September 1, 1995AJP Heart and Circulatory Physiology
Inhibition of the creatine kinase reaction decreases the contractile reserve of isolated rat hearts
Key result
Inhibition of creatine kinase to <2% of control activity by iodoacetamide reduced the contractile reserve of isolated rat hearts by approximately 50%.
Population
Isolated perfused rat hearts
Comparison
Iodoacetamide exposure to chemically inhibit… vs Control hearts (uninhibited CK activity)
Design
Preclinical
Follow-up
30 min
Authors
Discussion
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Member takes
Implication
Suggests CK is vital for contractile reserve under stress; leaves open translation to intact models or humans.
Key Points
- To determine the role of creatine kinase-mediated phosphoryl transfer in sustaining cardiac work and contractile reserve during acute physiological stress.
- Isolated perfused rat hearts were treated with iodoacetamide to selectively inhibit creatine kinase activity without altering mitochondrial respiration, actomyosin ATPase, or adenylate kinase.
- Hearts were subjected to three stress models: hypercalcemic perfusion (n = 7), norepinephrine infusion (n = 6), or hypoxic buffer perfusion (n = 5).
- Myocardial performance and high-energy phosphate kinetics were evaluated using hemodynamic tracking and 31P magnetization transfer.
- Iodoacetamide reduced creatine kinase activity to near zero by 31P magnetization transfer and to 2% of control in homogenates, without altering baseline hemodynamics at physiological perfusion pressures for at least 30 minutes.
- Inotropic stimulation was impaired, as the stress-induced increase in left ventricular developed pressure dropped by 39% under hypercalcemic perfusion and by 54% during norepinephrine infusion.
- During hypoxia, the phosphocreatine depletion rate declined by 57%, left ventricular developed pressure fell, and end-diastolic pressure escalated more rapidly than controls, reflecting an overall ~50% drop in contractile reserve.
Structured PICO
P
Population
Isolated perfused rat hearts (n=18: n=7 for hypercalcemic buffer perfusion, n=6 for norepinephrine infusion, n=5 for hypoxic buffer perfusion)
I
Intervention
Iodoacetamide (IA) exposure to chemically inhibit creatine kinase (CK) activity
C
Comparator
Control hearts (uninhibited CK activity)
O
Outcome
Cardiac performance (end-diastolic pressure, left ventricular developed pressure, and heart rate) under physiological and acute stress conditionssurrogate
Inhibition of creatine kinase activity significantly reduces contractile reserve during acute stress in isolated rat hearts, demonstrating its essential role in myocardial performance.
Cite This Study
Hamman et al. (1995) studied Isolated rat hearts (n=18). Iodoacetamide (IA) vs. Control was evaluated on Contractile reserve (left ventricular developed pressure during stress). Inhibition of creatine kinase to <2% of control activity by iodoacetamide reduced the contractile reserve of isolated rat hearts by approximately 50%.