心肌缺血预处理精品PPT教学课件
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EARLY SIGNALING PATHWAY IN HEART PROTECTION BY ISCHEMIC PRECONDITIONING
2020/12/6
1
Ischemic preconditioning (PC) is the phenomenon describing protection of the heart against reperfusion injury following prolonged ischemia, by virtue of prior short episode (or episodes) of ischemia and reperfusion.
D ev.Pressur e (recov ery % )
120
100
80
60
40
20
0 0
2020/12/6
Control CPC
20
40
60
80
7
Duration Ischemia (min)
+dP/dt (%) Versus Ischemic Time ±Preconditioning (CPC)
Several possibilities have been suggested including:
•adenosine activation;
•preservation of high-energy phosphates;
•washout of metabolites;
•rol20e20o/12f/6Ca++-channels;
We work with the isolated rat heart, and will focus on the first
window.
2020/12/6
5
Cardiac Function without and with PC has been studied. Below the following parameters are presented:
E DP (m mH g)
100
Control CPC 80
60
40
20
0
0
20
40
60
80
2020/12/6
Duration of Ischemia (min)
9
BIOCHEMISTRY
• Biochemical parameters of the heart tissue: a similar protection was observed for ATP, energy charge, ascorbate and other parameters.
0
2020/12/6
SP
Ino AA
UA
Control: ischemia of 35’- no PC Preconditioning fo11llowed by 35’ ischemia
Currently Proposed Mechanisms of Protection by PC
The detailed understanding of the mechanism of PC is still under investigation.
12
•increase in antioxidants activity; •synthesis of heat-shock proteins, G-proteins; •nitric oxide production; •role of K+-channels; •role of PKC
•WE HAVE BEEN STUDYING THE ROLES OF IRON,
2020/12/6
2
An analogous phenomenon of cardiac protection against reperfusion injury by pre-administration of a drug is called drug-induced PC.
We have developed a family of drugs that can do it.
+ d P /d t (r eco ve ry % )
120
100
80 60
40
20
0 0
2020/12/6
Control CPC
20
40
60
80
Duration of Ischemia (min)
8
EDP (mmHg) Versus Ischemic Time ±Preconditioning (CPC)
• in the coronary flow: leakage into the CF of cellular metabolites:
2020/12/6
10
HPLC Analysis of the First 10-CFFs Following 35’ Global Ischemia PC
70 60 50 40 30 20 10 SA
2020/12/6
3
The System: Isolated rat heart The procedure : Three episodes of 2’ global ischemia separated by 3’ reperfusion
PC
Stabilization Pc R Pc R Pc R
10 min
1 12 23 3
Reperfusion
20 min
Ischemia
2020/12/6
4
Two windows of protection by ischemic PC have been identified: 1 – 3 hours following PC, and 24
hour following PC.
DP = PSP - EDP
+dP/dt
EDPBaidu Nhomakorabea
other parameters not shown
2020/12/6
6
Developed Pressure (DP) (% of pre-ischemic value) Versus Ischemic Time ± Preconditioning (PC)
COPPER AND FREE RADICALS IN ISCHEMIA AND
OBTAINED INDICATIONS FOR THEIR
I2N02V0/1O2/6LVEMENT IN CARDIAC PC
2020/12/6
1
Ischemic preconditioning (PC) is the phenomenon describing protection of the heart against reperfusion injury following prolonged ischemia, by virtue of prior short episode (or episodes) of ischemia and reperfusion.
D ev.Pressur e (recov ery % )
120
100
80
60
40
20
0 0
2020/12/6
Control CPC
20
40
60
80
7
Duration Ischemia (min)
+dP/dt (%) Versus Ischemic Time ±Preconditioning (CPC)
Several possibilities have been suggested including:
•adenosine activation;
•preservation of high-energy phosphates;
•washout of metabolites;
•rol20e20o/12f/6Ca++-channels;
We work with the isolated rat heart, and will focus on the first
window.
2020/12/6
5
Cardiac Function without and with PC has been studied. Below the following parameters are presented:
E DP (m mH g)
100
Control CPC 80
60
40
20
0
0
20
40
60
80
2020/12/6
Duration of Ischemia (min)
9
BIOCHEMISTRY
• Biochemical parameters of the heart tissue: a similar protection was observed for ATP, energy charge, ascorbate and other parameters.
0
2020/12/6
SP
Ino AA
UA
Control: ischemia of 35’- no PC Preconditioning fo11llowed by 35’ ischemia
Currently Proposed Mechanisms of Protection by PC
The detailed understanding of the mechanism of PC is still under investigation.
12
•increase in antioxidants activity; •synthesis of heat-shock proteins, G-proteins; •nitric oxide production; •role of K+-channels; •role of PKC
•WE HAVE BEEN STUDYING THE ROLES OF IRON,
2020/12/6
2
An analogous phenomenon of cardiac protection against reperfusion injury by pre-administration of a drug is called drug-induced PC.
We have developed a family of drugs that can do it.
+ d P /d t (r eco ve ry % )
120
100
80 60
40
20
0 0
2020/12/6
Control CPC
20
40
60
80
Duration of Ischemia (min)
8
EDP (mmHg) Versus Ischemic Time ±Preconditioning (CPC)
• in the coronary flow: leakage into the CF of cellular metabolites:
2020/12/6
10
HPLC Analysis of the First 10-CFFs Following 35’ Global Ischemia PC
70 60 50 40 30 20 10 SA
2020/12/6
3
The System: Isolated rat heart The procedure : Three episodes of 2’ global ischemia separated by 3’ reperfusion
PC
Stabilization Pc R Pc R Pc R
10 min
1 12 23 3
Reperfusion
20 min
Ischemia
2020/12/6
4
Two windows of protection by ischemic PC have been identified: 1 – 3 hours following PC, and 24
hour following PC.
DP = PSP - EDP
+dP/dt
EDPBaidu Nhomakorabea
other parameters not shown
2020/12/6
6
Developed Pressure (DP) (% of pre-ischemic value) Versus Ischemic Time ± Preconditioning (PC)
COPPER AND FREE RADICALS IN ISCHEMIA AND
OBTAINED INDICATIONS FOR THEIR
I2N02V0/1O2/6LVEMENT IN CARDIAC PC