Is skeletal muscle ventricle chronic stability dependent on wall stress? Design implications.

Chronic skeletal muscle ventricle (SMV) stability is essential for clinical implementation. SMVs in animal models have chronically expanded or collapsed when exposed to physiologic pressures. SMV wall stress is a more appropriate indicator than pressure or geometry to compare SMVs between studies. SMV wall tensions during conditioning were determined for SMVs that collapsed, expanded, or were isovolumetric in a previous study. Wall stresses in SMVs that expanded (2.76 +/- 0.803 N/cm(2)) were significantly greater than isovolumetric SMVs (0.89 +/- 0.450) and SMVs that collapsed (0.88 +/- 0.451). These data support the existence of minimum and maximum wall stresses for SMV volume stability and provide empiric estimates for SMV design. Scaling SMV designs from animal models with smaller volumes and similar pressures may result in greater wall stresses in clinical designs. Therefore, the use of volume limiting implants or an isovolumetric conditioning phase to increase the wall stress expansion threshold may be required.

Diabetes-induced alterations in latissimus dorsi muscle properties impair effectiveness of dynamic cardiomyoplasty in rats.

Short-term diabetes was induced in male Wistar rats with streptozotocin injection. The effects of diabetes on latissimus dorsi (LD) muscle contractile and biochemical properties and acute cardiomyoplasty (CDM) were assessed and compared with data from 16 control rats. Isometric force, contractile properties, and fatigue were measured in electrically stimulated muscles (0.3 ms, 1-256 Hz), and Na+K+ and Ca2+ATPase activities were quantified in muscle membrane preparations. Systolic arterial pressure and aortic blood flow were recorded at rest and during LD muscle stimulation. Compared with control muscle, diabetic muscle showed smaller maximum specific tetanic tension and lower rates of rise and fall in force. Diabetic LD muscle also showed lower muscle enzyme activities. Twitch tension and fatigue did not differ between groups. Smaller increases in aortic flow and systolic pressure after CDM were found in diabetic rats compared to controls. The marked decrease in CDM effectiveness in diabetic rats likely reflected the alterations in muscle properties associated with diabetes.

Skeletal muscle ventricle pressure-volume properties conform to dynamic and static conditioning.

BACKGROUND: Chronic changes in skeletal muscle ventricle (SMV) size and strength can directly affect performance and stability. These changes may depend on the conditioning protocol or implant system. Therefore the effects of conditioning protocols on SMV geometry and contractility must be identified for optimal SMV design and application. METHODS: Skeletal muscle ventricles were constructed in 14 goats using the left latissimus dorsi muscle. The SMVs were conditioned with a 40 mL constant-volume isovolumetric implant (n = 5, IsoVol group) or a compliant pneumatic system that allowed dynamic shortening and direct exposure to resting pressures. Dynamic SMV resting pressure was either progressively increased from 40 to 100 to 120 mm Hg (n = 5, high pressure [HiP] group) or maintained at 40 mm Hg (n = 4, low pressure [LowP] group) during conditioning. The SMV pressure and volume characteristics were monitored daily. RESULTS: All HiP SMVs expanded in volume during conditioning after exposure to physiologic pressures. Three of 4 LowP SMVs decreased in volume during conditioning. Skeletal muscle ventricle passive and active (isovolumetric evoked pressure) pressure-volume curves shifted toward the increasing, stable, and decreasing volumes in HiP, IsoVol, and LowP SMVs respectively. CONCLUSIONS: Frequent monitoring of SMV characteristics during conditioning enabled progressive pressure training and is a valuable tool to evaluate SMV conformation. Chronic SMV adaptation is dependent on the conditioning protocol or implant system utilized. Demonstration of SMV expansion at physiologic pressures suggests that clinical sized SMVs may be chronically unstable unless a supporting implant system is utilized or SMV compliance is reduced. Therefore the mechanisms effecting chronic expansion should be further defined to optimally design SMVs for clinical implementation.

Contractile response of different segments of the latissimus dorsi muscle to chronic stimulation.

OBJECTIVE: This study was planned to investigate if there is any difference in terms of the muscle force between the distal and proximal segments of the latissimus dorsi muscle. SUBJECTS AND METHODS: An inplantable mock circulation system was placed around the latissimus dorsi muscle. The wrapping procedure around the implantable mock circulation was performed by using two different latissimus dorsi muscle segments. In group 1, the very proximal and in group 2, very distal part of the latissimus dorsi were wrapped. The main difference is the blood supply to the distal part of the latissimus dorsi that was interrupted during dissection. During the stimulation period which lasted 120 minutes, the pressure developed in this system and adenosine triphosphate (ATP) levels were measured. RESULTS: The stimulation at 20 Hz did not result in any change in pressure and metabolic data. When it was switched to 43 and 85 Hz, ATP levels decreased with a resultant drop in pressure in group 2. However ATP levels were 15.9 +/- 2.2 micromol/gr and 14.8 +/- 2.5 micromol/gr in group 1, 12.0 +/- 1.4 micromol/gr and 6.1 +/- 1.2 micromol/gr in group 2 at 43 and 85 Hz respectively (p < 0.05) at the end of the 90 minutes. The pressures at the same time interval were 89 +/- 11 and 102 +/- 7 mmHg in group 1, 61 +/- 7 and 65 +/- 8 mmHg in group 2 (p < 0.05). CONCLUSION: In this study, we demonstrated that changes in the distal segment of the latissimus dorsi muscle affects its performance in terms of metabolic and pressure changes during high frequency electrical stimulation at 43 and 85 Hz.

A durable load bearing muscle to prosthetic coupling.

Skeletal muscles have been successfully linked to power mechanical support devices acutely. However, the required load bearing muscle to prosthetic interfaces have not been consistently durable. Tissue simply may not tolerate the repetitive pressure generated, ranging to 40,000 mm Hg, when necessary forces meet the crosssectional areas accessible by suture or clamp fixation. Dramatically increasing the force transfer surface by dispersing ultrafine polymer fibers in the distal muscle substance is the principle of a coupling device termed the MyoCoupler. Earlier, effective force transfer was computationally projected and confirmed in a pilot 30 day rabbit trial, with pull-out strength several times need. This investigation tested bonding strength after longer periods and examined the postulated fiber tissue integration. Devices and controls (buttressed suture fixation alone) were implanted contralaterally in the posterior tibial muscles of 28 rabbits for up to 90 days. Of the 28 rabbits, 21 were used for bond strength testing, and 3 were used for histology. Infection or procedural error disqualified 4 of the rabbits. Pull-out strength levels at 10-30 days (n = 7), 31-60 days (n = 10), 61-90 days (n=4), and all (n=21) were, respectively, 107.1 +/- 58.1, 111.4 +/- 42.7, 97.0 +/- 21.3, and 107.2 +/- 43.9 for MyoCouplers and 58.4 +/- 19.4, 52.3 +/- 34.7, 40.5 +/- 13.0, and 52.1 +/- 26.9 for the control animals. Differences were statistically significant (one-tailed t-test for paired data) and at progressively higher standards of probability for each successive period (p < 0.05 at 10-30 days, p < 0.01 at 31-60 days, p < 0.001 at 90 days, and p < 0.00001 for all). Histology showed fibrous tissue insinuation. Of 360 random fiber surface sites, 88% were closer to fibrous tissue structures than to other fibers. These findings support the aggressive pursuit of muscle powered mechanisms for artificial hearts, assist devices, and heart wall actuators.

A review of the concept of circulatory bioassist focused on the "new" demand dynamic cardiomyoplasty: the renewal of dynamic cardiomyoplasty?

After the initial enthusiasm, the dynamic cardiomyoplasty lost its reputation owing to the poor long-term results, caused by the muscular degeneration subsequent to chronic continuous electrical stimulation of the latissimus dorsi. An activity-rest stimulation protocol that avoids full transformation of the skeletal muscle, maintaining muscular properties over time, has been successfully tried. This "demand" stimulation protocol showed in humans good results improving NYHA class, ejection fraction value, and survival. The discussion about the capability of this and a unique kind of cardiocirculatory bioassist is due to be reopened. In fact, heart transplant, percutaneous circulatory-supporting device, multisites stimulation therapy, and total artificial heart have some drawbacks, one of which is the economic cost. In developing countries the more economic demand dynamic cardiomyoplasty may still play a role.

Maintained benefits and improved survival of dynamic cardiomyoplasty by activity-rest stimulation: 5-year results of the Italian trial on "demand" dynamic cardiomyoplasty.

OBJECTIVE: Latissimus dorsi (LD) muscular degeneration caused by continuous electrical stimulation has been the main cause of the poor results of dynamic cardiomyoplasty (DCMP) and its exclusion from the recent international guidelines on heart failure. To avoid full transformation of the LD and to improve results, a new stimulation protocol was developed; fewer impulses per day are delivered, providing the LD wrap with daily periods of rest ("demand" stimulation), based on a heart rate cut-off. The aim of this work is to report the results at 5 years of follow-up of the Italian Trial of Demand Dynamic Cardiomyoplasty and to discuss their impact on the destiny of this type of cardiac assistance. METHODS: Twelve patients with dilated myocardiopathy (M/F=11/1, mean age 58.2+/-5.8 years, sinus rhythm/atrial fibrillation=11/1) were submitted during the period 1993-1996 to DCMP and at different intervals to demand protocol. Clinical, echocardiographic, mechanographic and cardiac invasive assessments were scheduled before initiating the demand protocol and during the follow-up at 0, 6 and every 12 months. RESULTS: The mean duration of follow-up was 40.2+/-13.8 months (range 18-64). There were no perioperative deaths. The demand stimulation protocol showed a decrease in 5 years in New York Health Association (NYHA) class (3.17+/-0.38-1.67+/-0.77, P=0.0001), an improvement of left ventricular ejection fraction (22.6+/-4.38-32.0+/-7.0, P<0.001), a 5-year actuarial survival of 83.3% (one patient was switched to heart transplantation programme due to clinical worsening and another one died of massive pulmonary embolism). CONCLUSIONS: Demand DCMP maintains over time LD muscular properties, enhances clinical benefits and improves survival of DCMP, thus reopening the debate whether this type of treatment should be considered in patients with end-stage heart failure.

Effects of acute dynamic cardiomyoplasty in a goat model of chronic ventricular dilatation: part 1.

BACKGROUND: The acute effects of cardiomyoplasty in an experimental model of chronic dilated heart have not been thoroughly investigated. Therefore, a model of chronic left ventricular (LV) dilatation was created to accurately determine actual changes shortly after passive and active wrapped skeletal muscle. 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.

Exercise as a treatment modality for congestive heart failure.

Chronic congestive heart failure is a clinical syndrome that affects nearly 5 million people in the United States alone. Patients with this condition have symptoms of dyspnea and exertional fatigue that often limit their daily activities and decrease their quality of life. There has recently been a paradigm shift in the management of congestive heart failure. Current strategies are focusing on improving the central cardiopulmonary abnormalities, such as decreased ejection fraction and increased capillary wedge pressure, and interventions aimed at improving the numerous peripheral changes that occur with congestive heart failure. Exercise as a treatment modality has been shown to affect many of these peripheral changes, specifically abnormalities in the skeletal muscle, peripheral blood flow, and neurohormonal milieu, which improve with appropriate exercise regimes. Exercise also reduces the symptoms of exertional fatigue, improves quality of life, and increases survival. This article reviews the current experience with exercise and congestive heart failure and discusses strategies used to implement an exercise program for patients.

Biomechanical hearts: muscular blood pumps, performed in a 1-step operation, and trained under support of clenbuterol.

BACKGROUND: As shown previously in goats, clenbuterol increased the power of electrically conditioned skeletal muscle ventricles (SMVs) of clinically relevant size (150 mL), which were constructed around a mock system. They pumped against a pressure of 60 to 70 mm Hg immediately during surgery and up to several months after, finally at >1 L/min. SMVs without clenbuterol administration failed. Thus, we expected that clenbuterol-supported SMVs might become integrated into the circulation by a 1-step operation instead of the 2-step procedure required up to now. METHODS AND RESULTS: In adult Boer goats (n=5), latissimus dorsi muscle was wrapped around a polyurethane chamber of 150 mL that was connected to the descending aorta. This muscular flow-through pumping chamber containing a stabilizing inner layer (called a biomechanical heart [BMH]) was formed and immediately made to work against a systemic load with the support of clenbuterol (5x150 microg/wk). During surgery, the mean stroke volume of BMHs was 53.8+/-22.4 mL. One month after surgery, in peripheral arterial pressure, the mean diastolic (P(MD)) and minimal diastolic (P(min)) pressures of BMH-supported heart cycles differed significantly from unsupported ones (P(MD)=+2.9+/-1.1 mm Hg [P<0.04], P(min)=-2.4+/-0.9 mm Hg [P<0.04]). After BMH-supported heart contractions, the subsequent maximal rate of pressure generation, dP/dt(max), increased by 20.5+/-8.1% (P<0.02). One BMH, catheterized 132 days after surgery, shifted a volume of 34.8 mL per beat and 1.4 L/min with a latissimus dorsi muscle of 330 g. Depending on duration of training, the percentage of myosin heavy chain type 1 ranged between 31% and 100%. CONCLUSIONS: Under support of clenbuterol, BMHs of a clinically relevant size can be trained effectively in the systemic circulation after a 1-step operation and offer the prospect of a sufficient volume shift and probably unloading of the left ventricle.

Assessment of skeletal muscle ventricle tissue blood flow using positron emission tomography.

In this pilot study, we assessed the feasibility of using positron emission tomography (PET) imaging for in vivo measurement of skeletal muscle ventricle (SMV) tissue blood flow. In 4 dogs, with SMVs prepared from their latissimus dorsi muscle, we quantified SMV tissue blood flow by PET and related it to the tissue flow measured by radiolabeled microspheres under similar physiologic conditions. The tissue blood flow was estimated in SMVs wrapped around a mandrel (not in circulation) at rest and during SMV stimulation (30 and 90 contraction-cycles/min). SMV tissue perfusion was heterogeneous, especially during SMV contraction. Furthermore, there was a linear relationship between SMV tissue flows estimated by PET and those measured by microspheres. We conclude that in vivo imaging of SMV is feasible by PET. Quantification of SMV tissue blood flow by PET has promise as a means of assessing changes in blood flow, but further technical progress needs to be made before absolute flows can be reliably measured.

Combination of preconditioning and delayed flap elevation: evidence for improved perfusion and oxygenation of the latissimus dorsi muscle for cardiomyoplasty.

BACKGROUND: Atrophy and fibrosis of the distal part of the latissimus dorsi muscle (LDM) wrap is a recognized complication of cardiomyoplasty that has been attributed to ischemia. Failure of the muscle wrap contributes to the late attrition seen in clinical cardiomyoplasty. In this study we examined the role of two-staged mobilization and of preconditioning by electrical stimulation on the regional perfusion and oxygenation of the LDM. METHODS: In a rabbit model (n = 36) the LDM was preconditioned as follows: group A muscles received preconditioning in situ; group B muscles were partially mobilized by dividing the intercostal perforators and then preconditioned; and group C muscles were completely mobilized and wrapped around a silicone-rubber mandrel before conditioning. Controls received no conditioning. The preconditioning regimen consisted of 2 weeks of continuous stimulation at 2.5 Hz. At completion of preconditioning the muscles were fully mobilized and mounted on a muscle-testing apparatus. Purpose-built microelectrodes measured regional PO2 and perfusion using a diffusible gas tracer technique. Muscles were weighed and processed for fiber typing and capillary counting. RESULTS: All preconditioned muscles demonstrated fiber transformation, with increased fatigue resistance. Perfusion of preconditioned muscles both at rest and during contraction was higher than control in the proximal part of the muscle. Distal regions of group B muscles had higher perfusion and capillary density than any other group (p < 0.05). Distal regions of group C had the lowest perfusion and capillary density, and showed muscle atrophy and histologic evidence of necrosis. During fatigue testing there was a decrease in the PO2 in the distal regions of the control and group C muscles (p < 0.05), whereas it was maintained at resting levels in both group A and B muscles. CONCLUSIONS: Conditioning in situ improves perfusion of the distal LDM and prevents a fall in tissue PO2 during contraction. Two-stage mobilization further improves distal perfusion and capillary density. In contrast, shortterm elevation followed by conditioning produces impaired distal perfusion, decrease in PO2, and fiber necrosis in the distal muscle. The present study suggests that partial mobilization of the LDM performed at the same time as placement of electrodes for preconditioning may prepare the LDM better for the demands of cardiomyoplasty.

Demand dynamic cardiomyoplasty: mechanograms prove incomplete transformation of the rested latissimus dorsi.

BACKGROUND: In dynamic cardiomyoplasty, standard stimulation produces high fatigue resistance but also undesirable dynamic characteristics of the latissimus dorsi (LD). Based on results of intermittent stimulation in animals we introduced demand stimulation, a lighter regimen of LD activity-rest stimulation, and the mechanogram, a noninvasive method to determine the contractile characteristics of LD wrap. METHODS: Surgery and standard stimulation was according to the technique of Carpentier and Chachques, demand stimulation and LD wrap mechanogram were as we previously described. The LD contraction is synchronized to heart systole by mechanogram and echocardiography, and extent of transformation by tetanic fusion frequency analysis. A total of 22 patients were studied to date. Data for the 8 subjects who attained 6-month follow-up are reported. Four of them were lightly stimulated from the conditioning period, whereas 4 others were converted to light and then demand stimulation after years of standard stimulation. Patients were followed up with respect to survival, functional class, hospital admission rate, medication used, cardiopulmonary exercise testing, and LD wrap mechanography. RESULTS: Latissimus dorsi wrap slowness reverses by the activity-rest regimen, even after years of standard stimulation (Tetanic fusion frequency of 11 +/- 2 Hz after standard stimulation vs 30 +/- 3 Hz after demand regimen, p < 0.0001). After demand dynamic cardiomyoplasty there are no deaths. Quality of life is substantially improved with significant reduction of heart failure symptoms (New York Heart Association class: preoperative 3.0 +/- 0.0, post-demand dynamic cardiomyoplasty 1.5 +/- 0.2, p < 0.0001). In the subgroup of patients lightly stimulated from LD conditioning, exercise capacity tends to increase over preoperative values more than 2 years after operation (VO2 max: preoperative 12.3 +/- 0.7 vs 16.6 +/- 1.7 post-demand dynamic cardiomyoplasty, p = 0.05). CONCLUSIONS: Demand stimulation and mechanography of the LD wrap are safe procedures that could offer long-term benefits of dynamic cardiomyoplasty to patients with pharmacologically intractable heart failure.

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.

Preparation of a skeletal muscle ventricle in sheep: severe damage to the Latissimus dorsi muscle due to mobilization before preconditioning.

As part of a study examining the use of a skeletal muscle ventricle for cardiac assistance in sheep, a new concept of muscle preconditioning was put into practice. We aimed to produce a latissimus dorsi muscle (LDM) capable of performing chronic work immediately after the construction of a skeletal muscle ventricle. The left LDM was detached from the thoracic wall, divided longitudinally and reattached in situ to achieve vascular delay. The right LDM was left unaffected. Thereafter, preconditioning of both LDM was started according to the clinically approved stimulation protocol for cardiomyoplasty. Preconditioning of the unaffected right LDM in situ resulted in a complete muscle fiber transformation with no signs of degeneration or necrosis. Mobilization of the left LDM before preconditioning led to a distinct damage of the muscle. During conditioning, the increase in burst duration from 2 to 3 impulses in sheep A and from 3 to 5 impulses in sheep B resulted in a homogenous degeneration of the muscle fibers of the left LDM. Histomorphological analysis showed a dramatic increase in the percent perimysial and endomysial connective tissue. The applied concept of muscle prefabrication proved to be a failure. Muscle splitting and mobilization followed by vascular delay and in situ conditioning as a concept of muscle prefabrication should be strictly avoided.

Salbutamol and the conditioning of latissimus dorsi for cardiomyoplasty.

BACKGROUND: Cardiomyoplasty is a new surgical alternative therapy for CHF. Although conditioning of muscle for cardiomyoplasty has a positive effect on fatigue resistance it also produces negative effects. In this study we assessed the effect of salbutamol, a beta2-agonist, on both the positive and the negative effects of conditioning. METHODS: In a control group of six animals one latissimus dorsi was subject to chronic, 1 Hz, low-frequency stimulation (CLFS) while the other served as a control. The experimental group of seven dogs received a continuous SC infusion of salbutamol and one latissimus dorsi was subjected to CLFS. The other muscle demonstrated the effects of salbutamol per se. After 42 days the animals were anesthetized and fatigue resistance, muscle mass, and mechanical properties of the muscles were evaluated. RESULTS: Salbutamol increased muscle mass, tetanic tension, and rate of rise and fall of tetanic tension. It diminished fatigue resistance and had no effect on shortening velocity. Chronic stimulation decreased muscle mass, tetanic tension, rate of rise and fall of tetanic tension, and muscle shortening velocity in both groups of dogs. Salbutamol diminished the declines in muscle mass, rate of tension development, and rate of muscle shortening due to CLFS, but did not change the effects of CLFS on tetanic tension and the rate of fall of tetanic tension. Salbutamol did not alter the increase in fatigue resistance induced by CLFS. CONCLUSIONS: The favorable effect of CLFS on fatigue resistance was unaffected by salbutamol. The unfavorable effects of CLFS on loss of muscle mass, rate of tension development, and decline in shortening velocity were partially blocked by salbutamol, improving the ability of the latissimus dorsi to augment cardiac systole.

Selective stimulation of latissimus dorsi muscle for cardiac assist.

The contractile power of the latissimus dorsi muscle (LDM) is used in skeletal muscle cardiac assist (SMCA) to augment the blood pumping ability of a failing heart. The LDM has three anatomically distinct, independently innervate segments-the transverse, oblique, and lateral. There are potential advantages to selectively stimulating these LDM regions. We hypothesized that (1) the three nerve branches could be stimulated selectively to activate individual muscle regions with little or no functional overlap, (2) the three muscle regions would generate similar force, and (3) nerves stimulated in combinations would generate forces corresponding to the sum of forces generated by the individual regions. In acute studies of canine LDM (n=5), regional electromyogram (EMG) and isometric force were recorded while branches of the thoracodorsal nerve were stimulated (via nerve-cuff electrodes) individually and in combinations. Analysis of regional EMG and force confirmed selective activation. Stimulation of lateral, oblique, and transverse branches of thoracodorsal nerve activated 53+/-5%, 20+/-9%, and 36+/-9% of the muscle, respectively; with corresponding developed forces of 48+/-6%, 21+/-8%, and 31+/-8% of total muscle force (R=0.98, p<0.05). Selective activation of LDM is possible with little or no functional overlap; however, the muscle regions were nonuniform. Selective stimulation may ultimately facilitate the use of performance enhancing stimulus protocols for SMCA.

Power output of pericardium-lined skeletal muscle ventricles, left ventricular apex to aorta configuration: up to eight months in circulation.

OBJECTIVE: The purpose of this experiment was to evaluate the potential for a skeletal muscle ventricle connected to the circulation between the left ventricle and the aorta to provide effective, long-term cardiac assist. METHODS: Skeletal muscle ventricles were constructed from the latissimus muscle in 10 dogs. After conditioning, the skeletal muscle ventricles were connected to the left ventricle and the aorta with 2 valved conduits. The skeletal muscle ventricle was programmed to contract during diastole. RESULTS: At time of implantation, skeletal muscle ventricles stimulated at 33 Hz and in a 1:2 ratio with the heart significantly decreased left ventricular work by 56% (P <.01) and at 50 Hz by 65% (P <.01). At a 1:2 ratio, the power output of the skeletal muscle ventricles was 59% of left ventricular power output at 33 Hz (P <. 01) and 93% at 50 Hz (P <.01). Animals survived 7, 11, 16, 17, 72, 99, 115, 214, and 249 days. Three deaths were directly related to the skeletal muscle ventricle. One animal is alive at 228 days. In the animal that survived 249 days, skeletal muscle ventricle power output at 8 months with a 33 Hz stimulation frequency and a 1:2 contraction ratio was 57% of left ventricular power output and 82% at 50 Hz. At a 1:1 ratio, skeletal muscle ventricle power output was 97% and 173% of the left ventricle at 33 and 50 Hz, respectively. CONCLUSIONS: Left ventricular assist with a skeletal muscle ventricle connected between the left ventricle and the aorta is the most hemodynamically effective configuration we have tested and can maintain significant power output up to 8 months.

Preconditioning of the latissimus dorsi muscle in cardiomyoplasty: vascular delay or chronic electrical stimulation.

OBJECTIVES: In standard single stage cardiomyoplasty (CMP), the latissimus dorsi muscle (LDM) is not preconditioned prior to surgery. We hypothesized that latissimus dorsi preconditioning by vascular delay or by chronic electrical stimulation would result in an improved LV hemodynamic function early (14 days) after CMP. METHODS: Mongrel dogs had preconditioning of the latissimus dorsi by a vascular delay procedure followed by CMP 14-18 days later (group I VD). Dogs in group II underwent 4 weeks of chronic stimulation (CS) of the latissimus dorsi (2 V/30 Hz, six bursts/min) followed by CMP. The latissimus dorsi muscle was fully stimulated from 48 h after cardiomyoplasty in both groups (2 V/30 Hz, three bursts/min). Two weeks after myoplasty, injecting 2.0-3.0 x 10(5) 90 microm latex microspheres in the left main coronary artery induced global cardiac dysfunction. Hemodynamic function was then evaluated for latissimus dorsi muscle assisted (S) beats and non-stimulated beats (NS) in each group by measuring peak systolic aortic pressure (AOP), left ventricular pressure (LVP) and end diastolic pressure (LVEDP), and by calculating maximum and minimum dP/dt. RESULTS: Dogs with vascular delay of the latissimus dorsi showed a marked increase for all hemodynamic indices (AOP: 23.9+/-2.5%, LVP: 23.5+/-2.2%, max dP/dt: 49.4+/-3.3%) for LDM assisted (S) beats compared to non-stimulated beats (P < 0.001). Animals with chronic electrical training did not demonstrate a significant increase in any hemodynamic parameter with LDM stimulation. CONCLUSION: Preconditioning the LDM may play an important role in providing early cardiac assistance in CMP. Preconditioning the LDM with vascular delay resulted in improving performance of the LDM with consistent increases in LV hemodynamics. This was not observed after preconditioning with chronic electrical stimulation. Vascular delay of the latissimus dorsi can significantly improve muscle performance in CMP and could provide hemodynamic assistance early after surgery.

Muscle transformation in cardiomyoplasty: the effect of conditioning and mobilisation on perfusion, oxygenation and fatigue resistance in the latissimus dorsi muscle.

BACKGROUND: In the clinical application of transformed skeletal muscle to cardiac assistance there is evidence that the latissimus dorsi muscle (LDM) wrap can undergo atrophy, which would prevent it from providing a sustained functional improvement. Possible causes are ischaemia and degeneration related to the conditioning process. We studied the nutritional and structural changes occurring under different stimulation regimes with the aim of improving the conditioning protocol. METHODS: Microelectrodes were used to measure regional perfusion and oxygenation in the rabbit LDM during mobilisation and subsequent repeated contraction. Group A muscles (n = 10) were conditioned for 6 weeks at 10 Hz, Group B muscles (n = 10) for 2 weeks at 2.5 Hz. Each muscle was then mobilised and tested in a hydraulic apparatus which recorded the pressure generated in a closed circuit. RESULTS: Muscles of Group A and Group B demonstrated transformation of fibre type, with a predominance of type I (62 +/- 4%) fibres in Group A and type IIa (68 +/- 9%) fibres in Group B. There was no evidence of muscle degeneration. After 10 min of fatigue testing the pressure produced was 53 +/- 5% of initial values in Group A and 51 +/- 8% in Group B, compared to 8 +/- 1% in the control group (P < 0.001). Maximum rate of relaxation was faster in Group B than in Group A (46 +/- 3% vs. 36 +/- 3% of control muscle, P < 0.05). Mobilisation resulted in a decrease in the distal perfusion of the control muscles (P < 0.05) and PO2 decreased by 8.7 +/- 1.7 mmHg during a fatigue test, which resulted in rapid loss of contractile function to 46 +/- 1% of the initial value within 1 min. In both Groups A and B the perfusion of all regions of the muscles both before and after mobilisation was greater than that of controls. During the same fatigue test, the PO2 of the distal regions was maintained and the contractile function fell more slowly to between 70 and 80% of initial values within 1 min. CONCLUSION: We showed that ischaemia in the distal region of the control LDM could result from mobilisation and repeated contraction. Muscle transformation improved perfusion and prevented a fall in tissue PO2 during a sustained series of contractions. Muscles that were conditioned at 2.5 Hz shared the improved perfusion of the fully transformed muscle, but had faster relaxation characteristics. Short periods of in situ conditioning prior to mobilisation may help to avoid ischaemic changes in distal parts of the LDM while achieving fatigue resistance in the grafted muscle at an earlier postoperative stage.