JACC Vol . 22, No. 3 758 September 1993 :758-67 Long-Term Follow-Up (12 to 35 Weeks) After Dynamic Cardlomyoplasty CAROLINE M. H. B. LUCAS, MD, FREDERIK H . VAN DER VEEN, PHD, EMILE C . CHERIEX, MD, ROBERTO LORUSSO, MD, MICHAEL HAVENITH, MD, OLAF C. K. M. PENN, MD, HEIN J . J. WELLENS, MD, FACC Maastricht, The Netherlands Objectives. To obtain Information on the long-term effects of nearly complete transformation to type I muscle fibers. The dynamic cardiomyoplasty on hemodynamics and muscle histol- remaining 14 goats showed extensive li mat is in the latissimus ogy, this surgical. method was evaluated In goats . dorsl muscle, with severe intlmal hyperplasia and proliferation of lilac rid. Dynamic c lomyoplasty has been introduced as smooth muscle cells in the walls of the thoracodorsal artery and Its a new method to treat patients with severe cardiac failure . branches . An Increase in endoneural and endomysial connective Methods. In 24 pats, the left iatissimus dorsi muscle was tissue was observed, with some goats showing destroy nerve wrapped around the heart . The muscle was then subjected to branches near the electrodes . These findings differed from those progressive electric stimulation . In 16 goats, invasive transesoph- observed after long-term electrical stimulation of goat latissimus Doppler echocardi phic measurements and histol is dorsi muscle in situ . evaluation of the lat us dorsi muscle were performed at a 12 Conclusions. Dynamic cardlomyoplasty is of use in the treat- weeks after the wrapping. ment of severe he failure if the histol is structure of the Res+dis. Only two `oats showed an increase in aortic and left wrapped latissimus dorsi muscle remains Intact . Long-term re and right ventricular pressures concomitant with increased aortic suits in goats suggest that the current approach used in dynamic flow during latissimus dorsi muscle stimulation both before and cardiomyoplasty may lead to deterioration of the wrapped muscle . after induction of cardiac failure using Imipramine. This was (J Ant Coll Cardiol 1993 ;22 :758-b7) accompanied by a preserved latissimus dorsi muscle structure and In the last decade, dynamic cardiomyoplasty has been Dynamic ca iomyoplesty procedure . Twenty-four goats introduced as a new surgical technique to treat patients with with a body weight varying from 28 to 55 kg were studied . severe heart failure . During this procedure, the latissimus Anesthesia was induced intravenously with sodium thiop, n- dorsi muscle is wrapped around the heart and electrically tal (Nesdonal, 15 mg(kg body weight). After endotracheal stimulated synchronously with cardiac contraction. intubation, goats were maintained with oxygen/nitrous oxide Since the first clinical application in 1985 (1), a number of (1:2) and 1.5% fluothane . During the experiments, the lungs reports (2-11) have examined acute and long-term effects of were ventilated with a positive pressure respirator (Pulmo- dynamic cardiomyoplasty in animal experiments and pa- mat). The entire procedure was performed under sterile tients. This report describes our experience during long-term conditions, with antibiotic coverage using ampicillin (Am- fellow-up in a large number of goats . fipen) (1,000 mg intravenously) before operation . Pedicle preparation . A left-sided midaxdlary incision was performed and the collateral blood vessels to the distal Methods part of the latissimus dorsi muscle coagulated . All attach- The experiments were performed according to the "Na. ments of the muscle were disconnected, with the exception tional Academy of Sciences Guide for the Care and Use of of the axillary pedicle to preserve the thoracodorsal artery, Laboratory Animals" (12) . vein and nerve . Two intramuscular electrodes (Medtronic SP5528) were implanted in the upper part of the latissimus dorsi muscle flap perpendicular to the main branches of the From the Departments of Cardiology, Pathology and Cardiothoracic thoracodorsal nerve . Threshold value of stimulation was Surgery, University of Limburg, Maastricht, The Netherlands . This study was supported in part by a grant from the Netherlands Heart Foundation, The measured during temporary connection of these electrodes Hague, The Netherlands . to a programmer (Medtronic SP3028) . Manuscript received July 7, 1992; revised manuscript received January Wrapping procedure . A partial resection of the anterior 19, 1993, accepted February 12, 1993 . Add= f coresn xk=: Caroline M. H. B. Lucas, MD, Department arch of the second rib was performed to transfer the muscle Of Cudiokw, Academic Hospital Maastricht, P .O. Box 5800, 6202 AZ and pacing leads into the thorax . The thoracic cavity was Maastricht, The Netherlands . opened at the fifth left intercostal space and the pericardiurr ®1993 by the American College of Cardiology 0735-1097!9316.00 JACC Vol . 22, No . 3 LUCAS ET AL . 759 September 1993 :758-67 LATISSIMLS DORSIMUSCLE FOR CARDIAC ASSIST Table t . Stimulation Protocol of to Situ Stimulated Latissimus visible contraction of the entire latissimus dorsi muscle Dorsi Muscles* without causing apparent discomfort to the arimal . The laaterpulse Interval muscle was stimulated continuously, 24 h/day, for a period No. of (ams)/Burst Bursts of 12 weeks . Week Pulses Frequency (11Z) Min After this period, biopsy specimens were taken from the Protocol A (n = 3) midportion of stimulated and nonstiroku'Lled latissimuss dorsi 1 to 2 1 50 muscles . One biopsy specimen from both sides was quickly 3W4 2 100/10 50 frozen in isopentane. A second specimen was stored in 4% 5 to 6 3 67115 50 paraformaldehyde . Small biopsy samples for electron micro- 7WS 6 33/30 50 9 to 10 6 33130 60 scopic evaluation were also taken from both muscles . After 11102 6 33/30 50 the 12-week period, all six goats were killed using an Protocol B (aa 3) overdose of thiopental . 1 to 2 3 33/30 30 Hemodynamic evaluation . The hemodynainic effects of 3w4 3 33/30 40 dynamic cardiomyoplasty were investigated using both in- 3 33/30 5 to 6 50 vasive and Doppler echocardiographic measurements . Mea- 7 to 8 6 33/30 50 surements were made both in the normal heart and after the 9 to 10 6 33B0 60 induction of cardiac failure by imipramine 11 to 12 6 33/30 80 (13). Anesthesia, ventilation, infusion and electrocardiographic "'AY0 slightly diflercat protocols were usck, ivc indicaled by A and B . recordings were performed as described for the wrapping procedure. Aortic blood pressure was measured with a 7F removed. A sensing electrode (Medtronic SP5548) was im- Millar catheter tip micromanometer (Millar FC470) posi- planted in the left ventricular wall . Subsequently, the left tioned in the aortic arch through the femoral artery . Left latissimus dorsi muscle was wrapped in a counterclockwise ventricular pressure measurements were obtained with a 7F fashion around both ventricles as described previously by Millar catheter tip micromanometer (Millar PC470) inserted Anderson et al . (8). All three electrodes were connected to a through the left brachial artery into the left ventricle . Left cardiomyostimulator (SP1005 Medtronic) that was subse- ventricular end-diastolic pressure was recorded at a sensi- quently positioned in the interscapular region . tivity of 20 nu i Hg. The first derivative of left ventricular All goats received ampicillin (1,000 mg/day intramuscu- pressure (pos:tzve and negative dP/dt max) was determined larly for 5 days) as antibiotic treatment and buprenorfine as described by Schaper et al . (14). Right ventricular pres- (Temgcsic, 0 .6 mg/day intramuscularly) for analgesia. Two sure was measured using a Millar catheter tip micromanom- weeks after the wrapping procedure, electrical stimulation eter inserted into the right ventricle through the left jugular was started using the protocol described by Chachques et al . vein. All catheters were flushed repeatedly with saline (6). One pacing burst was synchronized to every heartbeat, solution . with an upper limit of 100 latissimus do rsi muscle contrac- Aortic blood flow velocity recordings were made using a tions/min . Hemodynamic studies were performed after a transesophageal approach. A 64-element 5-MHz phased follow-up period of 2:12 weeks, that ig,, after the end of the array transducer was positioned at the level of the ascending conditioning period of the wrapped latissimus dorsi muscle . aorta perpendicular to the aortic valve plane, allowing In situ latisshnus dorsi stimulation. Six healthy goats with registration of the blood flow just above the valve using a body weight ranging from 29 to 54 kg were studied . The pulsed Doppler echocardiography . The flow integrals were animals were anesthetized initially with sodium thiopental recorded using a strip chart recorder with a paper speed of (15 mg/kg) into the jugular vein, intubated and ventilated 50 inm/s and were traced offline on a digitizing tablet with oxygen/nitrous oxide (1:2) and 1 .5% halothane . A (Summasketch II) using a scientific measurement program 15-cm longitudinal skin incision was made in the left mid- (Sigmascan) . axillary line under sterile conditions, with preoperative To stimulate the wrapped muscle, different modes of antibiotic coverage using ampicillin (1,000 m j) intravenous- stimulation were used in the order given in Table 2 . Con- ly). Subsequently, two intramuscular electrodes (Medtronic traction of the latissimus dorsi muscle was synchronized to SP5528) were attached approximately 6 err, apart in the every 3rd heartbeat as long as the cardiac frequency re- proximal part of the latissimus dorsi muscle perpendicular to mained >100 beats/min . When the heart rate was less than the main branches of the left thoracodorsal nerve and this value, the cardiomyostimulator switched automatically connected to an Itrell pulse generator (Medtronic SP7420). to a synchronization ratio of one latissimus dorsfi muscle Stimulation of the left latissimus dorsi muscle was started contraction to every other cardiac contraction . Voltage of 2 weeks after this operation according to the protocol shown stimulation was programmed at 5 V and subsequently in- in Table 1, which is comparable to that commonly used after creased to S V when no effect was seen on hewn ynamic a dynamic cardiumyoplasty procedure .