Cardiomyocyte hypercontracture Gao Qin
Cardiomyocyte hypercontracture Gao Qin
Background The first minutes of reperfusion repre-sent a window of opportunity for cardioprotection Development of cardiomyocyte hyper- contracture is a predominant feature of reperfusion injury
Background • The first minutes of reperfusion repre-sent a window of opportunity for cardioprotection • Development of cardiomyocyte hypercontracture is a predominant feature of reperfusion injury
Backg round A pattern of contracture and necrotic cell injury "Contraction band necrosis" can be found during the early stage of the infarct ·“Contraction band necrosis”reflects hypercontracture of myocytes
Background • A pattern of contracture and necrotic cell injury “Contraction band necrosis” can be found during the early stage of the infarct • “Contraction band necrosis” reflects hypercontracture of myocytes
Infarct size Contraction band necrosis
Infarct size Contraction band necrosis
(i)Time 0s 20μM (ii)Time 284 s (iin)Time 338 s (iv)Time 538s (v)Time 763s Confocal image of adult ventricular myocyte loaded with TMRM
Confocal image of adult ventricular myocyte loaded with TMRM
What causes contracture
Mechanisms of contracture Ischemia-induced contracture Rigor-type mechanism Reperfusion-induced hypercontracture Ca2+overload-induced contracture Rigor-type contracture
Mechanisms of contracture • Ischemia-induced contracture Rigor-type mechanism • Reperfusion-induced hypercontracture Ca2+ overload-induced contracture Rigor-type contracture
Ischemia-induced contracture Rigor-type mechanism Low cytosolic ATP myefibrillar shortening cytoskeletal defects -cardiomyocytes more fragile and susceptible to mechanical damage
Ischemia-induced contracture • Rigor-type mechanism Low cytosolic ATP myofibrillar shortening cytoskeletal defects cardiomyocytes more fragile and susceptible to mechanical damage
Reperfusion-induced hypercontracture Much greater myofibrillar shortening and cytoskeletal damage Aggravated form of contracture lead to a marked rise in end-diastolic pressure
Reperfusion-induced hypercontracture • Much greater myofibrillar shortening and cytoskeletal damage • Aggravated form of contracture lead to a marked rise in end-diastolic pressure
Two causes for reperfusion- induced hypercontracture Ca2+overload-induced contracture -energy recovery rapid but cytosolic Ca2+load high Rigor-type contracture -energy recovery very slow
Two causes for reperfusioninduced hypercontracture • Ca2+ overload-induced contracture energy recovery rapid but cytosolic Ca2+ load high • Rigor-type contracture energy recovery very slow