We aimed to test if stimulation of both adenosine A2A and A2B receptors is required to produce an effective cardioprotection against reperfusion injury. Isolated rat hearts were subjected to 30 min regional ischemia followed by 2 h of reperfusion. The adenosine A1/A2 receptor agonist 5′-(N-ethylcarboxamido) adenosine (NECA) given at reperfusion reduced infarct size, an effect that was reversed by both the adenosine A2A antagonist SCH58261 and the A2B antagonist MRS1706. The A2B agonist BAY 60-6583 but not the selective A2A agonist CGS21680 reduced infarct size. Interestingly, a combination of BAY 60-6583 and CGS21680 further reduced infarct size. These results suggest that both A2A and A2B receptors are involved in NECA’s anti-infarct effect at reperfusion. NECA attenuated mitochondrial swelling upon reperfusion and this was blocked by both SCH58261 and MRS1706, indicating that activation of A2 receptors with NECA can modulate reperfusion-induced mitochondrial permeability transition pore (mPTP) opening. In support, NECA also prevented oxidant-induced loss of mitochondrial membrane potential (ΔΨm) and matrix Ca2+ overload in cardiomyocytes via both the A2 receptors. In addition, NECA increased mitochondrial glycogen synthase kinase 3β (GSK-3β) phosphorylation upon reperfusion and this was again blocked by SCH58261 and MRS1706. In conclusion, A2A and A2B receptors work in concert to prevent reperfusion injury in rat hearts treated with NECA. NECA may protect the heart by modulating the mPTP opening through inactivating mitochondrial GSK-3β. A simultaneous stimulation of A2A and A2B receptors at reperfusion is required to produce a strong cardioprotection against reperfusion injury.

Our previous study demonstrated that zinc prevents cardiac reperfusion injury by targeting the mitochondrial permeability transition pore (mPTP) via Akt and glycogen synthetase kinase 3beta (GSK-3beta). We aimed to address the mechanism by which zinc activates Akt. Treatment of H9c2 cells with ZnCl(2) (10 microM) in the presence of the zinc ionophore pyrithione (4 microM) for 20 min enhanced Akt phosphorylation (Ser(473)), indicating that zinc can rapidly activate Akt. Zinc did not alter either phosphatase and tensin homolog deleted on chromosome 10 (PTEN) phosphorylation and total PTEN protein levels or PTEN oxidation, implying that PTEN may not play a role in the action of zinc. However, zinc-induced Akt phosphorylation was blocked by both the nonselective receptor tyrosine kinase (RTK) inhibitor genistein and the selective insulin-like growth factor-1 RTK (IGF-1RTK) inhibitor AG1024, indicating that zinc activates Akt via IGF-1RTK. Zinc-induced phosphorylation of protein tyrosine and Ser/Thr was also abolished by AG1024. In addition, zinc markedly enhanced phosphorylation of IGF-1 receptor (IGF-1R), which was again reversed by genistein and AG1024. A confocal imaging study revealed that AG1024 abolished the preventive effect of zinc on oxidant-induced mPTP opening, confirming that IGF-1RTK plays a role in zinc-induced cardioprotection. Furthermore, zinc decreased the activity of protein phosphatase 2A (PP2A), a major protein Ser/Thr phosphatase, implying that protein Ser/Thr phosphatases may also play a role in the action of zinc on Akt activity. Taken together, these findings demonstrate that exogenous zinc activates Akt via IGF-1RTK and prevents the mPTP opening in cardiac cells. Inactivation of Ser/Thr protein phosphatases may also contribute to zinc-induced Akt activation.

Hip dysplasia (HD) scores, based on the five grades, as defined by the Fédération Cynologique Internationale, were compared between anaesthetized (group 1, n = 3839) and non-sedated non-anaesthetized dogs (group 2, n = 1517). Each dog was radiographed in the standard ventro-dorsal hip joint extended position. Each radiograph was evaluated by the same reader blinded regarding the dog's status of anaesthesia. Results showed that there was a significant difference in hip dysplasia prevalence between group 1 (22%) compared with group 2 (9%) (P < 0.005). This difference was the result of a lower rate of hip-joint laxity assessment and the measurement of Norberg-Olsson angle <105 degrees in group 2 compared with group 1. The acetabular and femoral morphologies were not significantly different between the groups. The data confirm that the scoring of dogs for HD on standard radiographs with the hip joints extended is influenced by anaesthesia.

Objectives Intracorporeal suturing and knot tying can complicate, prolong or preclude minimally invasive surgical procedures, reducing their advantages over conventional approaches. An automated knot-tying device has been developed to speed suture fixation during minimally invasive cardiac surgery while retaining the desirable characteristics of conventional hand-tied surgeon's knots: holding strength and visual and haptic feedback. A rotating slotted disk (at the instrument's distal end) automates overhand throws, thereby eliminating the need to manually pass one suture end through a loop in the opposing end. Electronic actuation of this disk produces left or right overhand knots as desired by the operator. Methods To evaluate the effectiveness of this technology, 7 surgeons with varying laparoscopic experience tied knots within a simulated minimally invasive setting, using both the automated knot-tying tool and conventional laparoscopic tools. Suture types were 2-0 braided and 4-0 monofilament. Results Mean knot-tying times were 246 ±116 seconds and 102 ±46 seconds for conventional and automated methods, respectively, showing an average 56% reduction in time per surgeon (p=0.003, paired t-test). The peak holding strength of each knot (the force required to break the suture or loosen the knot) was measured using tensile testing equipment. These peak holding strengths were normalized by the ultimate tensile strength of each suture type (57.5 N and 22.1 N for 2-0 braided and 4-0 monofilament, respectively). Mean normalized holding strengths for all knots were 68.2% and 71.8% of ultimate tensile strength for conventional and automated methods, respectively (p= 0.914, paired t-test). Conclusions Experimental data reveal that the automated suturing device has great potential for advancing minimally invasive surgery: it significantly reduced knot-tying times while providing equivalent or greater holding strength than conventionally tied knots.

These results revealed that exercise had a minor effect on CK disposition and that the equivalent amount of muscle damaged by moderate exercise was negligible. This study illustrates the relevance for use of the minimally invasive and quantitative pharmacokinetic approach when estimating muscle damage.