younger age-groups, to a cyclic decrease in pertussis cases, or to a combination of both. Continued surveillance will provide information on the epidemiological trend of hospitalisations for pertussis complications in the first European country to have introduced vaccination with acellular vaccines on a large scale.
Increased expression of the inhibitory G protein Gia-2 is assumed to contributed to desensitizati... more Increased expression of the inhibitory G protein Gia-2 is assumed to contributed to desensitization of adenylyl cyclase in human heart failure. The mechanisms of upregulation involve increases in myocardial Gia-2 protein, mRNA and gene transcriptional activity. To elucidate these mechanisms in more detail, the 5' flanking region of the human Gia-2 gene (-1214/+115 bp) was cloned upstream of the bacterial
Norepinephrine has growth-promoting effects in cardiac myocytes. The present study in cultured ne... more Norepinephrine has growth-promoting effects in cardiac myocytes. The present study in cultured neonatal rat cardiac myocytes tested the hypothesis that norepinephrine also stimulates expression of vascular endothelial growth factor (VEGF), an important angiogenic factor. As assessed by polymerase chain reaction cardiac myocytes and nonmyocytes expressed all three isoforms of rat VEGF, with the short isoform (VEGF121) preferentially expressed in non-myocytes. When cardiac myocytes were stimulated with 1 lM norepinephrine for 24 h in the presence or absence of the specific a-and b-adrenoceptor antagonists prazosin and propranolol, respectively, VEGF mRNA levels and splice variant pattern did not change, whereas atrial natriuretic peptide mRNA levels increased 3 to 4-fold. CoCl 2 increased VEGF mRNA levels in cardiac myocytes five-fold. When cardiac myocytes were cultured with conditioned medium from non-myocytes that had been stimulated with norepinephrine for 24 h VEGF mRNA increased 2-fold. The increase was blocked by antibodies neutralizing TGFb. These data suggest that norepinephrine stimulates myocardial angiogenesis by a paracrine mechanism that involves cardiac non-myocytes and TGFb.
Background —The role of the L-type calcium channel in human heart failure is unclear, on the basi... more Background —The role of the L-type calcium channel in human heart failure is unclear, on the basis of previous whole-cell recordings. Methods and Results —We investigated the properties of L-type calcium channels in left ventricular myocytes isolated from nonfailing donor hearts (n=16 cells) or failing hearts of transplant recipients with dilated (n=9) or ischemic (n=7) cardiomyopathy. The single-channel recording technique was used (70 mmol/L Ba 2+ ). Peak average currents were significantly enhanced in heart failure (38.2±9.3 fA) versus nonfailing control hearts (13.2±4.5 fA, P =0.02) because of an elevation of channel availability (55.9±6.7% versus 26.4±5.3%, P =0.001) and open probability within active sweeps (7.36±1.51% versus 3.18±1.33%, P =0.04). These differences closely resembled the effects of a cAMP-dependent stimulation with 8-Br-cAMP (n=11). Kinetic analysis of the slow gating shows that channels from failing hearts remain available for a longer time, suggesting a defec...
ABSTRACT Thromboembolische Ereignisse als Folge intravasaler Thrombusbildung stellen eine klinisc... more ABSTRACT Thromboembolische Ereignisse als Folge intravasaler Thrombusbildung stellen eine klinisch bedeutsame Komplikation kardiovaskulärer Erkrankungen dar. Therapeutisch kommen einerseits Heparine anderseits orale Antikoagulanzien zum klinischen Einsatz. Beide Substanzklassen sind in der Prävention und Behandlung venöser und arterieller thromboembolischen Erkrankungen wirksam. Neuere Wirkstoffe wie z. B. direkte Thrombininhibitoren wurden in den letzten Jahren mit zunehmender Intensität und bei spezifischen kardiologischen Fragestellungen klinisch geprüft, können aber derzeit noch nicht für eine Routineanwendung im klinischen Alltag empfohlen werden. Im Gegensatz zu den Antikoagulanzien werden Thrombozytenaggregationshemmer fast ausschließlich bei arteriellen thromboembolischen Erkrankungen eingesetzt. Die größten klinischen Erfahrungen liegen mit Acetylsalicylsäure vor, doch haben inzwischen neue Thrombozyteninhibitoren, wie Thienopyridine und Glykoprotein IIb/IIIa-Rezeptor-Antagonisten einen hohen Stellenwert in der Behandlung der koronaren Herzkrankheit, letztere v. a. beim akuten Koronarsyndrom. Die individuelle Nutzen-Risiko-Abwägung hat stets das erhöhte Blutungsrisiko unter der Therapie zu berücksichtigen.
Einschränkung der Operationsfähigkeit Was muss der Internist wissen? Schwerpunkt: Schnittstellen ... more Einschränkung der Operationsfähigkeit Was muss der Internist wissen? Schwerpunkt: Schnittstellen mit anderen Disziplinen Der Altersaufbau der westlichen Bevölkerung ändert sich dramatisch. Schätzungen zufolge benötigen ältere Menschen 4-mal so viele chirurgische Eingriffe wie der Rest der Bevölkerung [19]. Auch aufgrund neuer und schonender Therapiemöglichkeiten werden in Zukunft mehr ältere Patienten behandelt werden. Es wird angenommen, dass in der Altersgruppe von 75-84 Jahren 19% der Männer und 12% der Frauen unter einer koronaren Herzerkrankung leiden [5]. Größere chirurgische Eingriffe sind mit einem Risiko für kardialen Tod von 0,5-1,5% und von größeren kardialen Komplikationen von 2,0-3,5% behaftet. Auf die Bevölkerung der EU hochgerechnet, in der ca. 7 Mio. Eingriffe/Jahr durchgeführt werden, ergibt sich somit eine Zahl von 150.000-250.000 lebensbedrohlichen, kardialen Komplikationen/Jahr. Dieser Artikel fokussiert auf die Bedeutung der kardialen Risikoabschätzung in der präoperativen Diagnostik. Ziel der prä-und perioperativen Risikoeinschätzung bzw. Stratifizierung ist die Verminderung von perioperativer Mortalität, Morbidität, assoziierten Krankenhausbehandlungstagen und-kosten. Allgemeines perioperatives Risiko Komorbiditäten wie Herzerkrankungen, Diabetes mellitus, Apoplex, Niereninsuffizienz und Lungenerkrankungen beeinflussen den perioperativen Verlauf. Hier-bei sind kardiale Erkrankungen von besonderem Interesse (. Tab. 1). Darüber hinaus wird das Risiko durch verschiedene Faktoren, die den chirurgischen Eingriff betreffen (z. B. Notfall, Blutverlust, Flüssigkeitsverschiebungen, Art und Dauer des Eingriffs) bestimmt. E Die Identifizierung von Risikofaktoren stellt das zentrale Element der präoperativen Vorbereitung dar. Hierdurch wird das perioperative Management entscheidend beeinflusst. Eine Vielzahl an verschiedenen Instrumenten zur Risikoabschätzung ("risk scores") sind hierfür verfügbar, deren Praktikabilität unterschiedlich bewertet wird.
Risikofaktor "Rauchen" Wege aus der Nikotinsucht bei Patienten mit kardiovaskulären Erkrankungen ... more Risikofaktor "Rauchen" Wege aus der Nikotinsucht bei Patienten mit kardiovaskulären Erkrankungen Nach aktuellen Erhebungen der World Health Organization rauchen weltweit mehr als 1 Mrd. Menschen [36]. Der chronische Nikotinabusus ist die häufigste, vermeidbare Ursache für einen vorzeitigen Tod. Schätzungen gehen davon aus, dass derzeit jährlich nahezu 6 Mio. Menschen an den Folgen des Tabakkonsums sterben. Die sozioökonomischen Auswirkungen auf die Gesellschaft sind enorm. D In Deutschland sind jährlich ca. 114.000 Todesfälle auf das Rauchen zurückzuführen.
Objective: The goal of this study was to investigate alterations of the endogenous opioid system ... more Objective: The goal of this study was to investigate alterations of the endogenous opioid system in cardiac hypertrophy, to elucidate mechanisms of preproenkephalin (ppENK) gene expression, and to assess effects of endogenous opioids on myocardial contractility and atrioventricular conduction. Methods: Hypertrophy was induced by ligation of a renal artery (2K1C) or chronic isoprenaline infusion (ISO). ppENK and opioid receptor (A-, y-, nOR) mRNA expression was quantified by Northern blot and quantitative RT-PCR, respectively. Isolated cardiac myocytes and nonmyocytes from neonatal rat heart were used for cell culture experiments. Results: Overall expression of OR in the heart was markedly lower than in brain tissue, with nOR being the most abundant isoform in the heart. We did not observe differences in nOR expression in ventricular and atrial myocardium. In contrast, y-OR expression was markedly higher in atria than in ventricles. A-OR expression in the heart was below the detection limit of the developed qRT-PCR assay. In left ventricular myocardium, ppENK mRNA levels were significantly increased in 2K1C rats but decreased in ISO rats. Cell culture experiments from neonatal rat hearts revealed that myocytes and non-myocytes express ppENK mRNA. In these cells, receptor-dependent andindependent stimulation of the h-adrenergic signalling pathway caused an increase in ppENK mRNA. Furthermore, inactivation of inhibitory G-proteins by pertussis toxin increased basal and noradrenaline-stimulated ppENK mRNA expression. The physiological significance of myocardial opioids was investigated in isolated perfused rat hearts. Opioid receptor antagonists (nor-BNI, naltrindol) and the enkephalinase inhibitor CPL had no effect on contractility but significantly altered atrioventricular conduction. Conclusion: These observations suggest that the cardiac opioid system is activated in cardiac hypertrophy. Pressure overload and stimulation of the h-adrenergic signalling pathway have been identified as a possible mechanism leading to increased ppENK expression, which may contribute to opioid system activation. Finally, endogenous opioids modulate the dromotropic response to catecholamine stimulation. The latter finding raises the possibility that endogenous opioids may contribute to the pathogenesis of arrhythmias.
Emotional stress is considered a risk factor for cardiovascular events, the underlying pathophysi... more Emotional stress is considered a risk factor for cardiovascular events, the underlying pathophysiology remains unclear. To evaluate how emotional stress effects hemodynamics, thirteen healthy German soccer fans (mean 37.6 years, 24-56 years) were studied during live TV coverage of the finals with German national team participation (GP) and the respective finals without German participation (noGP). Peripheral blood pressure, heart rate, central blood pressure, augmentation pressure and index, cardiac output and peripheral resistance were measured. In the 1st hour before the match all parameters were not significantly different between the groups. In the GP group peripheral systolic pressure (1st halftime noGP 118 ± 1(s.e.m) versus GP 126 ± 2 mmHg, p<0.05, 2nd 117 ± 1 vs. 125 ± 2 mmHg, p<0.05), mean blood pressure, diastolic blood pressure, heart rate (1st 73 ± 2 vs. 86 ± 3 bpm, p<0.05, 2nd 75 ± 2 vs. 87 ± 2 bpm, p<0.05), cardiac output (1st 4,4 ± 0,1 versus 4,8 ± 0,1L/min, p<0.05, 2nd 4,6 ± 0,1 versus 4,7 ± 0,11 L/min, p>0.05) and peripheral resistance were significantly increased compared to the noGP group during the matches. Systolic central aortic pressure (noGP: 101 ± 2 versus GP 107 ± 2 mmHg, p<0.05) and central pulse pressure (noGP: 31.3 ± 1.3 mmHg vs. GP: 38.5 ± 2.7 mmHg, p<0,05) remained elevated during the second hour after the match. We observed persistent changes in central hemodynamics 2h after emotional stress. Despite normalization of peripheral values after the end of the finals, we observed prolonged elevation of central systolic blood and pulse pressure. Our findings contribute to the understanding of the increased risk of cardiovascular events in emotional stress.
We received a letter by Jin et al on our article published recently in Circulation. 1 The followi... more We received a letter by Jin et al on our article published recently in Circulation. 1 The following points should be clarified: It was argued that we did not measure, but extrapolated, cardiovascular risk. We neither extrapolated nor measured risk in the article. We only reported blood pressure data. Jin et al argue that the proportions of patients at 3, 6 and 12 months are different. This is due to different follow-up periods, as stated in the article as a potential limitation. 1 We reported that no major differences existed in medications before and after renal denervation but did not provide doses and drug classes. The study was not aimed to provide an in-depth analysis of drug classes or doses. Jin et al claim that we provided different classifications in the abstract and Methods section. Classification of patients was done in classic way. 1 Jin et al also claim that there are contradictions in the summary statistics. They mention that Table 3 provides only the odds that office blood pressure declined by >10 mm Hg. This was a defined criterion of response and was evaluated as described in the article. They argue that there is a disproportion between the responses in office and ambulatory blood pressures. These were the data, which correspond to most of the drug trials in hypertension. The assertion that our center would have performed >600 renal denervations is incorrect; it was ≈200 at that time of Der Spiegel publication. 2 Health insurances would cover renal denervation in some countries. Most of the procedures were not reimbursed because patients were treated in trials or investigative protocols. Today, there is indeed a reimbursement, which does not cover the costs of the procedure and the materials. Many centers, at least in Germany, pay the cost of this procedure from their own scientific budgets. In conclusion, our study aimed to investigate the effects of renal denervation on 24-hour blood pressure. Therefore, the involved centers pooled their data and shared their experiences. 1,3 The goal is to facilitate and improve the design of randomized and controlled trials, being well aware that these investigations cannot substitute them. The authors of the letter acknowledge concerns already raised by the authors themselves. 4,5 Disclosures Drs Mahfoud, Ukena, and Böhm are supported by the Ministry of Science and Economy of the Saarland and Deutsche Forschungsgemeinschaft (KFO 196
Growth factors such as transforming growth factor-beta (TGF beta) are believed to have an essenti... more Growth factors such as transforming growth factor-beta (TGF beta) are believed to have an essential role in cardiac fibrosis. Tranilast (N(3,4-dimethoxycinnamoyl) anthranilic acid) attenuates the increased expression of TGF beta mRNA in vitro. To investigate whether tranilast reduces cardiac fibrosis in rats with two-kidney, one-clip (2K1C) renovascular hypertension. In addition, we tested the in-vitro effects of tranilast on cardiac myocytes and non-myocyte cells. We analysed hearts from four groups of rats: sham-operated controls; rats with 2K1C renovascular hypertension; rats with 2K1C renovascular hypertension treated for 12 weeks with the angiotensin converting enzyme (ACE) inhibitor, quinapril (6 mg/kg per day); rats with 2K1C renovascular hypertension treated for 12 weeks with tranilast (400 mg/kg per day). Systolic blood pressure was reduced after quinapril treatment. Tranilast did not alter blood pressure (2K1C: 223 +/- 19 mmHg; 2K1C + quinapril: 149 +/- 15 mmHg (P < 0.01 compared with 2K1C); 2K1C + tranilast: 204 +/- 32 mmHg). Left ventricular weight was likewise reduced significantly by quinapril, but not significantly by tranilast (2K1C: 1.52 +/- 0.2 g; 2K1C + quinapril: 1.26 +/- 0.18 g (P < 0.05 compared with 2K1C); 2K1C + tranilast: 1.37 +/- 0.27 g). Using a computer-aided image analysis system, we demonstrated that tranilast prevented cardiac fibrosis in a blood-pressure-independent manner (P…
Emotional stress is considered a risk factor for cardiovascular events, the underlying pathophysi... more Emotional stress is considered a risk factor for cardiovascular events, the underlying pathophysiology remains unclear. To evaluate how emotional stress effects hemodynamics, thirteen healthy German soccer fans (mean 37.6 years, 24-56 years) were studied during live TV coverage of the finals with German national team participation (GP) and the respective finals without German participation (noGP). Peripheral blood pressure, heart rate, central blood pressure, augmentation pressure and index, cardiac output and peripheral resistance were measured. In the 1st hour before the match all parameters were not significantly different between the groups. In the GP group peripheral systolic pressure (1st halftime noGP 118 ± 1(s.e.m) versus GP 126 ± 2 mmHg, p<0.05, 2nd 117 ± 1 vs. 125 ± 2 mmHg, p<0.05), mean blood pressure, diastolic blood pressure, heart rate (1st 73 ± 2 vs. 86 ± 3 bpm, p<0.05, 2nd 75 ± 2 vs. 87 ± 2 bpm, p<0.05), cardiac output (1st 4,4 ± 0,1 versus 4,8 ± 0,1L/min, p<0.05, 2nd 4,6 ± 0,1 versus 4,7 ± 0,11 L/min, p>0.05) and peripheral resistance were significantly increased compared to the noGP group during the matches. Systolic central aortic pressure (noGP: 101 ± 2 versus GP 107 ± 2 mmHg, p<0.05) and central pulse pressure (noGP: 31.3 ± 1.3 mmHg vs. GP: 38.5 ± 2.7 mmHg, p<0,05) remained elevated during the second hour after the match. We observed persistent changes in central hemodynamics 2h after emotional stress. Despite normalization of peripheral values after the end of the finals, we observed prolonged elevation of central systolic blood and pulse pressure. Our findings contribute to the understanding of the increased risk of cardiovascular events in emotional stress.
t Mfinchen * Supported by research grants 86.015.1 and 86.015.2 of the Wilhelm Sander Foundation ... more t Mfinchen * Supported by research grants 86.015.1 and 86.015.2 of the Wilhelm Sander Foundation and grant DFG Ge-399/3-3 of the Deutsche Forschungsgemeinschaft in resting and particularly exercise hemodynamics during antihypertensive therapy.
, admissions to paediatric departments for Bordetella pertussis complications were reported to a ... more , admissions to paediatric departments for Bordetella pertussis complications were reported to a nationwide, hospitalbased active surveillance system. The case definition included pertussis complicated by pneumonia, apnoea requiring assisted ventilation, seizures, encephalopathy or a combination of these. Two hundred sixteen cases of pertussis complications were registered. 57.4% of them were in infants, 50.9% of them less than 6 months old. There were five deaths, three previously healthy children died. At the time of hospital admission, 106 cases would have been eligible for at least three doses of pertussis vaccine, only four (3.8%) had received the recommended number of immunisations. From the second quarter of 1995, the reported number of cases declined. The decrease coincides with an improvement of pertussis vaccination coverage between 1992 and 1995 due to an increased use of acellular vaccines. The reduction of complicated pertussis was observed even in age-groups too young for the recommended vaccinations. The observed decrease could be due to the increase in vaccination coverage with interuption of the chain of transmission to the younger age-groups, to a cyclic decrease in pertussis cases, or to a combination of both. Continued surveillance will provide information on the epidemiological trend of hospitalisations for pertussis complications in the first European country to have introduced vaccination with acellular vaccines on a large scale.
Increased expression of the inhibitory G protein Gia-2 is assumed to contributed to desensitizati... more Increased expression of the inhibitory G protein Gia-2 is assumed to contributed to desensitization of adenylyl cyclase in human heart failure. The mechanisms of upregulation involve increases in myocardial Gia-2 protein, mRNA and gene transcriptional activity. To elucidate these mechanisms in more detail, the 5' flanking region of the human Gia-2 gene (-1214/+115 bp) was cloned upstream of the bacterial
Norepinephrine has growth-promoting effects in cardiac myocytes. The present study in cultured ne... more Norepinephrine has growth-promoting effects in cardiac myocytes. The present study in cultured neonatal rat cardiac myocytes tested the hypothesis that norepinephrine also stimulates expression of vascular endothelial growth factor (VEGF), an important angiogenic factor. As assessed by polymerase chain reaction cardiac myocytes and nonmyocytes expressed all three isoforms of rat VEGF, with the short isoform (VEGF121) preferentially expressed in non-myocytes. When cardiac myocytes were stimulated with 1 lM norepinephrine for 24 h in the presence or absence of the specific a-and b-adrenoceptor antagonists prazosin and propranolol, respectively, VEGF mRNA levels and splice variant pattern did not change, whereas atrial natriuretic peptide mRNA levels increased 3 to 4-fold. CoCl 2 increased VEGF mRNA levels in cardiac myocytes five-fold. When cardiac myocytes were cultured with conditioned medium from non-myocytes that had been stimulated with norepinephrine for 24 h VEGF mRNA increased 2-fold. The increase was blocked by antibodies neutralizing TGFb. These data suggest that norepinephrine stimulates myocardial angiogenesis by a paracrine mechanism that involves cardiac non-myocytes and TGFb.
Background —The role of the L-type calcium channel in human heart failure is unclear, on the basi... more Background —The role of the L-type calcium channel in human heart failure is unclear, on the basis of previous whole-cell recordings. Methods and Results —We investigated the properties of L-type calcium channels in left ventricular myocytes isolated from nonfailing donor hearts (n=16 cells) or failing hearts of transplant recipients with dilated (n=9) or ischemic (n=7) cardiomyopathy. The single-channel recording technique was used (70 mmol/L Ba 2+ ). Peak average currents were significantly enhanced in heart failure (38.2±9.3 fA) versus nonfailing control hearts (13.2±4.5 fA, P =0.02) because of an elevation of channel availability (55.9±6.7% versus 26.4±5.3%, P =0.001) and open probability within active sweeps (7.36±1.51% versus 3.18±1.33%, P =0.04). These differences closely resembled the effects of a cAMP-dependent stimulation with 8-Br-cAMP (n=11). Kinetic analysis of the slow gating shows that channels from failing hearts remain available for a longer time, suggesting a defec...
ABSTRACT Thromboembolische Ereignisse als Folge intravasaler Thrombusbildung stellen eine klinisc... more ABSTRACT Thromboembolische Ereignisse als Folge intravasaler Thrombusbildung stellen eine klinisch bedeutsame Komplikation kardiovaskulärer Erkrankungen dar. Therapeutisch kommen einerseits Heparine anderseits orale Antikoagulanzien zum klinischen Einsatz. Beide Substanzklassen sind in der Prävention und Behandlung venöser und arterieller thromboembolischen Erkrankungen wirksam. Neuere Wirkstoffe wie z. B. direkte Thrombininhibitoren wurden in den letzten Jahren mit zunehmender Intensität und bei spezifischen kardiologischen Fragestellungen klinisch geprüft, können aber derzeit noch nicht für eine Routineanwendung im klinischen Alltag empfohlen werden. Im Gegensatz zu den Antikoagulanzien werden Thrombozytenaggregationshemmer fast ausschließlich bei arteriellen thromboembolischen Erkrankungen eingesetzt. Die größten klinischen Erfahrungen liegen mit Acetylsalicylsäure vor, doch haben inzwischen neue Thrombozyteninhibitoren, wie Thienopyridine und Glykoprotein IIb/IIIa-Rezeptor-Antagonisten einen hohen Stellenwert in der Behandlung der koronaren Herzkrankheit, letztere v. a. beim akuten Koronarsyndrom. Die individuelle Nutzen-Risiko-Abwägung hat stets das erhöhte Blutungsrisiko unter der Therapie zu berücksichtigen.
Einschränkung der Operationsfähigkeit Was muss der Internist wissen? Schwerpunkt: Schnittstellen ... more Einschränkung der Operationsfähigkeit Was muss der Internist wissen? Schwerpunkt: Schnittstellen mit anderen Disziplinen Der Altersaufbau der westlichen Bevölkerung ändert sich dramatisch. Schätzungen zufolge benötigen ältere Menschen 4-mal so viele chirurgische Eingriffe wie der Rest der Bevölkerung [19]. Auch aufgrund neuer und schonender Therapiemöglichkeiten werden in Zukunft mehr ältere Patienten behandelt werden. Es wird angenommen, dass in der Altersgruppe von 75-84 Jahren 19% der Männer und 12% der Frauen unter einer koronaren Herzerkrankung leiden [5]. Größere chirurgische Eingriffe sind mit einem Risiko für kardialen Tod von 0,5-1,5% und von größeren kardialen Komplikationen von 2,0-3,5% behaftet. Auf die Bevölkerung der EU hochgerechnet, in der ca. 7 Mio. Eingriffe/Jahr durchgeführt werden, ergibt sich somit eine Zahl von 150.000-250.000 lebensbedrohlichen, kardialen Komplikationen/Jahr. Dieser Artikel fokussiert auf die Bedeutung der kardialen Risikoabschätzung in der präoperativen Diagnostik. Ziel der prä-und perioperativen Risikoeinschätzung bzw. Stratifizierung ist die Verminderung von perioperativer Mortalität, Morbidität, assoziierten Krankenhausbehandlungstagen und-kosten. Allgemeines perioperatives Risiko Komorbiditäten wie Herzerkrankungen, Diabetes mellitus, Apoplex, Niereninsuffizienz und Lungenerkrankungen beeinflussen den perioperativen Verlauf. Hier-bei sind kardiale Erkrankungen von besonderem Interesse (. Tab. 1). Darüber hinaus wird das Risiko durch verschiedene Faktoren, die den chirurgischen Eingriff betreffen (z. B. Notfall, Blutverlust, Flüssigkeitsverschiebungen, Art und Dauer des Eingriffs) bestimmt. E Die Identifizierung von Risikofaktoren stellt das zentrale Element der präoperativen Vorbereitung dar. Hierdurch wird das perioperative Management entscheidend beeinflusst. Eine Vielzahl an verschiedenen Instrumenten zur Risikoabschätzung ("risk scores") sind hierfür verfügbar, deren Praktikabilität unterschiedlich bewertet wird.
Risikofaktor "Rauchen" Wege aus der Nikotinsucht bei Patienten mit kardiovaskulären Erkrankungen ... more Risikofaktor "Rauchen" Wege aus der Nikotinsucht bei Patienten mit kardiovaskulären Erkrankungen Nach aktuellen Erhebungen der World Health Organization rauchen weltweit mehr als 1 Mrd. Menschen [36]. Der chronische Nikotinabusus ist die häufigste, vermeidbare Ursache für einen vorzeitigen Tod. Schätzungen gehen davon aus, dass derzeit jährlich nahezu 6 Mio. Menschen an den Folgen des Tabakkonsums sterben. Die sozioökonomischen Auswirkungen auf die Gesellschaft sind enorm. D In Deutschland sind jährlich ca. 114.000 Todesfälle auf das Rauchen zurückzuführen.
Objective: The goal of this study was to investigate alterations of the endogenous opioid system ... more Objective: The goal of this study was to investigate alterations of the endogenous opioid system in cardiac hypertrophy, to elucidate mechanisms of preproenkephalin (ppENK) gene expression, and to assess effects of endogenous opioids on myocardial contractility and atrioventricular conduction. Methods: Hypertrophy was induced by ligation of a renal artery (2K1C) or chronic isoprenaline infusion (ISO). ppENK and opioid receptor (A-, y-, nOR) mRNA expression was quantified by Northern blot and quantitative RT-PCR, respectively. Isolated cardiac myocytes and nonmyocytes from neonatal rat heart were used for cell culture experiments. Results: Overall expression of OR in the heart was markedly lower than in brain tissue, with nOR being the most abundant isoform in the heart. We did not observe differences in nOR expression in ventricular and atrial myocardium. In contrast, y-OR expression was markedly higher in atria than in ventricles. A-OR expression in the heart was below the detection limit of the developed qRT-PCR assay. In left ventricular myocardium, ppENK mRNA levels were significantly increased in 2K1C rats but decreased in ISO rats. Cell culture experiments from neonatal rat hearts revealed that myocytes and non-myocytes express ppENK mRNA. In these cells, receptor-dependent andindependent stimulation of the h-adrenergic signalling pathway caused an increase in ppENK mRNA. Furthermore, inactivation of inhibitory G-proteins by pertussis toxin increased basal and noradrenaline-stimulated ppENK mRNA expression. The physiological significance of myocardial opioids was investigated in isolated perfused rat hearts. Opioid receptor antagonists (nor-BNI, naltrindol) and the enkephalinase inhibitor CPL had no effect on contractility but significantly altered atrioventricular conduction. Conclusion: These observations suggest that the cardiac opioid system is activated in cardiac hypertrophy. Pressure overload and stimulation of the h-adrenergic signalling pathway have been identified as a possible mechanism leading to increased ppENK expression, which may contribute to opioid system activation. Finally, endogenous opioids modulate the dromotropic response to catecholamine stimulation. The latter finding raises the possibility that endogenous opioids may contribute to the pathogenesis of arrhythmias.
Emotional stress is considered a risk factor for cardiovascular events, the underlying pathophysi... more Emotional stress is considered a risk factor for cardiovascular events, the underlying pathophysiology remains unclear. To evaluate how emotional stress effects hemodynamics, thirteen healthy German soccer fans (mean 37.6 years, 24-56 years) were studied during live TV coverage of the finals with German national team participation (GP) and the respective finals without German participation (noGP). Peripheral blood pressure, heart rate, central blood pressure, augmentation pressure and index, cardiac output and peripheral resistance were measured. In the 1st hour before the match all parameters were not significantly different between the groups. In the GP group peripheral systolic pressure (1st halftime noGP 118 ± 1(s.e.m) versus GP 126 ± 2 mmHg, p<0.05, 2nd 117 ± 1 vs. 125 ± 2 mmHg, p<0.05), mean blood pressure, diastolic blood pressure, heart rate (1st 73 ± 2 vs. 86 ± 3 bpm, p<0.05, 2nd 75 ± 2 vs. 87 ± 2 bpm, p<0.05), cardiac output (1st 4,4 ± 0,1 versus 4,8 ± 0,1L/min, p<0.05, 2nd 4,6 ± 0,1 versus 4,7 ± 0,11 L/min, p>0.05) and peripheral resistance were significantly increased compared to the noGP group during the matches. Systolic central aortic pressure (noGP: 101 ± 2 versus GP 107 ± 2 mmHg, p<0.05) and central pulse pressure (noGP: 31.3 ± 1.3 mmHg vs. GP: 38.5 ± 2.7 mmHg, p<0,05) remained elevated during the second hour after the match. We observed persistent changes in central hemodynamics 2h after emotional stress. Despite normalization of peripheral values after the end of the finals, we observed prolonged elevation of central systolic blood and pulse pressure. Our findings contribute to the understanding of the increased risk of cardiovascular events in emotional stress.
We received a letter by Jin et al on our article published recently in Circulation. 1 The followi... more We received a letter by Jin et al on our article published recently in Circulation. 1 The following points should be clarified: It was argued that we did not measure, but extrapolated, cardiovascular risk. We neither extrapolated nor measured risk in the article. We only reported blood pressure data. Jin et al argue that the proportions of patients at 3, 6 and 12 months are different. This is due to different follow-up periods, as stated in the article as a potential limitation. 1 We reported that no major differences existed in medications before and after renal denervation but did not provide doses and drug classes. The study was not aimed to provide an in-depth analysis of drug classes or doses. Jin et al claim that we provided different classifications in the abstract and Methods section. Classification of patients was done in classic way. 1 Jin et al also claim that there are contradictions in the summary statistics. They mention that Table 3 provides only the odds that office blood pressure declined by >10 mm Hg. This was a defined criterion of response and was evaluated as described in the article. They argue that there is a disproportion between the responses in office and ambulatory blood pressures. These were the data, which correspond to most of the drug trials in hypertension. The assertion that our center would have performed >600 renal denervations is incorrect; it was ≈200 at that time of Der Spiegel publication. 2 Health insurances would cover renal denervation in some countries. Most of the procedures were not reimbursed because patients were treated in trials or investigative protocols. Today, there is indeed a reimbursement, which does not cover the costs of the procedure and the materials. Many centers, at least in Germany, pay the cost of this procedure from their own scientific budgets. In conclusion, our study aimed to investigate the effects of renal denervation on 24-hour blood pressure. Therefore, the involved centers pooled their data and shared their experiences. 1,3 The goal is to facilitate and improve the design of randomized and controlled trials, being well aware that these investigations cannot substitute them. The authors of the letter acknowledge concerns already raised by the authors themselves. 4,5 Disclosures Drs Mahfoud, Ukena, and Böhm are supported by the Ministry of Science and Economy of the Saarland and Deutsche Forschungsgemeinschaft (KFO 196
Growth factors such as transforming growth factor-beta (TGF beta) are believed to have an essenti... more Growth factors such as transforming growth factor-beta (TGF beta) are believed to have an essential role in cardiac fibrosis. Tranilast (N(3,4-dimethoxycinnamoyl) anthranilic acid) attenuates the increased expression of TGF beta mRNA in vitro. To investigate whether tranilast reduces cardiac fibrosis in rats with two-kidney, one-clip (2K1C) renovascular hypertension. In addition, we tested the in-vitro effects of tranilast on cardiac myocytes and non-myocyte cells. We analysed hearts from four groups of rats: sham-operated controls; rats with 2K1C renovascular hypertension; rats with 2K1C renovascular hypertension treated for 12 weeks with the angiotensin converting enzyme (ACE) inhibitor, quinapril (6 mg/kg per day); rats with 2K1C renovascular hypertension treated for 12 weeks with tranilast (400 mg/kg per day). Systolic blood pressure was reduced after quinapril treatment. Tranilast did not alter blood pressure (2K1C: 223 +/- 19 mmHg; 2K1C + quinapril: 149 +/- 15 mmHg (P < 0.01 compared with 2K1C); 2K1C + tranilast: 204 +/- 32 mmHg). Left ventricular weight was likewise reduced significantly by quinapril, but not significantly by tranilast (2K1C: 1.52 +/- 0.2 g; 2K1C + quinapril: 1.26 +/- 0.18 g (P < 0.05 compared with 2K1C); 2K1C + tranilast: 1.37 +/- 0.27 g). Using a computer-aided image analysis system, we demonstrated that tranilast prevented cardiac fibrosis in a blood-pressure-independent manner (P…
Emotional stress is considered a risk factor for cardiovascular events, the underlying pathophysi... more Emotional stress is considered a risk factor for cardiovascular events, the underlying pathophysiology remains unclear. To evaluate how emotional stress effects hemodynamics, thirteen healthy German soccer fans (mean 37.6 years, 24-56 years) were studied during live TV coverage of the finals with German national team participation (GP) and the respective finals without German participation (noGP). Peripheral blood pressure, heart rate, central blood pressure, augmentation pressure and index, cardiac output and peripheral resistance were measured. In the 1st hour before the match all parameters were not significantly different between the groups. In the GP group peripheral systolic pressure (1st halftime noGP 118 ± 1(s.e.m) versus GP 126 ± 2 mmHg, p<0.05, 2nd 117 ± 1 vs. 125 ± 2 mmHg, p<0.05), mean blood pressure, diastolic blood pressure, heart rate (1st 73 ± 2 vs. 86 ± 3 bpm, p<0.05, 2nd 75 ± 2 vs. 87 ± 2 bpm, p<0.05), cardiac output (1st 4,4 ± 0,1 versus 4,8 ± 0,1L/min, p<0.05, 2nd 4,6 ± 0,1 versus 4,7 ± 0,11 L/min, p>0.05) and peripheral resistance were significantly increased compared to the noGP group during the matches. Systolic central aortic pressure (noGP: 101 ± 2 versus GP 107 ± 2 mmHg, p<0.05) and central pulse pressure (noGP: 31.3 ± 1.3 mmHg vs. GP: 38.5 ± 2.7 mmHg, p<0,05) remained elevated during the second hour after the match. We observed persistent changes in central hemodynamics 2h after emotional stress. Despite normalization of peripheral values after the end of the finals, we observed prolonged elevation of central systolic blood and pulse pressure. Our findings contribute to the understanding of the increased risk of cardiovascular events in emotional stress.
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