| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Ann Thorac Surg 2002;74:507-513
© 2002 The Society of Thoracic Surgeons
a Department of Cardiology, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands
b Department of Cardiothoracic Surgery, Tel Aviv Medical Center, Tel Aviv, Israel
c Department of Cardiac Surgery, Civic Hospital, Brescia, Italy
d Department of Cardiac Surgery, St Raphael Hospital, Milan, Italy
e Department of Cardiac Surgery, Bundes Krankenhaus, Koblenz, Germany
Accepted for publication April 21, 2002.
* Address reprint requests to Dr Bolotin, Department of Cardiothoracic Surgery, Tel Aviv Sourasky Medical Center, 6 Weizmann St., Tel Aviv, 64239, Israel
e-mail: bolotin{at}netvision.net.il
 |
Abstract |
|---|
 Top Abstract IntroductionMaterial and methodsResultsCommentAcknowledgmentsReferences |
|---|
Methods. A carotid-jugular shunt model in 8 goats was used to induce progressive dilatation of the cardiac ventricles. Geometric modifications induced by the arteriovenous shunt were monitored by transthoracic echocardiography. After 8 weeks, cardiomyoplasty was performed, and the acute hemodynamic changes obtained with static cardiomyoplasty soon after the wrapping procedure were determined. Hence, hemodynamic variables recorded during assisted cardiac beats were then compared with data collected with unassisted cardiac beats using the conductance catheter method to generate pressure-volume loops.
Results. During electrical stimulation of the unconditioned skeletal muscle wrapped around the dilated left ventricle, a significant increase in stroke volume (117 ± 48 mL versus 87 ± 38 mL; p < 0.05) was observed. Early wrapped latissimus dorsi muscle activation also induced a reduction in LV end-systolic volume (from 51 ± 28 mL to 27 ± 14 mL; p < 0.05) when compared with unassisted LV contraction.
Conclusions. In a chronic model of cardiac dilatation, acute dynamic cardiomyoplasty was shown to increase LV contractile performance and reduce LV volume. Further evaluation is necessary to show the effects of a conditioned wrapped muscle on LV systolic function and dimensions in the long-term.
|
Introduction |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsReferences |
|---|
|
Material and methods |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsReferences |
|---|
Dilated cardiomyopathy was induced by a left carotid-jugular arteriovenous (AV) shunt. The animal’s condition was followed 8 to 10 weeks using echocardiography, after which acute CMP was performed. Monitoring with pressure-volume loops using the conductance catheter technique was performed during the AV shunt procedure and at the final acute CMP experiment (12 to 15 weeks later).
Arteriovenous shunt procedure
General anesthesia was induced by thiopental sodium (Pentotal Abbot s.p.a., Italy), administered intravenously at 15 mg/kg body weight, and maintained after endotracheal intubation with oxygen/nitrous oxide (1:2) and 1.5% halothane (Fluothane, Zeneca Ltd., Macclesfield, Cheshire, U.K.).
During the experiments, the lungs were ventilated with a positive-pressure respirator (Harvard, Apparatus Inc., South Natick, MA), and body temperature was kept constant with a heating mattress. A single dose of 10,000 IU of heparin intravenous was administered. Through a cervical incision, the left jugular vein and the left carotid artery were mobilized for a length of approximately 5 cm and ligated distally. After cross-clamping of the left carotid artery, an end-to-side anastomosis of approximately 1 cm in diameter was performed between the free end of the vein and the side of the artery, using 6-0 polypropylene nonabsorbable running sutures (Ethicon, Somerville, NJ). Clamps were removed, and patency of the fistula was confirmed visually by the pulsatile filling of the jugular vein.
Baseline measurements
Cardiac output was measured before and after performing the AV shunt. Left heart pressure-volume loops were obtained before and after performing the AV shunt, using the conductance catheter method. Baseline LV dimensions were measured by transthoracic echocardiography. Left ventricular dimensions were measured by echocardiography 2, 4, and 8 weeks after establishing the AV shunt.
The final experiment, performed 8 to 10 weeks after the AV shunt procedure once LV end-diastolic diameter had increased significantly, included left and right heart catheterization followed by the CMP procedure and a subsequent immediate stimulation protocol.
Heart catheterization
A Swan-Ganz catheter (7F) was positioned in the pulmonary artery through the right jugular vein to measure central venous pressure, and both pulmonary artery and capillary wedge pressures, as well as to calculate thermodilution cardiac output (cardiac output computer; Baxter Healthcare Corporation, Santa Ana, CA). A dual-field 12-electrode conductance catheter (F 7 Sentron, Roden, The Netherlands) was inserted through the left femoral artery into the LV. Correct positioning was confirmed by fluoroscopy and by inspection of segmental conductance signals. The position of the conductance catheter was then secured by a pursestring suture around the site of insertion. A balloon-tipped vena cava occlusion catheter (Cordis SP Cath, 15 mL) was introduced through the left femoral vein.
For analysis of LV pressure-volume relations, the method described by Baan and asociates [11] was used. This method is based on measuring the time-varying electrical conductances of up to five segments of blood within the LV cavity. Total LV volume was calculated from the sum of these segmental conductances. The dual-field modification [11] has been shown to improve the accuracy of the method, and was used in all animals. The conductance catheter used a Leycom Sigma-5-DF signal conditioner processor (CardioDynamics, Zoetermeer, The Netherlands) to compute LV volume [11]. To analyze pressure and volume signals, the data analysis program CONDUCT-PC (CardioDynamics) was used on a 486 microprocessor. To correct the volume signal for parallel conductance of the tissue surrounding the LV cavity, 7.5 mL of hypertonic saline solution (8%) was injected into the pulmonary artery to calculate the parallel conductance offset term (Vc).
Blood resistance was measured repeatedly by 5 mL of blood in a four-electrode cuvette to correct for conductance changes caused by hematocrit and electrolyte changes throughout the study. During the assessment of baseline values, cardiac output measurements by the thermodilution technique were repeatedly performed to obtain reliable estimations of mean cardiac output matching conductance stroke volume.
Cardiomyoplasty procedure
General anesthesia was induced as described for the AV shunt surgical procedure. A left-sided, midaxillary incision was performed, and all collateral blood vessels to the distal part of the LD muscle were coagulated. All attachments of the muscle, except the axillary pedicle, were disconnected to keep the thoracodorsal artery, vein, and nerve intact. Two intramuscular electrodes (Telectronics IML 04B) were implanted in the upper part of the LD muscle flap, perpendicular to the main branches of the thoracodorsal nerve, as described by Chachques and coworkers [12]. To assure proper positioning, threshold (0.3 to 0.6 V), total recruitment (1.0 to 2.5 V), and impedance (220 to 300 ohms) of the stimulation electrodes were measured using a pacing system analyzer (Telectronics Pacing System PSA 2401). A 5-cm segment of the anterior portion of the third rib, including the periosteum, was then resected to allow transposition of the LD muscle into the thorax. The muscle was inserted into the chest cavity, and its tendon was cut and sutured to the periosteum of the fourth rib, while closing the thoracic window. The thoracic cavity was opened at the fourth left intercostal space, and the pericardium was opened. A sensing and pacing electrode (Telectronics 033 S72) was implanted in the right ventricular wall, and sensing and impedance were verified to assure proper positioning. The left LD muscle flap was wrapped in a counterclockwise fashion around both ventricles. The muscle was first positioned around the right ventricle and fixed with interrupted sutures near the atrioventricular groove at the base of the heart. Subsequently the remaining part of the muscle was wrapped around the LV. The distal portion was sutured to the proximal part of the muscle.
The stimulation protocol was initiated approximately 45 minutes after accomplishing the wrapping, and the hemodynamic effects were recorded by LV conductance catheters presenting real-time, beat-to-beat pressure-volume loops.
The first part of the stimulation protocol included bursts of six pulses (5 V, 650 µs pulse width, and 160 ms burst duration) at varying delays. The measurements were obtained during stimulation with varying delays between the QRS complex and the beginning of the stimulation burst (25, 50, 75, 100, 125, and 150 ms). The second measurement was performed at an amplitude of 10 V instead of 5 V, using the best delay, as determined during the previous experiment, according to the shape of the pressure-volume loops. All hemodynamic monitoring and recording was conducted just after discontinuing mechanical ventilation to prevent potential interference of ventilatory-induced changes of cardiac loading conditions.
The third part of the study protocol included LD muscle stimulation with only one pulse every four spontaneous heartbeats for 10 minutes. Subsequently, the stimulator was blocked electrically to demonstrate reversibility, if this existed, for another period of 10 minutes.
Statistical analysis was performed with Student’s t test for paired variates. Values are presented as mean ± SD. Significance was assumed at p less than 0.05.
|
Results |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsReferences |
|---|
In the long-term, a gradual increase in LV end-diastolic diameter was observed after 2 (45 ± 4 mm), 4 (48 ± 5 mm), and 8 weeks (53 ± 4 mm), reaching a 26% increase, as compared with the baseline measurements (42 ± 4 mm, p < 0.01).
Other indices of the change in cardiac hemodynamics were obtained by comparing pressure-volume loops at baseline, immediately after the shunt, and after 8 weeks (Fig 1). There was a significant rise in the LV end-diastolic volume (104 ± 27 mL) compared with the baseline volume (75 ± 26 mL). None of the animals showed signs of heart failure or distress in relation to the AV shunt.
|
|
The pressure-volume loop presented in Figure 2 shows a 55% decrease in LV end-systolic volume (from 97 ± 0.7 mL in the unassisted beats to 44 ± 1.2 mL in the assisted beats). Stroke volume appeared to be significantly increased at all settings when assisted beats were compared with unassisted beats (Table 1).
|
|
Single-pulse stimulation every two spontaneous heartbeats during 10 minutes of monitoring produced only a small hemodynamic effect accompanied by an increase of LV pressure (5 to 10 mm Hg) for a short time (10% of the duration of systole). However, there was no significant change in the LV end-diastolic volume and the LV end-systolic volume at the end of the 10-minute one-pulse stimulation period, nor was there a change 10 minutes later as compared with the baseline.
|
Comment |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsReferences |
|---|
Carotid jugular arteriovenous shunt model
This study demonstrated that the AV shunt is capable of producing an immediate and stable high cardiac output state with subsequent marked ventricular dilatation caused by persistent overload, and can be a valuable model for assessing effects of ventricular wrapping by transposed skeletal muscles. However, despite evident and significant ventricular dilatation, none of the 8 goats showed clinical signs of pulmonary congestion or of heart failure, and no death was recorded. These results were in contrast with the high mortality rates (77%) and signs of pulmonary congestion occurring commonly within 24 hours after performing the AV shunt in small animals, as reported by Flaim and coworkers [14]. This discrepancy is probably related to the relatively small AV shunt, of approximately 10 mm, used in our study. Moreover, animals in the present investigation did not present other hemodynamic signs of heart failure, such as tachycardia or an increase in LV end-diastolic pressure, as was observed with inferior vena cava-aortic AV shunt applied in mongrel dogs [15]. Therefore, in contrast to the clinical situation, the model described herein should be considered a compensatory overload dilatation model rather than a heart failure model. Nonetheless, it was extremely valuable as, despite a hypercontractile and relatively healthy state of the native myocardium, marked ventricular enlargement was established and clear mechanical influence by the wrapped skeletal muscle on hemodynamics as well as on geometry of the dilated LV could be demonstrated.
Latissimus dorsi muscle stimulation
It has been well documented that patients with CMP often exhibit cardiac and clinical deterioration soon after operation, probably because of the surgical stress and the passive burden of the newly transposed and wrapped skeletal muscle around a severely compromised LV [16]. An early activation of the wrapped muscle would therefore be advisable from a cardiocirculatory standpoint in an attempt to begin cardiocirculatory assistance as soon as possible. On the other hand, early activation may be critical owing to the ongoing peripheral ischemia secondary to the surgical severance of perforating vessels [17]. Despite this regional hypoperfusion, systolic augmentation was considerable in the present study, if compared to the data presented by Yamauchi and colleagues [18]. A possible explanation is that Yamauchi and coworkers [18] applied an LD muscle-to-heart stimulation contraction ratio of 1:1, whereas we used a 1:4 ratio. Moreover, their use of a nondilated canine heart may be the reason for obtaining a smaller systolic augmentation. Acute and chronic skeletal muscle ischemia is a critical factor for structural and mechanical preservation. Standard clinical protocols of electrical stimulation have implied a recognized overuse representing an additional determinant of the progressive postoperative muscle degeneration with inevitable negative effects on CMP results [19]. Some investigators showed that modified stimulation regimens and more prudent activation patterns may reduce postoperative damage and, by maintaining a structural profile closer to the original one (type 2A fibers), may ensure more effective muscle flap mechanics. The LD muscle preconditioning was proposed by Ali and collaborators [20], who showed impressive postoperative improvement in functional and structural features of the muscle flap. Furthermore, Arpesella and coworkers [21] recently showed that a rest-working regimen may provide an additional advantage to the LD in terms of structural and contractile preservation. It is therefore possible, using these new concepts in muscle preparation and stimulation, that postoperative muscle damage and mechanical failure may be overcome or limited, also making an early LD activation possible. The beneficial effects of such an early contribution of an unconditioned LD muscle have been clearly documented in our study, although heart failure was not present. It was therefore confirmed that unconditioned, but electrically stimulated muscle, is capable of improving LV systolic function in the presence of dilated cardiac ventricles. Obviously, because of the lack of complete type 1 fiber transformation and of muscle fatigue resistance, skeletal muscle activation should be instituted with extremely prudent LD-to-heart contraction ratio and for a limited time during the day with expected benefits on muscle structure and mechanics.
Acute passive and active effects of cardiomyoplasty
The reports of Schreuder and associates [5] and Kass and colleagues [6], demonstrating gradual reverse remodeling of the LV after CMP, have given evidence to a new working mechanism of the procedure which was previously suggested by experimental data [22]. The dilated LVs in the patients were reduced to approximately 50% of the preoperative volume 1 year after the operation, as demonstrated by the pressure-volume loops. In an attempt to investigate whether a light stimulation protocol could induce some geometric change and to gather more information about a potential beginning of the remodeling process, we conducted the 10-minute one-pulse stimulation test. This part of the protocol was studied because it resembles the clinical situation at the beginning of the conditioning protocol, 2 weeks after vascular delay. In the present study, there was no detectable significant change in the LV volume after 10 minutes of single-pulse stimulation. These findings underline the need for a longer monitoring period to assess the effects of systolic light LD muscle stimulation, if any. Indeed, there is some consensus that augmentation of LV systole may play a secondary role in CMP mechanisms of action, whereas a constant mechanical action on LV chambers seems to be the primary mechanism of actionm which leads, to some extent, to late ventricular reverse remodeling and mechanical recovery. Whether these changes warrant a vigorous or light active girdling by the wrapped LD muscle or are just the consequence of a permanent ventricular binding represents a fundamental topic for additional investigation.
Study limitations
This study investigated the feasibility of the carotid-jugular fistula for inducing a marked and stable cardiac dilatation and subsequently submitted to biologic and dynamic ventricular binding. The subsequent high cardiac output state induced by the AV shunt did not eventually lead to heart failure, probably because of the limited follow-up period (8 weeks) after the shunt creation. The absence of heart failure may have affected the actual effects of wrapped LD muscle and, therefore, limited data interpretation. It is important, however, to underscore that the wrapped LD muscle was capable of modifying the geometry of a hypertrophic myocardium, which is certainly less amenable to external mechanical compression than a thinner and diseased myocardium, such as that encountered in chronic cardiomyopathy. This study specifically addressed LV hemodynamic and function; therefore, no thorough investigation was performed on the right side of the heart. Finally, the analysis of LD-heart synchronization achieved by an activated unconditioned LD muscle flap in our study may completely change because of the intervening modifications induced by chronic electrical stimulation, which are known to reduce muscle power and contraction and relaxation times, with expected influence on LD-heart coupling.
In conclusion, the AV shunt heart dilatation model is suitable for demonstrating the geometric changes induced by acute LD wrapping on a chronically dilated heart. This study also demonstrated that an electrically stimulated unconditioned wrapped skeletal muscle substantially increases LV systolic kick in dilated LV and further reduces enlarged LV volumes. No acute LV diastolic dysfunction is apparently induced by CMP. A chronic evaluation would be mandatory to monitor the hemodynamic and geometric changes during an ongoing trigger of cardiac dilatation such as the AV fistula. Another important aspect to be further investigated would be the relevance of passive versus active cardiac binding to the overall ventricular geometry and hemodynamics in the long-term.
|
Acknowledgments |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsReferences |
|---|
|
References |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsReferences |
|---|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
