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The aim of this study was to investigate cardiomyocyte Ca2+ handling and contractile function in freshly excised human atrial tissue from diabetic and non‐diabetic patients undergoing routine surgery. Multicellular trabeculae (283 ± 20 μm in diameter) were dissected from the endocardial surface of freshly obtained right atrial appendage samples from consenting surgical patients. Trabeculae were mounted in a force transducer at optimal length, electrically stimulated to contract, and loaded with fura‐2/AM for intracellular Ca2+ measurements. The response to stimulation frequencies encompassing the physiological range was recorded at 37°C. Myofilament Ca2+ sensitivity was assessed from phase plots and high potassium contractures of force against [Ca2+]i. Trabeculae from diabetic patients (n = 12) had increased diastolic (resting) [Ca2+]i (p = 0.03) and reduced Ca2+ transient amplitude (p = 0.04) when compared to non‐diabetic patients (n = 11), with no difference in the Ca2+ transient time course. Diastolic stress was increased (p = 0.008) in trabeculae from diabetic patients, and peak developed stress decreased (p ≤ 0.001), which were not accounted for by reduction in the cardiomyocyte, or contractile protein, content of trabeculae. Trabeculae from diabetic patients also displayed diminished myofilament Ca2+ sensitivity (p = 0.018) compared to non‐diabetic patients. Our data provides evidence of impaired calcium handling during excitation‐contraction coupling with resulting contractile dysfunction in atrial tissue from patients with type 2 diabetes in comparison to the non‐diabetic. This highlights the importance of targeting cardiomyocyte Ca2+ homeostasis in developing more effective treatment options for diabetic heart disease in the future. [ABSTRACT FROM AUTHOR]

Ventricular muscle has a biphasic response to stretch. There is an immediate increase in force that coincides with the stretch which is followed by a second phase that takes several minutes for force to develop to a new steady state. The initial increase in force is due to changes in myofilament properties, whereas the second, slower component of the stretch response (known as the "slow force response" or SFR) is accompanied by a steady increase in Ca2+ transient amplitude. Evidence shows stretch-dependent Ca2+ influx during the SFR occurs through some mechanism that is continuously active for several minutes following stretch. Many of the candidate ion channels are located primarily in the t-tubules, which are consequently lost in heart disease. Our aim, therefore, was to investigate the impact of t-tubule loss on the SFR in non-failing cardiac trabeculae in which expression of the different Ca2+ handling proteins was not altered by any disease process. For comparison, we also investigated the effect of formamide detubulation of trabeculae on β-adrenergic activation (1 μM isoproterenol), since this is another key regulator of cardiac force. Measurement of intracellular calcium ([Ca2+]i) and isometric stress were made in RV trabeculae from rat hearts before, during and after formamide treatment (1.5 M for 5 min), which on washout seals the surface sarcolemmal t-tubule openings. Results showed detubulation slowed the time course of Ca2+ transients and twitch force, with time-to-peak, maximum rate-of-rise, and relaxation prolonged in trabeculae at optimal length (Lo). Formamide treatment also prevented development of the SFR following a step change in length from 90 to 100% Lo, and blunted the response to β-adrenergic activation (1 μM isoproterenol). [ABSTRACT FROM AUTHOR]

The mechanical response of the heart to myocardial stretch has been understood since the work of muscle physiologists more than 100 years ago, whereby an increase in ventricular chamber filling during diastole increases the subsequent force of contraction. The stretch-induced increase in contraction is biphasic. There is an abrupt increase in the force that coincides with the stretch (the rapid response), which is then followed by a slower response that develops over several minutes (the slow force response, or SFR). The SFR is associated with a progressive increase in the magnitude of the Ca2+ transient, the event that initiates myocyte cross-bridge cycling and force development. However, the mechanisms underlying the stretch-dependent increase in the Ca2+ transient are still debated. This review outlines recent literature on the SFR and summarizes the different stretch-activated Ca2+ entry pathways. The SFR might result from a combination of several different cellular mechanisms initiated in response to activation of different cellular stretch sensors. [ABSTRACT FROM AUTHOR]

Recently, a family of guanine nucleotide exchange factors have been identified in many cell types as important effectors of cyclic adenosine 3',5'-monophospahte (cAMP) signalling that is independent of protein kinase A (PKA). In the heart, investigation of exchange protein directly activated by cAMP (Epac) has yielded conflicting results. Since cAMP is an important regulator of cardiac contractility, this study aimed to examine whether Epac activation modulates excitation- contraction coupling in ventricular preparations from rat hearts. The study used 8-(4-chlorophenylthio)-2'-O-methyladenosine- 3', 5'-cyclic monophosphate (cpTOME), an analogue of cAMP that activates Epac, but not PKA. In isolated myocytes, cpTOME increased Ca2+ spark frequency from about 7 to 32/100 μm3/s (n = 10), P = 0.05 with a reduction in the peak amplitude of the sparks. Simultaneous measurements of intracellular Ca2+ and isometric force in multicellular trabeculae (n = 7, 1.5 mmol/L [Ca2+]o) revealed no effect of Epac activation on either the amplitude of Ca2+ transients (Control 0.7 ± 0.1 vs cpTOME 0.7 ± 0.1; 340/380 fura-2 ratio, P = 0.35) or on peak stress (Control 24 ± 5 mN/mm2 vs cpTOME 23 ± 5 mN/mm2, P = 0.20). However, an effect of Epac in trabeculae was unmasked by lowering extracellular [Ca2+]o. In these depotentiated trabeculae, activation of the Epac pathway increased myofilament Ca2+ sensitivity, an effect that was blocked by addition of KN-93, a Ca2+/calmodulin- dependent protein kinase II (CaMK-II) inhibitor. This study suggests that Epac activation may be a useful therapeutic target to increase the strength of contraction during low inotropic states. [ABSTRACT FROM AUTHOR]

Background: Hyperbaric oxygen therapy (HBOT) is a treatment option for chronic nonhealing wounds. Transcutaneous oximetry (TCOM) is used for wound assessment. We undertook a randomized prospective controlled trial to evaluate the role of HBOT in healing of chronic nonhealing wounds and to determine whether TCOM predicts healing. Materials and Methods: This study was conducted in 30 consenting patients with nonhealing ulcer. The patients were randomized into group HT (receiving HBOT in addition to conventional treatment) and group CT (receiving only conventional treatment). Duration of treatment in both the groups was 30 days. Wound ulcer was analyzed based on size of the wound, exudates, presence of granulation tissue, and wound tissue scoring. Tissue oxygenation (TcPO2) was measured on 0, 10th, 20th, and 30th day. Results: There was 59% reduction in wound area in group HT and 26% increase in wound area in group CT. Ten patients in group HT showed improvement in wound score as compared to five patients in group CT. Complete healing was seen in three patients in group HT as compared to none in group CT. Surgical debridement was required in 6 patients in group HT and 10 patients in group CT. One patient in group HT required amputation as compared to five patients in group CT. A positive correlation was found between TcPO2 value and various markers of wound healing. Conclusion: HBOT has a definitive adjunctive role in the management of chronic nonhealing ulcers. It decreases the amputation rate and improves patient outcome. Periwound TcPO2 may be used as a predictor of response to HBOT and has a positive correlation with wound healing. [ABSTRACT FROM AUTHOR]

This article discusses the use of electronic resources (e-resources) at Himachel Pradesh University in Shimla, India focusing on the development of library collaborations like the University Grants Commission (UGC) Infonet. Topics include the global phenomenon of library consortia such as the Online Computer Literacy Centre, Inc.'s (OCLC) Net Library, the usage statistics for the online resources available via full-text, and the user awareness and instruction programs undertaken by Himachel Pradesh University to educate students and faculty in e-resources management, information search, and copyright concerns.

We describe for the first time, the perioperative care of a patient with a rare combination of Eisenmenger syndrome with β-thalassemia major presenting for splenectomy. Patients with Eisenmenger syndrome have polycythemia because of chronic hypoxia but our patient was anaemic and had thrombocytopenia because of thalassemia major. The management of such a case can be challenging for any anaesthesiologist because of severe V/Q mismatch (high shunt fraction and restrictive lung disease because of hypersplenism), decreased oxygen carrying capacity (anaemia) and increased risk of haemorrhage (thrombocytopenia), along with the potential increase in intracardiac shunt during anaesthesia. [ABSTRACT FROM AUTHOR]