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 + ]| 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. ADDITIONAL KEY WORDSstrength-interval relationships sucrose gap poststimulation potentiation extrasystolic potentiation depolarization contracture calcium movements voltage clamp sarcoplasmic reticulum intracellular calcium ions ventricular fiber membrane potentials and contractility

The reliability of graded maximal exercise treadmill testing and right atrial pacing in diagnosing significant obstructive coronary artery disease was evaluated in 74 consecutive patients referred to a cardiac unit with chest pain consistent with angina pectoris. The results of maximal exercise testing and right atrial pacing, with regard to the presence or absence of the patient's characteristic chest pain or discomfort and ischemic ST segment depression, were compared with the findings determined by selective coronary arteriography. Ischemic ST segment depression was defined as a downward displacement of one full mm or more of a horizontal or downward sagging ST segment.Forty-nine of the 74 patients studied were found to have significant coronary arteriographic obstruction, i.e., greater than 75% obstruction of one major coronary artery. The occurrence of the patient's characteristic chest pain or discomfort during maximal exercise testing or right atrial pacing is an excellent indicator of the presence of obstructive coronary artery disease, since all of the 41 patients developing their characteristic pain on maximal exercise testing had coronary arteriograms positive for obstructive coronary disease (no false positives), and 46 of 47 patients with characteristic chest pain on right atrial pacing had selective coronary arteriograms positive for obstructive coronary disease. When present, one mm ST depression during maximal exercise treadmill testing also reliably indicates arteriographic obstructive coronary disease (26 of 27 patients). However, the presence or absence of ischemic ST depression during right atrial pacing is a particularly unreliable indication of the presence or absence of arteriographic obstructive coronary disease: 15 of 25 false positive tests, and 13 of 49 false negative tests.Additional Indexing Words: Coronary arteriographyChest pain T HE ABILITY to distinguish chest pain due to obstructive coronary artery disease from chest pain from other causes is of obvious clinical importance. Two methods of stressing the heart that have been used extensively, and that appear to be most useful in making this differentiation, are maximal exercise testingl-5 and right atrial pacing. 61

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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.