Heppner, Richard L.

Abstract A method for controlling the plasma creatinine concentration is described. This method uses continuous determination of the plasma creatinine concentration and a servomechanism which drives an infusion pump at a rate proportional to the difference between the actual and desired creatinine concentrations. The rate and volume of creatinine infusion necessary to maintain the desired plasma concentration provide information related to kidney function and the accumulation of creatinine in the body. Experiments using this technic and the method of data analysis are described. It has been shown that under certain conditions this technic may be used to estimate the renal clearance of creatinine and the size and nature of the space into which creatinine is distributed in the dog.

I. Tension was recorded from a segment of a thin bundle of calf or sheep ventricular fibers in which the membrane potential could be changed electrically, using a sucrose-gap technique. After reversal of membrane potential and consequent contracture for 2 to 3 seconds, a positive inotropic effect 2 to 12 times that which occurred during paired-pulse stimulation was obtained. The decay of this potentiated state was slow in resting preparations (average half-life, 95 seconds), but was determined by the number of beats in driven preparations (about eight beats to return to control amplitude). Lengthening consecutive action potentials by subthreshold constant depolarizing currents or 5-mv shifts in the membrane potential by 50-msec current pulses during the plateau phase of successive action potentials caused positive inotropic effects, attaining a steady state in about eight beats. Reversing the polarity of such currents (hyperpolarization) caused negative inotropic effects with the same phase dependency as for depolarizing currents. These negative inotropic effects attained a steady state in six to eight beats. The first action potential after cessation of these currents was close to normal, whereas return to control tension required six to eight beats. The half-life of decay of these negative inotropic states at rest was similar to that of positive inotropic states. Decay of inotropic states in contracting preparations was phase dependent, occurring only during the rapid depolarization and plateau phases of the action potential. II. These and other strength-interval effects on cardiac contractility in a constant chemical and physical environment are consistent with two hypotheses. (1) The presystolic level of intracellular calcium bound to specific (rapid release) sites on the sarcoplasmic reticulum, the inner surfaces of the sarcolemma and T tubules, is a major determinant of the level of [Ca 2+ ] 1 attained during the initial phase of an action potential and hence the tension developed by mammalian cardiac muscle (that is, its inotropic state) at that particular instant. (2) The amount of intracellular calcium present at these sites at any instant after an action potential (that is, the moment-to-moment inotropic state of the muscle) is predetermined in the inverse direction of the intersystolic intervals of prior systoles and in the positive direction by the duration and magnitude of the plateau phases of prior action potentials and (for rest periods as long as 10 seconds) the elapsed time, in an exponentially decreasing fashion, since termination of the last absolute refractory period.