Fiber, nerve: A single nerve cell; a neuron--classified on the absence of myelin. Myelinated cells have diameters typically in the range 2 to 20 um and conduction velocities of 5 to 12 unmyelinated nerves have diameters from 0.3 to 1.3 um and conduction velocities of 0.6 to 2.3 m/s Fiber lengths may be up to 1 m. The term nerve usually refers to a bundle of nerve fibers. Membrane: The functional boundary of a cell. Nerve cells possess membranes that are excitable by virtue of their nonlinear electrical conductance properties(see Action potential) Myelinated nerve: A nerve fiber insulated with a fatty substance called myelin and having periodically expose nodes of Ranvier. Neuron: A nerve cell. Sensory neurons carry information from sensory receptors in the peripheral nervous Refr System to the brain; motor neurons carry information from the brain to the muscles ctory period: A period of time after the initiation of an action potential during which further excitation is impossible(absolute refractory period)or requires a greater stimulus(relative refractory period) Rheobase: The minimum current necessary to cause nerve excitation--applicable to a long-duration current (e. Strength-duration curve: A curve expressing the functional relationship between the threshold of excitation of a nerve fiber and the duration of a unidirectional square -wave electrical stimulus References B Frankenhaeuser and A. F. Huxley, The action potential in the myelinated nerve fiber of Xenopus laevis a computed on the basis of voltage clamp data, "J. Physiol., vol. 171, Pp. 302-315, 1964 A. L. Hodgkin and A. F. Huxley, "A quantitative description of membrane current and its application to conduction and excitation in nerve, J. Physiol., vol. 117, pp. 500-544, 1952. . J. B. Jack, D Noble, and R. w. Tsien, Electric Current Flow in Excitable cells, Oxford Clarendon Press, 1983 D.R. McNeal,"Analysis of a model for excitation of myelinated nerve, " IEEE Trans. Biomed. Eng, vol. BME 2,Pp.329-337,1976 J. P. Reilly, V. T. Freeman, and W. D. Larkin,Sensory effects of transient electrical stimulation--Evaluation with a neuroelectric model, IEEE Trans. Biomed. Eng, vol. BME-32, no. 12, pp. 1001-1011, 1985. Further Information For further information, the reader is directed to the references listed at the end of this chapter. Additional R. Plonsey and R.C. Barr, Biolectricity--A Quantitive Approach, New York: Plenum, 1988 Prostheses, Englewood Cliffs, N J: E.R. Kandel, J.H. Schwartz, and T M. Jessell (Eds ) Principles of Neural Science, 3rd ed, New York: Elsevier, 1991 Several journals treat engineering applications of neuroelectric principles, such as IEEE Transactions on Biomedical Engineering, Medical and Biological Engineering and Computing, and Annals of Biomedical Engineering Of the many conferences treating bioelectric responses, one having a broad range of applications is the IEEE Annual Conference on Engineering in Medicine and Biology 113.2 Bioelectric Events L. A Geddes to monitor and guide vps ploited for the diagnostic information that they contain. Such signals are often used rapy. Although all living cells exhibit bioelectric phenomena, a small variety produce potential changes that reveal their physiological function. The most familiar bioelectric recordings are the lectrocardiogram, ECG (which reflects the excitation and recovery of the whole heart), the electromyogram EMG(which reflects the activity of skeletal muscle), and the electroencephalogram, EEG(which reflects the activity of the outer layers of the brain, the cortex). The following paragraphs will describe(1)the origin of e 2000 by CRC Press LLC
© 2000 by CRC Press LLC Fiber, nerve: A single nerve cell; a neuron—classified on the presence or absence of myelin. Myelinated nerve cells have diameters typically in the range 2 to 20 mm and conduction velocities of 5 to 120 m/s; unmyelinated nerves have diameters from 0.3 to 1.3 mm and conduction velocities of 0.6 to 2.3 m/s. Fiber lengths may be up to 1 m. The term nerve usually refers to a bundle of nerve fibers. Membrane: The functional boundary of a cell. Nerve cells possess membranes that are excitable by virtue of their nonlinear electrical conductance properties (see Action potential). Myelinated nerve: A nerve fiber insulated with a fatty substance called myelin and having periodically exposed nodes of Ranvier. Neuron: A nerve cell. Sensory neurons carry information from sensory receptors in the peripheral nervous system to the brain; motor neurons carry information from the brain to the muscles. Refractory period: A period of time after the initiation of an action potential during which further excitation is impossible (absolute refractory period) or requires a greater stimulus (relative refractory period). Rheobase: The minimum current necessary to cause nerve excitation—applicable to a long-duration current (e.g., several milliseconds). Strength-duration curve: A curve expressing the functional relationship between the threshold of excitation of a nerve fiber and the duration of a unidirectional square-wave electrical stimulus. References B. Frankenhaeuser and A. F. Huxley, “The action potential in the myelinated nerve fiber of Xenopus laevis as computed on the basis of voltage clamp data,” J. Physiol., vol. 171, pp. 302–315, 1964. A. L. Hodgkin and A. F. Huxley, “A quantitative description of membrane current and its application to conduction and excitation in nerve,” J. Physiol., vol. 117, pp. 500–544, 1952. J. J. B. Jack, D. Noble, and R. W. Tsien, Electric Current Flow in Excitable Cells, Oxford: Clarendon Press, 1983. D. R. McNeal, “Analysis of a model for excitation of myelinated nerve,” IEEE Trans. Biomed. Eng., vol. BME- 22, pp. 329–337, 1976. J. P. Reilly, V. T. Freeman, and W. D. Larkin, “Sensory effects of transient electrical stimulation—Evaluation with a neuroelectric model,” IEEE Trans. Biomed. Eng., vol. BME-32, no. 12, pp. 1001–1011, 1985. J. P. Reilly, Electrical Stimulation and Electropathology, New York: Cambridge University Press, 1992. Further Information For further information, the reader is directed to the references listed at the end of this chapter. Additional references are: R. Plonsey and R.C. Barr, Biolectricity—A Quantitive Approach, New York: Plenum, 1988. W. Agnew and D. McCreery, Neural Prostheses, Englewood Cliffs, N.J.: Prentice-Hall, 1990. E.R. Kandel, J.H. Schwartz, and T. M. Jessell (Eds.), Principles of Neural Science, 3rd ed., New York: Elsevier, 1991. Several journals treat engineering applications of neuroelectric principles, such as IEEE Transactions on Biomedical Engineering, Medical and Biological Engineering and Computing, and Annals of Biomedical Engineering. Of the many conferences treating bioelectric responses, one having a broad range of applications is the IEEE Annual Conference on Engineering in Medicine and Biology. 113.2 Bioelectric Events L. A. Geddes Bioelectric signals are exploited for the diagnostic information that they contain. Such signals are often used to monitor and guide therapy. Although all living cells exhibit bioelectric phenomena, a small variety produce potential changes that reveal their physiological function. The most familiar bioelectric recordings are the electrocardiogram, ECG (which reflects the excitation and recovery of the whole heart), the electromyogram, EMG (which reflects the activity of skeletal muscle), and the electroencephalogram, EEG (which reflects the activity of the outer layers of the brain, the cortex). The following paragraphs will describe (1) the origin of
MEDICAL CARDIAC PACEMAKER Wilson greatbatch Patented october 9. 1962 #3,057,356 A excerpt from Greatbatch's patent application he primary object of this invention is to provide an improved artificial cardiac pacemaker for atisfactory heart rhythm to a heart which is functioning inadequately due to conduction defects in the auricular-ventricular bundle Another object of this invention is to provide an artificial cardiac pacemaker requiring low power con sumption,so that battery operation is feasible for long uninterrupted periods without battery replacement. Another object of this invention is to provide an artificial cardiac pacemaker which may be directly connected to the surface of the ventricle of the heart A still further object of this invention is to provide an artificial cardiac pacemaker which is constructed from materials compatible to the body environment and is of such an electrical and mechanical configuration, that permanent implantation of the device within the human body is both feasible and practical. Greatbatch's pacemaker was the first to be compact enough and use such low power that it could be implanted within the body and run for five years before requiring battery replacement. Wilson Greatbatch Inc is a leading producer of pacemaker batteries and other medical products. Copyright 1995, Dew Ray Products, Inc. Used with permission. e 2000 by CRC Press LLC
© 2000 by CRC Press LLC MEDICAL CARDIAC PACEMAKER Wilson Greatbatch Patented October 9, 1962 #3,057,356 An excerpt from Greatbatch’s patent application: The primary object of this invention is to provide an improved artificial cardiac pacemaker for restoring satisfactory heart rhythm to a heart which is functioning inadequately due to conduction defects in the auricular-ventricular bundle. Another object of this invention is to provide an artificial cardiac pacemaker requiring low power consumption, so that battery operation is feasible for long uninterrupted periods without battery replacement. Another object of this invention is to provide an artificial cardiac pacemaker which may be directly connected to the surface of the ventricle of the heart. A still further object of this invention is to provide an artificial cardiac pacemaker which is constructed from materials compatible to the body environment and is of such an electrical and mechanical configuration, that permanent implantation of the device within the human body is both feasible and practical. Greatbatch’s pacemaker was the first to be compact enough and use such low power that it could be implanted within the body and run for five years before requiring battery replacement.Wilson Greatbatch, Inc. is a leading producer of pacemaker batteries and other medical products. (Copyright © 1995, DewRay Products, Inc. Used with permission.)
↓ ic+iR MEMBRANE EQUIVALENT Stimulus id ACTION POTENTIAL FIGURE 113.9 (A)Typical charged membrane, (B)its equivalent circuit, and( C)action potential resulting from a stimulus all bioelectric phenomena;(2)the nature of the electrical activity of the heart, skeletal muscle, and the brain and(3)the characteristics of instrumentation used to display these events. Origin of Bioelectricity Cell membranes resemble charged capacitors operating near the dielectric breakdown voltage. Assuming a typical value of 90 mV for the transmembrane potential and a membrane thickness of 100 A, the voltage gradient across the membrane is 0.9 x 105 VIcm. a typical value for the capacitance is about 1 uF/cm The transmembrane charge is the result of a metabolic process that creates ionic gradients with a high concentration of potassium ions(K*)inside and a high concentra de. there are concentration gradients for other ions, the cell wall being a semipermeable membrane that obeys the Nernst quation(60 mV/decade concentration gradient for univalent ions). The result of the ionic gradient is the transmembrane potential that, in the cells referred to earlier, is about 90 mV, the interior being negative with respect to the exterior. Figure 113.9 illustrates this concept for a cylindrical cell The transmembrane potential is stable in inexcitable cells, such as the red blood cell. However, in excitable cells, a reduction in transmembrane potential (either physiological or induced electrically) results in excitation characterized by a transmembrane ion flux, resulting from a membrane permeability change. When the trans- nembrane potential is reduced by about one-third, Na* ions rush in; K+ ions exit slightly later while the cell depolarizes, reverse polarizes, then repolarizes. The resulting excursion in transmembrane potential is a prop- agated action potential that is characteristic for each type of cell In Fig. 113.10 are shown the action potentials of (A)a single cardiac ventricular muscle cell,(C)a skeletal muscle cell, and(E)a nerve cell. In(B)and(D), he ensuing muscular contractions are shown. An important property of the action potential is that it is propagated without decrement over the entire surface of the cell, the depolarized region being the stimulus for adjacent polarized regions. In contractile cells it is the action potential that triggers release of mechanical energy as shown in Figs. 113.10(B)and(D) Law of stimulation Although action potentials are generated physiologically, it should be obvious that excitable cells can be made to respond by the application of a negative pulse of sufficient current density (n and duration(d) to reduce the transmembrane potential to a critical value by removing charge, thereby reducing the membrane potential to the threshold potential (TP), as shown in Fig. 113.9. The law of stimulation is I= b/(1-e/t), where b is the threshold current density for an infinitely long-duration pulse and t is the cell membrane time constant, ing different for each type of excitable tissue. Figure 113 11 is a plot of the threshold current (n)versus duration(d)for mammalian cardiac muscle, sensory receptors, and motor nerve. This relationship is known as the strength-duration curve. e 2000 by CRC Press LLC
© 2000 by CRC Press LLC all bioelectric phenomena; (2) the nature of the electrical activity of the heart, skeletal muscle, and the brain; and (3) the characteristics of instrumentation used to display these events. Origin of Bioelectricity Cell membranes resemble charged capacitors operating near the dielectric breakdown voltage. Assuming a typical value of 90 mV for the transmembrane potential and a membrane thickness of 100 Å, the voltage gradient across the membrane is 0.9 ¥ 105 V/cm. A typical value for the capacitance is about 1 mF/cm2 . The transmembrane charge is the result of a metabolic process that creates ionic gradients with a high concentration of potassium ions (K+) inside and a high concentration of sodium ions (Na+) outside. There are concentration gradients for other ions, the cell wall being a semipermeable membrane that obeys the Nernst equation (60 mV/decade concentration gradient for univalent ions). The result of the ionic gradient is the transmembrane potential that, in the cells referred to earlier, is about 90 mV, the interior being negative with respect to the exterior. Figure 113.9 illustrates this concept for a cylindrical cell. The transmembrane potential is stable in inexcitable cells, such as the red blood cell. However, in excitable cells, a reduction in transmembrane potential (either physiological or induced electrically) results in excitation, characterized by a transmembrane ion flux, resulting from a membrane permeability change. When the transmembrane potential is reduced by about one-third, Na+ ions rush in; K+ ions exit slightly later while the cell depolarizes, reverse polarizes, then repolarizes. The resulting excursion in transmembrane potential is a propagated action potential that is characteristic for each type of cell. In Fig. 113.10 are shown the action potentials of (A) a single cardiac ventricular muscle cell, (C) a skeletal muscle cell, and (E) a nerve cell. In (B) and (D), the ensuing muscular contractions are shown. An important property of the action potential is that it is propagated without decrement over the entire surface of the cell, the depolarized region being the stimulus for adjacent polarized regions. In contractile cells it is the action potential that triggers release of mechanical energy as shown in Figs. 113.10(B) and (D). Law of Stimulation Although action potentials are generated physiologically, it should be obvious that excitable cells can be made to respond by the application of a negative pulse of sufficient current density (I) and duration (d) to reduce the transmembrane potential to a critical value by removing charge, thereby reducing the membrane potential to the threshold potential (TP), as shown in Fig. 113.9. The law of stimulation is I = b/(1 – e–d/t), where b is the threshold current density for an infinitely long-duration pulse and t is the cell membrane time constant, being different for each type of excitable tissue. Figure 113.11 is a plot of the threshold current (I) versus duration (d) for mammalian cardiac muscle, sensory receptors, and motor nerve. This relationship is known as the strength-duration curve. FIGURE 113.9 (A) Typical charged membrane, (B) its equivalent circuit, and (C) action potential resulting from a stimulus I of duration d
ACTION POTENTIAL FIGURE 113. 10 The action of()cardiac muscle and (b) its contraction, (C)skeletal muscle and(D)and its contraction. The action potential of nerve is shown in(E) dd/ FIGURE 113 11 The strength-duration curve for heart, sensory receptors, and motor nerve. I is the stimulus current, bis the rheobasic current, and t is the membrane time constant. The stimulus duration is d Recording Action Potentials Action potentials of single excitable cells are recorded with transmembrane electrodes(micron diameter)only research studies. When action potentials are used for diagnostic purposes, extracellular electrodes are used nat are both large and distant from the population of cells which become active and recover. The depolarization e 2000 by CRC Press LLC
© 2000 by CRC Press LLC Recording Action Potentials Action potentials of single excitable cells are recorded with transmembrane electrodes (micron diameter) only in research studies. When action potentials are used for diagnostic purposes, extracellular electrodes are used that are both large and distant from the population of cells which become active and recover. The depolarization FIGURE 113.10 The action of (A) cardiac muscle and (B) its contraction, (C) skeletal muscle and (D) and its contraction. The action potential of nerve is shown in (E). FIGURE 113.11 The strength-duration curve for heart, sensory receptors, and motor nerve. I is the stimulus current, b is the rheobasic current, and t is the membrane time constant. The stimulus duration is d
relaxation FIGURE 113. 12 Genesis of the ECG. The SA node is the pacemaker, setting the rate. Excitation is propagated from the atria to the Av node, then to the bundle of His, and to the ventricular muscle via the Purkinje fibers. The SA node has a reasing membrane potential that reaches the threshold potential(TP), resulting in spontaneous excitation(inset) and repolarization processes send small currents through the conducting environmental tissues and fluids, resulting in a time-varying potential field. Appropriately placed electrodes allow recording the electrical activity of the bioelectric generators. However, the waveforms of such recordings are vastly different from those of the transmembrane action potentials shown in Fig. 113.10. By using cable theory, it is possible to show that such extracellular recordings resemble the second derivative of the excursion in transmembrane potential [Geddes and Baker, 1989. Despite the difference in waveform, extracellular recordings identify the excitation and recovery processes very well. The Electrocardiogram(ECG) The heart is two double-muscular pumps. The atria pump blood into the ventricles, then the two ventricles ontract. The right ventricle pumps venous blood into the lungs, and the left ventricle pumps oxygen-rich blood into the aorta. Figure 113.12 is a sketch of the heart and great vessels, along with genesis of the ECG The ECG consists of two parts: the electrical activity of the atria and that of the ventricles. Both components have an excitation wave and a recovery wave. Within the right atrium is a specialized node of modified cardiac muscle, the sinoatrial ( SA) node, that has a spontaneously decreasing transmembrane potential which reaches the threshold potential (TP), resulting in self-excitation(Fig. 113. 12, upper left). Therefore the SA node is the cardiac pacemaker, establishing the heart rate. The SA node action potential stimulates the adjacent atrial muscle, completely exciting it and giving rise to the first event in the cardiac cycle, the P wave, the trigger for atrial contraction. Atrial excitation is propagated to another specialized node of tissue in the base of the ventricles, the atrioventricular (AV)node, the bundle of His and the Purkinje fibers. Propagation of excitation rer the ventricles gives rise to the QRS, or simply the R wave, which triggers ventricular contraction. Meanwhile luring the QRS wave, the atria recover, giving rise to the T, wave, following which the atria relax. The T, wave e 2000 by CRC Press LLC
© 2000 by CRC Press LLC and repolarization processes send small currents through the conducting environmental tissues and fluids, resulting in a time-varying potential field. Appropriately placed electrodes allow recording the electrical activity of the bioelectric generators. However, the waveforms of such recordings are vastly different from those of the transmembrane action potentials shown in Fig. 113.10. By using cable theory, it is possible to show that such extracellular recordings resemble the second derivative of the excursion in transmembrane potential [Geddes and Baker, 1989]. Despite the difference in waveform, extracellular recordings identify the excitation and recovery processes very well. The Electrocardiogram (ECG) Origin The heart is two double-muscular pumps. The atria pump blood into the ventricles, then the two ventricles contract. The right ventricle pumps venous blood into the lungs, and the left ventricle pumps oxygen-rich blood into the aorta. Figure 113.12 is a sketch of the heart and great vessels, along with genesis of the ECG. The ECG consists of two parts: the electrical activity of the atria and that of the ventricles. Both components have an excitation wave and a recovery wave. Within the right atrium is a specialized node of modified cardiac muscle, the sinoatrial (SA) node, that has a spontaneously decreasing transmembrane potential which reaches the threshold potential (TP), resulting in self-excitation (Fig. 113.12, upper left). Therefore the SA node is the cardiac pacemaker, establishing the heart rate. The SA node action potential stimulates the adjacent atrial muscle, completely exciting it and giving rise to the first event in the cardiac cycle, the P wave, the trigger for atrial contraction. Atrial excitation is propagated to another specialized node of tissue in the base of the ventricles, the atrioventricular (AV) node, the bundle of His and the Purkinje fibers. Propagation of excitation over the ventricles gives rise to the QRS, or simply the R wave, which triggers ventricular contraction. Meanwhile during the QRS wave, the atria recover, giving rise to the Tp wave, following which the atria relax. The Tp wave FIGURE 113.12 Genesis of the ECG. The SA node is the pacemaker, setting the rate. Excitation is propagated from the atria to the AV node, then to the bundle of His, and to the ventricular muscle via the Purkinje fibers. The SA node has a decreasing membrane potential that reaches the threshold potential (TP), resulting in spontaneous excitation (inset)