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Date of Award
1994
Document Type
Thesis - Pacific Access Restricted
Degree Name
Master of Science (M.S.)
Department
Physiology and Pharmacology
First Advisor
Denis J. Meerdink
First Committee Member
James W. Blankenship
Second Committee Member
Robert Oberlender
Third Committee Member
Howell I. Runion
Abstract
The effect of carbonylcyanide m-chlorophenylhydrazone (CCCP) on the performance of isolated retrograde-perfused rabbit hearts was investigated in the present study. CCCP was first investigated as the blocking agent of photosynthesis. CCCP is also commonly used as the metabolic inhibitor of energy production. The animals were heparinized and anesthetized, the hearts were quickly removed and perfused with Krebs-Henseleit buffer in Langendorff's mode. Two parallel perfusion systems were used to distinguish the control and the treated heart. Two different concentrations of CCCP, low-dose (0.1 μM) and high-dose (0.5 μM), were used to study the dose-dependent relationship. The hemodynamic parameters used in the present study are aortic pressure (AOP), end diastolic pressure (EDP), peak systolic pressure (PSP), left ventricular developed pressure (LVDP), the rate of change of left ventricular pressure (positive dP/dt & negative dP/dt), and heart rate (HR).
In general, CCCP impaired the mechanical performance of the heart by decreasing cardiac contractility. Positive and negative dP/dt were decreased 49.4% and 55.6%, respectively, by the low-dose of CCCP. High-doses of CCCP also decreased positive dP/dt and negative dP/dt by 81.4% and 88.9%, respectively. In addition, low-dose CCCP caused decreases of peak systolic pressure and left ventricular pressure developed by 50.4% and 61.6%. Similarly, high-dose CCCP decreased PSP and LVDP by 74.8% and 92.5%, respectively. The end diastolic pressure was increased 66.8% by low-dose CCCP. CCCP had no significant effects on aortic pressure and the heart rate.
In conclusion, CCCP impaired the mechanical performance of the isolated perfused hearts as evidenced by decreasing PSP, LVDP, positive dP/dt and negative dP/dt. This degradation of myocardial performance showed a dose-dependent relationship. CCCP also caused a higher incidence rate of arrhythmia. Because CCCP uncoupled the electron transport from the ATP production in the mitochondria, the present study suggested that the development of contracture and heart failure was due to the energy depletion by CCCP.
Pages
51
Recommended Citation
Song, Shiunn-Li Robert. (1994). Effects of carbonylcyanide m-chlorophenylhydrazone (CCCP) on the performance of isolated perfused rabbit hearts. University of the Pacific, Thesis - Pacific Access Restricted. https://scholarlycommons.pacific.edu/uop_etds/2278
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