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.

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.

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.

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.

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.

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.

Optimization of synchronization delay in latissimus dorsi dynamic cardiomyoplasty.

BACKGROUND: Optimal synchronization delay (SD) for triggering the implanted cardiomyostimulators in patients undergoing latissimus dorsi dynamic cardiomyoplasty has not been clearly defined. Generally a synchronization delay time of 45 to 60 ms is used in the current practice, in which the implanted cardiomyostimulator stimulates the latissimus dorsi muscle 45 to 60 ms after mitral valve closure acquired with M-mode echocardiography. We investigated the effect of shortening or prolonging the delay time on cardiac functions. METHODS: We studied 10 patients who were in their first 2 years postoperatively. Three values for SD (SD = 0 ms, 45 to 60 ms, and 150 to 160 ms) were echocardiographically evaluated for their influence on both systolic and diastolic left ventricular parameters. RESULTS: Ejection fractions were 0.27 +/- 0.07, 0.28 +/- 0.07, and 0.32 +/- 0.06; peak aortic velocities were 0.85 +/- 0.8, 0.86 +/- 0.11, and 0.92 +/- 0.8 m/s; and velocity-time integrals were 0.16 +/- 0.03, 0.16 +/- 0.03, and 0.19 +/- 0.03 m for the SD values of 0, 45 to 60 ms, and 150 to 160 ms, respectively. Diastolic parameters were also measured. Isovolumetric diastolic relaxation time was 97.5 +/- 49, 97.20 +/- 44, and 111.8 +/- 49 ms; deceleration time was 83.67 +/- 32, 88.48 +/- 35, and 92.68 +/- 34 ms; and ratio or velocity-time integral of e wave to velocity-time integral of a wave was 3.09 +/- 0.98, 2.48 +/- 0.69, and 2.38 +/- 0.65 for the SD values of 0, 45 to 60 ms, and 150 to 160 ms, respectively. Systolic functions were better when SD was set at 150 to 160 ms, but there was a diastolic compromise. On the other hand, diastolic parameters were more favorable when SD = 0 (i.e., cardiomyostimulator triggered without delay) but the systolic assist was suboptimal. Systolic and diastolic parameters seemed relatively well-balanced with the current practice of setting the synchronization delay at 45 to 60 ms. CONCLUSIONS: The most favorable systolic effects were obtained with a prolonged delay of synchronization (150 to 160 ms), at some expense of diastolic functions. On the other hand, with a short or absent delay, diastolic parameters were improved but systolic parameters became suboptimal. Therefore, the current practice of setting the SD between 45 and 60 ms after echocardiographic mitral valve closure is suggested for the optimal timing for cardiomyostimulator stimulation in patients who have undergone latissimus dorsi dynamic cardiomyoplasty. Yet a great deal of individualization is necessary, and fixed preset values cannot definitely be determined because one setting does not fit all patients.

Growth potential and left ventricular diastolic function in cardiomyoplasty.

BACKGROUND: Dynamic cardiomyoplasty is an experimental operation for advanced heart failure. Current clinical results bring the possibility of its application to children. This study was designed to obtain information about the relationship between cardiomyoplasty and growth of the heart. METHODS: Six beagles, 9 to 10 weeks old, underwent cardiomyoplasty without electric stimulation (cardiomyoplasty group), and another 5 beagles underwent median sternotomy and pericardiotomy (control group). Six months later, weights of hearts, wrapped latissimus dorsi muscles, and unwrapped right latissimus dorsi muscles and pressure-volume relationships were obtained. RESULTS: Wrapped latissimus dorsi muscles weighed 33 +/- 3 g (mean +/- standard deviation), and unwrapped muscles weighed 68 +/- 5 g. The heart weight was 82 +/- 3 g in the cardiomyoplasty group and 89 +/- 7 g in the control group. Left ventricular maximum elastance was 3.8 +/- 0.8 mm Hg/mL in the cardiomyoplasty group and 3.9 +/- 0.9 mm Hg/mL in the control group. End-diastolic pressure versus end-diastolic volume ratios were 0.52 +/- 0.03 and 0.54 +/- 0.05, respectively. Pathologic examination showed fat infiltration and muscle fiber atrophy in the cardiomyoplasty group. CONCLUSIONS: The wrapped latissimus dorsi muscle flaps were growing and the diastolic function was not impaired. This indicates a potentially safe clinical application of dynamic cardiomyoplasty for children.

Mechanisms of cardiomyoplasty: comparative effects of adynamic versus dynamic cardiomyoplasty.

BACKGROUND: The apparent paradox seen in patients who have undergone dynamic cardiomyoplasty and shown substantial clinical and functional improvements with only modest hemodynamic changes may be due to inappropriate end points chosen for study, a result of incomplete understanding of mechanisms involved. The purpose of this study was to compare the relative role of the passive "girdling effect" and the dynamic "systolic squeezing effect" of the wrapped muscle in cardiomyoplasty. METHODS: The control group of 6 dogs underwent 4 weeks of rapid pacing (250 beats/min) to induce severe heart failure followed by 8 weeks of observation without rapid pacing. The trajectory of recovery in hemodynamics and cardiac dimensions was followed with echocardiography and Swan-Ganz catheters. In the "adynamic" cardiomyoplasty group (n=4), the left latissimus dorsi muscle was wrapped around the ventricles and allowed to stabilize and mature for 4 weeks. This was followed by rapid pacing and recovery as in the control group. In the "dynamic" cardiomyoplasty group (n=3), the same protocol for the adynamic group was followed except that a synchronizable cardiomyostimulator was attached to the thoracodorsal nerve of the muscle wrap. This allowed the latter to be transformed during the rapid-pacing phase and permitted dynamic squeezing of the muscle wrap to be generated by burst stimulation synchronized with cardiac contraction in a 1:2 ratio. RESULTS: Baseline data were comparable in all groups prior to rapid pacing. After 4 weeks of rapid pacing, the left ventricular ejection fraction was higher in the adynamic (27.0%+/-3.9%; p < 0.05) and dynamic (33.3%+/-2.3%; p < 0.02) cardiomyoplasty groups compared with controls (18.8%+/-8.3%). Similarly, ventricular dilatation in both systole and diastole was less in the adynamic (51.8+/-8.7 mL, [p < 0.002] and 38.2+/-7.2 mL [p < 0.001], respectively) and dynamic (62.0+/-7.2 [p < 0.02] and 41.3+/-3.5 mL [p < 0.005], respectively) cardiomyoplasty groups compared with controls. In the dynamic group, on and off studies were carried out after cessation of rapid pacing while the heart was still in severe failure, and they demonstrated a systolic squeezing effect in stimulated beats. Only this group recovered fully to baseline after 8 weeks. CONCLUSIONS: By reducing myocardial stress, both the passive girdling effect and the dynamic systolic squeezing effect have complementary roles in the mechanisms of dynamic cardiomyoplasty.

Health-related physical function and quality of well-being prior to and following cardiomyoplasty. A preliminary report.

OBJECTIVE: The purpose of this study was to obtain preliminary data regarding the effects of cardiomyoplasty on health-related physical function and quality of well-being. EXPERIMENTAL DESIGN: Quasi-experimental with repeated measures. Patients were interviewed prior to surgery, with post-surgical follow-up interviews at 6 weeks, 6 months, and 12 months. SETTING: Interviews were usually conducted by telephone with patients who were at home at the time of data collection. PATIENTS OR PARTICIPANTS: Four patients receiving cardiomyoplasty at Allegheny General Hospital in Pittsburgh, Pennsylvania. INTERVENTIONS: Patients received cardiomyoplasty between November 1992 and April 1993. Cardiomyoplasty using the right latissimus dorsi muscle was performed on the first patient. A left muscle-wrap was performed on the subsequent three patients. MEASURES: Self-reported function and well-being were measured using the Sickness Impact Profile (SIP), the Quality of Well-Being Scale (QWB), and the Medical Outcome Study 36-Item Short-Form Health Survey (SF-36). RESULTS: Patient responses on the SF-36 demonstrated general improvement in cardiomyoplasty survivors. Results on the QWB and SIP are mixed. CONCLUSIONS: Due to the small, incomplete sample and lack of any comparison group, extreme caution must be used in drawing any clinical conclusions from this preliminary data. Future randomized clinical trials of cardiomyoplasty need to include quality of life and health-related physical function as dependent variables. Further psychometric study is necessary which compares the usefulness of these various methods for assessing the value of outcomes for patients with end-stage heart disease.

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.

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.

Power generation from four skeletal muscle configurations. Design implications for a muscle powered cardiac assist device.

The development of long term cardiac assist devices is currently limited by the lack of an appropriate totally implantable power source. Transformed fatigue resistant skeletal muscle has been proposed as such a power source. The goal of this study was to determine the optimal latissimus dorsi muscle (LDM) configuration capable of obtaining maximum power output. Four separate in situ configurations were prepared: a latex compliance chamber placed between the LDM and chest wall (Sub-Dorsi), a chamber wrapped in a skeletal muscle ventricle (Circular), linear measurements from the thoracolumbar origin (Linear Origin), and linear measurements from the humeral insertion (Linear Insertion). A device was designed to measure the power output from each configuration in watts per kilogram of muscle. Eight LDMs were acutely studied at varying levels of pre-load. Performance characteristics were measured in each configuration. Peak power outputs were as follows: Sub-Dorsi: 8.3 +/- 1.6 W/kg at 50 cc or 11.6 N pre-load; Circular: 16.4 +/- 6.2 W/kg at 50 cc or 16.9 N; Linear Origin: 47.1 +/- 4.4 W/kg at 23.4 N; and Linear Insertion generated 59.9 +/- 12.1 W/kg at 26 N. Analysis of variance comparison revealed a significance of p < 0.0001. A linear oriented LDM is capable of generating maximal power output. Confirmation of these findings in transformed, conformed, fatigue resistant muscle will provide important performance information essential for the optimal design of implantable muscle powered ventricular assist systems.

A computer simulation study of isometric contraction of latissimus dorsi muscle used for cardiac assistance.

This study was designed to investigate the feasibility of a skeletal muscle pump employing latissimus dorsi muscle (LDM) for cardiac assistance. We developed and used a 2-dimensional mathematical model for LDM to investigate how the size of pneumatic balloons (30, 38, and 45 ml) and the three different locations (proximal, center, and distal) affect the pressure applied to the balloon by LDM. The computer simulation was performed by coding a visco-elastic and nonlinear 2-dimensional program that employed the finite element method (FEM). The muscle specific parameters of LDM were obtained from animal experiment results. The model is based on Hill's characteristic equation and composed of a contractile component and a passive element. The simulation results indicated that the intermediate and largest sized balloon lead to the highest and the lowest power (volume reduction per unit time interval), respectively. On the other hand, when the balloon is inserted in the distal LDM, the power is lower than in the other two positions, regardless of the balloon size. The above results suggest that the optimal size of the balloon should be selected depending on the muscle specific parameters of the actuator, and that the balloon should be inserted either in the proximal portion or center of the actuator.

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.

Cardiomyoplasty: hemodynamic benefit to normal and depressed canine left ventricular function.

This study examined the effects of cardiomyoplasty with vascular delay on canine normal and depressed left ventricular (LV) function. To improve viability of the latissimus dorsi muscle (LDM), vascular delay was performed 2 weeks before cardiomyoplasty in 10 mongrel dogs. Two weeks after cardiomyoplasty, LV function was evaluated by simultaneously measuring LV and aortic pressure, and aortic flow. The LDM was stimulated at a ratio of 1:4-1:7 synchronously with ventricular systole. Microspheres (90 mu) were sequentially injected into the left coronary artery to depress LV function. Data were acquired and analyzed on a beat to beat basis. Results were as follows: LDM stimulation significantly augmented LV systolic pressure (LVSP) from 138 +/- 2 to 161 +/- 2* mmHg, the peak rate of change of LV pressure (+dP/dt) from 1888 +/- 46 to 2584 +/- 43* mmHg/sec, aortic systolic pressure (AoSP) from 140 +/- 2 to 159 +/- 2* mmHg, stroke volume (SV) from 11.2 +/- 0.3 to 13.3 +/- 0.3* ml, stroke work (SW) from 19 +/- 1 to 26 +/- 1* gm.m, peak aortic flow (P Qa) from 5542 +/- 142 to 7190 +/- 161* ml/min, and decreased -dP/dt from -1683 +/- 31 to -1689 +/- 49* mmHg/sec (* = p < 0.05). Microsphere injections depressed LV function, but did not affect the magnitude of the net changes between stimulated and nonstimulated beats. However, the percent changes significantly increased. Preconditioning of LDM with vascular delay augments cardiac function in LDM assisted beats. This improved performance was present in both normal as well as depressed LV function groups. Thus, investigations of cardiomyoplasty may not necessarily require a model of severe myocardial dysfunction. Vascular delay offers an important preconditioning method of LDM to augment cardiac function in cardiomyoplasty.

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.

Stroke volume validation and energy evaluation for the dynamic training of skeletal muscle ventricles.

Skeletal muscle ventricles used for cardiac assistance were trained dynamically by shifting volume within an elastic training device. To optimize this dynamic training that is by variation of stimulation patterns and application of drugs, methods for stroke volume and energy evaluation were required. A volume shift induced by a muscle contraction resulted in a pressure rise in the training device. Stroke volume was calculated by relating the pressure difference of a muscle contraction to the device's compliance. For validation of the calculated stroke volume, a mock system was built to simulate muscle contractions under various conditions. The stroke volume measured independently and calculated by means of the pressure rise inside the training device, showed an approximately one-to-one relation (R=0.996). Calculation of delivered energy from skeletal muscle ventricles thereby became possible. This method offers a simple, reliable and practical procedure to quantify the dynamic training of skeletal muscle ventricles for use in cardiac assistance.

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.