M. Hünlich - Academia.edu (original) (raw)
Papers by M. Hünlich
BioMed Research International
Positive results of MitraClip in terms of improvement in clinical and left ventricular parameters... more Positive results of MitraClip in terms of improvement in clinical and left ventricular parameters have been described in detail. However, long-term effects on secondary pulmonary hypertension were not investigated in a larger patient cohort to date. 70 patients with severe mitral regurgitation, additional pulmonary hypertension, and right heart failure as a result of left heart disease were treated in the heart centers Hamburg and Göttingen. Immediately after successful MitraClip implantation, a reduction of the RVOT diameter from 3.52 cm to 3.44 cm was observed reaching a statistically significant value of 3.39 cm after 12 months. In contrast, there was a significant reduction in the velocity of the tricuspid regurgitation (TR) from 4.17 m/s to 3.11 m/s, the gradient of the TR from 48.5 mmHg to 39.3 mmHg, and the systolic pulmonary artery pressure (PAPsyst) from 58.6 mmHg to 50.0 mmHg. This decline continued in the following months (Vmax TR 3.09 m/s, peak TR 38.6 mmHg, and PAPsyst ...
Deutsche medizinische Wochenschrift (1946), 2014
There is little published evidence on the treatment of mobile masses in the right heart. We repor... more There is little published evidence on the treatment of mobile masses in the right heart. We report the clinical courses of three consecutive patients presenting with acute pulmonary embolism and mobile masses in the right heart. Three women, aged 75, 72 and 52 years, were hospitalized within three months because of dyspnea and suspected pulmonary embolism. Transthoracic echocardiography revealed right ventricular dysfunction and highly mobile masses, which were considered as in-transit right heart thrombi in all cases. All patients received immediate thrombolytic therapy (alteplase). No bleeding complications occurred. Thrombolysis was successful in the first two cases. However, the mass in the right ventricle did not disappear after thrombolysis in the third case and was removed surgically later on. The definite histological diagnosis was a myxoma of the right ventricle. According to literature, in-transit right heart thrombi are a potentially life-threatening complication of pulmo...
Progress in Experimental Cardiology, 2003
In this study, the contribution of key myofibrillar contractile elements in myocardial failure wa... more In this study, the contribution of key myofibrillar contractile elements in myocardial failure was investigated. Specifically, we assessed the mechanical implications of myosin isoform shifting, troponin T isoform shifting, and troponin I phosphorylation by protein kinase A. The two cardiac myosin isoforms have distinct functional differences which appear to be preserved across mammalian species. V1 cardiac myosin translocates actin filaments 2–3 times faster than V3 myosin but only generates one half the force. Calculated power estimates for the cardiac myosin isoforms are similar. The two adult beef troponin T isoforms have compositional similarities when compared to the two human isoforms differentially expressed in the transition to myocardial failure. Using the in vitro motility assay, no functional differences were elicited between the two isoforms in terms of unloaded shortening, isometric force, calcium sensitivity, or cooperative activation. Lastly, protein kinase A phosphorylation of troponin I resulted in a large increase in the calcium sensitive activation of the thin filament with no change in maximal activation. These results are interpreted in the context of a molecular model of contractile protein function and applied to evolving concepts of the role of the myofibril in myocardial failure.
Coronary Artery Disease, 2010
Atrial fibrillation (AF) causes atrial contractile dysfunction. The focus of this study was to de... more Atrial fibrillation (AF) causes atrial contractile dysfunction. The focus of this study was to determine whether the contractile deficit of human AF is the result of altered contractile protein abundance and/or function. Atrial tissue from patients with chronic AF undergoing open-heart surgery was compared with the tissue from patients in normal sinus rhythm (NSR). Myosin isoform composition and content were determined. Intact native thin filament and cardiac myosin contractile protein performance were independently assessed in an in-vitro motility assay. Myosin isoform expression and total myosin content were not different between AF and NSR. Calcium-activated native thin filament function was similar between AF and NSR as measured by calcium sensitivity and maximal activation. Myosin isolated from the atria of AF and NSR groups showed similar unloaded shortening speeds and isometric force generation. Unlike human ventricular dysfunction where contractile protein function is directly affected, the contractile deficit of AF is not the result of alterations in myosin content or contractile protein function.
Clinical Research in Cardiology, 2014
Circulation, 2004
Background-The contribution of the sarcomere's thin filament to the contractile dysfunction of hu... more Background-The contribution of the sarcomere's thin filament to the contractile dysfunction of human cardiomyopathy is not well understood. Methods and Results-We have developed techniques to isolate and functionally characterize intact (native) thin filaments obtained from failing and nonfailing human ventricular tissue. By use of in vitro motility and force assays, native thin filaments from failing ventricular tissue exhibited a 19% increase in maximal velocity but a 27% decrease in maximal contractile force compared with nonfailing myocardium. Native thin filaments isolated from human myocardium after left ventricular assist device support demonstrated a 37% increase in contractile force. Dephosphorylation of failing native thin filaments resulted in a near-normalization of thin-filament function, implying a phosphorylation-mediated mechanism. Tissue expression of the protein kinase C isoforms ␣,  1 , and  2 was increased in failing human myocardium and reduced after left ventricular assist device support. Conclusions-These novel findings demonstrate that (1) the thin filament is a key modulator of contractile performance in the failing human heart, (2) thin-filament function is restored to near normal levels after LVAD support, and the alteration of thin-filament function in failing human myocardium is mediated through phosphorylation, most likely through activation of protein kinase C. (Circulation. 2004;110:982-987.)
Journal of the American College of Cardiology, 2011
We investigated whether increased Ca 2ϩ /calmodulin-dependent kinase II (CaMKII) activity aggrava... more We investigated whether increased Ca 2ϩ /calmodulin-dependent kinase II (CaMKII) activity aggravates defective excitation-contraction coupling and proarrhythmic activity in mice expressing R4496C mutated cardiac ryanodine receptors (RyR2).
BioMed Research International
Positive results of MitraClip in terms of improvement in clinical and left ventricular parameters... more Positive results of MitraClip in terms of improvement in clinical and left ventricular parameters have been described in detail. However, long-term effects on secondary pulmonary hypertension were not investigated in a larger patient cohort to date. 70 patients with severe mitral regurgitation, additional pulmonary hypertension, and right heart failure as a result of left heart disease were treated in the heart centers Hamburg and Göttingen. Immediately after successful MitraClip implantation, a reduction of the RVOT diameter from 3.52 cm to 3.44 cm was observed reaching a statistically significant value of 3.39 cm after 12 months. In contrast, there was a significant reduction in the velocity of the tricuspid regurgitation (TR) from 4.17 m/s to 3.11 m/s, the gradient of the TR from 48.5 mmHg to 39.3 mmHg, and the systolic pulmonary artery pressure (PAPsyst) from 58.6 mmHg to 50.0 mmHg. This decline continued in the following months (Vmax TR 3.09 m/s, peak TR 38.6 mmHg, and PAPsyst ...
Deutsche medizinische Wochenschrift (1946), 2014
There is little published evidence on the treatment of mobile masses in the right heart. We repor... more There is little published evidence on the treatment of mobile masses in the right heart. We report the clinical courses of three consecutive patients presenting with acute pulmonary embolism and mobile masses in the right heart. Three women, aged 75, 72 and 52 years, were hospitalized within three months because of dyspnea and suspected pulmonary embolism. Transthoracic echocardiography revealed right ventricular dysfunction and highly mobile masses, which were considered as in-transit right heart thrombi in all cases. All patients received immediate thrombolytic therapy (alteplase). No bleeding complications occurred. Thrombolysis was successful in the first two cases. However, the mass in the right ventricle did not disappear after thrombolysis in the third case and was removed surgically later on. The definite histological diagnosis was a myxoma of the right ventricle. According to literature, in-transit right heart thrombi are a potentially life-threatening complication of pulmo...
Progress in Experimental Cardiology, 2003
In this study, the contribution of key myofibrillar contractile elements in myocardial failure wa... more In this study, the contribution of key myofibrillar contractile elements in myocardial failure was investigated. Specifically, we assessed the mechanical implications of myosin isoform shifting, troponin T isoform shifting, and troponin I phosphorylation by protein kinase A. The two cardiac myosin isoforms have distinct functional differences which appear to be preserved across mammalian species. V1 cardiac myosin translocates actin filaments 2–3 times faster than V3 myosin but only generates one half the force. Calculated power estimates for the cardiac myosin isoforms are similar. The two adult beef troponin T isoforms have compositional similarities when compared to the two human isoforms differentially expressed in the transition to myocardial failure. Using the in vitro motility assay, no functional differences were elicited between the two isoforms in terms of unloaded shortening, isometric force, calcium sensitivity, or cooperative activation. Lastly, protein kinase A phosphorylation of troponin I resulted in a large increase in the calcium sensitive activation of the thin filament with no change in maximal activation. These results are interpreted in the context of a molecular model of contractile protein function and applied to evolving concepts of the role of the myofibril in myocardial failure.
Coronary Artery Disease, 2010
Atrial fibrillation (AF) causes atrial contractile dysfunction. The focus of this study was to de... more Atrial fibrillation (AF) causes atrial contractile dysfunction. The focus of this study was to determine whether the contractile deficit of human AF is the result of altered contractile protein abundance and/or function. Atrial tissue from patients with chronic AF undergoing open-heart surgery was compared with the tissue from patients in normal sinus rhythm (NSR). Myosin isoform composition and content were determined. Intact native thin filament and cardiac myosin contractile protein performance were independently assessed in an in-vitro motility assay. Myosin isoform expression and total myosin content were not different between AF and NSR. Calcium-activated native thin filament function was similar between AF and NSR as measured by calcium sensitivity and maximal activation. Myosin isolated from the atria of AF and NSR groups showed similar unloaded shortening speeds and isometric force generation. Unlike human ventricular dysfunction where contractile protein function is directly affected, the contractile deficit of AF is not the result of alterations in myosin content or contractile protein function.
Clinical Research in Cardiology, 2014
Circulation, 2004
Background-The contribution of the sarcomere's thin filament to the contractile dysfunction of hu... more Background-The contribution of the sarcomere's thin filament to the contractile dysfunction of human cardiomyopathy is not well understood. Methods and Results-We have developed techniques to isolate and functionally characterize intact (native) thin filaments obtained from failing and nonfailing human ventricular tissue. By use of in vitro motility and force assays, native thin filaments from failing ventricular tissue exhibited a 19% increase in maximal velocity but a 27% decrease in maximal contractile force compared with nonfailing myocardium. Native thin filaments isolated from human myocardium after left ventricular assist device support demonstrated a 37% increase in contractile force. Dephosphorylation of failing native thin filaments resulted in a near-normalization of thin-filament function, implying a phosphorylation-mediated mechanism. Tissue expression of the protein kinase C isoforms ␣,  1 , and  2 was increased in failing human myocardium and reduced after left ventricular assist device support. Conclusions-These novel findings demonstrate that (1) the thin filament is a key modulator of contractile performance in the failing human heart, (2) thin-filament function is restored to near normal levels after LVAD support, and the alteration of thin-filament function in failing human myocardium is mediated through phosphorylation, most likely through activation of protein kinase C. (Circulation. 2004;110:982-987.)
Journal of the American College of Cardiology, 2011
We investigated whether increased Ca 2ϩ /calmodulin-dependent kinase II (CaMKII) activity aggrava... more We investigated whether increased Ca 2ϩ /calmodulin-dependent kinase II (CaMKII) activity aggravates defective excitation-contraction coupling and proarrhythmic activity in mice expressing R4496C mutated cardiac ryanodine receptors (RyR2).