With interest, I read the paper about histidine-tryptophan-ketoglutarate (HTK) solution for heart transplantation, and I congratulate Mokbel and colleagues1Mokbel M. Zamani H. Lei I. et al.Histidine-tryptophan-ketoglutarate solution for donor heart preservation is safe for transplantation.Ann Thorac Surg. 2020; 109: 763-770Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar for this study demonstrating noninferiority of this solution. Allow me the following comments: Organ protective solutions are categorized as (1) blood-containing solutions or (2) crystalloid solutions. The latter is subdivided into “extracellular” and “intracellular” solutions. This difference is solely determined by their Na content.2Preusse C.J. Custodiol cardioplegia: a single-dose hyperpolarizing solution.J Extra Corpor Technol. 2016; 48: P15-P20PubMed Google Scholar Consequently, the authors should have defined the HTK solution as “intracellular” rather than “extracellular” (see their Introduction). This basic difference impacts its clinical applicability. The authors precisely described their clinical approach to heart implantation in the operating room. They routinely infuse 600 mL of cold Buckberg solution (ratio 8:1) into the donor heart. From a pathophysiological point of view, this represents a blend of extracellular and intracellular applications to heart protection, making it difficult to properly ascribe positive vs negative effects on postoperative outcome. Without a doubt, ischemia leads to myocardial injury, which does not develop linearly, but exponentially! Donor hearts are exposed to high ischemic stress due to transport time before arriving in the operating room, while—in this study—all hearts are protected by Buckberg solution. This means that already ischemically stressed hearts are exposed to a protective solution that routinely requires intermittent cardioplegic reperfusions. It is reasonable to raise concern that this approach may enhance myocardial injury, even if ischemic time after perfusion with Buckberg solution is only short. For an overall evaluation, primary graft dysfunction should be primarily considered. This Michigan study reports outcomes of 15 patients (4.2%) in whom mechanical support was required due to primary dysfunction of the graft, whereas a study of 1290 transplants being solely protected by HTK solution reported superior results. Primary graft dysfunction occurred in only 8 patients (1%).3Tjang Y.S. van der Heijden G.J. Tenderich G. Grobbee D.E. Körfer R. Survival analysis in heart transplantation: results from an analysis of 1290 cases in a single center.Eur J Cardiothorac Surg. 2008; 33: 856-861Crossref PubMed Scopus (27) Google Scholar A final note relates to the initial perfusion protocol for harvesting donor hearts. The authors administered 2000 mL of HTK solution, which is in contrast to a study of 794 heart transplants in a German Heart Center.4Koerner M.M. Tenderich G. Posival H. et al.Cardiac transplant survival in relation to preservation.in: Collins G.M. Dubernard J.M. Land W. Persijn G. Procurement, Preservation and Allocation of Vascularized Organs. Kluwer Academic Publishers, Dordrecht, Netherlands1997: 285-289Crossref Google Scholar The average ischemia time of these heart transplants lasted 194 minutes (= 3.2 hours) vs 162 minutes (= 2.7 hours) in the Michigan study. On the other hand, Koerner and colleagues4Koerner M.M. Tenderich G. Posival H. et al.Cardiac transplant survival in relation to preservation.in: Collins G.M. Dubernard J.M. Land W. Persijn G. Procurement, Preservation and Allocation of Vascularized Organs. Kluwer Academic Publishers, Dordrecht, Netherlands1997: 285-289Crossref Google Scholar clearly demonstrated that for heart transplantation, superior results were achieved if the perfusion rate was approximately 3500 mL within 10 minutes. This perfusion protocol is different than the one used for intraoperative cardioplegia (1500-2000 mL within 68 min). Histidine-Tryptophan-Ketoglutarate Solution for Donor Heart Preservation Is Safe for TransplantationThe Annals of Thoracic SurgeryVol. 109Issue 3PreviewVarious solutions are used for donor heart preservation. We examined the outcomes in our heart transplant population where histidine-tryptophan-ketoglutarate (HTK) solution has been used for heart preservation since 2004. Full-Text PDF A Discussion on Interpreting Primary Graft Dysfunction Outcomes: ReplyThe Annals of Thoracic SurgeryVol. 111Issue 2PreviewI thank Dr Preusse for the insightful comments on our article1 outlined in his letter to The Annals of Thoracic Surgery.2 My colleagues and I first would like to address the primary graft dysfunction (PGD) rates. As noted by previous investigators, reported PGD rates can vary depending on definitions that range from strictly the use of an intraaortic balloon pump or other forms of mechanical support to the use of high-dose inotropic agents or hemodynamic and echocardiographic findings.3 Even at high-volume heart transplant centers, reported PGD rates after heart transplantation vary widely, from 0.8% to 7.1%. Full-Text PDF

OBJECTIVE:The aim of this research was to investigate if dielectric spectroscopy between 100 Hz and 1 MHz provides reliable information about water distribution in ischaemic heart tissue and to investigate the influence of temperature on oedema formation.METHODS:We examined hearts of landrace piglets (n = 13) during ischaemia at 35 °C, 25 °C, and 15 °C. The dielectric permittivity ε'(f) and conductivity σ'(f) were calculated from impedance spectra measured between 100Hz and 1MHz. Gap junction uncoupling (GJU) was identified in the sigmoidal time course of ε'(13 kHz). The extracellular space index (ECSI) was estimated by the ratio σ'(100 Hz)/σ'(1 MHz). Intercalated water was analysed in electron microscopy images of the myocardial samples and was used to calculate the extracellular space index ECSIhisto. The ECSI and ECSIhisto were compared during ischaemia. GJU and oedema formation were simulated with an electrical heart model.RESULTS:At the onset of ischaemia, the ECSI was significantly higher than the ECSIhisto (p < .01). GJU during ischaemia was temperature-dependent. After GJU, the values of the ECSI and ECSIhisto matched very well. The simulations confirmed the influence of GJU on the ECSI.SIGNIFICANCE:The estimation of cell oedema with the ECSI is reliable only after GJU. The development of oedema estimated by the ECSI was delayed at cooler temperatures.

Good morning, ladies and gentlemen. Mr. Chairman, it is my great pleasure, but mainly it is an honor for me to be invited for lecturing this audience. I hope I can inform you about some new aspects concerning myocardial protection. The title of my lecture is “Custodiol Cardioplegia: A Single-Dose Hyperpolarizing Solution.” The impact of a low-sodium solution on electrophysiology, physiology, solution’s composition and experimental results, mode of administration, clinical results, and last but not least, the take-home message is demonstrated step by step.

Objectives: In congenital heart surgery, ischemia-induced myocardial edema formation often influences postoperative care, especially after long lasting ischemic periods, since delayed sternal closure is necessary. To evaluate differences in ischemic processes between neonatal and adult hearts we investigated gap junction closure (GJC) and edema formation during normothermic ischemia (35°C) using bioelectrical impedance spectroscopy.

Objectives: Patients suffering from coronary artery disease undergo, according to the guidelines, interventional or surgical treatment. However, there are only limited data of the influence of previous PTCA/stent implantation on the clinical outcome of patients who receive subsequent operative coronary revascularization.

Objectives: Bioelectrical impedance spectroscopy is a non-invasive method to determine ischemia-induced alterations of various tissues. Therefore, neonatal and adult porcine hearts were examined during ischemia at different temperatures to analyze distinctive myocardial changes properly.

Ischemia (35 degrees C) induced alterations of the bioelectric impedance were analysed for the first time in neonatal hearts (piglets). The changes of impedance principally did not differ from adult hearts, but great differences could be detected regarding time course and intensity. The reasons for different courses of the bioelectric impedance are most probably related to different metabolic variations of the ischemic neonatal heart.

BACKGROUNDThe pathomechanisms underlying aortic valve degeneration are incompletely understood. Therefore, the aim of our work was to assess the quantitative changes of proliferation and apoptosis accompanied by cellular phenotype alternations and matrix secretionin aortic sclerotic and stenotic valves and degenerative bioprostheses, as well as to detect the expression pattern of the rapamycin receptor FKBP12 across these three valve types.METHODSMild-to-moderate sclerotic and stenotic valves and degenerative bioprostheses from 30 patients (n = 10 per group) were collected at autopsy or by surgery. Ki67+, FKBP12+, alpha-actin+, HSP47+ and TUNEL+ apoptotic cells were analyzed by immunohistochemistry.RESULTSThe main finding was the reduced proliferation and increased apoptosis in stenotic valves (ST) compared to the sclerotic ones (SC) (proliferation: ST: 20.8 ± 2.0% vs. SC: 30.1 ±2.2%, apoptosis: ST: 40.7 ± 5.0% vs. SC: 28.0 ± 5.1%, p < 0.05, respectively). Analogical alternations were found in degenerative bioprostheses (BP) (proliferation: 4.8 ± 2.3%; apoptosis: 13.1 ± 6.8%). Corresponding changes were observed in the valve cellularity (ST: 893 ± 168, SC: 1034 ± 284, BP: 385 ± 179 cells/mm2, p < 0.05, respectively). The FKBP12 signaling was reduced in diseased valves and bioprostheses (ST: 28.1 ± 3.6%, SC: 42.2 ± 3.8%, BP: 5.8 ± 1.9%, p < 0.05, respectively). Further, the augmented alpha-actin expressionwas observed as the degenerative process progressed (ST: 30.3 ± 5.0%, SC: 22.6 ± 2.7%, BP:8.7 ± 4.0%, p < 0.05, respectively), followed by the upregulation of HSP47 (ST: 22.6 ± 2.8%,SC: 15.4 ± 2.1%, BP: 3.4 ± 1.0%, p < 0.05, respectively) and consecutive matrix accumulation.CONCLUSIONSThe imbalance between proliferation and apoptosis with cellular phenotypical shift and subsequent matrix secretion may contribute to aortic valve stenosis and bioprosthesis degeneration. The identification of FKBP12 expression may implicate potential therapeutic strategies.

We read with interest the article of Kim and associates [1] and the following comments concerning hyponatremia caused by the use of histidine-tryptophane-ketoglutarate (HTK) solution in pediatric cardiac surgical procedures.

The scope of this paper was to determine whether ischemic and reperfusion damage in cardiac surgery can be detected by measurement of electrical bioimpedance (EBI). Conventional pacing wires were replaced by pacing wires with sputtered iridium coating in order to reduce polarization associated with two-electrode impedance measurements. A custom-built bioimpedance analyzer (Osypka Medical GmbH, Berlin, Germany) measured the real part of impedance Re( Z) and the phase (φ) at three frequencies (1, 10, and 1000 kHz) and determined an extracellular space index (EZRI) as the quotient of Re( Z) at 1000 kHz and Re(Z) at 1 kHz. Our study included six patients (conventional coronary artery bypass graft, age 68.1 ± 8.3 years) subject to routine cardioplegic ischemia and reperfusion. Preischemic bioimpedance measurements were not impaired by interference of the beating heart. Intraischemically, bioimpedance at 1 kHz and phase at 10 kHz increased until opening of a bypass graft, which is probably induced by closure of gap junctions and cell swelling processes. After cross clamping, EZRI slowly decreased as an effect of mild cell swelling. After ischemia, values returned almost to baseline measurements, indicating sufficient reperfusion processes. Measurement of EBI correlates with myocardial ischemic injury and is applicable in a two-electrode setup providing low-polarization pacing wires.

Background and aim of the study: The presence of five pathogens was assessed, together with a possible correlation of the total pathogen burden on inflammation and (auto)immunity in aortic stenosis (AS) and degenerative aortic valve bioprosthesis (BP).Methods: Diseased valve specimens from a total of 68 patients (52 with AS, 16 with BP) were studied. The presence and localization was assessed of Chlamydia pneumoniae (cHSP60), Helicobacter pylori (HP), cytomegalovirus (CMV), Epstein-Barr virus (EBV) and herpes simplex virus (HSV), as well as of macrophages (CD68), C-reactive protein (CRP) and human heat shock protein 60 (hHSP60), by using immunohistochemical and morphometric analyses.Results: In the majority of degenerative aortic valves, specific pathogens, inflammation and immunity were localized predominantly in the fibrosa of AS patients, and in superficial regions of the BP. The categorization of valves as having four or more pathogens (n = 37) or fewer pathogens (n = 31) demonstrated an increased signaling of CD68 (p = 0.03) and CRP (p = 0.02). Specifically, cHSP60, HP and hHSP60 levels were increased in valves where one or two bacteria were identified (n 59) compared to those without bacterial presence (n 9) (p = 0.04).Conclusion: The pathogen burden may contribute to valvular degeneration by promoting further deleterious inflammatory and (auto)immune processes at the level of the valvular fibrosa.

BACKGROUND AND AIM OF THE STUDY Although degenerative calcific aortic valve stenosis is the most common valvular disease among the elderly, neither the etiology underlying the condition nor degeneration of the bioprostheses is yet fully understood. The study aim was to assess the expression profile of those OPG/RANKL/RANK-system determinants known to act as key regulators of bone metabolism and the immune system in calcific aortic valve stenosis and porcine aortic bioprostheses. METHODS Valve probes from a total of 69 patients (41 with end-stage aortic stenosis, 11 with mild-to-moderate aortic sclerosis, 17 with degenerative porcine aortic bioprostheses) were explanted either during surgery or at autopsy. The presence and localization of OPG, RANKL, RANK and NF-kappaB were analyzed by immunostaining and morphometry. RESULTS The majority of stenotic and sclerotic valves exhibited cell-bound signals of OPG, RANKL, RANK and NF-kappaB, while bioprostheses showed only sparse signaling. As key findings, the percentage of cells labeled by OPG, RANK and NF-kappaB was increased in sclerotic valves compared with stenotic valves (each p < 0.001), whereas the frequency of RANKL was higher in stenotic compared to sclerotic valves (p < 0.001). As a consequence, the OPG/RANKL ratio was decreased in stenotic (0.83) compared to sclerotic valves (20.2). CONCLUSION The differential expression profile of specific members of the OPG/RANKL/RANK axis suggests an involvement of their determinants in native valve calcification, but not in the degeneration of porcine bioprostheses. Thus, these mediators of bone homeostasis may represent new targets for a more specified prevention and/or therapy of native aortic stenosis.

Five thousand consecutive percutaneous transluminal coronary angioplasties (PTCA) were electively performed between January 1988 and June 1993. They were analysed for the incidence of acute coronary occlusion, its acute treatment and subsequent course. In 133 patients (2.7%) the occlusion persisted. Recanalization by repeat PTCA was attempted in all of them, but succeeded in only 68 (51%). In 65 patients recanalization was impossible. In 25 of the latter--patients with a small infarct vessel and infarction having already occurred in the vessel's supply area while the haemodynamics remained stable--conservative treatment was practised. Acute surgical revascularization was undertaken in 30 patients (23%) with a large area and/or haemodynamic instability. In all, 14 patients died (overall death rate 0.28%, death rate of patients with occlusion 11%), ten of them before operative intervention was possible.--Not all coronary artery occlusions can be treated nonsurgically. Consequently, availability of surgical intervention at the place of elective PTCA is mandatory.

BACKGROUNDThe occurrence of a skin neoplasm close to the position of an implanted pacemaker or cardioverter-defibrillator device is not very common.CASE REPORTWe report on an 82-year-old patient who developed a basal cell carcinoma in the skin directly above a subcutaneously implanted pacemaker generator. The patient presented with a history of recurrent basalioma at various locations. The pacemaker (Kappa KDR 731; Medtronic) was implanted 17 months before and represented a series that was recalled because of problems occurring after submuscular implantation.CONCLUSIONPrimary submuscular implantation of pacemaker devices should be carefully considered in elderly patients with a history of previous skin tumors.

Background: The performance of temporary pacing wires is still limited by capture and sensing problems. Fractal coating can enhance electrical properties and reliability. We therefore investigated fractal‐laminated wires in comparison with conventional wires. Methods: In 21 patients two unipolar, fractal‐coated pacing wires (fe) and one conventional bipolar electrode (se) were implanted in ventricular position. Afterward pacing threshold (V), R‐wave sensing (mV), lead impedance (ohm), and slew‐rate (mV/s) were measured. Loss of capture or sensing and dislocation was documented. fe wires were examined with energy dispersive x‐ray diffraction (EDX)‐analysis and scanning electrode microscopy (SEM). Results: Failure in pacing was less frequent in fe wires. Also fe leads had lower pacing thresholds at implantation (0.76 ± 0.15 V vs 1.51 ± 0.95 V, P< 0.0001) and afterward. Furthermore fe wires showed lower increase of pacing threshold/time (0.25 V/day vs 0.42 V/day). R‐wave sensing and slew‐rate values in the fe group on day of operation (5.81 ± 4.80 mV; 0.63 ± 0.71 V/s) were lower than in the se group (10.37 ± 6.89 mV; 1.85 ± 1.71 V/s P< 0.0001) and afterward. Nevertheless, decrease of amplitude/time was lower in fe wires (0.17mV/day vs 0.46 mV/day). fe wires always had lower impedance values. Conclusions: Lower pacing threshold and increase of threshold/time in fe wires indicate more reliable function. Initial lower sensitivity values are still not understandable and must be investigated. However, fe wires, constancy of sensing and impedance values was more stable, so fe epicardial wires can be recommended for safe and feasible use.

A 78-year-old woman with a history of S-A block originally received a DDDR pacemaker on the right thoracic side in October 2000. After several re-operations (ventricular lead replacement, generator dislocation), the device was replaced due to battery depletion in April 2005. In May 2005, the patient was re-admitted with intermittent fever, but no evidence for any inflammatory …