Objective To evaluate the effects of morphine preconditioning-postconditioning on ischemia-reperfusion (I/R) injury in isolated rat hearts. Methods Male SD rats weighing 180-200 g were killed after intraperitoneal injection of heparin 500 U/kg. The hearts were immediately removed and perfused in a Langendorff apparatus with K-H solution gassed with 95%O2-5%CO2 .HR and left ventricular systolic pressure (LVSP) were measured from a fluid-filled latex balloon in the left ventricle. Global myocardial ischemia was induced by interrupting perfusion for 45 min followed by 60 min reperfusion. Forty isolated rat hearts were randomly divided into 5 groups (n = 8 each): group 1 (I/R); group II morphine preconditioning (M1 ); group Ⅲ morphine postconditioning (M2); group IV M1 + M2; group V 5-hydroxydecanoate (5-HD) + M2. Group M1 was perfused with K-H solution containing morphine 3.0 μmol/L for 20 min 30 min before ischemia followed by 10 min normal K-H solution perfusion. Group M2 was perfused with K-H solution containing morphine 3.0 μmol/L for 10 min at the beginning of reperfusion followed by 50 min normal K-H solution perfusion. Group 5-HD + M2 was perfused with K-H solution containing morphine 3.0 μmol/L+ 5-HD 10-4 mmol/L for 10 min at the beginning of reperfusion followed by 50 min normal K-H solution perfusion. Myocardial CK-MB activity was measured and myocardial infarct size (IS/AAR) detennined (by 2,3,5-triphenyl tetrazolium staining) at the end of 60 min reperfusion. Results The preconditioning, postconditioning and combination of preconditioning and postconditioning with morphine 3.0 μmol/L perfusion for 10 min all provided cardio-protective effects in terms of IS/AAR and myocardial activation of CK-MB. Conclusion Although the combination of morphine preconditioning and postconditioning can protect the heart against I/R injury, the effects are similar to those of either of them alone, and the reason may be that either of them alone protects the heart against I/R injury via activating mitoKATP .

Objective To determine whether morphine postconditioning (MP) could protect the heart against ischemia reperfusion (I/R) injury and which specific type(s) of the opioid receptor is involved in the cardioprotective effect produced by hiP. Methods Male SD rots weighing 180-200 g were killed after intraperitoneal heparin 500 U/kg. The hearts were immediately removed and passively perfused in a Langendorff apparatus with K-H solution gassed with 95% O2-5% CO2. HR and left ventricular systolic pressure (LVSP) were measured from a fluid-filled latex balloon in the left ventricle. Global myocardial ischemia was induced by interrupting perfusion for 45 min followed by 60 min reperfusion. The experiment was performed in 3 parts. In Part Ⅰ 32 isolated rat hearts were randomly divided into 4 groups (n = 8 each): group Ⅰ control received no treatment; group Ⅱ ,Ⅲ,Ⅳ were first perfused with K-H solution containing morphine 0.3, 3.0 and 30 μmol/L respectively for 10 min immediately after the end of ischemia followed by 50 min normal K-H solution perfusion. In part Ⅱ,the concentration of morphine in K-H solution which provided the best cardio-protective effects was chosen according to the result of Part Ⅰ , 32 isolated rat hearts were randomly divided into 4 groups ( n = 8 each) : group Ⅰ received no treatment; gvoup Ⅱ,ⅢⅣ were first perfused with K-H solution containing morphine for 5, 10, 20 min respectively immediately after ischemia followed by 50 min peffusion with normal K-H solution. In part Ⅲ,the MP method which provided the best cardio-protective effects was chosen according to the result of Part Ⅱ , 37 isolated rat hearts were randomly divided into 5 groups: group Ⅰ control (n=8);group Ⅱ-Ⅴ were first perfused for 10 min with K-H solution containing morphine (Ⅱ,n = 8)/morphine + naloxone 10 μmol/L(Ⅲ, n = 7)/morphine + nor-binaltorphimine 5 μmol/L (specific κ receptor antagonist, n = 7)/morphine + nalu'indole 5 μmol/L (specific δ receptor antagonist, n = 7) followed by 50 min reperfusion with normal K-H solution. Myocardial CK-MB activity was measured and myocardial infarct size (IS/AAR) determined (by 2,3,5-triphenyl tetrazolium staining) at the end of 60 min reperfusion.Results The postconditioning with morphine 3.0 μmol/L perfusion for 10 min provided the best cardio-protective effects in terms of IS/AAR and myocardial release of CK-MB. Nuloxone completely abolished the cardio-protective effects of MP. Nor-binaltorphimine partly reversed the protective effect of MP, while naltrindole had no effects on MP. Conclusion MP protects the heart against I/R injury via activating κ receptor.

Objective:To explore the clinical and imaging characteristics of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) caused by mitochondrial DNA 14453G>A (m.14453G>A) mutation.Methods:A case of MELAS caused by m.14453G>A mutation in the First Affiliated Hospital of Harbin Medical University on October 12, 2021 was reported. At the same time, the reported cases of MELAS and Leigh syndrome (LS) caused by the m.14453G>A mutation were reviewed. This enabled a comprehensive summarization, analysis, and comparison of these cases.Results:The patient was a female. She has suffered from the disease since 13-year old with seizures, accompanied by the disturbance of mood and the loss of memory. Brain magnetic resonance imaging findings consisted of lesions in frontal, parietal, occipital, temporal lobe and cerebellar. The patient was initially considered with autoimmune encephalitis and posterior reversible encephalopathy syndrome. Since direct sequencing of the complete mitochondrial genome from blood of the patient revealed m.14453G>A mutation in ND6 gene, and the mutation rate was 17.0%, the patient eventually diagnosed with MELAS based on clinical manifestations, imaging examinations, and genetic testing results. Using "m.14453G>A" as the search term, the relevant literature in China and abroad was retrieved and those with complete clinical data were identified. A total of 11 cases of m.14453G>A mutation including this case were reported, of whom 5 patients were diagnosed as MELAS, and 6 patients were diagnosed as LS. Among the 11 patients, those being adolescent or adult and with lesions in the cortex and subcortical white matter were probably be MELAS; those being infant or young child and with lesions in basal ganglia, thalamus and brainstem could be LS. Conclusions:Mitochondrial disease caused by m.14453G>A gene mutation shows a great heterogeneity, which can cause MELAS and LS. The clinical phenotype of the m.14453G>A mutation may be related to the age of onset and lesion′ s location.