Heart failure is one of the fastest-growing epidemics worldwide in health care today. Although a wide variety of animal models exist to create chronic heart failure, there are few truly successful, reproducible models with ischemic dilation and mitral regurgitation. Six healthy sheep (36 ± 5 kg) underwent multiple, strategic coronary artery ligations on the left ventricle (LV). Six to eight ligations were performed transmurally on three of four segments of the LV: anterior, lateral, and posterior. Side branches of the left anterior descending and circumflex arteries were ligated to create multiple, patchy areas of myocardial infarction. Cardiac global and regional systolic function was assessed by echocardiography and cardiac magnetic resonance imaging (MRI). The extent, the characteristics, and the location of the myocardial infarction were qualitatively and quantitatively assessed by late gadolinium enhancement imaging. The overall mortality rate was 16.7% (1/6 animals). Animals who survived showed a significantly reduced ejection fraction (mean 60 ± 5% to 28 ± 7%; P < 0.05); additionally, two out of the remaining five (40%) animals developed mild to moderate mitral regurgitation quantified by cardiac MRI. Furthermore, each animal developed clinical signs of heart failure (tachycardia, dyspnea, and tachypnea) consistent with global, dilated cardiomyopathy noted on MRI. Creating and reproducing a model of global, ischemic cardiomyopathy with functional mitral regurgitation is an arduous task. We have developed a promising model of ischemic heart failure using multiple ligations, which mimics the sequelae of human cardiomyopathy. Our proposed model is highly effective, reproducible, and may be used for experimental research on heart failure (cardiac assist devices, heart transplant, etc.).
Coronary ligation; Chronic heart failure; Animal model; Sheep
Clinical data relating to rabbit antithymocyte globulin (rATG) induction in heart transplantation are far less extensive than for other immunosuppressants, or indeed for rATG in other indications. This was highlighted by the low grade of evidence and the lack of detailed recommendations for prescribing rATG in the International Society for Heart and Lung Transplantation (ISHLT) guidelines. The heart transplant population includes an increasing frequency of patients on mechanical circulatory support (MCS), often with ongoing infection and/or presensitization, who are at high immunological risk but also vulnerable to infectious complications. The number of patients with renal impairment is also growing due to lengthening waiting times, intensifying the need for strategies that minimize calcineurin inhibitor (CNI) toxicity. Additionally, the importance of donor-specific antibodies (DSA) in predicting graft failure is influencing immunosuppressive regimens. In light of these developments, and in view of the lack of evidence-based prescribing criteria, experts from Germany, Austria, and Switzerland convened to identify indications for rATG induction in heart transplantation and to develop an algorithm for its use based on patient characteristics.
antithymocyte globulin; heart transplantation; rabbit antithymocyte globulin; Thymoglobulin
Left ventricular assist devices are increasingly important in the management of advanced heart failure. Most patients who benefit from these devices have had some prior cardiac surgery, making implantation of higher risk. This is especially true in patients who have had prior pectoralis flap reconstruction after sternectomy for mediastinitis. We outline the course of such a patient, in whom the use of robotic assistance allowed for a less invasive device implantation approach with preservation of the flap for transplantation.
Robotics; Heart Failure; Device; Minimally Invasive Surgery
Atrial fibrillation (AF) is the most common supraventricular arrhythmia and a major cause of morbidity. Arrhythmogenic foci originating within the pulmonary veins (PVs) are an important cause of both paroxysmal and persistent AF. A variety of endovascular and surgical techniques have been used to electrically isolate the PV from the left atrium. Pulmonary venography for localization of the PV ostium can be difficult to perform during the ablation procedure. While the anatomy of the PV is patient-specific, non-invasive imaging techniques may provide useful diagnostic information prior to the intended intervention. In this context, multidetector computed tomography (MDCT) visualization of the left atrial and PV anatomy prior to left atrial ablation and PV isolation is becoming increasingly important. MDCT imaging provides pre-procedural information on the left atrial anatomy, including atrial size and venous attachments, and it may identify potential post-procedural complications, such as pulmonary vein stenosis or cardiac perforations. Here, we review the relevant literature and present the current “state-of-the-art” of left atrial anatomy, PV ostia as well as the clinical aspects of refractory AF, MDCT imaging protocols and procedural aspects of PV ablation.
Atrial fibrillation; Multidetector computed tomography; Pulmonary veins; Pulmonary vein ablation
Pronounced extracellular acidosis reduces both cardiac contractility and the β-adrenergic response. In the past, this was shown in some studies using animal models. However, few data exist regarding how the human end-stage failing myocardium, in which compensatory mechanisms are exhausted, reacts to acute mild metabolic acidosis. The aim of this study was to investigate the effect of mild metabolic acidosis on contractility and the β-adrenergic response of isolated trabeculae from human end-stage failing hearts.
Intact isometrically twitching trabeculae isolated from patients with end-stage heart failure were exposed to mild metabolic acidosis (pH 7.20). Trabeculae were stimulated at increasing frequencies and finally exposed to increasing concentrations of isoproterenol (0 to 1 × 10-6 M).
A mild metabolic acidosis caused a depression in twitch-force amplitude of 26% (12.1 ± 1.9 to 9.0 ± 1.5 mN/mm2; n = 12; P < 0.01) as compared with pH 7.40. Force-frequency relation measurements yielded no further significant differences of twitch force. At the maximal isoproterenol concentration, the force amplitude was comparable in each of the two groups (pH 7.40 versus pH 7.20). However, the half-maximal effective concentration (EC50) was significantly increased in the acidosis group, with an EC50 of 5.834 × 10-8 M (confidence interval (CI), 3.48 × 10-8 to 9.779 × 10-8; n = 9), compared with the control group, which had an EC50 of 1.056 × 10-8 M (CI, 2.626 × 10-9 to 4.243 × 10-8; n = 10; P < 0.05), indicating an impaired β-adrenergic force response.
Our data show that mild metabolic acidosis reduces cardiac contractility and significantly impairs the β-adrenergic force response in human failing myocardium. Thus, our results could contribute to the still-controversial discussion about the therapy regimen of acidosis in patients with critical heart failure.
Chest compressions have saved the lives of countless patients in cardiac arrest as they generate a small but critical amount of blood flow to the heart and brain. This is achieved by direct cardiac massage as well as a thoracic pump mechanism. In order to optimize blood flow excellent chest compression technique is critical. Thus, the quality of the delivered chest compressions is a pivotal determinant of successful resuscitation. If a patient is found unresponsive without a definite pulse or normal breathing then the responder should assume that this patient is in cardiac arrest, activate the emergency response system and immediately start chest compressions. Contra-indications to starting chest compressions include a valid Do Not Attempt Resuscitation Order. Optimal technique for adult chest compressions includes positioning the patient supine, and pushing hard and fast over the center of the chest with the outstretched arms perpendicular to the patient's chest. The rate should be at least 100 compressions per minute and any interruptions should be minimized to achieve a minimum of 60 actually delivered compressions per minute. Aggressive rotation of compressors prevents decline of chest compression quality due to fatigue. Chest compressions are terminated following return of spontaneous circulation. Unconscious patients with normal breathing are placed in the recovery position. If there is no return of spontaneous circulation, then the decision to terminate chest compressions is based on the clinical judgment that the patient's cardiac arrest is unresponsive to treatment. Finally, it is important that family and patients' loved ones who witness chest compressions be treated with consideration and sensitivity.
Adenosine monophosphate – activated kinase (AMPK) plays a key role in the coordination of the heart’s anabolic and catabolic pathways. It induces a cellular cascade at the center of maintaining energy homeostasis in the cardiomyocytes.. The activated AMPK is a heterotrimeric protein, separated into a catalytic α - subunit (63kDa), a regulating β - subunit (38kDa) and a γ - subunit (38kDa), which is allosterically adjusted by adenosine triphosphate (ATP) and adenosine monophosphate (AMP). The actual binding of AMP to the γ – subunit is the step which activates AMPK.
AMPK serves also as a protein kinase in several metabolic pathways of the heart, including cellular energy sensoring or cardiovascular protection. The AMPK cascade represents a sensitive system, activated by cellular stresses that deplete ATP and acts as an indicator of intracellular ATP/AMP. In the context of cellular stressors (i.e. hypoxia, pressure overload, hypertrophy or ATP deficiency) the increasing levels of AMP promote allosteric activation and phosphorylation of AMPK. As the concentration of AMP begins to increase, ATP competitively inhibits further phosphorylation of AMPK. The increase of AMP may also be induced either from an iatrogenic emboli, percutaneous coronary intervention, or from atherosclerotic plaque rupture leading to an ischemia in the microcirculation. To modulate energy metabolism by phosphorylation and dephosphorylation is vital in terms of ATP usage, maintaining transmembrane transporters and preserving membrane potential.
In this article, we review AMPK and its role as an important regulatory enzyme during periods of myocardial stress, regulating energy metabolism, protein synthesis and cardiovascular protection.
Adenosine monophosphate - activated protein kinase; AMPK; heart failure; cardiac energy metabolism.
Increasing number of scientists are enthusiastic about using free, open source software for their research purposes. Authors' specific goal was to examine whether a Linux-based operating system with open source software packages would allow to prepare a submission-ready scientific manuscript without the need to use the proprietary software.
Preparation and editing of scientific manuscripts is possible using Linux and open source software. This letter to the editor describes key steps for preparation of a publication-ready scientific manuscript in a Linux-based operating system, as well as discusses the necessary software components. This manuscript was created using Linux and open source programs for Linux.
Linux; operating system; manuscript; scientific software
The reported incidence of deep sternal wound infection (DSWI) after cardiac surgery is 0.4-5% with Staphylococcus aureus being the most common pathogen isolated from infected wound sternotomies and bacteraemic blood cultures. This infection is associated with a higher morbidity and mortality than other known aetiologies. Little is reported about the optimal antibiotic management. The aim of the study is to quantify the application of daptomycin treatment of DSWI due to gram-positive organisms post cardiac surgery.
We performed an observational analysis in 23 cases of post sternotomy DSWI with gram-positive organisms February 2009 and September 2010. When the wound appeared viable and the microbiological cultures were negative, the technique of chest closure was individualised to the patient.
The incidence of DSWI was 1.46%. The mean dose of daptomycin application was 4.4 ± 0.9 mg/kg/d and the average duration of the daptomycin application was 14.47 ± 7.33 days. In 89% of the patients VAC therapy was used. The duration from daptomycin application to sternal closure was 18 ± 13.9 days. The parameters of infection including, fibrinogen (p = 0.03), white blood cell count (p = 0.001) and C-reactive protein (p = 0.0001) were significantly reduced after daptomycin application. We had no mortality and wound healing was successfully achieved in all patients.
Treatment of DSWI due to gram-positive organisms with a daptomycin-containing antibiotic regimen is safe, effective and promotes immediate improvement of local wound conditions.
Based on these observations, daptomycin may offer a new treatment option for expediting surgical management of DSWI after cardiac surgery.
Cardiac surgery; Sternal infection; Antibiotic therapy; Daptomycin
We present a case of sternal steel strut dislodgement and migration in a patient undergoing Ravitch repair for pectus excavatum (PE) 37 years ago. Broken struts perforated the right ventricle and right ventricular outflow tract (RVOT) and additionally migrated into the left upper lobar bronchus.
Dislodged sternal struts represent rare complications after surgical repair of patients suffering from pectus excavatum. Reviewing the literature, only five cases of intrapericardial migration of dislodged sternal struts or wires have been reported so far.
In our case, the first strut was removed from the airways through a left antero-lateral thoracotomy. Using cardiopulmonary bypass, a second strut was removed via ventriculotomy. These life-threatening sequelae underscore the importance of postoperative follow-up and early removal of osteosynthetic materials used in open PE repair. Accurate preoperative localization of migrated materials and availability of CPB support are crucial for successful surgical removal.
The migration of dislodged sternal steel struts or wires into the pericardium and cardiac cavities is a rare but life-threatening complication of open pectus excavatum (PE) repair . Removal of these materials poses a challenge for cardiothoracic surgeons. Herein, the authors report a case of migration of dislodged steel struts through the right ventricle and right ventricular outflow tract (RVOT) into the left upper lobar bronchus in a patient who underwent Ravitch repair 37 years ago.
Traumatic pericardial rupture is a rare presentation. Pericardial rupture itself is asymptomatic unless complicated by either hemorrhage or herniation of the heart through the defect. Following diagnosis surgical repair of the pericardium is indicated because cardiac herniation may result in vascular collapse and sudden death.
Here we present a case of traumatic, non-herniated pericardial rupture with complete skeletonization of the phrenic nerve.
An 18-year-old healthy male suffered multi-trauma after falling 50 feet onto concrete. The patient could not be stabilized despite exploratory laparotomy with splenectomy, IR embolization and packing for a liver laceration. Right posterolateral thoracotomy revealed a ruptured pericardium with a completely skeletonized phrenic nerve. The pericardium was repaired with a Goretex(R) patch.
A high level of suspicion for pericardial rupture is necessary in all patients with high-velocity thoracic injuries.
Training of cardiothoracic surgeons in Europe and the United States has expanded to incorporate new operative techniques and requirements. The purpose of this study was to compare the current structure of training programs in the United States and Germany.
We thoroughly reviewed the existing literature with particular focus on the curriculum, salary, board certification and quality of life for cardiothoracic trainees.
The United States of America and the Federal Republic of Germany each have different cardiothoracic surgery training programs with specific strengths and weaknesses which are compared and presented in this publication.
The future of cardiothoracic surgery training will become affected by technological, demographic, economic and supply factors. Given current trends in training programs, creating an efficient training system would allow trainees to compete and grow in this constantly changing environment.
Low cardiac output (LCO) after corrective surgery remains a serious complication in pediatric congenital heart diseases (CHD). In the case of refractory LCO, extra corporeal life support (ECLS) extra corporeal membrane oxygenation (ECMO) or ventricle assist devices (VAD) is the final therapeutic option. In the present study we have reviewed the outcomes of pediatric patients after corrective surgery necessitating ECLS and compared outcomes with pediatric patients necessitating ECLS because of dilatated cardiomyopathy (DCM).
A retrospective single-centre cohort study was evaluated in pediatric patients, between 1991 and 2008, that required ECLS. A total of 48 patients received ECLS, of which 23 were male and 25 female. The indications for ECLS included CHD in 32 patients and DCM in 16 patients.
The mean age was 1.2 ± 3.9 years for CHD patients and 10.4 ± 5.8 years for DCM patients. Twenty-six patients received ECMO and 22 patients received VAD. A total of 15 patients out of 48 survived, 8 were discharged after myocardial recovery and 7 were discharged after successful heart transplantation. The overall mortality in patients with extracorporeal life support was 68%.
Although the use of ECLS shows a significantly high mortality rate it remains the ultimate chance for children. For better results, ECLS should be initiated in the operating room or shortly thereafter. Bridge to heart transplantation should be considered if there is no improvement in cardiac function to avoid irreversible multiorgan failure (MFO).
Hemodynamic function may be depressed in the early postoperative stages after cardiac surgery. The aim of this study was the analysis of the myocardial contractility in neonates after cardiopulmonary bypass (CPB) and mild hypothermia.
Three indices of left ventricular myocardial contractile function (dP/dt, (dP/dt)/P, and wall thickening) were studied up to 6 hours after CPB in neonatal piglets (CPB group; n = 4). The contractility data were analysed and then compared to the data of newborn piglets who also underwent median thoracotomy and instrumentation for the same time intervals but without CPB (non-CPB group; n = 3).
Left ventricular dP/dtmax and (dP/dtmax)/P remained stable in CPB group, while dP/dtmax decreased in non-CPB group 5 hours postoperatively (1761 ± 205 mmHg/s at baseline vs. 1170 ± 205 mmHg/s after 5 h; p < 0.05). However, with regard to dP/dtmax and (dP/dtmax)/P there were no statistically significant differences between the two groups. Comparably, although myocardial thickening decreased in the non-CPB group the differences between the two groups were not statistically significant.
The myocardial contractile function in survived neonatal piglets remained stable 6 hours after cardiopulmonary bypass and mild hypothermia probably due to regional hypercontractility.
We present a case of a 77-year old female who had undergone a coronary artery bypass grafting with an aortic valve replacement and developed three month later a Methicillin-Resistant Staphylococcus aureus (MRSA) sternal wound infection which was successful treated with Daptomycin combined with vacuum-assisted closure (VAC).
The aim of this study was to investigate the prevalence of extracardiac findings diagnosed by 64-multidetector computed tomography (MDCT) examinations prior to circumferential pulmonary vein (PV) ablation of atrial fibrillation (AF). A total of 158 patients (median age, 60.5 years; male 68%) underwent 64-MDCT of the chest and upper abdomen to characterize left atrial and PV anatomy prior to AF ablation. MDCT images were evaluated by a thoracic radiologist and a cardiologist. For additional scan interpretation, bone, lung, and soft tissue window settings were used. CT scans with extra-cardiac abnormalities categorized for the anatomic distribution and divided into two groups: Group 1—exhibiting clinically significant or potentially significant findings, and Group 2—patients with clinically non-significant findings. Extracardiac findings (n = 198) were observed in 113/158 (72%) patients. At least one significant finding was noted in 49/158 patients (31%). Group 1 abnormalities, such as malignancies or pneumonias, were found in 85/198 findings (43%). Group 2 findings, for example mild degenerative spine disease or pleural thickening, were observed in 113/198 findings (72%). 74/198 Extracardiac findings were located in the lung (37%), 35/198 in the mediastinum (18%), 8/198 into the liver (4%) and 81/198 were in other organs (41). There is an appreciable prevalence of prior undiagnosed extracardiac findings detected in patients with AF prior to PV-Isolation by MDCT. Clinically significant or potentially significant findings can be expected in ~40% of patients who undergo cardiac MDCT. Interdisciplinary trained personnel is required to identify and interpret both cardiac and extra cardiac findings.
Extra cardiac findings; Atrial fibrillation; 64-MDCT; Pulmonary vein ablation
We report a case of a male patient who received an implantation of a Starr-Edwards-caged-ball-valve-prosthesis in 1967. The surgery and postoperative course were without complications and the patient recovered well after the operation. For the next four decades, the patient remained asymptomatic - no restrictions on his lifestyle and without any complications. In 2006, 39 years after the initial operation, we performed a Bentall-Procedure to treat an aortic ascendens aneurysm with diameters of 6.0 × 6.5 cm: we explanted the old Starr-Edwards-aortic-caged-ball-valve-prosthesis and replaced the ascending aorta with a 29 mm St.Jude Medical aortic-valve-composite-graft and re-implanted the coronary arteries.
This case represents the longest time period between Starr-Edwards-caged-ball-valve-prothesis-implantation and Bentall-reoperation, thereby confirming the excellent durability of this valve.
A surgical fire is a serious complication not previously described in the literature with regard to the thoracic cavity. We report a case in which an intrathoracic fire developed following an air leak combined with high pressure oxygen ventilation in a patient with severe chronic obstructive pulmonary disease. The patient presented to our institution with diffuse coronary artery disease and angina pectoris. He was treated with coronary artery bypass graft surgery, including left internal thoracic artery harvesting. Additionally to this rare presentation of an intrathoracic fire, a brief review of surgical fires is included to this paper.
Hypertrophic obstructive cardiomyopathy (HOCM) is treated by surgical myectomy or transcoronary ablation of septal hypertrophy (TASH). The aim of this study was to visualize the feasibility, success and short-term results of TASH on the basis of cardiac MRI (CMR) in comparison with cardiac catheterization and echocardiography.
In this in vivo study, nine patients with HOCM were treated with TASH. Patients were evaluated by transthoracic echocardiography, invasive cardiac angiography and CMR. Follow-up examinations were carried out after 1, 3 and 12 months. MR imaging was performed on a 1.5-T scanner. All images were processed using the semiautomatic Argus software and were evaluated by an attending thoracic radiologist and cardiologist.
The echocardiographic pressure gradient (at rest) was 69.3 ± 15.3 mmHg before and 22.1 ± 5.7 mmHg after TASH (P < 0.01, n = 9). The flux acceleration over the aortic valve examined (Vmax) was 5.1 ± 0.6 m/s before and 3.4 ± 0.3 m/s after the TASH procedure (P < 0.05). Also, there was a decrease of septum thickness from 22.0 ± 1.2 to 20.2 ± 1.0 mm (P < 0.05) after 6 ± 3 weeks. The invasively assessed pressure gradient at rest was reduced from 63.7 ± 15.2 to 21.2 ± 11.1 mmHg (P < 0.01) and the post-extrasystolic gradient was reduced from 138.9 ± 12.7 to 45.6 ± 16.5 mmHg (P < 0.01). All differences as well as the quantity of injected ethanol were plotted against the size or amount of scar tissue as assessed in the MRI. There was a statistically significant correlation between the post-extrasystolic gradient decrease and the amount of scar tissue (P = 0.03, r2 = 0.5). In addition, the correlation between the quantity of ethanol and scar tissue area was highly significant (P < 0.01, r2 = 0.6), whereas the values for the gradient deviation (P = 0.10, r2 = 0.34), ΔVmax (P = 0.12, r2 = 0.31), as well as the gradient at rest (P = 0.27, r2 = 0.17) were not significant.
TASH was consistently effective in reducing the gradient in all patients with HOCM. In contrast to the variables investigated by echocardiography, the invasively measured post-extrasystolic gradient correlated much better with the amount of scar tissue as assessed by CMR. We conclude that the optimal modality to visualize the TASH effect seems to be a combination of CMR and the invasive identification of the post-extrasystolic gradient.
HOCM; TASH; CMR; Cardiac imaging
Despite the existence of controversial debates on the efficiency of coronary endarterectomy (CE), it is still used as an adjunct to coronary artery bypass grafting (CABG). This is particularly true in patients with endstage coronary artery disease. Given the improvements in cardiac surgery and postoperative care, as well as the rising number of elderly patient with numerous co-morbidities, re-evaluating the pros and cons of this technique is needed.
Patient demographic information, operative details and outcome data of 104 patients with diffuse calcified coronary artery disease were retrospectively analyzed with respect to functional capacity (NYHA), angina pectoris (CCS) and mortality. Actuarial survival was reported using a Kaplan-Meyer analysis.
Between August 2001 and March 2005, 104 patients underwent coronary artery bypass grafting (CABG) with adjunctive coronary endarterectomy (CE) in the Department of Thoracic-, Cardiac- and Vascular Surgery, University of Goettingen. Four patients were lost during follow-up. Data were gained from 88 male and 12 female patients; mean age was 65.5 ± 9 years. A total of 396 vessels were bypassed (4 ± 0.9 vessels per patient). In 98% left internal thoracic artery (LITA) was used as arterial bypass graft and a total of 114 vessels were endarterectomized. CE was performed on right coronary artery (RCA) (n = 55), on left anterior descending artery (LAD) (n = 52) and circumflex artery (RCX) (n = 7). Ninety-five patients suffered from 3-vessel-disease, 3 from 2-vessel- and 2 from 1-vessel-disease. Closed technique was used in 18%, open technique in 79% and in 3% a combination of both. The most frequent endarterectomized localization was right coronary artery (RCA = 55%). Despite the severity of endstage atherosclerosis, hospital mortality was only 5% (n = 5). During follow-up (24.5 ± 13.4 months), which is 96% complete (4 patients were lost caused by unknown address) 8 patients died (cardiac failure: 3; stroke: 1; cancer: 1; unknown reasons: 3). NYHA-classification significantly improved after CABG with CE from 2.2 ± 0.9 preoperative to 1.7 ± 0.9 postoperative. CCS also changed from 2.4 ± 1.0 to 1.5 ± 0.8
Early results of coronary endarterectomy are acceptable with respect to mortality, NYHA & CCS. This technique offers a valuable surgical option for patients with endstage coronary artery disease in whom complete revascularization otherwise can not be obtained. Careful patient selection will be necessary to assure the long-term benefit of this procedure.
We report an unusual case of a 32-year old man who was treated for a hypertrophic obstructive cardiomyopathy (HOCM) with a DDD pacing with short AV delay reduction in the past. Without prior notice the patient developed ventricular fibrillation and an invasive cardiac diagnostic was performed, which revealed a myocardial bridging around of the left anterior descending artery (LAD). We suspected ischemia that could be either related to LAD artery compression or perfusion abnormalities due to AV delay reduction with related to diastolic dysfunction.
We report a case of successful treatment of postoperative saphenectomy wound infection of the upper left leg with the antibiotic drug Daptomycin.
In heart failure, intracellular Ca2+ leak from cardiac ryanodine receptors (RyR2s) leads to a loss of Ca2+ from the sarcoplasmic reticulum (SR) potentially contributing to decreased function. Experimental data suggest that the 1,4-benzothiazepine K201 (JTV-519) may stabilise RyR2s and thereby reduce detrimental intracellular Ca2+ leak. Whether K201 exerts beneficial effects in human failing myocardium is unknown. Therefore, we have studied the effects of K201 on muscle preparations from failing human hearts. K201 (0.3 μM; extracellular [Ca2+]e 1.25 mM) showed no effects on contractile function and micromolar concentrations resulted in negative inotropic effects (K201 1 μM; developed tension −9.8 ± 2.5% compared to control group; P < 0.05). Interestingly, K201 (0.3 μM) increased the post-rest potentiation (PRP) of failing myocardium after 120 s, indicating an increased SR Ca2+ load. At high [Ca2+]e concentrations (5 mmol/L), K201 increased PRP already at shorter rest intervals (30 s). Strikingly, treatment with K201 (0.3 μM) prevented diastolic dysfunction (diastolic tension at 5 mmol/L [Ca2+]e normalised to 1 mmol/L [Ca2+]e: control 1.26 ± 0.06, K201 1.01 ± 0.03, P < 0.01). In addition at high [Ca2+]e, K201 (0.3 μM) treatment significantly improved systolic function [developed tension +27 ± 8% (K201 vs. control); P < 0.05]. The beneficial effects on diastolic and systolic functions occurred throughout the physiological frequency range of the human heart rate from 1 to 3 Hz. Upon elevated intracellular Ca2+ concentration, systolic and diastolic contractile functions of terminally failing human myocardium are improved by K201.
Electronic supplementary material
The online version of this article (doi:10.1007/s00395-009-0057-8) contains supplementary material, which is available to authorized users.
Human; Heart failure; Contractile performance; Sarcoplasmic reticulum; Ryanodine receptor; K201