SECTION I CELLULAR PHYSIOLOGY Cardiomyoplasty for Ventricular Aneurysn In a currently experinental treatrent,a patient with a left ventricular aneurysn underwent an operation in which the aneurysa was surgically removed.To help the weakened heart,the left latissinus dorsi (skeletal)muascle was dissected free from its normal location in the lover back where it inserts on the hunerus and is active in all pulling movenents.Maintaining its major neurovascular conmections (pedicle).the muscle was moved into the thoracic cavity and wrapped around the heart in an oriemtation that would compress the left ventricle on contraction of the latissimus dorsi.A"cardiomostimulator"was implanted to electrically stirulate the latissimus dorsi via its motor nerves in synchrony with the heartbeat.After a conditioning and training period of several weeks,the functional capacity of the patient to undertake modest activity was improved by the operation (termed dynanic cardioayoplasty). 1.Is the latissimus dorsi a suitable substitute for cardiac muscle if one assumes that the formidable technical problems could be overcome? 2.Could a standard cardiac pacemaker be used to drive the latissimus dorsi? 3.How can the problem of fatigue be solved? 4.What vascular adaptations would be required in the latissimus dorsi? 5.Before the operation the sarcomere length of the latissinus dorsi would be near the optimal for force generation,or around 2.2 m at rest.How might this change after surgery? 6.The skeleton normlly prevents significant shorteming of skeletal muscle cells.How can the latissimus dorsi gemerate large forces if there are no skeletal restraints to shortening? 7.In the process of establishing an adequate vascular system there is considerable proliferation and growth of vaseular smooth muscle cells in the
SECTION I CELLULAR PHYSIOLOGY Cardiomyoplasty for Ventricular Aneurysm In a currently experimental treatment, a patient with a left ventricular aneurysm underwent an operation in which the aneurysm was surgically removed. To help the weakened heart, the left latissimus dorsi (skeletal) muscle was dissected free from its normal location in the lower back where it inserts on the humerus and is active in all pulling movements. Maintaining its major neurovascular connections (pedicle), the muscle was moved into the thoracic cavity and wrapped around the heart in an orientation that would compress the left ventricle on contraction of the latissimus dorsi. A "cardiomyostimulator" was implanted to electrically stimulate the latissimus dorsi via its motor nerves in synchrony with the heartbeat. After a conditioning and training period of several weeks, the functional capacity of the patient to undertake modest activity was improved by the operation (termed dynamic cardiomyoplasty). 1. Is the latissimus dorsi a suitable substitute for cardiac muscle if one assumes that the formidable technical problems could be overcome? 2. Could a standard cardiac pacemaker be used to drive the latissimus dorsi? 3. How can the problem of fatigue be solved? 4. What vascular adaptations would be required in the latissimus dorsi? 5. Before the operation the sarcomere length of the latissimus dorsi would be near the optimal for force generation, or around 2.2 m at rest. How might this change after surgery? 6. The skeleton normally prevents significant shortening of skeletal muscle cells. How can the latissimus dorsi generate large forces if there are no skeletal restraints to shortening? 7. In the process of establishing an adequate vascular system there is considerable proliferation and growth of vascular smooth muscle cells in the
latissinus dorsi.Why doesn't this occur in the myocardiun with proliferation and replacement of cardiac mscle cells to repair the damage? 8.Beart failure is fairly common.Is cardiomoplasty likely to supersede cardiac tramsplants as a surgical therapy? 9.Why wouldn't pulling efforts with the left arm postoperatively lead to compression of the heart by the latissinus dorsi? 10.The pacemaker should activate the afferent sensory merve fibers as well as the motor nerve fibers.What are the potential results? ANSVER 1.The heart is a pump.All cardiac cells contract in synchrony in a prolonged twitch (heartheat).The force and frequency of the heartbeat are physiologically regulated to adjust cardiac output to metabolic needs.The heart is continuously active and does not fatigue,although it is absolutely dependent on the maintenance of oxidative netaholisa.Skeletal muscles are composed of independent fast and slow motor units that rarely contract in synchrony.Force is varied by recruitnent of more motor units and tetanization.Skeletal muscles exhibit fatigue,with fast glycolytic (type I)notor units unable to mintain continuous activity.Arguably skeletal muscle could not substitute for cardiac muscle:however,as indicated in the case study.a conditioned skeletal muscle has some potential to assist a weakened heart. 2.No.for the following reasons.(1)The heart still has its normal nechanisas to adjust its frequency of contraction.Therefore,the stimlator must be modified so that it is triggered by the endogemous cardiac cycle to synchromize contraction of the myocardiun and the skeletal muscle.(2)Skeletal muscle twitches are brief and produce relatively low forces compared with cardiac systole.A practical cardionyostimulator must generate bursts of action potentials to induce brief tetani matched to the ventricular systole.(3)Action potentials are not propagated from one skeletal ruscle cell to another.and there is no paceraker region in the
latissimus dorsi. Why doesn't this occur in the myocardium with proliferation and replacement of cardiac muscle cells to repair the damage? 8. Heart failure is fairly common. Is cardiomyoplasty likely to supersede cardiac transplants as a surgical therapy? 9. Why wouldn't pulling efforts with the left arm postoperatively lead to compression of the heart by the latissimus dorsi? 10. The pacemaker should activate the afferent sensory nerve fibers as well as the motor nerve fibers. What are the potential results? ANSWER l. The heart is a pump. All cardiac cells contract in synchrony in a prolonged twitch (heartbeat). The force and frequency of the heartbeat are physiologically regulated to adjust cardiac output to metabolic needs. The heart is continuously active and does not fatigue, although it is absolutely dependent on the maintenance of oxidative metabolism. Skeletal muscles are composed of independent fast and slow motor units that rarely contract in synchrony. Force is varied by recruitment of more motor units and tetanization. Skeletal muscles exhibit fatigue, with fast glycolytic (type I) motor units unable to maintain continuous activity. Arguably skeletal muscle could not substitute for cardiac muscle; however, as indicated in the case study, a conditioned skeletal muscle has some potential to assist a weakened heart. 2. No, for the following reasons. (1) The heart still has its normal mechanisms to adjust its frequency of contraction. Therefore, the stimulator must be modified so that it is triggered by the endogenous cardiac cycle to synchronize contraction of the myocardium and the skeletal muscle. (2) Skeletal muscle twitches are brief and produce relatively low forces compared with cardiac systole. A practical cardiomyostimulator must generate bursts of action potentials to induce brief tetani matched to the ventricular systole. (3) Action potentials are not propagated from one skeletal muscle cell to another, and there is no pacemaker region in the
latissimus dorsf.The stimulating electrodes of a cardfomyostimulator must be placed so as to stimlate most of the notor nerves to the motor units of the skeletal mascle. 3.Some 4 to 6 weeks of progressive training by low-frequency electrical stimulation transforms fast,glycolytic notor unfts to slow.oxidative motor units that express the slow twitch isoform of myosin.The oxidative capacity of most type I slow motor units vould be increased.In practice,sufficient resistance to fatigue can occur for indefinite pacing at normal heart rates. 4.Some loss of collateral circulation is an inevitable consequence of such surgery,and an increased vascularization is necessary to meet the oxidative metabolic demands associated with continuous activity in all motor units. Considerable neovascularization and revascularization occur during adaptation. 5.It is unlikely that sarcomeres would be mch longer.because that would require stretching the muscle against the passive elasticity of the connective tissue and coapression of the ventricles during diastole.The surgeon carefully avoids this because it would interfere with cardiac filling.However,it is inevitable that many fibers will be shortened as a result of the radical changes in geonetry caused by surgery.The museles adapt by removing sarcomeres at the ends of cells to shorten the cells and restore optimal sarcomere lengths.The mechanisas governing the addition or renoval of sarcomeres are unknown. 6.The muscle may sot generate large forces because studies suggest that this operation does not produce high stroke volumes or ejection fractions.Note.however. that the heart is a thick-walled organ.Hence it would not require a large anount of shorteming of the latissinus dorsi to greatly reduce the volume of the ventricles. 7.Although striated muscle cells can hypertrophy in response to increased loads, they have a very limited regenerative capacity,in contrast to smooth muscle. 8.There is no clear ansser,but some factors to consider inelude the following. (1)This is still an experimental procedure,and improverents can be expected with further research.Although technical success has been achieved.there is no hard evidence for major improvements in cardiac function.(2)The procedure avoids the problems of tissue rejection,cardiac denervation,and sustained ischemia.(3)The
latissimus dorsi. The stimulating electrodes of a cardiomyostimulator must be placed so as to stimulate most of the motor nerves to the motor units of the skeletal muscle. 3. Some 4 to 6 weeks of progressive training by low-frequency electrical stimulation transforms fast, glycolytic motor units to slow, oxidative motor units that express the slow twitch isoform of myosin. The oxidative capacity of most type I slow motor units would be increased. In practice, sufficient resistance to fatigue can occur for indefinite pacing at normal heart rates. 4. Some loss of collateral circulation is an inevitable consequence of such surgery, and an increased vascularization is necessary to meet the oxidative metabolic demands associated with continuous activity in all motor units. Considerable neovascularization and revascularization occur during adaptation. 5. It is unlikely that sarcomeres would be much longer, because that would require stretching the muscle against the passive elasticity of the connective tissue and compression of the ventricles during diastole. The surgeon carefully avoids this because it would interfere with cardiac filling. However, it is inevitable that many fibers will be shortened as a result of the radical changes in geometry caused by surgery. The muscles adapt by removing sarcomeres at the ends of cells to shorten the cells and restore optimal sarcomere lengths. The mechanisms governing the addition or removal of sarcomeres are unknown. 6. The muscle may not generate large forces because studies suggest that this operation does not produce high stroke volumes or ejection fractions. Note, however, that the heart is a thick-walled organ. Hence it would not require a large amount of shortening of the latissimus dorsi to greatly reduce the volume of the ventricles. 7. Although striated muscle cells can hypertrophy in response to increased loads, they have a very limited regenerative capacity, in contrast to smooth muscle. 8. There is no clear answer, but some factors to consider include the following. (l) This is still an experimental procedure, and improvements can be expected with further research. Although technical success has been achieved, there is no hard evidence for major improvements in cardiac function. (2) The procedure avoids the problems of tissue rejection, cardiac denervation, and sustained ischemia. (3) The
technique is not suited for terminally ill patients,because of hoth the extent of the surgery and the prolonged time required to condition the muscle.(4)Because the pacemaker can be driven by the heart's own pacemaker region,it is theoretically possible to provide a better match between cardiac output and metabolic needs than with a transplant.(5)The procedure provides a dranatic example of the capacity of skeletal muscle fibers to adapt to activity patterns.Nevertheless,the special characteristics of muscle in hollow organs,such as mechanically and electrically coupled cells,are never achieved. 9.Because all the orizinal neural circuitry is preserved.it is likely that motor units are recruited inappropriately for assisting cardiac funetion.Factors that may minimize resistance to cardiac filling include the following:(1)nost skeletal muscle actions involve only part of the motor units and they act asynchronously,so the forces might be low:(2)the electrical pacing at the heart rate frequencies will induce antidromic action potentials that will block normal action potentials elicited at the motor nerve cell bodies in the spinal cord:and (3)some learning process presumably takes place for appropriate use of the remaining muscles acting on the humerus to perform an act:this replaces motor unit activation in the left latissimus dorsi. 10.This would mimic the effects of activation of muscle spindles.Golgi tendon organs,and nociceptive nerves.The muscle spindles would contribute to reflex activation of the left latissinus dorsi and influence the recruitnent of motor units in other ruscles.The nociceptive nerves would induce the sensation of pain.The practicality of the procedure depends on the capacity of the nervous system to adapt, so that the conscious perception of pain disappears and functionally adaptive recruitment of rotor units is reestablished
technique is not suited for terminally ill patients, because of both the extent of the surgery and the prolonged time required to condition the muscle. (4) Because the pacemaker can be driven by the heart's own pacemaker region, it is theoretically possible to provide a better match between cardiac output and metabolic needs than with a transplant. (5) The procedure provides a dramatic example of the capacity of skeletal muscle fibers to adapt to activity patterns. Nevertheless, the special characteristics of muscle in hollow organs, such as mechanically and electrically coupled cells, are never achieved. 9. Because all the original neural circuitry is preserved, it is likely that motor units are recruited inappropriately for assisting cardiac function. Factors that may minimize resistance to cardiac filling include the following: (l) most skeletal muscle actions involve only part of the motor units and they act asynchronously, so the forces might be low; (2) the electrical pacing at the heart rate frequencies will induce antidromic action potentials that will block normal action potentials elicited at the motor nerve cell bodies in the spinal cord; and (3) some learning process presumably takes place for appropriate use of the remaining muscles acting on the humerus to perform an act; this replaces motor unit activation in the left latissimus dorsi. 10. This would mimic the effects of activation of muscle spindles, Golgi tendon organs, and nociceptive nerves. The muscle spindles would contribute to reflex activation of the left latissimus dorsi and influence the recruitment of motor units in other muscles. The nociceptive nerves would induce the sensation of pain. The practicality of the procedure depends on the capacity of the nervous system to adapt, so that the conscious perception of pain disappears and functionally adaptive recruitment of motor units is reestablished