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1.
Herz ; 47(6): 513-517, 2022 Dec.
Article in German | MEDLINE | ID: mdl-36331569

ABSTRACT

The interventional treatment of high-risk patients remains challenging and has a high potential for improvement despite all technical innovations. Mechanical circulatory support (MCS) systems can be meaningful depending on the clinical situation, although a clear study situation for this is so far lacking. Multivessel coronary disease and a high SYNTAX score combined with impaired ventricular function is a possible predictor combination for the use of MCS that justifies the higher risk of complications.


Subject(s)
Coronary Artery Disease , Extracorporeal Membrane Oxygenation , Heart-Assist Devices , Percutaneous Coronary Intervention , Humans , Intra-Aortic Balloon Pumping/adverse effects , Coronary Artery Disease/complications , Shock, Cardiogenic/therapy
2.
Neth Heart J ; 30(6): 328-334, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34910278

ABSTRACT

INTRODUCTION: Sex disparities exist in coronary artery disease (CAD) in terms of risk profile, clinical management and outcome. It is unclear if differences are also present in coronary aneurysms, a rare variant of CAD. METHODS: Patients were selected from the international Coronary Artery Aneurysm Registry (CAAR; ClinicalTrials.gov: NCT02563626), and differences between groups were analysed according to sex. The CAAR database is a prospective multicentre registry of 1565 patients with coronary aneurysms (336 females). Kaplan-Meier method was used for event-free survival analysis for death, major adverse cardiac events (MACE: composite endpoint of death, heart failure and acute coronary syndrome) and bleeding. RESULTS: Female patients were older, were more often hypertensive and less frequently smoker. They were treated conservatively more often compared to male patients and received significantly less frequently aspirin (92% vs 88%, p = 0.002) or dual antiplatelet therapy (DAPT) (67% vs 58%, p = 0.001) at discharge. Median DAPT duration was also shorter (3 vs 9 months, p = 0.001). Kaplan-Meier analysis revealed no sex differences in death, MACE or bleeding during a median follow-up duration of 37 months, although male patients did experience acute coronary syndrome (ACS) more often during follow-up (15% vs 10%, p = 0.015). CONCLUSIONS: These CAAR findings showed a comparable high-risk cardiovascular risk profile for both sexes. Female patients were treated conservatively more often and received DAPT less often at discharge, with a shorter DAPT duration. ACS was more prevalent among male patients; however, overall clinical outcome was not different between male and female patients during follow-up.

3.
Herz ; 45(Suppl 1): 95-104, 2020 Dec.
Article in English | MEDLINE | ID: mdl-31209520

ABSTRACT

BACKGROUND: Limited data exist on bioresorbable scaffolds (BRS) in patients with acute coronary syndrome (ACS). The aim of the present study was to evaluate novolimus-eluting BRS (DESolve) as interventional treatment for patients with ACS, and to compare its 12-month outcomes with the everolimus-eluting bioresorbable scaffolds (Absorb). METHODS: In this retrospective study, patients with ACS (including unstable angina pectoris, ST-segment elevation myocardial infarction, or non-ST-segment elevation myocardial infarction) treated with either the Absorb or the DESolve BRS were evaluated in a 1:1 matched-pair analysis. Major adverse cardiac events (MACE), including death, myocardial infarction, and target lesion revascularization, were evaluated as a major endpoint. The occurrence of scaffold thrombosis was also assessed. RESULTS: A total of 102 patients were eligible for this analysis. The rate of MACE at 12 months was comparable between the Absorb and the DESolve group (8.3% vs. 6.8%, p = 0.738). The occurrence of target lesion revascularization (6.2% vs. 4.7%; p = 0.700) and scaffold thrombosis (4.1% vs. 2.1%; p = 0.580) was comparable as well. All instances of scaffold thrombosis occurred within 30 days of the index procedure. CONCLUSION: In this study, similar 12-month event rates were observed for both BRS types after implantation for the treatment of ACS.


Subject(s)
Acute Coronary Syndrome , Cardiovascular Agents , Coronary Artery Disease , Percutaneous Coronary Intervention , Absorbable Implants , Acute Coronary Syndrome/surgery , Everolimus , Humans , Macrolides , Prosthesis Design , Retrospective Studies , Treatment Outcome
4.
Herz ; 44(2): 161-169, 2019 Apr.
Article in German | MEDLINE | ID: mdl-29052748

ABSTRACT

To evaluate the awareness and knowledge of the German population regarding diseases in general, a survey of 1446 people aged 60 years or older was conducted in 14 German towns. The focus was on heart valve diseases with special emphasis on aortic valve stenosis (AS). While cancer was the disease that respondents were most concerned about (25.2%), only 3.3% were concerned about heart valve diseases. In this respect, the knowledge was broadly limited: only 7.4% of participants claimed to have some familiarity with heart valve diseases and only 12.5% could correctly describe the symptoms of AS. Even so, 35.0% of the participants could correctly name the number of human heart valves, 71.6% knew at least one therapy option for AS and 30.6% were familiar with transcatheter aortic valve implantation (TAVI). After providing a brief clarification of the prevalence, symptoms and course of AS, 45.6% of respondents were more concerned about the condition, 15.7% wanted to know more about the symptoms of AS and 4.7% even recognized the typical symptoms in themselves. Most of the participants would like to seek more information preferably in discussion with a specialist physician (77.2%), with their general practitioner (43.2%) or using the internet (29.7%). Despite its high prevalence, high morbidity and mortality, the vast majority of the German population were neither concerned nor fully aware of treatment options for AS. There is a strong case for public awareness campaigns that provide better knowledge of AS, and support check-ups that enable timely treatment and the avoidance of unnecessary hospitalization and death.


Subject(s)
Aortic Valve Stenosis , Health Knowledge, Attitudes, Practice , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Transcatheter Aortic Valve Replacement , Aortic Valve , Cardiac Catheterization , Germany , Humans , Middle Aged , Treatment Outcome
5.
Eur Radiol ; 29(3): 1565-1573, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30159622

ABSTRACT

OBJECTIVES: The aim of this study was to assess native T1 mapping in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) before and 6 months after balloon pulmonary angioplasty (BPA) and compare the results with right heart function and pulmonary haemodynamics. METHODS: Magnetic resonance imaging at 1.5 T and right heart catheterisation were performed in 21 consecutive inoperable CTEPH patients before and 6 months after BPA. T1 values were measured within the septal myocardium, the upper and lower right ventricular insertion points, and the lateral wall at the basal short-axis section. In addition, the area-adjusted septal native T1 time (AA-T1) was calculated and compared with right ventricular function (RVEF), mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR). RESULTS: The mean AA-T1 value decreased significantly after BPA (1,045.8 ± 44.3 ms to 1,012.5 ± 50.4 ms; p < 0.001). Before BPA, native T1 values showed a moderate negative correlation with RVEF (r = -0.61; p = 0.0036) and moderate positive correlations with mPAP (r = 0.59; p < 0.01) and PVR (r = 0.53; p < 0.05); after BPA correlation trends were present (r = -0.21, r = 0.30 and r = 0.35, respectively). CONCLUSIONS: Native T1 values in patients with inoperable CTEPH were significantly lower after BPA and showed significant correlations with RVEF and pulmonary haemodynamics before BPA. Native T1 mapping seems to be indicative of reverse myocardial tissue remodelling after BPA and might therefore have good potential for pre-procedural patient selection, non-invasive therapy monitoring and establishing a prognosis. KEY POINTS: • BPA is a promising treatment option for patients with inoperable CTEPH • Native septal T1 values significantly decrease after BPA and show good correlations with right ventricular function and haemodynamics before BPA • Prognosis and non-invasive therapy monitoring might be supported in the future by native T1 mapping.


Subject(s)
Angioplasty, Balloon , Hemodynamics , Hypertension, Pulmonary/diagnostic imaging , Hypertension, Pulmonary/therapy , Magnetic Resonance Imaging , Ventricular Function, Right , Aged , Cardiac Catheterization , Chronic Disease , Female , Heart/diagnostic imaging , Heart/physiopathology , Heart Ventricles/diagnostic imaging , Heart Ventricles/physiopathology , Humans , Hypertension, Pulmonary/complications , Hypertension, Pulmonary/physiopathology , Male , Middle Aged , Pulmonary Embolism/complications , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/physiopathology
6.
Internist (Berl) ; 59(9): 981-992, 2018 09.
Article in German | MEDLINE | ID: mdl-29978350

ABSTRACT

BACKGROUND: Approximately 40-50% of patients with cryptogenic stroke have a patent foramen ovale (PFO). A concomitant atrial septal aneurysm aggravates the risk of recurrent stroke. OBJECTIVE: The most important changes regarding the evidence for interventional closure of a PFO in patients with cryptogenic stroke are described. This includes the prerequisites for making a diagnosis and the indications for interventional treatment. The article also provides an overview about platelet aggregation inhibitor treatment with and without oral anticoagulation. CURRENT DATA: The balance between benefits and risks of interventional versus pharmaceutical treatment in patients with cryptogenic stroke and PFO has so far not been sufficiently proven. In 2017 two prospective randomized trials (CLOSE and REDUCE) and the long-term follow-up results of the RESPECT study were published, followed by the results of the DEFENSE-PFO study in 2018. A better assessment of the weighing up of the treatment options can now be made. All four studies showed that the interventional treatment of PFO is superior to pharmaceutical treatment alone for patients with cryptogenic stroke under 60 years of age. CONCLUSION: There was a significant reduction in the incidence of recurrent stroke in patients with interventional PFO closure compared with pharmaceutical treatment. The complication rate of PFO closure is very low and younger patients (<60 years) in particular benefit from PFO closure.


Subject(s)
Foramen Ovale, Patent , Septal Occluder Device , Stroke , Foramen Ovale, Patent/drug therapy , Foramen Ovale, Patent/surgery , Humans , Middle Aged , Prospective Studies , Randomized Controlled Trials as Topic , Recurrence , Stroke/prevention & control , Treatment Outcome
7.
Int J Cardiol ; 265: 40-46, 2018 Aug 15.
Article in English | MEDLINE | ID: mdl-29885699

ABSTRACT

BACKGROUND: N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) levels correlate with higher peri-procedural mortality after transcatheter aortic valve replacement (TAVR). The long-term prognostic value of NT-proBNP within the first days after TAVR, however, remains unclear. This study examined early changes in NT-proBNP prior to and within 6 days after TAVR, the diagnostic value of this biomarker regarding aortic regurgitation (AR), and its prognostic value regarding one-year mortality. METHODS AND RESULTS: NT-proBNP concentrations were measured in 504 consecutive patients undergoing transapical (TA) or transfemoral (TF) TAVR before and directly after TAVR as well as 4 h and 1, 2, 3, and 6 days after TAVR. The follow-up period was 1 year. NT-proBNP was elevated in all patients at baseline (median 2141 ng/L [IQR 1021-5319 ng/L]). NT-proBNP changes in the first 6 days after TAVR showed significant differences depending on the approach, with a greater and more prolonged rise evident in TA-TAVR patients. NT-proBNP was an independent predictor of mortality in TA patients with AR, with an AUC of 0.794 (95% CI 0.663-0.925; P = 0.003) when measured on day 3 after TAVR. For TF patients with AR and reduced left ventricular systolic function, the AUC for prediction of mortality was 0.897 (95% CI 0.778-1.0; P = 0.004) on day 2. CONCLUSIONS: The prognostic information of early post-procedural NT-proBNP concentrations is superior to pre-procedural values regarding all-cause mortality within 1 year. Post-procedural NT-proBNP must be interpreted in relation to the TAVR approach. NT-proBNP predicts mortality in TF-TAVR patients with AR and reduced left ventricular function.


Subject(s)
Aortic Valve Insufficiency/blood , Aortic Valve Insufficiency/mortality , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Transcatheter Aortic Valve Replacement/mortality , Ventricular Dysfunction, Left/blood , Ventricular Dysfunction, Left/mortality , Aged , Aged, 80 and over , Aortic Valve Insufficiency/surgery , Biomarkers/blood , Female , Follow-Up Studies , Humans , Male , Mortality/trends , Prospective Studies , Time Factors , Transcatheter Aortic Valve Replacement/trends , Ventricular Dysfunction, Left/surgery
8.
Herz ; 42(2): 211-228, 2017 Apr.
Article in German | MEDLINE | ID: mdl-28233037

ABSTRACT

Acute coronary syndrome without persistent ST-segment elevation (non-ST segment elevation myocardial infarction and instable angina pectoris NSTEMI-ACS) is common and is associated with a high mortality. In addition to 12-channel echocardiograph (ECG) assessment, measurement of cardiac troponins I and T are important for risk stratification and diagnosis. The introduction of high-sensitivity cardiac troponin assays and their implementation into clinical practice has influenced risk stratification and treatment of these patients. Additional diagnostic validation must supplement routine clinical chemistry testing following the initial measurement to distinguish between different possible causes of troponin elevation above the 99th percentile. The time point for the additional troponin measurement depends on the different protocols and troponin assays and is stipulated in the current guidelines. The use of both 1­hour and 3­hour protocols together with the clinical presentation and work-up of possible differential diagnoses provide optimal care of patients. Patients who test positive for troponin dynamics should undergo invasive diagnostics and treatment within 24 h of presentation and within 2 h is recommended for unstable patients. Clopidogrel is indicated only in patients requiring oral anticoagulation.


Subject(s)
Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/therapy , Critical Care/methods , Myocardial Revascularization/methods , Troponin I/blood , Troponin T/blood , Acute Coronary Syndrome/blood , Biomarkers/blood , Diagnosis, Differential , Evidence-Based Medicine , Humans , ST Elevation Myocardial Infarction/blood , ST Elevation Myocardial Infarction/complications , ST Elevation Myocardial Infarction/diagnosis , Treatment Outcome
9.
Herz ; 42(3): 316-324, 2017 May.
Article in English | MEDLINE | ID: mdl-27491767

ABSTRACT

This analysis of the data of the obligatory quality assurance programme AQUA shows the perioperative risk as well as the procedural outcome evaluated by the observed versus expected in-hospital mortality ratio (O/E ratio) of 62,872 patients undergoing isolated surgical (sAVR), transcatheter transvascular (TV-), or transapical (TA-) aortic valve replacement (TAVI) from 2012 to 2014 in Germany. The number of TAVI procedures increased from 9,352 in 2012 to 13,278 in 2014, whereas the number of sAVR remained constant (2012: 9,949; 2014: 9,953). Between 2012 and 2014, the number of TAVI implanted in patients with a logistic EuroScore I (logESI) of ≤10 % (2012: 21 %; 2014: 26 %) as well as with a logESI <20 % (2012: 57 %; 2014: 64 %) increased. In-hospital mortality in TAVI patients decreased from 5.2 % (TV: 5.0 %; TA: 7.4 %) in 2012 to 4.2 % (TV: 3.8 %; TA: 5.5 %) in 2014, whereas it was stable for sAVR patients (2012: 2.8 %; 2014: 2.6 %). The O/E ratio of TAVI patients decreased from 0.91 (TV: 0.79; TA: 1.2) to 0.73 (TV: 0.69; TA: 0.89), whereas this ratio remained constant for sAVR patients (2012: 0.92; 2014: 0.93). In summary, estimated surgical risk, in-hospital mortality, as well as the O/E ratio for patients undergoing TAVI declined constantly during the last 3 years.


Subject(s)
Aortic Valve Stenosis/mortality , Aortic Valve Stenosis/surgery , Cardiac Valve Annuloplasty/mortality , Cardiac Valve Annuloplasty/statistics & numerical data , Hospital Mortality/trends , Transcatheter Aortic Valve Replacement/mortality , Transcatheter Aortic Valve Replacement/statistics & numerical data , Adult , Aged , Aged, 80 and over , Cardiac Valve Annuloplasty/trends , Female , Germany/epidemiology , Heart Valve Prosthesis/statistics & numerical data , Humans , Male , Middle Aged , Practice Patterns, Physicians'/statistics & numerical data , Practice Patterns, Physicians'/trends , Prevalence , Survival Rate , Transcatheter Aortic Valve Replacement/trends , Treatment Outcome
10.
Anaesthesist ; 65(8): 635-52, 2016 Aug.
Article in German | MEDLINE | ID: mdl-27492004

ABSTRACT

Pulmonary hypertension (PH) comprises a group of pulmonary vascular diseases that are characterized by progressive exertional dyspnea and right heart insufficiency ultimately resulting in right heart decompensation. The classification is into five clinical subgroups that form the absolutely essential basis for decisions on the indications for different pharmacological and non-pharmacological forms of treatment. The guidelines were updated in 2015 and in addition to the hitherto existing pharmacological treatment options of phosphodiesterase type 5 inhibitors, endothelin receptor antagonists and prostacyclins, the soluble guanylate cyclase stimulator riociguat has now been incorporated for treatment of certain forms of PH. This article provides an overview of the new treatment recommendations in the current guidelines, e. g. for PH patients who are in intensive care units due to surgical interventions or progressive right heart insufficiency.


Subject(s)
Hypertension, Pulmonary/therapy , Enzyme Inhibitors/therapeutic use , Humans , Hypertension, Pulmonary/drug therapy , Phosphodiesterase 5 Inhibitors/therapeutic use , Prostaglandins I/therapeutic use , Receptors, Endothelin/drug effects , Soluble Guanylyl Cyclase/antagonists & inhibitors
12.
Curr Cardiol Rev ; 9(4): 274-80, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24313644

ABSTRACT

During the past years transcatheter aortic valve implantation (TAVI) has evolved to a standard technique for the treatment of high risk patients suffering from severe aortic stenosis. Worldwide the number of TAVI procedures is increasing exponentially. In this context both the transapical antegrade (TA) and the transfemoral retrograde (TF) approach are predominantly used and can be considered as safe and reproducible access sites for TAVI interventions. As a new technology TAVI is in a constant progress regarding the development of new devices. While in the first years only the Edwards SAPIEN(TM) and the Medtronic CoreValve(TM) prostheses were commercial available, recently additional devices obtained CE-mark approval and others have entered initial clinical trials. In addition to enhance the treatment options in general, the main driving factor to further develop new device iterations is to solve the drawbacks of the current TAVI systems: paravalvular leaks, occurrence of AV-blocks and the lack of full repositionability.


Subject(s)
Aortic Valve/surgery , Cardiac Catheterization/methods , Heart Valve Prosthesis Implantation/methods , Heart Valve Prosthesis , Prosthesis Design , Aortic Valve Stenosis/etiology , Aortic Valve Stenosis/surgery , Aortic Valve Stenosis/therapy , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis Implantation/trends , Humans , Treatment Outcome
13.
Herz ; 38(5): 513-26; quiz 527-8, 2013 Aug.
Article in German | MEDLINE | ID: mdl-23897600

ABSTRACT

Coronary artery disease (CAD) is a leading cause of morbidity and mortality in western countries and is of significant socio-economic importance due to its increasing prevalence. Until percutaneous coronary interventions (PCI) were established, CAD could only be treated by surgical revascularization or pharmacological therapy. In-stent restenosis remains a major problem after stent implantation. However, the use of new materials and stent coatings have led to a significant reduction in in-stent restenosis. Thus, surgical revascularization and PCI are currently of equal value for the treatment of CAD. The decision-making for PCI or surgical revascularization depends on various factors such as number of diseased vessels, complexity of the coronary stenoses, concomitant diseases, and the patient's general condition. The therapeutic regime of every patient should be adjusted to the recommendations of the European and German Society for Cardiology, while controversial and complex cases should be discussed in an interdisciplinary case conference ("heart team").


Subject(s)
Blood Vessel Prosthesis/adverse effects , Coronary Artery Disease/surgery , Graft Occlusion, Vascular/etiology , Graft Occlusion, Vascular/prevention & control , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/methods , Stents/adverse effects , Coronary Artery Disease/complications , Humans , Treatment Outcome
15.
Internist (Berl) ; 54(1): 28-34, 36-8, 2013 Jan.
Article in German | MEDLINE | ID: mdl-23263747

ABSTRACT

Due to increasing life expectancy in the coming decades the number of elderly patients with aortic valve stenosis (AS) and various concomitant diseases will increase. Conventional surgical aortic valve replacement represents the treatment of choice in patients with severe and symptomatic AS. Transfemoral and transapical aortic valve implantation (T-AVI) has evolved as a standard procedure for patients with severe AS who are technically inoperable or at very high risk for surgical valve replacement. The T-AVI approach has been shown to be superior to the standard medical treatment in these high-risk patients. All patients to be considered for T-AVI should be discussed in a consensus conference consisting of cardiac surgeons and cardiologists (heart team).


Subject(s)
Aortic Valve Stenosis/diagnosis , Aortic Valve Stenosis/surgery , Aortic Valve/surgery , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis Implantation/methods , Heart Valve Prosthesis , Humans , Prosthesis Design
16.
Internist (Berl) ; 53(9): 1063-75; quiz 1076-8, 2012 Sep.
Article in German | MEDLINE | ID: mdl-22836917

ABSTRACT

Coronary artery disease (CAD) is a leading cause of morbidity and mortality in western countries and is of significant socio-economic importance due to its increasing prevalence. Until percutaneous coronary interventions (PCI) were established, CAD could only be treated by surgical revascularization or pharmacological therapy. In-stent restenosis remains a major problem after stent implantation. However, the use of new materials and stent coatings have led to a significant reduction in in-stent restenosis. Thus, surgical revascularization and PCI are currently of equal value for the treatment of CAD. The decision-making for PCI or surgical revascularization depends on various factors such as number of diseased vessels, complexity of the coronary stenoses, concomitant diseases, and the patient's general condition. The therapeutic regime of every patient should be adjusted to the recommendations of the European and German Society for Cardiology, while controversial and complex cases should be discussed in an interdisciplinary case conference ("heart team").


Subject(s)
Coronary Artery Disease/complications , Coronary Artery Disease/surgery , Myocardial Revascularization/adverse effects , Myocardial Revascularization/methods , Humans , Treatment Outcome
18.
J Int Med Res ; 39(6): 2169-77, 2011.
Article in English | MEDLINE | ID: mdl-22289532

ABSTRACT

Little is known about the impact of early invasive treatment in patients following out-of-hospital cardiac arrest (OHCA). The present study investigated the clinical characteristics and long-term prognosis of 1254 patients with suspected acute coronary syndrome, including 65 with OHCA who underwent successful cardiopulmonary resuscitation (CPR) and 1189 patients who did not require CRP. All patients underwent immediate coronary angiography even if clear signs of myocardial infarction (MI) were absent. The incidence of ST-elevation and non-ST-elevation MI did not differ between the two groups. Cardiac biomarkers were significantly higher in CPR patients despite a shorter period from symptom onset to admission. The 6-month mortality rate was 29% in the CPR group and 4% in the non-CPR group, with > 90% of fatalities occurring ≤ 3 weeks after admission. In summary, early invasive treatment leads to a considerably reduced mortality and improved prognosis in patients after OHCA.


Subject(s)
Out-of-Hospital Cardiac Arrest/therapy , Acute Coronary Syndrome/physiopathology , Acute Coronary Syndrome/therapy , Aged , Biomarkers/metabolism , Blood Pressure/physiology , Cardiopulmonary Resuscitation , Female , Germany/epidemiology , Heart Rate/physiology , Hospitalization , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Out-of-Hospital Cardiac Arrest/diagnosis , Out-of-Hospital Cardiac Arrest/mortality , Out-of-Hospital Cardiac Arrest/physiopathology , Risk Assessment , Stroke Volume/physiology , Treatment Outcome
19.
Pflugers Arch ; 434(5): 534-42, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9242716

ABSTRACT

In smooth muscle, the state of prolonged contraction (latch state) is associated with very slow energy turnover and cycling of crossbridges that are dephosphorylated. A similar state may be reproduced in skinned fibres when the calcium-induced contraction is terminated by calcium removal with ethylenebis(oxonitrilo)tetraacetate (EGTA) and, during the slow relaxation that follows, force is maintained by dephosphorylated crossbridges that cycle slowly or not at all and may cooperatively reattach after detachment (Khromov et al. 1995, Biophys J 69:2611-2622). In guinea-pig skinned taenia coli that has been pretreated by prolonged incubation with caldesmon (5 microM), the rate of relaxation is approximately 1.6 times greater than in untreated controls, with half-times of relaxation being 1.3 and 2.1 min, respectively. In contrast, preloading the fibres with calponin does not accelerate relaxation. Preloading the fibres with caldesmon also accelerates the relaxation of skinned fibres from the state of rigor contraction when the latter is terminated by immersion into an ATP-containing relaxing solution or, in the presence of inorganic phosphate (Pi), also by flash-photolytic release of ATP from caged-ATP. Even in the latter case, relaxation is comparatively slow, possibly because of cooperative reattachment of dephosphorylated crossbridges which delays net crossbridge detachment and hence relaxation. We propose that by inhibition of cooperative reattachment caldesmon accelerates relaxation, even in the presence of Pi, and that the latch-like state of skinned fibres is supported by dephosphorylated cooperatively attaching crossbridges and may be regulated by the activity of caldesmon in the smooth muscle cell.


Subject(s)
Calmodulin-Binding Proteins/pharmacology , Colon/drug effects , Muscle Relaxation , Muscle, Smooth/drug effects , Adenosine Triphosphate/analogs & derivatives , Adenosine Triphosphate/pharmacology , Animals , Calcium/pharmacology , Calcium-Binding Proteins/pharmacology , Colon/physiology , Guinea Pigs , Histological Techniques , Microfilament Proteins , Muscle Contraction/drug effects , Muscle Fibers, Skeletal/drug effects , Muscle, Smooth/physiology , Myofibrils/metabolism , Octoxynol/pharmacology , Phosphorylation , Photic Stimulation , Photolysis , Rabbits , Calponins
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