LD-PACE II: a new cardiomyostimulator for cardiac bioassist.

The LD-PACE II was designed for use in cardiomyoplasty, aortomyoplasty, and skeletal muscle ventricles. All parameters specified as programmable can be changed in a noninvasive manner (using a programming interface wand connected to a computer using the Windows 95/98 environment). Two new functions may be very useful clinically, based on experimental research. 1. Work-rest regimen. The LD-PACE II is able to deliver alternating periods of muscle contractions and rest. Work and rest periods may be programmed independently between 1 and 120 minutes in increments of 1 minute. The work-rest regimen may be useful clinically if muscle contractions are needed for cardiac assist postoperatively. 2. Night/day regimen. This feature allows for a change in the ratio of muscle contractions according to a patient's activity level. During the day the cardiosynchronization ratio may be set from 1:1 to 1:4, and during the night it may be set for 1:8 to 1:16. This allows the muscle to have a long rest period, prevents overuse, and prolongs battery life. These two new features make this cardiomyostimulator very attractive for cardiomyoplasty in particular. The addition of the work-rest and night-day regimens allow the muscle to rest for periods during the day to prevent overuse, subsequent damage, and potential atrophy.

Effects of electrical stimulation postcardiomyoplasty in a model of chronic heart failure: hemodynamic results after daily 12-hour cessation versus a nonstop regimen.

The hemodynamic effects of cardiomyoplasty (CMP) have been investigated in many centers, but the question of whether it is necessary to stimulate the latissimus dorsi muscle (LDM) 24 hours a day has not been answered. The main goal of our investigation was to determine whether hemodynamic results after CMP were impaired when continuous electrical stimulation (ES) was off for 12 hours a day. A model of chronic heart failure was created in 12 sheep by performing an arteriovenous anastamosis and administering doxorubicin. Two weeks after the anastomosis, CMP was performed in eight sheep (experimental series); ES training was begun at 2 weeks after CMP. After completion of the initial ES conditioning (8 weeks after CMP), one group of sheep continued to receive ES 24 hours daily. Another group of sheep had only 12 hours of ES daily. Hemodynamic parameters were investigated 2 weeks later with the stimulator turned on and then off. With doxorubicin administration, arteriovenous anastamosis created a stable model of biventricular heart failure (right atrial pressure 20 +/- 3 mmHg vs 6 +/- 2 mmHg at baseline; pulmonary capillary wedge pressure 18 +/- 3 mmHg vs 9 +/- 2 mmHg; left ventricular end-diastolic area 15.2 +/- 1.2 cm2 vs 6.4 +/- 0.7 cm2; left ventricular ejection fraction 0.38 +/- 0.6 vs 0.65 +/- 0.7). Cardiomyoplasty improved hemodynamic status in all eight experimental sheep. However, when the investigation was performed with the stimulator off, this improvement was statistically insignificant. With stimulation on, there was decreased right atrial pressure, pulmonary capillary wedge pressure, left ventricular end-diastolic volume, and increased left ventricular ejection fraction. With the stimulator turned off for 12 hours daily, hemodynamic measurements did not differ from data with continuous ES for 24 hours daily. Because hemodynamic results do not seem to be impaired, we recommend daily, periodic cessation of stimulation to prevent damage to the LDM after CMP.

Comparison of different regimens of electrical stimulation applied to nonmobilized and newly mobilized latissimus dorsi muscle.

We investigated the possibility of preventing further aggravation of muscle ischemia and necrosis in newly mobilized, unconditioned latissimus dorsi muscle (LDM) by utilizing short increments of stimulation with intervening rest periods. Adult St. Croix sheep (N = 12) weighing 30 +/- 8 kg were used in this study. Fatigue tests (30 min) using different stimulation regimens before and after LDM mobilization were performed on all animals; the length of time to return to baseline levels was also measured. Our investigation yielded results that contradict the conventional wisdom that any electrical stimulation damages newly mobilized LDM and will cause a considerable decrease in contractile force (CF). Stimulation regimens using continuous contractions at 30 and 60 contractions per minute (CPM) for 30 minutes were damaging to the LDM. CF also dropped significantly and returned slowly to baseline values: at 60 CPM, CF dropped to 50 +/- 4% and did not return to baseline even after 90 minutes of rest; at 30 CPM, CF dropped to 61 +/- 4% and baseline was restored after 80 minutes of rest. Electrical stimulation using continuous contractions at a slower rate (15 CPM) was tolerable, although a 23% decrease in CF was noted (p < 0.05 when compared to 60 CPM). These results did not satisfy us that such a regimen would be useful for cardiac assistance immediately after cardiomyoplasty. The work-rest regimen at 30 CPM also gave poor results: CF decreased to 75 +/- 2% and baseline was restored after 80 minutes of rest. Promising results were seen when utilizing a work-rest regimen at 15 CPM. The newly mobilized LDM showed no visible signs of fatigue: CF decreased minimally to 92 +/- 3% (p < 0.05 when compared to 30 CPM), and light microscopic analysis of biopsies revealed no morphological damage exceeding that typically seen after subtotal mobilization. Such results open avenues for future investigations: beginning electrical stimulation immediately after cardiomyoplasty (using a single impulse and a slow rate of contraction); decreasing the length of time necessary to obtain full cardiac assistance; and beginning partial cardiac assistance immediately after cardiomyoplasty (if needed) for approximately 30 minutes several times a day.

Biologic glue increases capillary ingrowth after cardiomyoplasty in an ischemic cardiomyopathy model.

The authors investigated the multi-step mechanism of healing after cardiomyoplasty, focusing on the process of angiogenesis. The authors contend that enhancement of angiogenesis and prevention of ischemia-reperfusion injuries immediately after muscle mobilization will be effective in improving cardiomyoplasty results. After cardiomyoplasty, autologous biologic glue (ABG) was administered between the latissimus dorsi muscle (LDM) and myocardium. By 2 months, a new pseudo interlayer was present that bridged the gap between the LDM and myocardium. Neovascularization was visible in the form of numerous small capillaries. Marked degeneration of the LDM was noted, possibly caused by muscle ischemia-reperfusion damage after mobilization. Pockets were created of ischemic and nonischemic LDM to test for angiogenesis. One was left free of ABG (control); one received ABG only; one received ABG and pyrrolostatin. Some of the capillaries were large and had erythrocytes inside. biopsy samples showed 9.4 +/- 1.9% of the sample was occupied by blood vessels (compared with 3.6 +/- 0.7% in control muscle). These preliminary studies prove the feasibility of the authors' concept and provide evidence that angiogenesis can accelerate the healing process and provide an organic bridge between the LDM and myocardium after cardiomyoplasty.

Skeletal muscle of a growing organism has a greater transformation after electrical stimulation than adult skeletal muscle.

Six adult sheep and four newborn lambs (5 days old) were implanted with stimulator leads into the latissimus dorsi muscle and connected to a Myostim 7220 pacing system (Telectronics Pacing Systems, Inc., Englewood, CO). Electrical stimulation was started immediately after the operation. After 8 weeks of electrical stimulation, contractile force (CF) in adult sheep decreased to 76-81%, and to 78-82% in lambs. After 2 weeks' delay, CF in adults was 96-98%, and only 89-93% in lambs. After a 30 min intensive stress test, unconditioned control muscle lost 39% in lambs and 43% in adults. Muscle conditioned for 8 weeks lost 7-8% CF. However, after 2 weeks' delay, CF in adult muscle lost 33%, but only 12% in lambs. After cessation of electrical stimulation, the LDH-5 and LDH-1 + 2 fractions reverted to initial levels in adults, whereas in lambs, these levels continued to follow trends established during electrical stimulation. In both adults and lambs, the percent area occupied by the mitochondria increased during electrical stimulation by 6.9% in adults and 6.5% in lambs. After electrical stimulation cessation, the percent area in adults returned to baseline levels, whereas it continued to be elevated in lambs (3.3% vs 5.1%, respectively). The transformed muscle of the lamb did not revert to baseline levels after a delay period.

Is it possible to perform immediate cardiac assist using untrained latissimus dorsi muscle in a work-rest regimen?

The authors investigated what contractile force (CF) could be obtained from unconditioned latissimus dorsi muscle immediately after mobilization and for the 2 week vascular period of recovery. Latissimus dorsi muscle mobilization was performed on seven adult (4 experimental and 3 control) sheep leaving only the pedicle and the peripheral muscle intact. Telectronics stimulators (Myostim 7220; Teletronics Pacing Systems, Inc, Englewood, CO) were implanted. Immediately after mobilization 11-35% of the initial CF was lost. A 30 min fatigue test was performed 1 hr after mobilization (20 g/kg preload, 10 V, 10 Hz, 15 BPM, 6 impulses per burst) using a 1 min work-1 min rest regimen. Two sheep lost 2-12% of initial CF; two increased CF by 14-24%. At the end of the fatigue test, CF consisted of 74-89% of immobilized CF. Electrical stimulation training of the muscle was then initiated with the following regimen in the experimental animals only: 15 BPM, single impulses, 5 V, 10 Hz. Every day the muscle was exercised using a work-rest regimen to mimic cardiac assist, starting with 20 min on day 2, and increasing by 2 min per day until a total of 50 min was reached on day 16. All animals were retested for CF using a 42 min fatigue test on days 6, 11, and 16. On day 6, there was no fatigue evident in the experimental group during the 42 min test. CF after testing was 59-81% (mean 67%) of initial data. In the control group (animals with no electrical stimulation training protocol), CF decreased by 11% (from 64 to 53%). On day 11, there was no fatigue evident in the experimental group; CF in all animals increased by 2-8%. On day 16, there was also no fatigue evident in the experimental group; CF increased by 0-9%. An additional 20 min of continuous contraction (15 BPM) fatigue testing was performed on the muscle without rest between the tests. No fatigue was evident at the end of testing. Light microscopic analysis of latissimus dorsi muscle biopsy specimens taken on the days of testing showed no evidence of necrotic damage. Our investigations suggest that it may be possible to start muscle transformation immediately after mobilization and use the untrained latissimus dorsi muscle for cardiac assist immediately after surgery for short periods.

Force enhancement of skeletal muscle used for dynamic cardiomyoplasty and as a skeletal muscle ventricle.

Some patients with pre end-stage congestive heart disease do not receive a significant hemodynamic benefit from dynamic cardiomyoplasty because, during prolonged preoperative immobilization, their latissimus dorsi muscle (LDM) becomes extremely weak. It is the authors' hypothesis that the local administration of an anabolic steroid into an electrically stimulated LDM will produce a thicker and stronger muscle with significant resistance to fatigue. The electrical stimulation training protocol of sheep continued for 8 weeks. For localized anabolic steroid administration an osmotic pump was placed in a subcutaneous pocket and the catheter was introduced into the LDM. The contractile force of electrically stimulated and unstimulated control muscle was studied. Control data were calculated as 100% and all other data were corrected to control. After 4 weeks there was no decrease in contractile force. The change seen was from 88 to 100% with different preloads (10, 15, and 20 g/kg) and amplitudes of impulses (5 and 10 V). After 8 weeks, the LDM was more powerful than before electrical stimulation, with a change of 97-133%. Usually after 8 weeks of electrical stimulation alone, contractile force decreases to 70-75%. During a fatigue test (30 min, 100 bursts per minute, 10-25 Hz, ripple frequency, 10 V impulse amplitude) after 4 and 8 weeks of our protocol, the LDM lost only 12% of its initial force, whereas control muscle lost 40%. Thus local anabolic steroid administration makes the LDM stronger and more useful for cardiomyoplasty.