Abstract-Stretch induces immediate and delayed inotropic effects in mammalian myocardium via distinct mechanosensitive pathways, but these effects are poorly characterized in human cardiac muscle. We tested the effects of stretch on immediate and delayed force response in failing human myocardium. Experiments were performed in muscle strips from 52 failing human hearts (37°C, 1 Hz, bicarbonate buffer). Muscles were stretched from 88% of optimal length to 98% of optimal length. The resulting immediate and delayed (ie, slow force response [SFR]) increases in twitch force were assessed without and after blockade of the sarcoplasmic reticulum (SR; cyclopiazonic acid and ryanodine), stretch-activated ion channels (SACs; gadolinium, streptomycin), L-type Ca 2ϩ -channels (diltiazem), angiotensin II type-1 (AT 1 ) receptors (candesartan), endothelin (ET) receptors (PD145065 or BQ123), Na ϩ /H ϩ exchange (NHE1; HOE642), or reverse-mode Na ϩ /Ca ϩ exchange (NCX; KB-R7493). We also tested the effects of stretch on SR Ca 2ϩ load (rapid cooling contractures [RCCs]) and intracellular pH (in BCECF-loaded trabeculae). Stretch induced an immediate (Ͻ10 beats), followed by a slow (5 to 10 minutes), force response. Twitch force increased to 232Ϯ6% of prestretch value during the immediate phase, followed by a further increase to 279Ϯ8% during the SFR. RCC amplitude significantly increased, but pHi did not change during SFR. Inhibition of SACs, L-type Ca 2ϩ channels, AT 1 receptors, or ET receptors did not affect the stretch-dependent immediate or SFR. In contrast, the SFR was reduced by NHE1 inhibition and almost completely abolished by reverse-mode NCX inhibition or blockade of sarcoplasmic reticulum function. The data demonstrate the existence of a functionally relevant, SR-Ca 2ϩ -dependent SFR in failing human myocardium, which partly depends on NHE1 and reverse-mode NCX activation.

The data are consistent with the hypothesis that SFR results from increases in [Ca(2+)](i) secondary to altered flux via NCX in part resulting from increases in [Na(+)](i) mediated by NHE1.

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Abstract. Gap junctional intercellular communication (GJIC) and connexin (Cx) expression were reported in association with carcinogenesis in various types of tumours. In an earlier histomorphometric study, the protein levels of Cx subtypes 26, 43 and 45 were differentially expressed in oral squamous cell carcinoma (OSCC), corresponding lymph node metastases and dysplasia-free oral mucosa. Moreover, membrane Cx43 acted as an independent prognostic marker in OSCC tissues. This study aimed to confirm the expression of described Cx subtypes at the mRNA level. Hence, a reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis of Cx26, Cx43 and Cx45 gene expressions was performed in paired carcinoma and mucosa samples of 15 OSCC patients. Additionally, we assessed the interaction between Cx subtype expression and clinicopathological routine parameters. The RT-qPCR analysis revealed that Cx26 was downregulated in OSCC (P=0.01), while Cx43 was marginally upregulated in cancer tissue (P=0.04). Cx45 was significantly overexpressed in OSCC tissue compared with the intraoral mucosa controls (P<0.01), and remained unchanged at different tumour stages. No significant interactions between differential Cx subtype expression and clinicopathological routine parameters were observed. In conclusion, Cx regulation at the transcriptional level appears to be an early event during the initiation and development of OSCC, and is maintained during further progression. However, the mRNA-protein correlation is variable. This may be indicative of post-transcriptional, translational and degradation regulations being associated with the determination of Cx protein concentration during oral carcinogenesis.

ZusammenfassungBei antikoagulierten Patienten muss vor invasiven Eingriffen das Blutungsrisiko einerseits gegen die Protektion vor thrombembolischen Ereignissen andererseits abgewogen werden. Wir stellen bezüglich der Durchführung von zahnärztlichen Eingriffen bei oral antikoagulierten Patienten die aktuellen Leitlinien von American Heart Association, American College of Cardiology und der Deutschen Gesellschaft für Zahn-, Mund-und Kieferheilkunde sowie deren wissenschaftliche Hintergründe vor. Zahnextraktionen, Osteotomien retinierter Zähne sowie Wurzelspitzenresektionen sind bei oral antikoagulierten Patienten ohne Änderungen der antikoagulatorischen Dauermedikation sicher durchführbar, wenn der Patient von Hausarzt und Operateur in enger Kooperation auf den Eingriff vorbereitet wird und postoperativ ebenfalls interdisziplinär engmaschig betreut wird. Spezielle Maßnahmen, die das Risiko von Blutungskomplikationen senken können sind neben möglichst atraumatischer Operationstechnik und speicheldichtem Wundverschluss das perioperative Monitoring der Antikoagulation, die Anfertigung einer Tiefziehschiene als Verbandplatte sowie die Anleitung zur Mundspülung mit Tranexamsäure. Treten postoperativ Blutungskomplikationen auf, sind diese in der überwiegenden Zahl der Fälle lokal sicher beherrschbar, so dass nur in seltenen Ausnahmefäl-len die Unterbrechung oder Antagonisierung der oralen Antikoagulation und damit der thrombembolischen Protektion notwendig ist. AbstractWhen patients who receive oral anticoagulation undergo dental surgery, the risk of thrombembolic events has to be balanced up against the risk of peri-or postoperative bleeding. We discuss the guidelines and their scientific background of the American Heart Association, the American College of Cardiology and of the German Dental Association referring to this subject. Dental surgery like dental extraction, removal of retained teeth or periapical surgery can be performed without changing the oral anticoagulatory drugs, if the patient is well prepared for the intervention by the surgeon and his general practitioner cooperatively and is well supervised postoperatively. Special measures preventing postoperative bleeding are non-traumatic surgery techniques, suturing of the alveolus, perioperative monitoring of the anticoagulatory effect, preparation of an acrylic splint for the case of subsequent bleeding and to instruct the patient to rinse his mouth postoperatively with an aqueous solution containing tranexamic acid. In cases of postoperative bleeding, these episodes can predominantly be controlled by local interventions without interruption or antagonism of the oral anticoagulation.

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