Medical Pharmacology: Cardiac Anesthesiology

Inhalational Agents and Baroreflex Control and the Sympathetic System

**Cranial Nerves**

¹"1. Olfactory Frontal Lobe, Smell 2. Optic Thalamus, Vision 3. Oculomotor Midbrain, Eye movement, constriction of the pupil, accommodation of the lens. 4. Trochlear Midbrain, Eye movement 5. Trigeminal Midbrain, Position sense for chewing, Trigeminal Pons: Motor control for chewing,facial sensations; Trigeminal Medulla, Facial sensations 6. Abducens Pons, Lateral eye movements 7. Facial Pons, Control of facial muscles: Facial Medulla, Taste sensation for the front part of the tongue, salivation and control of lacrimation. 8. Vestibulocochlear Pons and Medulla, Balance and Hearing 9. Glossopharyngeal Medulla, Motor control of swallowing, salivation, taste sensation from the back part of the tongue, some control of cardiovascular and pulmonary reflexes. 10. Vagus Medulla, Sensation from the pharnyx and larynx,motor control of swallowing, phonation,autonomic control of viscera, taste 11. Accessory Medulla, Control of sternomastoid and upper, trapezius muscles 12. Hypoglossal Medulla, Motor control of the tongue"

²Baroreflex components
- Principal components consist of stretch receptors which are localized in the aortic arch and carotid sinuses.
  - Cardiac depressor nerves (traveling with the vagus) as well as the carotid sinus nerve (Hering's nerve, a glossopharyngeal nerve branch) constitute the afferent component.
  - The medullary vasomotor center is another element. Finally, efferent components controls heart rate and muscle tone by means of autonomic nerve fibers.
- The afferent component provides input with respect to mean arterial pressure (MAP) as well as rate of change of pressure.
  - For a given MAP, nerve impulses/sec. increase with heart rate.
  - The baroreflex is effective between 50 mm Hg and 170 mm Hg; however, the relationship between neuronal activity and map is sigmoidal with a linear range around the midpoint.
  - A similar relationship exists with respect to the aortic arch receptors, although the system exhibits a somewhat higher threshold and lower gain compared to the carotid sinus system.
- With an increase in mean arterial pressure or pulse pressure, the increase in afferent neuronal activity induces a decrease in efferent sympathetic tone to arterioles and capacitance vessels and at the same time increases parasympathetic (cholinergic) cardiac tone.
  - These effects, in combination, reduce blood pressure to a lower level and as a result, this process is referred to as the "depressor reflex".
- Reduction in blood pressure causes an opposite effect characterized by an increase in sympathetic outflow which increases arterial tone by promoting arterial smooth muscle contraction as well as increasing cardiac contractility, heart rate and reducing venous vessel capacitance. In this case also the system responds to return blood pressure to more normal values.
²Effects of inhalational agents on the baroreflex
- Most inhalational anesthetic agents attenuate the baroreflex system.
  - For example, halothane reduces both threshold and gain of baroreflexes in humans (and dogs).
    - A pressor test slope, which is determined by the R-R interval change induced by an angiotensin bolus, was reduced (slope reduced) to about 16% of the control at 0.7% halothane with the effect eliminated at 1.1% halothane.
      - "The baroreflex function is evaluated by scanning 5 min interbeat interval and blood pressure recording for sequences in which systolic blood pressure and the subsequent RR interval progressively increase or decrease over three consecutive beats; sequences are selected if successive pressure pulses differ by at least 1.0 mm Hg and successive R-R intervals differ by at least 5.0 milliseconds.
      - Linear regressions relating RR interval to systolic blood pressure are plotted for each sequence, and the slope of the function is used as an estimate of baroreflex sensitivity"³
    - Halothane also reduces baroreflex control systemic vascular resistance (SVR)
    - Enflurane anesthesia is also associated with baroreflex attenuation; this effect is also seen with isoflurane albeit to a reduced extent.
    - Reduction of baroreflex sensitivity with desflurane or sevoflurane because of about the same order is that seen with isoflurane in humans.
    - Nitrous oxide depresses baroreflex-mediated tachycardia which had been induced by nitroprusside, although reflex-mediated enhancement of skeletal muscle sympathetic nerve activity was unaffected.
      - Nitrous oxide itself tends to increase sympathetic nerve activity but does not cause an increase in blood pressure, suggesting that the depressor component of the baroreflex is operative.

Baroreflex Regulation of Heart Rate (R-R interval) as Affected by Reduced Pressure (Nitroprusside) or Increased Pressure (Phenylephrine)--Figure 16-11 from Reference 2

^{2, 2a}"These data were acquired in healthy volunteers who were randomized to receive either isoflurane, desflurane, or sevoflurane. With increasing MAC, each of the volatile anesthetics led to a progressive reduction in the cardiac baroslope (an index of baroreflex sensitivity derived by relating changes in mean pressure to changes in R-R interval). There were no statistical differences between anesthetics"

¹Williams, JM, Neuropsychology
²Park, KW, Haering, JM, Reiz, S, Lowenstein, E Effects of Inhalation Anesthetics on Systemic Hemodynamics and the Coronary Circulation in Cardiac Anesthesia, Fourth Edition (Kaplan, JA, ed; Reich, Dl and Konstadt, SN, Assoc eds) W.B. Saunders Co. A Division of Harcourt Brace and Company, Philadelphia, 1999. This chapter is the primary reference for all above material, except as noted.
- ^2aEbert TJ, Harkin CP, Muzi, M: Cardiovascular responsis to sevoflurane: A review. Anesth Analg 81:S11, 1995--second sourced from reference 2.
³FORENAP-PHARMA, Neurocardiology, Autonomic Nervous System Assessment