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2.
Arthrosc Tech ; 13(3): 102896, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38584633

ABSTRACT

Arthroscopic-assisted anterior cruciate ligament reconstruction follows standardized protocols. Multiple fixation techniques are known. Discussion has been raised about osseus fixation and integration. To improve a biological osseous fixation of the anterior cruciate ligament transplant, a Press-Fit-Hybrid technique has been developed. The basic principle is to recycle bony cylinders obtained from the femoral and tibial tunnel to fix the transplant in the femoral and tibial tunnel. In addition to the biological advantage, there are additional economic benefits, such as no extra fixation material is necessary compared with common fixation techniques, and the overall surgical procedure requires minimal effort.

3.
J Pers Med ; 14(4)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38672979

ABSTRACT

Addressing non-unions involves stabilizing the affected area through osteosynthesis and improving bone biology using bone grafts. However, there is no consensus on the optimal treatment method. This study aims to compare outcomes of non-union surgery using conventional treatment methods (metal hardware ± graft) versus osteosynthesis with the human allogeneic cortical bone screw (Shark Screw®) alone or in combination with a metallic plate. Thirty-four patients underwent conventional treatment, while twenty-eight cases received one or more Shark Screws®. Patient demographics, bone healing, time to bone healing, and complications were assessed. Results revealed a healing rate of 96.4% for the Shark Screw® group, compared to 82.3% for the conventionally treated group. The Shark Screw® group exhibited a tendency for faster bone healing (9.4 ± 3.2 vs. 12.9 ± 8.5 weeks, p = 0.05061). Hardware irritations led to six metal removals in the conventional group versus two in the Shark Screw® group. The Shark Screw® emerges as a promising option for personalized non-union treatment in the foot, ankle, and select lower leg cases, facilitating effective osteosynthesis and grafting within a single construct and promoting high union rates, low complications, and a rapid healing process.

4.
Orthopadie (Heidelb) ; 53(5): 341-347, 2024 May.
Article in English | MEDLINE | ID: mdl-38498205

ABSTRACT

BACKGROUND: The use of allografts and autografts has been met with mixed views on whether allografts are a suitable alternative to autografts. QUESTION: We aimed to investigate if chemically sterilized allografts show similar rerupture rates to those reported in the literature for allografts and autografts in anterior (ACL) and posterior cruciate ligaments (PCL) and complex knee surgery. MATERIALS AND METHODS: Retrospective data on knee reconstructions performed between 2011 and 2015 with tendon/ligamnet allografts sterilized with peracetic acid were collected in the form of a questionnaire. The inclusion criteria of 2 years for each patient were met by 38 patients, representing 22 ACL reconstructions, 5 PCL reconstructions, 3 OTHER surgeries, including the Larson technique and medial patellofemoral ligament (MPFL) reconstruction and 8 COMPLEX surgeries. The main endpoints were rerupture and complication rate. Secondary endpoints included stability of the knee (Lachman test, Pivot shift test) and the range of motion. RESULTS: The rerupture rate was 7.9% (3 grafts). Reruptures only occurred in the ACL group. No reruptures were observed in the PCL, OTHER and COMPLEX surgery groups. Stability improved significantly after surgery and the range of motion returned to values similar to that of healthy knees. CONCLUSIONS: Tendon allografts sterilized with peracetic acid show promising low rerupture rates and good clinical scores and the results are comparable to the literature on autografts and other allografts.


Subject(s)
Allografts , Peracetic Acid , Sterilization , Tendons , Humans , Male , Female , Retrospective Studies , Adult , Tendons/transplantation , Middle Aged , Sterilization/methods , Anterior Cruciate Ligament Reconstruction/methods , Posterior Cruciate Ligament Reconstruction/methods , Posterior Cruciate Ligament/surgery , Transplantation, Homologous/methods
5.
Shoulder Elbow ; 15(4): 411-423, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37538518

ABSTRACT

Background: The purpose of this retrospective study was to analyze whether chemically sterilized tendon allografts perform as well as other non-sterilized allografts and autografts as described in the literature for anatomical acromioclavicular joint stabilization for the treatment of Rockwood III-V. Allografts are still described as a factor for higher re-rupture rates. Methods: Retrospective data were collected from 21 acromioclavicular joint stabilizations performed by a single surgeon and performed between 2011 and 2014 using sterilized semitendinosus allografts. The primary endpoints were re-rupture and complication rates. Secondary endpoints were AC-joint stability, pain level, return to work and sport and the range of motion. Results: No re-ruptures occurred during the mean follow-up time of 33 months. Zero complications occurred directly after surgery, but three complications later than three weeks after surgery. All cases resolved without further surgery. After surgery, stability significantly improved for all patients. Post-surgery, 19 patients had stable acromioclavicular joints and only two patients showed minor instabilities. Range of motion returned to the range of the healthy shoulders for all patients. Conclusion: Chemically sterilized semitendinosus allograft use for anatomic AC-joint stabilization is equivalent to the use of other allografts or autografts and required no hardware removal. No donor age or graft size dependence was observed, due to zero re-ruptures.

6.
J Orthop Traumatol ; 24(1): 6, 2023 Feb 10.
Article in English | MEDLINE | ID: mdl-36765020

ABSTRACT

BACKGROUND: Allograft bone screws are rarely described for the fixation of the scaphoid. When fresh fractures are treated, metal screws are mainly used; when pseudarthrosis is the indication, plates in combination with vascularized or non-vascularized bone grafts are mainly used. The necessity of metallic screw removal is under debate, but it is mandatory for plates because of movement restrictions due to the plate. The use of biomaterials in scaphoid fracture fixation was described as leading to union rates of between 64 and 100%. Brcic showed the incorporation of an allogeneic cortical bone screw at 10 weeks postoperative, along with revascularization and stable osteosynthesis with primary bone healing, without any signs of immunological rejection. The purpose of this retrospective study was to explore the results obtained using an allogenic cortical bone screw (Shark Screw®) in patients with fresh scaphoid fracture fixation and pseudarthroses with respect to union rates and time to union. PATIENTS AND METHODS: We retrospectively analyzed 75 patients: 31 with fresh fractures and 44 pseudarthrosis patients. The Shark Screw® was used for the fixation of the scaphoid in the fresh-fracture and pseudarthrosis patients. We evaluated the union rate, complication rate and time to union. RESULTS: Using the human allogeneic cortical bone screw for scaphoid fracture fixation led to a high union rate (94-96%). There were two nonunions in the fresh fracture group and two nonunions in the pseudarthrosis group. The complication rate was 1.3% (1 patient). Median time to union was 16, 18 and 29 weeks for the fresh-fracture, pseudarthrosis and delayed-union patients, respectively. The treatment of fresh scaphoid fractures and pseudarthroses showed similar union rates to those described in the literature, uses a shorter and less invasive surgical method with no need for hardware removal, and has a low complication rate. CONCLUSION: Using the human allogenic cortical bone screw (Shark Screw®) led to similar union rates in fresh fractures-but better union rates in pseudarthrosis patients-compared to those presented in the literature for other scaphoid fracture fixation techniques, and it enabled a short and low-invasive procedure without any donor site morbidity and without the necessity to remove the hardware in a second surgery. The pseudarthrosis patient group showed a particularly strong benefit from this new procedure. The physiological bone metabolism remodels the cortical bone screw without scars. LEVEL OF EVIDENCE: III: retrospective cohort study, therapeutic investigation of a treatment.


Subject(s)
Fractures, Bone , Fractures, Ununited , Hematopoietic Stem Cell Transplantation , Pseudarthrosis , Scaphoid Bone , Wrist Injuries , Humans , Fractures, Bone/surgery , Pseudarthrosis/surgery , Retrospective Studies , Scaphoid Bone/surgery , Fracture Healing/physiology , Fracture Fixation, Internal/methods , Bone Screws , Cortical Bone
7.
Arch Orthop Trauma Surg ; 143(7): 4557-4564, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36757467

ABSTRACT

INTRODUCTION: The prime requisites of a good digital arthrodesis are a painless and stable union in a proper position. Arthrodesis of the distal interphalangeal joint of the fingers is not without potential complications including nonunion, malunion, and deep tissue infections. The Shark Screw® is a human, cortical bone allograft for osteosynthesis and an alternative to metal or bioabsorbable devices in orthopedics and trauma surgery. The primary hypothesis is that the fusion and complication rate, using the Shark Screw®, is at least similar to those reported in the literature, using metal or bioabsorbable screws. MATERIAL AND METHODS: This retrospective cohort study analyzes the fusion and complication rate and the patient satisfaction of distal interphalangeal joint arthrodesis of 27 fingers with the human allogeneic cortical bone screw. Complications, Disabilities of Arm, Shoulder, and Hand Questionnaire (Quick-DASH) score and Michigan Hand Outcomes Questionnaire (MHQ) score, grip and pinch strength and fusion angle were investigated. RESULTS: The mean follow-up was 23 months. At 6 weeks after surgery, fusion was obtained for all fingers. There was no surgical complication that required revision surgery. An average fusion angle of 13.6° ± 10.7° was measured. VAS pain score decreased significantly from 6.9 before surgery to 0.14 after surgery. The Quick-DASH score decreased from 10.7 to 7.8. The MHQ score improved in all sub-scores. CONCLUSION: The complication rates, using the Shark Screw® for DIP joint arthrodesis, are lower compared to the results reported in the literature for other surgical techniques. Complications related to the human allograft cortical bone screw itself were not observed. The bone screw is completely remodeled into the host bone and further hardware removal is not necessary. LEVEL OF EVIDENCE: IV.


Subject(s)
Finger Joint , Hematopoietic Stem Cell Transplantation , Humans , Follow-Up Studies , Retrospective Studies , Finger Joint/surgery , Arthrodesis/methods , Cortical Bone , Bone Screws
8.
J Pers Med ; 13(2)2023 Feb 17.
Article in English | MEDLINE | ID: mdl-36836584

ABSTRACT

BACKGROUND: Distal femur fractures are challenging in surgical management as the outcome is crucial for restoring the biomechanical stability and longitudinal axis of the leg and function of the knee joint. METHODS: A retrospective review of all distal femoral fractures treated in a level I trauma center over a decade was performed. The radiographs were reviewed for fracture entity, osseous healing, implant failure, mechanical axis, and degenerative joint changes. Clinical outcome was reviewed regarding postoperative complications and postoperative range of motion of the knee joint. RESULTS: 130 patients who were managed with screw fixation (n = 35), plating systems (n = 92) or intramedullary nailing systems (n = 3) remained for evaluation. Mean follow up was 26 months. Clinical outcome was significantly better for flexion degrees following screw fixation (p = 0.009). Delayed fracture union (p = 0.002) or non-union (p = 0.006) rates were significantly higher in plate osteosynthesis. Mild pathologic deformity for varus and valgus collapse was found following plate osteosynthesis. CONCLUSIONS: Screw fixation shows fewer postoperative complications than plate fixation and is favored for extra and partial intraarticular distal femur fractures. Plating constructs remain the superior fixation method in complex distal femur fractures but are associated with higher rates of non-union and leg axis deviation.

9.
Arch Orthop Trauma Surg ; 143(2): 935-949, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35290503

ABSTRACT

BACKGROUND: There is currently no consensus regarding the preferred surgical procedure for the reconstruction of anterior cruciate ligament (ACL). The interference screw technique is widely used, but has been associated with a risk of graft damage. The Press-Fit-Hybrid®-technique is one of the alternatives for biological ACL-reconstruction with minimal implant requirements. The hypothesis of this retrospective analysis is, that the Press-Fit-Hybrid®-technique leads to better results with respect to re-rupture rate and secondary meniscal lesion than the interference-screw-technique. METHODS: To compare the re-rupture rate of the interference-screw-technique (IF) used until 2015 with the currently used Press-Fit-Hybrid®-technique (PFH), the last 100 patients of the IF-group and the first 100 patients of the PFH-group were retrospectively analyzed. Primary outcomes were re-rupture rate, complications and secondary meniscal injury. Additionally, laxity, Lachman and Pivot-shift and range of motion were evaluated. RESULTS: A mean follow-up of 4.2 and 5.3 years revealed 4% and 9% re-rupture rates and 1% and 2% complication rates in the PFH- and IF-group, respectively. In the PFH-group there were no re-ruptures in patients older than 23 years. Secondary meniscal injury post-surgery was 6% and 9% for the PFH and IF-group, respectively. Knee stability was similar in both groups. Range of motion was significantly better in the PFH-group, with 136° of flexion, 6 months after surgery. CONCLUSION: For ACL-reconstruction the Press-Fit-Hybrid®-technique is an alternative new method. Low level of secondary meniscal lesions after surgery and high stability, is known to prevent later arthrosis of the knee. The encouraging observed trend of the reduction of the re-rupture rate in revision surgery and in young patients using the Press-Fit-Hybrid®-technique in comparison to the interference-screw-technique must be confirmed with further studies. LEVEL OF EVIDENCE: Therapeutic Level III, retrospective cohort study.


Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament Reconstruction , Humans , Retrospective Studies , Follow-Up Studies , Knee Joint/surgery , Bone Screws , Anterior Cruciate Ligament Injuries/surgery , Rupture/surgery , Anterior Cruciate Ligament Reconstruction/adverse effects , Anterior Cruciate Ligament Reconstruction/methods
10.
Foot Ankle Orthop ; 7(3): 24730114221112944, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35924004

ABSTRACT

Background: Different fixation techniques are established for first metatarsophalangeal joint (MTPJ) arthrodesis, including compression screws, plates, Kirschner wires, metal- and bioabsorbable screws as well as staples. The purpose of this study was to investigate and present first clinical and radiologic results using a novel human, allogeneic cortical bone screw for arthrodesis of the first MTPJ. Methods: Arthrodesis of the first MTPJ was performed in 31 patients with hallux rigidus. Percentage union and time to union were the first outcomes; visual analog scale for pain, hallux valgus angle (HVA), intermetatarsal angle, and American Orthopaedic Foot & Ankle Society (AOFAS) hallux score were secondary outcomes. Results: Median time to union was 89 days, and union was observed in all patients. There were 4 complications (2 osteolysis margin, 1 cystic brightening, and 1 severe swelling at the first follow-up) all of that resolved at last follow-up. Pain significantly decreased from visual analog scale 8.0 to 0.2 points (P < .0001). The HVA decreased from 30.4 to 10.2 degrees in the patient group with deformities. The total AOFAS score increased significantly from 48 to 87 (P < .0001). Conclusion: Primary and revision arthrodesis of hallux rigidus with the human, allogeneic cortical bone screw reveals satisfying results similar to clinical and radiologic outcomes of other surgical techniques. Within 1 year, the human, allogeneic cortical bone screw is fully remodeled to host bone. Level of Evidence: Level IV, retrospective case series without control group.

11.
Life (Basel) ; 12(7)2022 Jul 11.
Article in English | MEDLINE | ID: mdl-35888116

ABSTRACT

The case describes the revision of an upper ankle prosthesis because of loosening. When ankle replacement is the first choice and actual bone quality does not allow a replacement of the prosthesis, arthrodesis is the only way of reducing pain and gaining stability. The amount of missing bone due to the removed prosthesis was severe. Shark Screws®, made of human allograft cortical bone, were used to fix an allograft femoral head and tibia as well as fibula and talus to each other for stabilization. This was performed without any autologous bone graft and without metal screws. The human matrix of the cortical allograft allows the creation of new vessels followed by osteoblastic activity and production of new bone. The revascularization of the allografts reduces the risk of infection and wound problems. Over time, the patient's bone metabolism allows the allografts to be remodeled into the patient's bone. The case reported here had severe multimorbidity. The loosening of the prosthesis mainly affected the ability to perform housework, mobility, enjoying leisure, and it had a great impact on the emotion and well-being of the patient. One year after surgery, the patient is very satisfied to be able to walk without pain and scratches for about 90 min.

12.
Exp Biol Med (Maywood) ; 238(2): 233-41, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23576804

ABSTRACT

The aim of this study was to find out whether opening of mitochondrial large-conductance Ca(2+)-activated potassium channels (BK(Ca)) protects cardiomyocytes against injury caused by simulated ischemia and reperfusion. This study also aimed to determine whether the protective mechanism involves signaling by reactive oxygen species (ROS) and phosphatidylinositol-3-kinase (PI3K). We used isolated ventricular myocytes, which are believed to contain no functional BK(Ca) channels in the sarcolemma. Cells were isolated from the left ventricles of adult male Wistar rats and subjected to 25-min metabolic inhibition with NaCN and 2-deoxyglucose followed by 30-min re-energization. NS11021 (0.1 µmol/L), a novel BK(Ca) channel opener, or hydrogen peroxide (2 µmol/L) added at re-energization, increased cell survival (the number of rod-shaped cells) and markedly reduced the release of lactate dehydrogenase (LDH). These cytoprotective effects of NS11021 were completely abolished by paxilline, a BK(Ca) inhibitor, or tempol, an antioxidant, but not by wortmannin, an inhibitor of PI3K. NS11021 slightly but significantly increased the fluorescence signal in 2'7'-dichlorodihydrofluorescein diacetate (DCF-DA)-loaded myocytes, indicating an increased ROS formation. The NS11021-induced ROS formation was abolished by paxilline or tempol. NS13558 (0.1 µmol/L), an inactive structural analogue of NS11021, affected neither cell survival/LDH release nor DCF-DA fluorescence. These results suggest that pharmacological activation of mitochondrial BK(Ca) channels effectively protects isolated cardiomyocytes against injury associated with simulated reperfusion. The mechanism for this form of protection requires ROS signaling, but not the activation of the PI3K pathway.


Subject(s)
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/agonists , Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/metabolism , Myocardial Reperfusion Injury/pathology , Myocardial Reperfusion Injury/prevention & control , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/physiology , Animals , Cardiovascular Agents/metabolism , Cell Survival/drug effects , Hydrogen Peroxide/metabolism , L-Lactate Dehydrogenase/analysis , Male , Rats , Rats, Wistar , Tetrazoles/metabolism , Thiourea/analogs & derivatives , Thiourea/metabolism
13.
Curr Pharm Des ; 19(39): 6880-9, 2013.
Article in English | MEDLINE | ID: mdl-23590154

ABSTRACT

The purpose of the present study was to assess the impact of brief daily reoxygenation during adaptation to chronic continuous hypoxia (CCH) on protective cardiac phenotype. Adult male Wistar rats were kept at CCH (10% oxygen) for 5, 15 or 30 days; a subgroup of animals was exposed to room air daily for a single 60-min period. While 5 days of CCH did not affect myocardial infarction induced by 20-min coronary artery occlusion and 3-h reperfusion, 15 days reduced infarct size from 62% of the area at risk in normoxic controls to 52%, and this protective effect was more pronounced after 30 days (41%). Susceptibility to ischemic ventricular arrhythmias exhibited reciprocal development. CCH increased myocardial abundance of mitochondrial superoxide dismutase (MnSOD) without affecting malondialdehyde concentration. Daily reoxygenation abolished both the infarct size-limiting effect of CCH and MnSOD upregulation, and increased malondialdehyde (by 53%). Ventricular cardiomyocytes isolated from CCH rats exhibited better survival and lower lactate dehydrogenase release caused by simulated ischemia/reperfusion than cells from normoxic and daily reoxygenated groups. The cytoprotective effects of CCH were attenuated by the large-conductance Ca2+-activated K+ (BKCa) channel blocker paxilline, while the opener NS1619 reduced cell injury in the normoxic group but not in the CCH group. Daily reoxygenation restored the NS1619- induced protection, whereas paxilline had no effect, resembling the pattern observed in the normoxic group. The results suggest that CCH is cardioprotective and brief daily reoxygenation blunts its salutary effects, possibly by a mechanism involving oxidative stress and attenuation of the activation of mitochondrial BKCa channels.


Subject(s)
Cardiotonic Agents/pharmacology , Hypoxia/metabolism , Oxidative Stress , Oxygen/metabolism , Potassium Channels/metabolism , Animals , Glycosylation , Large-Conductance Calcium-Activated Potassium Channel alpha Subunits , Male , Malondialdehyde/metabolism , Rats , Rats, Wistar , Superoxide Dismutase/metabolism
14.
Am J Physiol Heart Circ Physiol ; 300(2): H507-13, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21112945

ABSTRACT

Chronic hypoxia protects the heart against injury caused by acute oxygen deprivation, but its salutary mechanism is poorly understood. The aim was to find out whether cardiomyocytes isolated from chronically hypoxic hearts retain the improved resistance to injury and whether the mitochondrial large-conductance Ca2+-activated K+ (BKCa) channels contribute to the protective effect. Adult male rats were adapted to continuous normobaric hypoxia (inspired O2 fraction 0.10) for 3 wk or kept at room air (normoxic controls). Myocytes, isolated separately from the left ventricle (LVM), septum (SEPM), and right ventricle, were exposed to 25-min metabolic inhibition with sodium cyanide, followed by 30-min reenergization (MI/R). Some LVM were treated with either 30 µM NS-1619 (BKCa opener), or 2 µM paxilline (BKCa blocker), starting 25 min before metabolic inhibition. Cell injury was detected by Trypan blue exclusion and lactate dehydrogenase (LDH) release. Chronic hypoxia doubled the number of rod-shaped LVM and SEPM surviving the MI/R insult and reduced LDH release. While NS-1619 protected cells from normoxic rats, it had no additive salutary effect in the hypoxic group. Paxilline attenuated the improved resistance of cells from hypoxic animals without affecting normoxic controls; it also abolished the protective effect of NS-1619 on LDH release in the normoxic group. While chronic hypoxia did not affect protein abundance of the BKCa channel regulatory ß1-subunit, it markedly decreased its glycosylation level. It is concluded that ventricular myocytes isolated from chronically hypoxic rats retain the improved resistance against injury caused by MI/R. Activation of the mitochondrial BKCa channel likely contributes to this protective effect.


Subject(s)
Hypoxia/physiopathology , Large-Conductance Calcium-Activated Potassium Channels/physiology , Mitochondria, Heart/physiology , Myocytes, Cardiac/physiology , Animals , Benzimidazoles/pharmacology , Blotting, Western , Cell Separation , Cell Survival , Cells, Cultured , Chronic Disease , Glycosylation , Indoles/pharmacology , Ischemic Preconditioning, Myocardial , L-Lactate Dehydrogenase/metabolism , Large-Conductance Calcium-Activated Potassium Channel beta Subunits/physiology , Large-Conductance Calcium-Activated Potassium Channels/antagonists & inhibitors , Male , Mitochondria, Heart/drug effects , Myocardial Reperfusion Injury/physiopathology , Myocardial Reperfusion Injury/prevention & control , Myocytes, Cardiac/drug effects , Potassium Channel Blockers/pharmacology , Rats , Rats, Wistar
15.
Am J Physiol Heart Circ Physiol ; 294(4): H1948-55, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18296566

ABSTRACT

Monounsaturated fatty acids such as oleic acid are cardioprotective, modify the physicochemical properties of cardiomyocyte membranes, and affect the electrical stability of these cells by regulating the conductance of ion channels. We have designed a nonhydrolysable oleic acid derivative, 2-hydroxyoleic acid (2-OHOA), which regulates membrane lipid structure and cell signaling, resulting in beneficial cardiovascular effects. We previously demonstrated that 2-OHOA induces PKA activation and PKCalpha translocation to the membrane; both pathways are thought to regulate transient outward K(+) current (I(to)) depending on the stimulus and the species used. This study was designed to investigate the effect of 2-OHOA on isolated cardiomyocytes. We examined the dose- and time-dependent effect of 2-OHOA on cytosolic Ca(2+) concentration ([Ca(2+)](i)) transient and contraction of myocytes isolated from different parts of the rat ventricular myocardium. Although this drug had no effect on [Ca(2+)](i) transient and cell shortening in myocytes isolated from the septum, it increased (up to 95%) [Ca(2+)](i) transient and cell shortening in subpopulations of myocytes from the right and left ventricles. The pattern of the effects of 2-OHOA was similar to that observed following the application of the I(to) blocker 4-aminopyridine, suggesting that the drug may act on this channel. Unlike the effect of 2-OHOA on [Ca(2+)](i) transient and cell shortening, PKCalpha translocation to membranes was not region specific. Thus 2-OHOA-induced effects on [Ca(2+)](i) transients and cell shortening are likely related to reductions in I(to) function, but PKCalpha translocation does not seem to play a role. The present results indicate that 2-OHOA selectively increases myocyte inotropic responsiveness, which could underlie its beneficial cardiovascular effects.


Subject(s)
Calcium Signaling/drug effects , Cardiotonic Agents/pharmacology , Myocardial Contraction/drug effects , Myocytes, Cardiac/drug effects , Oleic Acids/pharmacology , 4-Aminopyridine/pharmacology , Animals , Cell Membrane/drug effects , Cell Membrane/metabolism , Cell Size/drug effects , Cell Survival/drug effects , Cells, Cultured , Cytosol/drug effects , Cytosol/metabolism , Dose-Response Relationship, Drug , Heart Septum/drug effects , Heart Septum/metabolism , Heart Ventricles/drug effects , Heart Ventricles/metabolism , Male , Myocytes, Cardiac/enzymology , Myocytes, Cardiac/metabolism , Potassium Channel Blockers/pharmacology , Potassium Channels/drug effects , Potassium Channels/metabolism , Protein Kinase C-alpha/metabolism , Protein Transport , Rats , Rats, Sprague-Dawley , Time Factors
16.
Am J Physiol Cell Physiol ; 290(2): C583-91, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16207797

ABSTRACT

We hypothesized that activation of heat shock protein 70 (HSP70) by preconditioning, which is known to confer delayed cardioprotection, attenuates the impaired handling of Ca(2+) at multiple sites. To test the hypothesis, we determined how the ryanodine receptor (RyR), sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), and Na(+)/Ca(2+) exchanger (NCX) handled Ca(2+) in rat ventricular myocytes preconditioned with a kappa-opioid receptor agonist, U50488H (UP), followed by blockade of HSP70 with a selective antisense oligonucleotide and subsequently subjected to simulated ischemia. We determined the following: 1) the Ca(2+) transients induced by electrical stimulation and caffeine, which provide the overall picture of Ca(2+) homeostasis; 2) expression of RyR, SERCA, and NCX; and 3) Ca(2+) fluxes via NCX by the use of (45)Ca(2+) in the rat ventricular myocyte. We found that UP increased the activity of RyR, SERCA, and NCX and the expression of RyR and SERCA. These effects led to increases in the release of Ca(2+) from the sarcoplasmic reticulum via RyR and in the removal of Ca(2+) from the cytoplasm by reuptake of Ca(2+) to the SR via SERCA and by extrusion of Ca(2+) out of the cell via NCX. UP also reduced mitochondrial Ca(2+) accumulation. All of the effects of UP were either abolished or significantly attenuated by blockade of HSP70 synthesis with a selective antisense oligonucleotide. The results are evidence that activation of HSP70 by preconditioning improves the ischemia-impaired Ca(2+) homeostasis at multiple sites in the heart, which may be responsible, at least partly, for attenuated Ca(2+) overload, improved recovery in contractile function, and cardioprotection.


Subject(s)
Calcium/metabolism , HSP70 Heat-Shock Proteins/metabolism , Heart Ventricles/cytology , Homeostasis , Ischemia , Myocytes, Cardiac/metabolism , 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer/pharmacology , Animals , Antihypertensive Agents/pharmacology , Caffeine/pharmacology , Calcium-Transporting ATPases/metabolism , Cells, Cultured , HSP70 Heat-Shock Proteins/genetics , Male , Mitochondria/metabolism , Myocytes, Cardiac/cytology , Myocytes, Cardiac/drug effects , Oligonucleotides, Antisense/genetics , Oligonucleotides, Antisense/metabolism , Phosphodiesterase Inhibitors/pharmacology , Rats , Rats, Sprague-Dawley , Sarcoplasmic Reticulum Calcium-Transporting ATPases , Sodium-Calcium Exchanger/metabolism
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