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Creatine kinase system in failing and nonfailing human myocardium
L Nascimben1, J S Ingwall, P Pauletto
1Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. luigin@bustoff.bwh.harvard.edu
Insights
The creatine kinase (CK) system, crucial for heart energy, shows reduced activity and creatine in failing and donor human hearts. This may impair ATP delivery, impacting cardiac function.
Area of Science:
- Cardiology
- Biochemistry
- Molecular Biology
Background:
- The creatine kinase (CK) reaction is vital for ATP resynthesis in the heart.
- Existing studies on the human cardiac CK system in failing and nonfailing hearts are limited and conflicting.
- This study aimed to clarify the CK system in human myocardium.
Purpose of the Study:
- To measure CK activity, isoenzyme levels, and creatine/CK-B content in human failing and nonfailing myocardium.
- To resolve conflicting data regarding the cardiac CK system in human heart failure.
- To assess the implications for ATP energy supply in the heart.
Main Methods:
- Myocardium samples were obtained from heart transplant recipients, intensive care unit patients awaiting heart harvesting, accident victims, and cardiac surgery patients.
- Data were analyzed for three groups: failing, donor, and control hearts.
- Activities of CK and its isoenzymes (CK-MM, CK-MB, mitochondrial CK) and contents of creatine and CK-B were measured in myocardial homogenates.
Main Results:
- CK activity was significantly lower in failing and donor ventricles compared to control.
- CK-MM and mitochondrial CK activities were reduced in failing and donor left ventricles (LV).
- CK-MB activity and CK-B content were elevated in failing and donor hearts, while creatine levels were decreased.
Conclusions:
- Failing and nonfailing donor human myocardium exhibit decreased CK activity and creatine content.
- This reduction may compromise the heart's ability to supply ATP to energy-dependent processes.
- The findings highlight potential energy deficits in cardiac dysfunction and donor hearts.
Background:
The creatine kinase (CK) reaction is important for rapid resynthesis of ATP when the heart increases its work. Studies defining the CK system in human failing and nonfailing myocardium are limited and in conflict. To resolve this conflict, we measured the activities of CK and its isoenzymes and the contents of creatine and CK-B in homogenates of human myocardium.
Methods And Results:
Myocardium was sampled from 23 subjects who underwent heart transplant, 36 subjects maintained in an intensive care unit before heart harvesting, 13 accident victims, and 2 patients undergoing heart surgery. Since the characteristics of myocardium of potential organ donors differed from those of myocardium of accident victims, data are presented for three groups: failing, donor, and control. CK activity was 7.7 +/- 1.9 and 6.0 +/- 1.4 IU/mg protein in left (LV) and right (RV) ventricles of failing, 9.4 +/- 2.5 and 10.7 +/- 2 IU/mg protein in LV and RV of donor, and 11.6 +/- 2.4 IU/mg protein in LV of control hearts. CK-MM and the mitochondrial isoenzyme activities were lower in failing and donor LV, and CK-MB activity and CK-B content were higher in failing and donor hearts. Creatine contents were 64 +/- 25 and 56 +/- 18.6 nmol/mg protein in LV and RV of failing, 96 +/- 30 and 110 +/- 24 nmol/mg protein in LV and RV of donor, and 131 +/- 28 nmol/mg protein in LV of control hearts.
Conclusions:
In failing and nonfailing donor human myocardium, there is a combined decrease of CK activity and creatine that may impair the ability to deliver ATP to energy-consuming systems.