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Published on: November 1, 2012
Effect of creatine phosphate on the contractile activity in acutely failing rat heart
P Kôrge1, M L Silber, P D Gollnick
1Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology College of Veterinary Medicine, Washington State University, Pullman 99164-6410, WA, USA.
Insights
Infusing creatine phosphate (CP) into rats with failing hearts restored normal cardiac function. This treatment normalized key metabolites and improved calcium uptake in heart muscle, unlike other tested solutions.
Area of Science:
- Cardiology
- Biochemistry
- Pharmacology
Background:
- Acute heart failure can result from cardiac overload.
- Metabolic changes, including depletion of adenosine triphosphate and creatine phosphate (CP), occur in failing hearts.
- Impaired calcium handling by sarcoplasmic reticulum is a feature of cardiac dysfunction.
Purpose of the Study:
- To investigate the efficacy of creatine phosphate (CP) infusion in restoring cardiac function in acutely failing rat hearts.
- To assess the impact of CP on cardiac metabolism and sarcoplasmic reticulum function.
Main Methods:
- Acute heart failure was induced in rats by constricting the ascending aorta.
- Following failure, rats were infused with solutions containing saline, CP, creatine, or creatine plus phosphate.
- Cardiac function was evaluated using hemodynamic parameters, and myocardial metabolites and sarcoplasmic reticulum Ca2+ uptake were measured.
Main Results:
- Infusion of CP, but not other tested solutions, restored normal cardiac function.
- CP infusion normalized depleted adenosine triphosphate and CP levels and reduced elevated lactate in the myocardium.
- CP treatment improved depressed Ca2+ uptake by isolated sarcoplasmic reticulum in failing hearts.
Conclusions:
- Creatine phosphate (CP) infusion is effective in restoring cardiac function in acute heart failure.
- CP's beneficial effects are linked to the restoration of myocardial energy metabolism and improved calcium handling.
- CP represents a potential therapeutic agent for managing acute cardiac dysfunction.
Abstract:
The hypothesis was tested that infusion of a solution containing creatine phosphate (CP) into rats with acutely failing hearts would enhance recovery of cardiac function. The acutely failing heart was produced by constricting the ascending aorta. This overload produced failure in approximately 25 min. At the point of failure the constriction was removed and solutions containing sterile physiological saline (PSS), PSS and CP, PSS and creatine, or PSS and creatine plus phosphate were infused. Cardiac function was assessed from systolic and diastolic blood pressure, +/- dp/dt, heart rate, and cardiac work. Ca2+ uptake by isolated sarcoplasmic reticulum and the concentrations of selected blood and tissue metabolites were measured. Normal cardiac function was restored in the PSS-CP infused rats whereas all other treatments did not restore cardiac function. Adenosine triphosphate and CP had declined in the myocardium of the failing hearts while lactate was elevated. The concentrations of these metabolites were normal in the PSS-CP infused animals. The glycogen concentration in the myocardium was reduced following the constriction. Ca2+ uptake by isolated sarcoplasmic reticulum was depressed in the failed hearts but normal in the hearts of CP-infused animals. These results demonstrate that the infusion of CP into animals with failing hearts can be effective in restoring cardiac function.
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