Date post: | 31-Dec-2015 |
Category: |
Documents |
Upload: | reynold-johns |
View: | 219 times |
Download: | 0 times |
Basic Knowledge
1.what is ischemic preconditioning (IPC)?A phenomenon by which a brief episodes of myocardial ischemia increases the ability of the heart to tolerate a subseqent prolonged period of ischemic injury.
2. Early phase (‘classical’conditioning ) and delayed phase (‘second window’of protection)
Early phase appears immediately; delayed phase appears at 24,48,72 hours following brief periods of preconditioning ischemia.
3.Triggers of ischemic preconditioning
1) Receptor dependent triggers
A. Adenosine receptors
B. Opioid receptors
2) Receptor independent triggers
A. Nitric oxide
B. Free radicals
•A1 adenosine receptor (A1AR)•A1AR is found in the myocytes and in the vascular smooth muscle.
•A2 adenosine receptor (A2AR)•A2AR including A2A and A2B,can be found in the endot
helium and the vascular smooth muscle .
•A3 adenosine receptor (A3AR)•Locate in the plasmatic membrane of the myocytes.
Fig.3.Values of left ventricular developed pressure (LVDP), in the control group,the group treated with adenosine, and the group where adenosine and DPCPX (A1 blocker) were administered.Note that adenosine attenuated the systolic alterations of post ischemic dysfunction. This effect was abolished with the administation of DPCPX.*P<0.05 vs. control.
Fig.4.Size of the infarct expressed as percentage of the area of the left ventricle in the control group, the group treated with adenosine,and the group where adenosine plus DDCPX(A1 blocker) was administered .*p<0.05 vs control.
Fig.5.The effect of 1microM MRS-1191 (adenosine A3 receptor antagonist ) upon
protection conferred by 2-Cl-IB-MECA at reperfusion.
Fig.7. Principal experimental evidence for participation of adenosine as a trigger of delayed preconditioning and for delayed myocardial protection induced by selective activation of adenosine receptor subtypes
Fig.8. Cellular protection against SI in A1AR- tgm compared with wt.(Wt:wild-type-mice;SMT, an iNOS inhibitor; Glb: a KATP channel blocker; 5-HD:a mitochondrial KATP channel blocker).
1.Molecules Invovled in Ischemic Preconditioning
•ATP-sensitive K channel
•PKC and tyrosine kinases
•p38 MAP kinase
•Heat shock protein (HSP27)
•Nuclear factor-κB and AP-1
•Superoxide dismutase
•Inducible nitric oxide symthase
1.Molecules Invovled in Ischemic Preconditioning
•ATP-sensitive K channel
•PKC and tyrosine kinases
•p38 MAP kinase
•Heat shock protein (HSP27)
•Nuclear factor-κB and AP-1
•Superoxide dismutase
•Inducible nitric oxide symthase
1.Molecules Invovled in Ischemic Preconditioning
•ATP-sensitive K channel
•PKC and tyrosine kinases
•p38 MAP kinase
•Heat shock protein (HSP27)
•Nuclear factor-κB and AP-1
•Superoxide dismutase
•Inducible nitric oxide symthase
1.Molecules Invovled in Ischemic Preconditioning
•ATP-sensitive K channel
•PKC and tyrosine kinases
•p38 MAP kinase
•Heat shock protein (HSP27)
•Nuclear factor-κB and AP-1
•Superoxide dismutase
•Inducible nitric oxide symthase
1.Molecules Invovled in Ischemic Preconditioning
•ATP-sensitive K channel
•PKC and tyrosine kinases
•p38 MAP kinase
•Heat shock protein (HSP27)
•Nuclear factor-κB and AP-1
•Superoxide dismutase
•Inducible nitric oxide symthase
1.Molecules Invovled in Ischemic Preconditioning
•ATP-sensitive K channel
•PKC and tyrosine kinases
•p38 MAP kinase
•Heat shock protein (HSP27)
•Nuclear factor-κB and AP-1
•Superoxide dismutase
•Inducible nitric oxide symthase
1.Molecules Invovled in Ischemic Preconditioning
•ATP-sensitive K channel
•PKC and tyrosine kinases
•p38 MAP kinase
•Heat shock protein (HSP27)
•Nuclear factor-κB and AP-1
•Superoxide dismutase
•Inducible nitric oxide symthase
Fig.18.Outline of the principal stages leading to cellular adaptation in delayed preconditioning .Several diffusible mediators including adenosine,contribute critically to the trigger phase that initiates the adaptive response.
Fig.19. Hypothetical pathways by which adenosine receptor activation might lead to the delayed protection