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Dissertation Information for Scott Michael Malinconico

NAME:
- Scott Michael Malinconico

DEGREE:
- Ph.D.

DISCIPLINE:
- Biochemistry

SCHOOL:
- Pennsylvania State University (USA) (1981)

ADVISORS:
- None

COMMITTEE MEMBERS:
- None

MPACT Status: Incomplete - Not_Inspected

Title: EFFECT OF HALOTHANE ON CARDIAC CALCIUM METABOLISM DURING CONTRACTION

Abstract: Heart cells in culture need no external stimulation to contract, they beat rhythmically at a rate and intensity dependent on culture conditions. These cells respond to the general anesthetic Halothane with a loss of beating intensity and a lessening of beating rate. Because of these characteristics, beating heart cells make an ideal system to study the theory that the anesthetic Halothane depresses cardiac beating at the membrane level by altering calcium flux across cell membranes.

In this study it has been shown that Halothane does affect calcium metabolism taking place during cardiac cell contraction. Halothane was found to depress both beating rate and intensity observed in heart cells in culture in a dose-related manner. Halothane depressed beating rate and intensity at concentrations of anesthetic used clinically to maintain anesthesia. Increased extracellular calcium in the growth medium of heart cells in culture was able to completely restore depressed beating intensity caused by Halothane. Depressed beating rate did not change during the calcium titration.

Calcium flux across the cardiac sarcolemma is affected by Halothane. Of the four phases of calcium flux (i.e., fast and slow influx, fast and slow efflux) Halothane only depresses the fast calcium influx. Increased calcium concentrations prevented Halothane depression of the fast calcium influx of heart cells in culture.

Calcium uptake and Ca('++)-ATPase activity of sarcoplasmic reticulum vesicles are depressed by exposure to Halothane. The magnitude of Halothane depression depends on the calcium concentration in the assay medium. Halothane depression of sarcoplasmic reticulum function occurs by an apparent competitive-type inhibition.

Results of these experiments support the theory that Halothane varies the amount of calcium ions participating in excitation-contraction coupling. A possible mechanism of Halothane depression of myocardial beating intensity involves the reduction of the amount of calcium available to the contractile proteins for initiation of contraction. The reduction takes place through a depression of calcium flux across both the cardiac sarcolemma and the cardiac sarcoplasmic reticulum membrane. Halothane appears to exert its effects through a depression of calcium binding to membrane proteins. This mechanism of Halothane action may extend to nerve tissue to explain the phenomenon of anesthesia.

MPACT Scores for Scott Michael Malinconico

A = 0
C = 1
A+C = 1
T = 0
G = 0
W = 0
TD = 0
TA = 0
calculated 2008-01-31 06:13:42

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