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Ann Thorac Surg 2001;72:S1100-S1104
© 2001 The Society of Thoracic Surgeons

Supplement: Cardiothoracic techniques and technologies

Spinal cord stimulation treatment for angina pectoris: more than a placebo?

Philippe A. Gersbach, MDa,d, Mustafa G. Hasdemir, MDb, Eric Eeckhout, MD, PhDc, Ludwig K. von Segesser, MDd

a Department of Thoracic and Cardiovascular Surgery, University Hospital of Bern, Bern, Switzerland
b Department of Neurosurgery, University Hospital of Bern, Bern, Switzerland
c Department of Cardiology, University Hospital of Lausanne, Lausanne, Switzerland
d Department of Cardiovascular Surgery, University Hospital of Lausanne, Lausanne, Switzerland

Address reprint requests to Dr Gersbach, Cardiovascular Surgery, University Hospital (CHUV), 1011 Lausanne, Switzerland
e-mail: philippe.gersbach{at}chuv.hospvd.ch

Presented at the Seventh Annual Cardiothoracic Techniques and Technologies Meeting 2001, New Orleans, LA, Jan 24–27, 2001.


   Abstract
Top
 Abstract
Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 
Background. The effects of thoracolumbal spinal cord stimulation (SCS) are confined to restricted microcirculatory areas. This limitation is generally attributed to a predominantly segmental mode of action on the autonomic nervous system. The goal of this study was to determine whether SCS applied close to supraspinal autonomic centers would induce generalized hemodynamic changes that could explain its alleged antianginal properties.

Methods. Invasive hemodynamic tests were performed in 15 anesthetized Göttingen minipigs submitted to iterative cervical SCS of various duration and intensity.

Results. Hemodynamic changes exceeding 10% were observed in 59 of 68 SCS sessions (87%). Their extent and time to peak varied with SCS intensity. At 2, 5, and 10 V, significant (t test p < 0.05) peak changes occurred in cardiac output (+34%, +29%, and +28%, respectively), stroke volume (+19%, +16%, +15%), mean pressure (+9%, +27%, +40%), heart rate (+14%, +23%, +14%), systemic (-17%, NS, NS), and pulmonary vascular (25%, NS, NS) resistances. Strikingly, at 2 V, the increase in cardiac output (+34%) was higher than the synchronous rise in rate pressure product (+22%), indicating efficient cardiac work. At 10 V, however, the cardiac work was inefficient (rate pressure product + 53%/cardiac output + 28%).

Conclusions. Low-voltage cervical neuromodulation reduces the postcharge and improves cardiac work efficiency. The resulting reduction in oxygen myocardial demand may account for decreased anginal pain.


   Introduction
Top
 Abstract
 Introduction
Material and methods
 Results
 Comment
 Acknowledgments
 References
 
Spinal cord stimulation (SCS) has been claimed a valuable alternative therapeutic option for severe angina pectoris refractory to medical, endovascular, and surgical treatment [1–5], as well as for otherwise intractable peripheral vascular diseases [6, 7]. Its hypothesized mechanisms of action are (1) a simple placebo effect [8]; (2) an analgesic action mediated by either stimulation of endogenous opiates [4, 7] or an action on the afferent transmission of noxious stimuli [8, 9], inducing a reduction of the sympathetic hyperactivity prevailing in painful areas [9]; (3) a liberation of vasoactive substances [6, 9]; or (4) an effect on the autonomic nervous system [6, 9] mediated by removal of inhibitory segmental spinal reflexes that modulate peripheral sympathetic activity, possibly combined with the recruitment of supraspinal autonomic centers. In peripheral vascular disease, SCS is commonly applied at the thoracolumbal level; a segmental mode of action on the autonomic nervous system [6, 9] seems to account for the confinement of its vasodilatory effect on restricted areas.

This study was designed to determine whether this segmental limitation may be counteracted by the recruitment of either the supraspinal autonomic centers or the afferent and efferent autonomic pathways located near the stimulation level. If so, the beneficial effect of SCS on refractory angina could result from a global neuromodu-lation leading to an afterload reduction with subsequent decrease in myocardial oxygen demand.


   Material and methods
Top
 Abstract
 Introduction
 Material and methods
Results
 Comment
 Acknowledgments
 References
 
Fifteen Göttingen minipigs (20 to 31 kg) anesthetized with azaperon (2 mg/kg intravenously [IV]) and metomidate (5 mg/kg IV) were intubated and hyperventilated slightly with a mixture of 30% oxygen/70% nitrous oxide/0.5% to 1.5% halothane delivered by a volume-controlled ventilator (Ventilog, Drägenwerk AG, Lübeck, Germany).

Instrumentation
Four catheters were surgically inserted in peripheral vessels: A 13 mm Seldicath in the distal aorta, a 7F thermodilution Swan Ganz catheter in the pulmonary artery, a 5.2F pigtail catheter in the left ventricle, and a 12F central vein catheter. All animals received 3 electrocardiogram chest leads, a urinary catheter, and a rectal thermometer. A bipolar epidural electrode with an interelectrode distance of 4 mm (Medtronic, Minneapolis, MN) was placed midline at the C2 level through a cervical laminectomy and connected to an external screener (Model 3625, Medtronic). The animals were then allowed to stabilize for 1 hour.

Measurements and hemodynamic assessment
Heart rate (HR) and electrocardiogram tracings, systemic blood pressure (BP), pulmonary artery pressure, left ventricular end-diastolic pressure, and central venous pressure were continually displayed on an 8-channel universal monitor (SMV 611 Hellige GmbH, Freiburg i.B, Germany) with selected modules, and analyzed every 15 minutes. Significant tracings were printed on-line for further analysis (8-channel printer SMR 821, Hellige GmbH). Cardiac output (CO) and stroke volume (SV) were determined every 15 minutes by thermodilution (Dilu module, Hellige GmbH) based on four consecutive measurements performed during expiration, allowing determination of systemic and pulmonary vascular resistances (SVR, PVR). Finally, the rate pressure product (RPP) was calculated to assess myocardial oxygen consumption and cardiac work [4]. The stability of the model was validated at intervals of 30 minutes by measurements of pH, blood gases, ventilatory measurements, hematocrit levels, and body temperature.

Stimulation parameters
Cervical SCS at 2, 5, and 10 V were successively delivered at a frequency of 80 Hz and a pulse width of 200 microseconds.

Study design
Each of the three intensities was tested for 60 minutes. The first delivered voltage differed for each animal. To avoid an overlapping effect, no SCS was performed before the return of all hemodynamic measurements to base line values. Successful long-lasting stimulations (defined as changes of more than 10% in at least two measurements during or after SCS) were then repeated. After 12 hours of anesthesia, stimulations of shorter duration (10 and 20 minutes) were repeatedly delivered at the intensities that had previously elicited significant hemodynamic changes.

Criteria leading to premature termination at any stage of the study included changes of more than 10% in base line values persisting for more than 90 minutes after SCS trial, ventilatory problems, and substantial changes in blood gases, hematocrit (± 25% of the initial value), and body temperature (± 2°C). The random occurrence of these adverse events accounts for differences in the number and type of stimulations performed in each animal.

All the data gathered in responders and nonresponders were included in the analysis, giving rise to often broad standard deviations.

Statistical analysis
To control prestimulation values, base data registered just before SCS onsets were compared with the values gathered during the preceding rest periods by means of the nonparametric Kruskal–Wallis test (test of equality of populations), the one-way analysis of variance (parametric, with Bonferroni test for multiple comparisons), and the nonparametric trend test for 2, 5, and 10 V. The Wilcoxon test and the two-tailed t test were used to compare the various effects of SCS. Differences between values at various SCS time intervals were analyzed against base values. Furthermore, the curve obtained for each measurement during SCS was analyzed with respect to maximum on Y-axis, slope, end point, and area under the curve. Each period and measurement was analyzed with respect to the effects of SCS using the Wilcoxon signed rank test for matched samples, the sign test, and the t test based on normal distributions. Finally, the specific influence of SCS intensity on each measurement was demonstrated by means of one-way analysis of variance (parametric Bonferroni test for multiple comparisons), Kruskal–Wallis, and trend tests.

The significance of parametric and nonparametric tests was concordant in more than 94% (312 of 331). The discordance in the remaining 6% was limited to values close to p = 0.05. However, a lack of normal distribution appeared in 14% (42 307) of the data subsets. Therefore, only results from the nonparametric tests have been reported in detail.


   Results
Top
 Abstract
 Introduction
 Material and methods
 Results
Comment
 Acknowledgments
 References
 
The initial hemodynamic measurements at rest were in normal range for anesthetized Göttingen minipigs [10] and consistently stable (less than ± 10%) throughout periods of long observation. Comparison of these data with the reference values sampled before each SCS session showed no statistically significant differences.

The 15 animals responded to at least one 10 V session; 4 pigs remained insensitive to the 5V intensity and 5 remained insensitive to 2 V. Of 68 stimulation sessions, 59 (87%) induced hemodynamic changes that had never occurred in any animal at rest. These changes were more systematic at 10 V (28/29 = 97%) than at 5 (17/20 = 85%) or 2 V (14/19 = 74%). Typically SCS induced an initial decrease in HR, BP, and pulmonary artery pressure lasting less than 1 minute, followed by a stimulus intensity-dependent increase in BP, CO, SV, and RPP, associated with moderate changes in HR, PAP, and PVR (Tables 1–3). Urinary output increased continually under SCS, probably reflecting a raised global splanchnic perfusion. At SCS discontinuation, all measurements tended to return to prestimulation values within a few minutes.


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  		Table 1. Hemodynamic Changes at 2 V

 

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  		Table 2. Hemodynamic Changes at 5 V

 

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  		Table 3. Hemodynamic Changes at 10 V

 
Changes in left ventricular end-diastolic pressure were minimal (± 1 to 2 mm Hg) and insufficient to substantially influence CO. A single inadvertent application of full-intensity SCS induced an acute and deep vagal shock, that could be quickly reversed by 0.5 mg atropine.

The characteristics of the hemodynamic changes elicited by SCS are intensity dependent (Figs 1 and 2): 10 V SCS induced important rises in BP and RPP, whereas 2 V SCS induced a drop in SVR and a mild increase in BP. Accordingly, the increase in CO and SV regularly observed under SCS was more pronounced and sustained at low SCS intensity. The trend test confirmed that changes in BP tended to appear earlier, and were more intense and more sustained at a higher voltage.



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  		Fig 1. Main effects of 2 and 5 V cervical spinal cord stimulation on hemodynamics. Substantial increases are shown in cardiac output and minimal variations in heart rate- and intensity-dependent rise in blood pressure. Typical short initial decreases ({downarrow}) in heart rate and blood pressure are evident. (ART1 = systemic blood pressure [systolic, mean diastolic]; ART2 = left ventricular pressure; HF = heart rate; HZV = cardiac output [scale 1 to 10 L, time on horizontal axis]; PAP = pulmonary artery pressure; ZVD = central venous pressure [artifacts due to cardiac output measurements].)

 


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  		Fig 2. Effects of high (10 V) and middle (5 V) intensity cervical spinal cord stimulation during short interval stimulation. Exhaustion mechanisms are absent. Changes include short initial decreases ({downarrow}) in heart rate and blood pressure followed by intensity-dependent increases, and a fast return to base line values after spinal cord stimulation. Major hemodynamic changes are seen at 10 V. *Compression of ocular globes. (ART1 = systemic blood pressure [systolic, mean diastolic]; ART2 = left ventricular pressure; HF = heart rate.)

 

   Comment
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
Acknowledgments
 References
 
Spinal cord stimulation applied at the high cervical level induces macrocirculatory changes detectable by routine hemodynamic tests. The occurrence of these changes in deeply anesthetized animals demonstrates that the vasoactive properties of SCS are independent of its pain-alleviating effect [6, 9]. In addition, the hypothetical implication of vasoactive polypeptides [6, 9] can be discarded when considering the fast return of all hemodynamic measurements to base line after SCS discontinuation. The changes elicited by cervical SCS are similar to the limited microcirculatory changes observed with thoracic SCS [11]. However, they occur in extended body areas, which suggests strongly that the hemodynamic response induced by cervical SCS is not limited by a segmental mode of action on the autonomic nervous system, as for thoracolumbal SCS [6, 9]. This hypothesis is in conformity with immunocytochemical data demonstrating that high-thoracic SCS affects parts of the brain specifically involved in control of autonomic function [12]. Moreover, stimulation of the periacqueductal gray has also been demonstrated to induce an increase in coronary, carotid, and femoral blood flow accompanied by tachycardia and visceral vasodilation [13].

The hemodynamic properties of high cervical SCS seem to support both a sympathetic and a parasympathetic effect. Differences in type and degree of responses may reflect different recruitment patterns of autonomic nerve fibers depending on intensity. Supporting this hypothesis, about one third of all spinothalamic afferents are concentrated in the C1/C2 segments, and 6% of vagal efferents project directly into this region [8]. Moreover, Chalmers and coworkers [14] pointed out the importance of the rostral ventrolateral medulla containing aminergic neurons regulating sympathetic activity. Several pathways diverge from these areas to major brainstem centers modulating autonomic activity. Our results suggest differences in the activation threshold of ascending and descending bulbospinal pathways. This hypothesis may account for the acute and short-lasting initial parasympathetic response and the subsequent overwhelming sympathetic response. The immediate vagal shock elicited by an accidental acute full-intensity stimulation also suggests an initial parasympathetic activation. However, the rise in HR, BP, and RPP occurring after about 1 minute of stimulation is consistent with a sympathetic activation, the extent of which closely correlates with stimulation intensity. These effects cannot be attributed to rebound mechanisms because the interruption of SCS during the initial short-lasting decrease of HR and BP was followed by a quick return of hemodynamic values to base line.

The SCS induced increase in CO may proceed from an inotropic effect. This hypothesis stands in agreement with data of Heusch and Deussen [15], demonstrating a marked increase in myocardial performance during electrical stimulation of the left inferior cardiac nerve. The decrease of peripheral resistance specifically observed at less than 2 V SCS may account for the significantly higher rise in CO elicited by low-voltage SCS.

Theoretically, SCS may influence myocardial ischemia either by alleviating anginal pain or by modifying the oxygen supply–demand ratio of the myocardium. The pain-relieving effect of SCS is well established. Anginal pain is known to induce a general and segmental rise in sympathetic tone [16] leading to vasoconstriction and further decrease in coronary blood flow; this deleterious sequence can be interrupted easily by thoracic epidural anesthesia [17]. Studies designed to show an increase in oxygen myocardial supply have demonstrated that the symptomatic and electrocardiographic improvement reported in angina patients treated by SCS are not linked with a rise in global coronary blood flow [18]. Nevertheless, a positron emission tomography study [19] has detected some redistribution of the coronary blood flow from nonischemic toward ischemic areas. This so-called "Robin Hood effect" was attributed to a blunting effect of adenosine activity, a substance known to divert the myocardial blood flow toward subepicardial layers [20].

In angina treatment, SCS is generally delivered at the C7/Th1 level [1, 3, 5]. Most of its alleged benefits may result from generalized vasoactive mechanisms: the decrease in number and duration of anginal attacks and in nitrates consumption [2, 4], the reduced ST-segment depression at comparable workloads [1, 3, 5], the increase in time to angina [3, 5, 19], and the improvement in New York Heart Association functional class repeatedly reported under SCS [1, 4] may all result from an afterload reduction leading to decreased myocardial oxygen consumption. Substantiating this hypothesis, an improvement in lactate metabolism and a slight decrease in coronary blood flow have been reported during SCS in anginal patients under atrial pacing [18]. These findings were considered indicative of a reduction in myocardial oxygen demand.

Some limitations of the study should be noted. Variable individual reactions to different voltages combined with a limited number of investigations may have overinfluenced the final results. However, the same trend was observed in all responders for each SCS intensity and a broad statistical approach has allowed to limit the impact of individual reactions on our conclusions.

The major hemodynamic changes observed in young and healthy animals suggest a possible mechanism of action of SCS in human angina. This hypothesis has to be confirmed in coronary patients. Further pharmacological studies and selective ablation experiments at bulbospinal and brainstem levels are also necessary to determine the mode of action of cervical SCS.

Cervical SCS induces intense global hemodynamic changes in anesthetized Göttingen minipigs that are easily detectable by routine invasive hemodynamic monitoring and reproducible. These changes are intensity dependent. Therefore, it is possible to modulate the hemodynamic response by modifying the stimulation voltage. Low-intensity SCS induces a substantial increase in cardiac output and a decrease in systemic vascular resistance, which provides ideal conditions for optimal cardiac work. This mechanism may underlie the beneficial effects of SCS in the treatment of refractory angina pectoris.


   Acknowledgments
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
References
 
We are grateful to Dr W. Berchtold, Associate Professor of Biometrics, Swiss Federal Institute of Technology, Zürich, for his precise work in the formulation and performance of the statistical evaluation and his pertinent remarks. We also wish to express our sincere gratitude to Dr A. Kléber, Professor of Physiology, University of Bern, for his careful review of the manuscript.


   References
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 

  1. TenVaarwerk I.A.M., Jessurun G.A.J., DeJongste M.J.L., et al. Working Group on Neurocardiology. Clinical outcome of patients treated with spinal cord stimulation for therapeutically refractory angina pectoris. Heart 1999;82:82-88.[Abstract/Free Full Text]
  2. Mannheimer C., Eliasson T., Augustinsson L.E., et al. Electrical stimulation versus coronary artery bypass surgery in severe angina pectoris. The ESBY study. Circulation 1998;97:1157-1163.[Abstract/Free Full Text]
  3. Hautvast R.W.M., DeJongste M.J.L., Staal M.J., van Gilst W.H., Lie K.I. Spinal cord stimulation in chronic intractable angina pectoris: a randomized, controlled efficacy study. Am Heart J 1998;136:1114-1120.[Medline]
  4. Sanderson J., Ibrahim B., Waterhouse D., Palmer R.B.G. Spinal electrical stimulation for intractable angina pectoris: long-term clinical outcome and safety. Eur Heart J 1994;15:810-814.[Abstract/Free Full Text]
  5. DeJongste M.J.L., Hautvast R.M., Hillege H.L., Lie K.I., Working Group on Neurocardiology. Efficacy of spinal cord stimulation as adjuvant therapy for intractable angina pectoris: a prospective randomized clinical study. J Am Coll Cardiol 1994;23:1592-1597.[Abstract]
  6. Augustinsson L.E., Carlsson C.A., Holm J., Jivegard M. Epidural electrical stimulation in severe limb ischemia. Pain relief, increased blood flow and possible limb-saving effect. Ann Surg 1985;202:104-110.[Medline]
  7. LoGerfo F.W. Epidural spinal cord stimulation: an unproven methodology for management of lower extremity ischemia. J Vasc Surg 1991;13:518-519.[Medline]
  8. Foreman R. Neurophysiological mechanisms of pain relief by spinal cord stimulation in angina pectoris. In: Horsch S., Claeys L., eds. Spinal cord stimulation: an innovative method in the treatment of PVD and angina. Darmstadt, Germany: Steinkopff, 1995:155-164.
  9. Linderoth B., Fedorcsak I., Meyerson B.A. Peripheral vasodilatation after spinal cord stimulation: animal studies of putative effector mechanisms. Neurosurgery 1991;28:187-195.[Medline]
  10. Becker M., Beglinger R. Hämodynamische, kardiale und respiratorische Veränderungen unter Enfluran-Mononarkose beim Göttinger Miniaturschwein. Anaesthesist 1982;31:145-150.[Medline]
  11. Linderoth B., Gunasekera L., Meyerson B.A. Effects of sympathectomy on skin and muscle microcirculation during dorsal column stimulation. Neurosurgery 1991;29:874-879.[Medline]
  12. DeJongste MJL. Neurostimulation as an adjuvant therapy for patients with intractable angina pectoris [thesis]. Groningen, The Netherlands: Rijkuniversiteit Groningen, 1994.
  13. DeJongste M.J.L., Cowie R.J., Holstege J. Neural regulation of coronary blood flow and its impact on angina pectoris and myocardial ischemia. In: van Gilst W.H., Lieds K.I., eds. Neurohumoral regulation of coronary flow. Role of the endothelium. Dordrecht, The Netherlands: Luwer Academic, 1993:42-56.
  14. Chalmers J.P., Kapoor V., Llewellyn-Smith I.J., Minson J.B., Pilowski P.M. Central control of blood pressure. Eur Heart J 1992;13(Suppl A):2-9.
  15. Heusch G., Deussen A. The effects of cardiac sympathetic nerve stimulation on perfusion of stenotic coronary arteries in the dog. Circ Res 1983;53:8-15.[Free Full Text]
  16. Collins P., Fox K.M. Pathophysiology of angina. Lancet 1990;335:94-96.[Medline]
  17. Blomberg S., Curelaru I., Emanuelsson H., Herlitz J., Pontén J., Ricksten S.E. Thoracic epidural anesthesia in patients with instable angina pectoris. Eur Heart J 1989;10:437-442.[Abstract/Free Full Text]
  18. Mannheimer C., Eliasson T., Andersson B., et al. Effects of spinal cord stimulation in angina pectoris induced by pacing and possible mechanisms of action. BMJ 1993;307:477-480.
  19. Hautvast R.W.M., Blanksma P.K., DeJongste M.J.L., et al. Effect of spinal cord stimulation on myocardial blood flow assessed by positron emission tomography in patients with refractory angina pectoris. Am J Cardiol 1996;77:462-467.[Medline]
  20. Gaspardone A., Crea F., Iamele M., et al. Bamiphylline improves exercise-induced myocardial ischemia through a novel mechanism of action. Circulation 1993;88:502-508.[Abstract/Free Full Text]



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