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CARDIOVASCULAR ANESTHESIA

Left Stellate Ganglion Block Has Only Small Effects on Left Ventricular Function in Awake Dogs Before and After Induction of Heart Failure

Jost Müllenheim, MD^*, Benedikt Preckel, MD, Detlef Obal, MD, Marc Heiderhoff, cand med^*, Juliane Hoff, cand med^*, Volker Thämer, MD, PhD^*, and Wolfgang Schlack, MD, PhD, DEAA

*Institut für Herz- und Kreislaufphysiologie and Institut für Klinische Anaesthesiologie, Heinrich-Heine-Universität, Düsseldorf, Germany

Address correspondence and reprint requests to Wolfgang Schlack, MD, DEAA, Institut für Klinische Anaesthesiologie, Heinrich-Heine-Universität, Postfach 10 10 07, D-40001 Düsseldorf, Germany. Address e-mail to wolfgang{at}herzkreis.uni-duesseldorf.de

	Abstract

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Left stellate ganglion block (LSGB) results in acute sympathetic denervation of the left ventricular (LV) posterobasal wall. We investigated the effects of LSGB in chronically instrumented awake dogs before and after the induction of pacing-induced congestive heart failure. Twelve dogs were instrumented for measurement of global hemodynamics [LV pressure (LVP)], its first derivative (dP/dt), cardiac output (CO), and regional myocardial function (systolic posterobasal segment length shortening, mean velocity [SLmv]). Before the induction of heart failure (n = 12), LSGB did not affect CO [3.2 ± 1.4 (control, mean ± SD) vs 3.3 ± 1.6 L/min (LSGB, P = 0.45)] and SLmv (11.1 ± 4.0 vs 10.8 ± 4.0 mm/s, P = 0.16), but slightly reduced LVP (130 ± 12 vs 125 ± 14 mm Hg, P = 0.04), dP/dt_max (3614 ± 755 vs 3259 ± 644 mm Hg/s, P = 0.003) and dP/dt_min (-3153 ± 663 vs -2970 ± 725 mm Hg/s, P = 0.03). During heart failure (n = 8), global hemodynamics [CO (2.8 ± 1.2 vs 2.7 ± 1.2 L/min, P = 0.04), LVP (119 ± 6 vs 112 ± 9 mm Hg, P = 0.01), dP/dt_max (1945 ± 520 vs 1824 ± 554 mm Hg/s, P = 0.03) and dP/dt_min (-2402 ± 678 vs -2243 ± 683 mm Hg/s, P = 0.04)], as well as regional myocardial function, were significantly different after LSGB [SLmv] (8.0 ± 3.8 vs 6.9 ± 3.4 mm/s, P = 0.02)]. In conclusion, even during heart failure, the hemodynamic changes after LSGB are small, confirming its broad margin of safety.

Implications: Left stellate ganglion blockade with local anesthetic produces only very small global hemodynamic and regional myocardial function changes in awake dogs, even in the presence of pacing-induced heart failure.

	Introduction

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Unilateral cervicothoracic sympathetic (or stellate ganglion) block (SGB) by injection of local anesthetics is an established procedure for the diagnosis and treatment of pain, impaired vascular circulation, sympathetic reflex dystrophy, causalgia, and herpes zoster (1). Unilateral SGB will not only block pain fibers, but will also lead to regional sympathetic denervation of part of the left ventricle (LV) because the right and left sympathetic system supply different regions within the LV (2). A left SGB (LSGB) impairs LV mechanical performance in dogs (3) and healthy patients (4). LSGB reduces myocardial contractile function in the posterobasal wall, causing LV asynchrony and prolonged LV relaxation. Cardiac output (CO) is unchanged as the adverse effects on LV function are within the compensatory range of the otherwise healthy dogs and patients (3,4). In heart failure, ventricular function depends, in part, on increased sympathetic tone and preexisting contractile dysfunction which may make the hearts more susceptible to the adverse effects of SGB. Thus, we hypothesized that LSGB during heart failure would result in pronounced hemodynamic changes, perhaps promoting LV decompensation and a decrease of CO.

In a first set of experiments, we investigated the effects of LSGB in chronically instrumented awake dogs in the presence of a normal resting sympathetic tone without the influence of anesthesia or surgery. To characterize the influence of LSGB on compromized hearts, congestive heart failure was induced by rapid cardiac pacing over 2–3 mo in the same dogs. In a second set of experiments, LSGB was performed in awake dogs with heart failure.

We determined global systolic and diastolic ventricular performance, as well as regional myocardial function, in two distinct LV regions assumed to be innervated predominantly by the right and left stellate ganglion, respectively.

	Methods

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The present study conforms to the Guiding Principles in the Care and Use of Animals, as approved by the Council of the American Physiologic Society, and was approved by the local bioethical committee of the District of Düsseldorf. Twelve female mongrel dogs weighing 25–32 kg were trained daily for 3 wk to become familiar with the laboratory environment and the investigators. Instrumentation of the dogs has been described previously (3).

In brief, in anesthetized dogs, a left thoracotomy and pericardiotomy was performed under sterile conditions. A polyethylene catheter (16-gauge; Portex Limited, Kent, UK) was implanted under the fascia alongside the left upper sympathetic chain. The spread of saline 3–5 cm down the sympathetic chain was clearly visible behind the fascia in all cases. Dogs were instrumented with an aortic catheter (Tygon R3603^TM; Norton, Akron, OH) for measurement of aortic pressure (AOP), a Konigsberg transducer^TM (LP 200; Konigsberg, Pasadena, CA) for measurement of LV pressure (LVP) and its first derivative (dP/dt), and with an ultrasonic flowprobe (T 208^TM]; Transonic Systems Inc., Ithaca, NY) around the pulmonary artery for measurement of CO. Two pairs of ultrasonic crystals (Triton Technology Inc., San Diego, CA) were implanted in the subendocardium in the LV anteroapical and posterobasal wall. For cardiac pacing, two electrodes were fixed epicardially at the left atrium. The pericardium was left partly opened, and the chest wound was closed in layers. All wires and catheters were tunneled and externalized between the scapulae of the dog. The dogs were allowed to recover for at least 2 wk. Postoperative analgesia was provided by intercostal nerve block (5 mL 0.25% bupivacaine) and intramuscular injection of piritramide 15 mg two times per day for 3 days. Antibiotic therapy (IV ceftriaxone 1 g two times per day) was continued for 7 days.

After recovery, LSGB was performed in awake dogs. Baseline values were measured once all hemodynamic variables had attained steady-state values. LSGB was then performed by injection of 5 mL of lidocaine 1% via the implanted catheter. Completeness of the block was verified by observation of a left sided Horner syndrome and by measuring an increased skin temperature of the left forelimb in comparison with the right forelimb 10 min after LSGB in all dogs. Hemodynamic measurements were then performed.

Congestive heart failure was induced by rapid left atrial pacing with a frequency of 240 bpm for 8 to 12 wk (Osypka Pace 101H, Berlin, Germany). A complete set of hemodynamic values and body weight were determined two times a week. Heart rate (HR) was measured daily to ensure permanent pacing. Heart failure was assumed when LV end-diastolic pressure (LVPED) increased to values >15 mm Hg, end-diastolic segment length (SLed) as a measure of end-diastolic ventricular volume increased, ascites and loss of appetite could be observed, and physical exercise tolerance was obviously decreased. LSGB was again performed as described above.

At the end of the experiments, the animals were killed by an overdose of IV thiopental, and, their hearts were excised for verification of correct crystal alignment and histological verification of dilatative cardiomyopathy. Postmortem injection of methylene blue into the stellate ganglion catheter was performed to verify correct catheter placement.

LVP, dP/dt, CO, AOP, and myocardial segment length (SL) in the anteroapical and posterobasal wall were continuously recorded on an ink-recorder (Recorder 2800^TM; Gould Inc., Cleveland, OH) during all experiments. The data were digitized by using an analogue-to-digital converter (Data Translation, Marlboro, MA) at a sampling rate of 500 Hz and later processed on a personal computer.

Global hemodynamics were assessed by measuring CO and mean aortic pressure (MAP) and by calculating systemic vascular resistance (SVR). Global systolic function was measured in terms of LVP and the maximal rate of pressure increase (dP/dt_max). dP/dt_min, as well as the time constant of LV isovolumic relaxation (), were used as indices of global LV diastolic function.

As in a previous study (3), regional myocardial systolic function was assessed separately in two regions: in the posterobasal wall that is mainly innervated by the left stellate ganglion and in the anteroapical wall, mainly innervated by the right stellate ganglion (2). Regional systolic contractile function was evaluated as mean systolic SL shortening velocity (SLmv), as well as percent systolic SL shortening (SLes%), calculated as:

where SLed represents end-diastolic SL and SLes represents end-systolic SL. The timing of regional wall motion within the cardiac cycle was assessed by a temporal Fourier transform of the posterobasal and anteroapical SL signals, and the phase of the first Fourier harmonic was determined; a complete cardiac cycle was defined as 360° starting with 0° at end-diastole (5). LV asynchrony was assessed by the phase difference () between the first Fourier harmonics of posterobasal and anteroapical wall motion.

Measured values are presented as means ± SD. Statistical analysis was performed by using Student’s t-test for paired observations (baseline values before and after the induction of heart failure and values before and after LSGB). Changes were considered statistically significant when P < 0.05. was described by using linear regression analysis.

	Results

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Twelve dogs were instrumented. In all animals, complete data sets for LSGB before the induction of heart failure were obtained. Four dogs died before LSGB could be performed during congestive heart failure. In three dogs, the reason for the sudden death was uncertain, but may have been linked to the occurrence of ventricular arrhythmias. In one dog, aortic bleeding occurred because of an infection of the aortic wall around the aortic catheter. Thus, in eight dogs, data sets were obtained during heart failure. In one of these, regional myocardial function in the anteroapical wall could not be measured because of a broken wire of the ultrasonic crystal.

Hemodynamic measurements presented were obtained 10 min after LSGB. At this time, the effectiveness of LSGB was verified by an increase of skin temperature of the left forelimb from 31.9° ± 2.4° to 33.2°C ± 2°C (P = 0.03) before the induction of heart failure and from 31.0° ± 2.0° to 32.8° ± 1.9°C (P = 0.05) after the induction of heart failure, whereas the temperature of the right forelimb remained stable. A left sided Horner syndrome could be observed in all dogs 10 min after the injection of lidocaine.

Hemodynamics and Myocardial Function Before and After the Induction of Heart Failure
The induction of heart failure led to a decrease of maximal LVP, dP/dt_max, and CO (Table 1). Diastolic function was impaired as evidenced by prolonged and increased dP/dt_min. Regarding regional myocardial function, SLed increased in the anteroapical wall and in the posterobasal wall reflecting an increase in end-diastolic volume (Table 2). SLmv as a variable of regional contractile function was reduced in the anteroapical and posterobasal wall.

Regional Myocardial Function.
After LSGB, posterobasal contractility was impaired, as reflected by a small but significant decrease of SLmv (by 14%, P = 0.02) and SLes% (by 10%, P = 0.03) (Table 4). This regional reduction of contractility resulted in a delayed timing of wall motion of the posterobasal wall during the cardiac cycle after LSGB (by 9°, P = 0.07). In the anteroapical wall, regional myocardial function was not affected. Consequently, increased by 10° (P = 0.17).

	Discussion

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The main finding of the present study is that LSGB had a small but significant depressant effect on global LV function in chronically instrumented awake dogs and impaired regional myocardial function after the induction of heart failure.

We used a canine rapid atrial pacing model of congestive heart failure. We did not measure plasma noradrenaline concentrations or activity of the sympathetic nervous system, which are increased in heart failure (6). LSGB was chosen because of the dominance of the left cervicothoracic sympathetic system within the LV wall (2). In addition, assessment of the normal pattern of sympathetic innervation in dogs had demonstrated reduced levels of norepinephrine at the apex compared with the base of the heart (7,8), and the same holds true for dogs with pacing-induced heart failure (9). Consequently, any effect on LV function should be more pronounced after LSGB than after right SGB.

In contrast to our previous studies (3,10), LSGB was performed in conscious dogs. Thus, we avoided the activation of the sympathetic nervous system by acute surgical trauma or the influence of anesthesia (11).

During the experiments, HR was kept constant by atrial pacing (160 bpm). Therefore, an effect of LSGB on spontaneous HR as described previously (12) could not be detected.

In a first set of experiments of our study, LSGB was performed in conscious dogs before the induction of heart failure. LSGB had only minor effects on regional and global myocardial function. We observed a small delay of posterobasal wall motion within the cardiac cycle. This finding is in accordance with the LV innervation pattern, because the posterobasal wall is mainly supplied by the left sympathetic system by fibers traveling across the left circumflex coronary artery, whereas the anteroapical wall is predominantly innervated by fibers from the right sympathetic system traveling alongside the left anterior descending coronary artery (2). However, unilateral "denervation" of sympathetic fibers caused by LSGB did not result in a significant increase of myocardial asynchrony. This is in contrast to our two previous studies (3,10). In these studies in -chloralose-anesthetized dogs, increased myocardial asynchrony was accompanied by a significant impairment of LV systolic and diastolic function. To preserve cardiovascular reflexes, chloralose was used, which maintains a high sympathetic tone leading to an increase in SVR and HR (13). In the present study, LSGB was performed in chronically instrumented dogs without the confounding difficulties engendered by the effects of surgical trauma and anesthesia on reflex pathways and the autonomic nervous system (11). After instrumentation, the dogs were allowed to recover for at least two weeks until hemodynamic measurements returned to normal values. Thus, resting sympathetic tone was expected to be low. This might explain the much smaller effects of LSGB on LV mechanical performance seen in this study before the induction of heart failure compared with the more pronounced effects in the previous studies (3,10). In an echocardiographic study in ASA physical status I patients (4), LSGB impaired ventricular relaxation, but as in healthy dogs, the hemodynamic changes were within the compensatory range and CO was maintained.

Animals with heart failure may be especially susceptible to the adverse effects of LSGB on cardiac dynamics because, during heart failure, ventricular function depends, in part, on an increased sympathetic tone, and contractile dysfunction is preexistent. Therefore, we hypothesized that, in dogs with heart failure, LSGB will lead to a further decrease of contractile function with a consecutive reduction of CO.

We used a well established experimental model of congestive heart failure produced by chronic rapid cardiac pacing, which has been shown to have many of the typical characteristics of dilated heart failure found in humans (14). There is general agreement that the activation of the sympathetic nervous system is important in the pathophysiology of congestive heart failure leading to an increase of plasma norepinephrine and renin in humans (6) and in the dog model of pacing-induced heart failure we used (14). The hemodynamic values obtained after two-three months of rapid cardiac pacing (Table 1) clearly demonstrated the presence of severe heart failure.

LSGB after the induction of pacing-induced congestive heart failure led only to a small but constant decrease of global myocardial function (Table 3). Myocardial contractility in the posterobasal wall was significantly reduced (Table 4). In contrast to the findings before the induction of heart failure, LSGB resulted in a small (5%) but constant reduction of CO in every dog. However, these effects were only small and probably without clinical relevance.

This result may be partially explained by LSGB affecting only regional sympathetic activity. Most of the increased norepinephrine in plasma arises from the peripheral sympathetic nerve endings throughout the body, whereas plasma epinephrine is believed to be primarily of adrenal origin (15). Therefore, LSGB may have only small effects on the increased systemic catecholamine levels during heart failure. Second, it is conceivable that a decrease in regional sympathetic innervation by LSGB had only a small further depressant effect because the chronically increased catecholamine levels resulted in a decrease in cardiac ß-adrenergic receptor density and ß-adrenergic signal transduction in cardiac sarcolemmal membranes (16). Reduced adenylate cyclase activity and an increase in inhibitory G proteins have been described during heart failure (17,18). Swedberg et al. (19) reported an increased release of norepinephrine from the myocardium during heart failure, indicating the activation of myocardial sympathetic nerve terminals. Furthermore, a diminished norepinephrine uptake (20) contributes to the depletion of myocardial norepinephrine stores (9). Thus, a reduction of regional sympathetic tone by LSGB may have caused only a minor further reduction in regional norepinephrine release.

To summarize, the hemodynamic effects of LSGB in awake, resting dogs were very small, most likely caused by their low resting sympathetic tone. Even in the presence of chronic congestive heart failure, LSGB had only minor effects on regional and global LV function, probably a result of the depletion of myocardial catecholamine stores and the downregulation of adrenergic receptors during heart failure. This small reduction of LV function may be clinically insignificant, which underlines the wide margin of safety of SGB known from its small clinical complication rate (21) and the absence of any reports of cardiac pump failure after SGB. However, even in healthy humans, an impairment of LV relaxation can be seen after LSGB (4), and it cannot be excluded from the present study that patients with acute heart failure, in whom the response to changes in sympathetic tone is maintained, may be more susceptible to the adverse effects of SGB on cardiac dynamics.

	Acknowledgments

 
This study was supported by a grant (SCHL 448/2-1) from the German Research Foundation (WS).

We thank E. Hauschildt, BTA, A. Moloschavij, MD, J. Fräßdorf, MD, M. Sager, MD and I. Schrey, MTA, for excellent technical assistance.

	References

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