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Dr. Ananda Prasad: Comment #3

Comment #3

In 1935 McLean and Hastings reported for the first time that 50% of the total calcium in the plasma was ionic and this fraction was physiologically critical and important including in the contractibility of the cardiac muscles.  They determined the ionic calcium by a frog-heart technique and showed that the partition of calcium obeyed the law of mass action and was dependent upon the plasma pH and protein concentration.  This partition of calcium in the plasma was questioned by a group of investigators in 1952 who used an ultrafiltration technique to measure the ionic calcium in the ultrafiltrate and they concluded that the level of ionic calcium was not physiologically relevant.  In 1953 I joined the Department of Medicine at the University of Minnesota Medical School under Professor Cecil Watson for training as a clinical scientist.  The same year Prof A. Baird Hastings from Harvard University came as a visiting professor in the department of medicine.  I had the great privilege of meeting Professor Hastings who expressed a great deal of concern regarding the partition of calcium in the plasma and the role of ionic calcium in physiological functions.  This topic was discussed in great detail and at the end, they assigned me to reassess the question of ionic calcium and its role in physiology, as a part of my PhD thesis.  It turned out to be a difficult task.  The plasma pH and temperature must remain constant near physiological level during the process of ultrafiltration.  I succeeded finally and we confirmed that our results of calcium partition in the plasma were similar to those reported by McLean and Hastings.  The problem with the investigators who disagreed with McLean and Hastings was that during the process of ultrafiltration they did not control the pH of the plasma and this created an artifact and gave fallacious results.  Needless to say that our results pleased Prof Hastings immensely. 

            During those days, it was observed that patients who underwent prolonged anesthesia for surgeries used to develop hypotension, shock, ventricular arrhythmia and this often resulted in death during early post hypercapnic phase.  It was known that serum potassium would increase as a result of respiratory acidosis but this increased level of potassium was not considered to be lethal.

            We conducted our experiments in dogs.  We subjected the dogs to either 30 minutes of respiratory alkalosis produced by over-ventilating with a positive pressure pump or to 30 minutes of respiratory acidosis produced by inhalation of 30% Coշ in Oշ.  As expected, ultrafiltrable calcium decreased during hyperventilation and increased during respiratory acidosis early.  A rebound increase in the level of ultrafiltrable calcium after hyperventilation and a rebound decrease in the ultrafiltrable calcium during the recovery phase of respiratory acidosis occurred in every case.  We also observed that plasma phosphate concentration also increased during respiratory acidosis and we postulated that increased phosphate-protein complex resulted in a significant decrease in ultrafiltrable calcium in post hypercapnic phase.  It’s during this phase that we observed cardiac arrhythmias, shock and death.  The increased serum potassium level and decreased ultrafiltrable calcium level were detrimental to the cardiac contractibility which resulted in cardiac arrhythmia.

            Our observations in the dogs were quickly confirmed by Clowers Jr. and Simeone from Cleveland clinic in patients who underwent prolonged anesthesia and surgery.  This led them to infuse calcium chloride in post hypercapnic phase and resulted in preventing this serious fatal complications in humans.  It is now a common procedure to use intravenous calcium infusion in patients who undergo prolonged anesthesia.


Prasad, A.S., Flink, E.B.  Effect of carbon dioxide on concentration of calcium in an ultrafiltrate of serum obtained by centrifugation.  J. Appl. Physiol., 10:103‑107, 1957.

Prasad, A.S., Brown, E.B., Flink, E.B.  Plasma ultrafiltrable calcium in respiratory alkalosis and acidosis.  Am. J. Physiol., 190:459‑461, 1957.

Brown, E.B., Prasad, A.S. Plasma ultrafiltrable calcium concentration in posthypercapnic ventricular fibrillation.  Am. J. Physiol., 190:462‑466, 1957.