Friday, May 7, 2021

Servoanalysis of Carotid Sinus Reflex Effects on Peripheral Resistance

In Chapter 10 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss feedback and control. Homework Problem 12 analyzes the feedback circuit that controls blood pressure.

Problem 12 from Chapter 10 of Intermediate Physics for Medicine and Biology.
Problem 12 from Chapter 10 of Intermediate Physics for Medicine and Biology.

The reference to the article by Allen Scher and Allan Young is

Scher AM, Young AC (1963) “Servoanalysis of Carotid Sinus Reflex Effects on Peripheral Resistance,” Circulation Research, Volume 12, Pages 152–165.
I downloaded this paper to learn more about their experiment. Below are excerpts from their introduction.
The baroceptors of the carotid sinus (and artery) and the aortic arch are the major sense organs which reflexly control the systemic blood pressure. Since the demonstration of the reflex function of these receptors… there has been much work on the responses of the blood pressure, heart, and peripheral vessels to changes in pressure in the carotid arteries and the aorta…. In our study, we subjected the isolated perfused carotid sinus to maintained pressures at different levels… and measured the resultant systemic pressures and pressure changes.
Two variables were measured: the systemic pressure (Russ and I call this the arterial pressure, part, in the homework problem) and the pressure in the carotid sinus (psinus). Let’s consider them one at a time.

Below I have drawn a schematic diagram of the circulatory system, consisting of the pulmonary circulation (blood flow through the lungs, pumped by the right side of the heart) and the systemic circulation (blood flow to the various organs such as the liver, kidneys, and brain, pumped by the left side of the heart). Scher and Young measured the arterial pressure in the systemic circulation. Most of the pressure drop occurs in the arterioles, capillaries, and venules, so you can measure the arterial pressure in any large artery (such a the femoral artery in the leg) and it is nearly equal to the pressure produced by the left side of the heart. Arterial pressure is pulsatile, but Scher and Young used blood reservoirs to even out the variation in pressure throughout the cardiac cycle, providing a mean pressure. 

A schematic diagram of the circulatory system.
The circulatory system.

My second drawing shows the carotid sinus, a region near the base of the carotid artery (the artery that feeds the brain) that contains baroceptors (nowadays commonly called baroreceptors; pressure sensors that send information about the arterial pressure to the brain so it can maintain the proper blood pressure). Scher and Young isolated the carotid sinus. They didn’t remove it completely from the animal—after all, they still needed to supply blood to the brain to keep it alive—but it was effectively removed from the circulatory system. In the drawing below I show it as being separate from the body. However, the nerves connecting the baroreceptors to the brain remain intact, so changes in the carotid sinus pressure still signal the brain to do whatever’s necessary to adjust the systemic pressure.

The carotid sinus was attached to a feedback circuit, similar to the voltage clamp used by Hodgkin and Huxley to study the electrical behavior of a nerve axon (see Sec. 6.13 of IPMB). I drew the feedback circuit as an operational amplifier (the green triangle), but this is metaphor for the real instrument. An operational amplifier will produce whatever output is required to keep the two inputs equal. In an electrical circuit, the output would be current and the inputs would be voltage. In Scher and Young’s experiment, the output was flow and the inputs were pressure. Specifically, one of the inputs was the pressure measured in the carotid sinus, and the other was a user-specified constant pressure (po in the drawing). The feedback circuit set psinus = po, allowing the sinus pressure to be specified by the experimenter.
A schematic diagram to represent the feedback circuit that controlled the sinus pressure.
A schematic diagram to represent the feedback circuit that controlled the sinus pressure.
 
Once this elaborate instrumentation was perfected, the experiment itself was simple: Adjust psinus to whatever value you want by varying po, wait several seconds for the system to come to a new equilibrium (so psinus and part have adjusted to a new constant value), and then measure part. Scher and Young obtained a plot of part versus psinus, similar to that given in our homework problem.

As always, details affect the results.
  • Any contribution from pressure sensors in the aortic arch was eliminated by cutting the vagus nerve. Only baroreceptors in the carotid sinus contributed to controlling blood pressure.
  • Scher and Young performed experiments on both dogs and cats. The data in Homework Problem 12 is from a cat.
  • The blood reservoirs acted like capacitors in an electrical circuit, smoothing changes with time.
  • In some experiments, a dog was given a large enough dose of anesthetic that the nerves sending information from the sinus baroreceptors to the brain were blocked. In other experiments, the nerve from the baroreceptors to the brain was cut. In both cases, the change in part with psinus disappeared.
  • Many of Scher and Young’s experiments examined how the feedback circuit varied with time in response to either a step change or a sinusoidal variation in psinus. All of these experiments were ignored in the homework problem, which considers steady state. 
  • Often my students are confused by Problem 12. They think there is only one equation relating part and psinus, but to solve a feedback problem they need two. To resolve this conundrum, realize that when the carotid sinus is not isolated but instead is just one of many large arteries in the body, its pressure is simply the arterial pressure and the second equation is psinus = part.
  • The study provided hints about how the brain adjusted arterial pressure—by changing heart rate, stroke volume, or systemic resistance—but didn’t resolve this issue. 
  • The experiments were performed at the University of Washington School of Medicine in Seattle
  • Allen Scher was a World War II veteran, serving as a Marine in the Pacific. He contributed to our understanding of the electrocardiogram, and was a coauthor on the Textbook of Physiology, cited often as “Patton et al. 1989” in IPMB.
  • Scher was born on April 17, 1921 and died May 12, 2011 at the age of ninety. Recently we celebrated the the hundred-year anniversary of his birth. Happy birthday, Dr. Scher!

No comments:

Post a Comment