Clinical features of relative focal hyperfusion in patients with intracerebral hemorrhage detected by contrast-enhanced xenon CT

Optimization of the skeletal muscle contraction during cardiac assist is important to achieve maximal cardiac assist and yet avoid overstimulation that may injure skeletal muscle. Dynamic cardiomyoplasty suffers from lack of an objective, reproducible, and accurate technique to measure skeletal muscle shortening fraction after wrap and training of the muscle. A recruitment curve is considered the best way to select the proper stimulation level to achieve supramaximal contraction without overstimulating the muscle. A fluoroscopic technique of determining latissimus dorsi recruitment curve was evaluated in five goats undergoing dynamic cardiomyoplasty with an anterior cardio-subcutaneous wrap. Two pairs of stainless steel targets (0.5 and 1 cm of diameter) were implanted on each side of the muscle wrap. One pair of sonomicrometer crystals was also implanted. Displacement of the targets was measured under fluoroscopy at five different stimulation levels. Correlation coefficients between targets on the inside surface of the wrap and the sonomicrometer crystals, and targets on the outside surface of the wrap and the sonomicrometer crystals were 0.71 (P < 0.05) and 0.60 (P < 0.05), respectively. Targets on the inside surface of the wrap were more accurate than targets on the outside surface of the wrap for measurement of skeletal muscle shortening fraction and establishment of a recruitment curve. Adverse effects from the targets were not observed.     

Delayed stimulation of the latissimus dorsi may result in disuse atrophy

BACKGROUND: The latissimus dorsi is usually left unstimulated for 2 weeks after cardiomyoplasty to allow the muscle to recover from the loss of the collateral circulation. To determine whether the 2-week delay may cause muscle atrophy, we randomized 15 mongrel dogs to a control group or a disuse atrophy group. METHODS: The collateral circulation to the latissimus dorsi was ligated in all animals before cardiomyoplasty to reduce the risk of ischemic injury to the muscle during mobilization. Two weeks after collateral ligation, the atrophy group had the tendinous attachment of the latissimus dorsi severed and then 2 weeks later underwent cardiomyoplasty. The control group had a 2-week delay after collateral ligation followed by cardiomyoplasty. Biopsies were performed before collateral ligation and before cardiomyoplasty. After heart failure was induced, hemodynamic function was assessed during synchronized contraction of the latissimus dorsi by measuring the maximum systolic elastance, stroke volume, preload recruitable stroke work index, and diastolic compliance. RESULTS: Comparison of muscle morphology between the two groups demonstrated the presence of muscle atrophy in those animals that had been randomized to the atrophy protocol. During synchronized contraction of the latissimus dorsi, there was no significant increase in maximum systolic elastance in either group. However, both stroke volume and pulmonary recruitable stroke work index were significantly higher in the control animals during assisted beats. The left ventricle was less compliant in the atrophy group, suggesting that muscle atrophy had adversely affected diastolic function. CONCLUSIONS: Delayed electrical stimulation of the latissimus dorsi may result in atrophy and loss of function.     

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.     

Dynamic cardiomyoplasty: clinical follow-up at 12 years

OBJECTIVE: The purpose of this study is to evaluate the long-term outcome of dynamic cardiomyoplasty. This surgical technique was conceived to assist the failing heart. The many proposed mechanisms of action of cardiomyoplasty are: (1) systolic assist; (2) limitation of ventricular dilation; (3) reduction of ventricular wall stress (sparing effect); (4) ventricular remodeling with an active girdling effect; (5) angiogenesis; and (6) a neurohumoral effect. METHODS: We investigated 95 patients in our hospital undergoing this procedure due to severe chronic heart failure, refractory to optimal medical treatment. Patients had a mean age of 51 +/- 12 years. The etiology of heart failure was ischemic 55%, idiopathic 34%, ventricular tumor 6%, and other 5%. The mean follow-up was 44 months. RESULTS: The mean New York Heart Association (NYHA) functional class improved postoperatively from 3.2 to 1.8. Average radioisotopic left ventricular (LV) ejection fraction increased from 17 +/- 5 to 27 +/- 4% (P < 0.05). Stroke volume index increased from 32 +/- 7 to 43 +/- 8 ml/beat per m2 (P < 0.05). The heart size remained stable over the long term. Following cardiomyoplasty, the number of hospitalizations due to congestive heart failure was reduced to 0.4 hospitalizations/patient per year (preoperative: 2.5, P < 0.05). Computed tomography scans showed at long term a preserved latissimus dorsi muscle structure in 84% of patients. Survival probability at 7 years is 54%. Six patients underwent heart transplant after cardiomyoplasty (mean delay: 25 months), due to the natural evolution of their underlying heart disease. There were no specific technical difficulties. CONCLUSIONS: Clinically, this procedure reverses heart failure, improves functional class and ameliorates quality of life. The latissimus dorsi muscle histological structure is maintained at long-term, when postoperative electrostimulation is performed, avoiding excessive stimulation. Cardiomyoplasty may delay or prevent the progression of heart failure and the indication of cardiac transplantation.     

Anti-metastatic and immunomodulating properties of the water extract from Celosia argentea seeds

Although dynamic cardiomyoplasty (DCMP) is currently being evaluated as an alternative to end-stage congestive heart failure, the overall results of DCMP are variable and inconclusive. We evaluated the effect of classic DCMP on systolic and diastolic cardiac function in normal heart using reliable indicators which minimize the influences of load conditions. Six experimental dogs were evaluated with the acute nonpreconditioning model. The slope of the linear preload recruitable stroke work relationship (Mw) showed a significant increase with latissimus dorsi muscle (LDM) stimulation (postwrap non-stimulation 59.1+/-6.3, postwrap stimulation 98.6+/-9.7 erg cm(-3) x 10(3); P < 0.01), and the x-intercept (V0) was unchanged; these were utilized as the indicators of left ventricular systolic function. The constant of pressure decay (tau) increased after LDM wrap (prewrap 45.8+/-6.0, postwrap nonstimulation 69.3+/-10.3, postwrap stimulation 72.3+/-13.9 ms; P < 0.05), and the peak filling rate was unchanged after LDM wrap, which were utilized as the indicators of diastolic function. We concluded that classic dynamic cardiomyoplasty is effective in assisting systolic cardiac function, but may to some degree have a detrimental effect on the diastolic cardiac function.     

Induced tissue transformation and heart surgery

This article reports the research which led to the use of animal connective tissues in the construction of valvular prostheses and those which led to the use of electrically stimulated skeletal muscle for cardiac assistance. Although, very different at first glance these research have in common the transformation of biological tissues by physical or chemical means to adapt them to a new function. 1) Once implanted in a different species, animal connective tissues are destroyed by immunological reactions and collagen degeneration. These lesions can be prevented by both maskage of the antigenic groups and intermolecular crosslinking using Glutaraldehyde. The durability of such chemically treated tissues is based upon the stability of the biological material (concept of bioprosthesis) and not upon cell survival or tissue regeneration by host cell ingrowth (concept of graft). The valvular bioprostheses made from Glutaraldehyde treated pericardial tissue, keep after this treatment their advantage of biological tissues: they are not thrombogenic and do not require anticoagulation contrary to mechanical valves. Although they have a limited durability up to 10 to 15 years due to tissue calcification, they represent 40% of the valvular prostheses used in clinical practice today. 2) The clinical use of electrostimulated skeletal muscle has been delayed for a long time because of fatigue lesions. An original protocol of progressive sequential stimulation prior to the use of muscle prevents fatigue by the transformation of type I fatigable myosin into type II non fatigable myosin. The conditionned muscle i.e.: the latissimus dorsi, is then wrapped around the ventricles to either reinforce cardiac contraction or to replace a portion of the heart. In the past 10 years, this new operation of "dynamic cardiomyoplasty", has been performed in 84 patients suffering from the end stage heart failure in our institution and in over 500 patients throughout the world with significant functional improvement.     

A comparison of the early and midterm results after dynamic cardiomyoplasty in patients with ischemic or idiopathic cardiomyopathy

OBJECTIVE: The main goal of this study is to determine the efficiency of the cardiomyoplasty procedure on patients with cardiomyopathy of different origins (ischemic and idiopathic origins). METHOD: Between June 1993 and August 1995, 24 patients underwent dynamic cardiomyoplasty with the left latissimus dorsi muscle in our institution. Early and midterm results, as well as the changes in hemodynamics and functional status during follow-up, were compared. RESULTS: Early mortality rate was 20.8% (five patients). Concomitant coronary revascularization, a preoperative left ventricular ejection fraction below 20%, and a functional capacity of class IV (intermittently) were associated with early mortality. The mean follow-up time was 17.3 months. Survival analysis (including early mortality) extending to the twenty-fourth month revealed no difference between the ischemic and idiopathic groups (55% vs 85%, respectively, p = 0.09). Functional status improved in the both groups. Ejection fractions were improved after cardiomyoplasty in all patients, regardless of their cause. Cardiac indices were higher 6 months after the operation. Changes in pulmonary capillary wedge pressure, peak pulmonary artery pressure, and left ventricular end-diastolic volume were not significant. CONCLUSION: Although cardiomyoplasty improves functional capacity and hemodynamics in patients with both idiopathic and ischemic cardiomyopathy, the idiopathic group is thought to achieve optimal benefit with regard to lower complication rates and lower early mortality expectancy owing to the absence of concomitant coronary revascularization.     

Quantification of early damage in latissimus dorsi muscle grafts

Acute damage in the latissimus dorsi muscle may account for variable clinical results following dynamic cardiomyoplasty and an ischemic cause has been suggested. Using established techniques, we set out to demonstrate and to quantify the acute muscle damage in a rodent model. The left latissimus dorsi muscle of 5 Sprague-Dawley rats was mobilized on its thoracodorsal vascular pedicle, thus interrupting the regional blood supply to its distal part. The undisturbed contralateral muscle served as a matched control. After 24 hours, the muscle was excised and divided into proximal, middle, and distal thirds. Damage was graded histologically and quantified by nitroblue tetrazolium macrohistochemistry. Both methods of assessment correlated well (r=-0.936; P < 0.001) and demonstrated significant damage, principally in the middle and the distal regions of the ischemic muscles. Therefore, the rodent model appears to be useful for investigating the pathogenesis and prevention of acute ischemic damage in the latissimus dorsi graft under conditions resembling the clinical scenario.     

Cardiomyoplasty - improvement of muscle fibre type transformation by an anabolic steroid (metenolone)

Dynamic cardiomyoplasty, a method to support ventricular function by the chronically stimulated latissimus dorsi muscle wrapped around the heart is accompanied by a loss of mass and force of the transplanted muscle. These effects and the fast-to-slow transformation of the muscle could be possibly influenced by the additional administration of anabolic steroids. In this study, the left latissimus dorsi muscles of 12 sheep were electrically conditioned (group A). In 12 other animals (group B), stimulation was combined with the administration of metenolone (100 mg/week). Biopsies were taken from the right and left muscles at the beginning and after 6 and 12 weeks of treatment, frozen and cross-sectioned. The muscle fibre type composition was studied enzymhistochemically (SDH-staining and Myosin-ATPase-reaction) and immunocytochemically (using antibodies against different myosin heavy chains, MHC). Furthermore, the expression of different MHC isoforms was investigated electrophoretically. The untreated latissimus dorsi muscle contains 20% type I fibres expressing slow MHC and 80% type II fibres expressing fast MHC. After 6 weeks, the respective fibre type composition was 42 and 58% (group A) and 80 and 20% (group B). After 12 weeks, the percentage of the type I fibres rose in group A to 59% and in group B to 98%. In accordance with these morphological results, the MHC pattern determined electrophoretically showed a corresponding shift from the fast to the slow isoform. Therefore, the administration of metenolone avoids severe muscle atrophy, and improves and accelerates fast to slow fibre type conversion necessary for successful cardiomyoplasty.     

Configuration of linear dynamic cardiomyoplasty for hypoplastic right ventricle

BACKGROUND: The purpose of this study is to determine feasibility of linear dynamic cardiomyoplasty with a briefly preconditioned latissimus dorsi in the experimental model simulating patch enlargement of the hypoplastic right ventricle. METHODS: In 8 mongrel dogs, a diminished right ventricular chamber was reconstructed with an extended pericardial patch. A left latissimus dorsi, preconditioned for 2 weeks (2 Hz) after a previous 2-week vascular delay period, was placed on the patch, with the muscle fiber oriented in parallel to the right ventricular long axis. RESULTS: Graft pacing with trained-pulses of 25 Hz at a 1:1 ratio showed significant augmentation of pulmonary flow and pressure (158% +/- 21%, 156% +/- 14%, respectively), contributing to restoring right ventricular function comparable with preoperative control, which was also confirmed by the right ventricular function curve and pressure-volume relationship analyzes. Continuous pacing was performed in 4 animals for 7 hours without evidence of muscle fatigue, implying feasibility of "working conditioning" after minimum preconditioning for this type of right heart assist. CONCLUSIONS: Linear latissimus dorsi myoplasty can restore normal right ventricular performance at a physiologic preload, and may provide a surgical option for the hypoplastic right ventricle.     

Study of muscular and ventricular function in dynamic cardiomyoplasty: a ten-year follow-up

BACKGROUND: The basic physiologic principle underlying cardiomyoplasty is long-term electrostimulation of a latissimus dorsi muscle (LDM) wrapped around the heart to obtain a phasic activity that could be integrated with ventricular kinetics. The aim of cardiomyoplasty is to prolong survival and to improve the quality of life of patients with severe chronic and irreversible myocardial failure by improving systolic contraction and correcting diastolic dysfunction. METHODS: To evaluate the long-term outcome of cardiomyoplasty, we investigated 82 patients electively undergoing this procedure in-our hospital. All patients had severe chronic heart failure that did not respond to optimal medical treatment. Patients had a mean age of 50 +/- 12 years (84% males). The cause of heart failure was ischemic (55%), idiopathic cardiomyopathy (34%), ventricular tumor (6%), and other (5%). The mean follow-up was 4.3 years. RESULTS: The mean New York Heart Association functional class improved after operation from 3.2 to 1.8. Average radioisotopic left ventricular ejection fraction increased from 17% +/- 6% to 28% +/- 3% (p < 0.05). Stroke volume index increased from 35 +/- 9 to 46 +/- 8 ml/beat/m2 (p < 0.05). The heart size remained stable at long term (evaluated by echo and computed tomography scanning). After cardiomyoplasty the number of successive hospitalizations resulting from congestive heart failure was reduced to 0.4 hospitalizations/patient/year (before operation 2.5, p < 0.05). Computed tomography scans showed at long-term a preserved LDM structure in 82% of patients who underwent operation. Survival probability at 7 years was 54% for the totality of patients, and 66% for patients who underwent operation in New York Heart Association functional class 3. Five patients underwent heart transplantation after cardiomyoplasty (mean delay 29 months), principally as a result of the natural evolution of their underlying heart disease, without major technical difficulties. CONCLUSIONS: Our 10-year clinical experience demonstrates that cardiomyoplasty increases ejection fraction, improves functional class, and ameliorates quality of life. Ventricular volumes and diameters remain stable long term. LDM structure is maintained long term if electrostimulation is performed avoiding excessive myostimulation. Patient selection is the most important determinant for early and late outcome. Late death in patients undergoing cardiomyoplasty is principally due to sudden death. Our future aim is to incorporate a cardioverter-defibrillator in the cardiomyostimulator, thus improving long-term results. Cardiomyoplasty may delay or prevent end-stage heart failure and the need for heart transplantation.     

Activity-rest stimulation of latissimus dorsi for cardiomyoplasty: 1-year results in sheep

BACKGROUND: In dynamic cardiomyoplasty electro-stimulation achieves full transformation of the latissimus dorsi (LD); therefore, its slowness limits the systolic support. Daily activity-rest could maintain partial transformation of the LD. METHODS: Sheep LD were burst-stimulated either 10 or 24 hours/day. Before and 2, 4, 6, and 12 months after stimulation, LD power output, fatigue resistance, and tetanic fusion frequency were assessed. Latissimus dorsi were biopsied at 6 months, and sheep sacrificed at 12 months. RESULTS: After 1 year of 10 hours/day stimulation LD was substantially conserved and contained large amounts of fast type myosin. From 2 months to 1 year of stimulation the power per muscle of the daily rested LD was greater than that of the left ventricle, being three to four times higher than in the 24-hour/day stimulation. CONCLUSIONS: If extended to humans, these results could be the rationale for the need of a cardiomyostimulator, whose discontinuous activity could offer to patients the long-standing advantage of a faster and powerful muscle contraction.     

The use of latissimus dorsi muscle flap in reconstructive heart surgery

Dynamic cardiomyoplasty is a technique for ventricular assistance indicated for the correction of left ventricle aneurysm and for cardiomyopathies in which heart transplantation is contraindicated. In this article, our first four patients to undergo cardiomyoplasty (from February 1991 until April 1992) with a left latissimus dorsi island flap, rotated into the thorax after a 3-week training period, are reviewed. Therapeutic indications were cardiomyopathy with contraindication for heart transplant in patients 1 and 4 and associated to surgery for left ventricle aneurysm for patients 2 and 3. Patient 1 died 4 months after surgery because of a cerebral embolism when he was at functional class II. The other three patients remain at functional class I, carrying out normal activities. All the data were evaluated with the paired t test. Ejection fraction values (obtained through echocardiography and scintigraphy studies) and maximum minute flow rate of blood (measured with an echo-Doppler) have increased significantly (p < 0.001, p < 0.05, and p < 0.01, respectively) after heart surgery. Clinical improvement has been found after cardiomyoplasty, which correlates with an increase in ejection fraction and maximum minute flow rate of blood.     

Skeletal muscle extra-aortic counterpulsation in dogs with dilated cardiomyopathy

Skeletal muscle extra-aortic counterpulsation was performed in seven dogs with dilated cardiomyopathy. A left latissimus dorsi dynamic descending thoracic aortomyoplasty was used as the autologous counterpulsator. Pulse train stimulation in diastole was used to initiate contraction and fibre type transformation. Two of the dogs died within 48 hours of surgery. The device was successfully activated in the five remaining dogs, but in one individual it failed within 48 hours of activation. Serial echocardiographic examinations of dogs in which the device functioned successfully (n = 4) showed trends towards the decrease in the left ventricular systolic internal dimension, left ventricular diastolic internal dimension, E-point to septal separation and left atrial diameter in systole seven to 14 days following the procedure, although these changes failed to persist in the long-term. The results suggest that skeletal muscle for cardiac assistances such as extra-aortic muscle counterpulsation, might be a therapeutic option for dogs with cardiac failure due to dilated cardiomyopathy.     

Hemodynamic response to in situ latissimus dorsi muscle stimulation: implications in dynamic cardiomyoplasty

Dynamic cardiomyoplasty (DCM) involves the electrical stimulation of a pedicled latissimus dorsi muscle flap wrapped around the falling ventricle as a means of cardiac assist. To further elucidate a potential neurohumoral mechanism for improvement of cardiac output after myoplasty, we evaluated the hemodynamic effects of in situ stimulation of the latissimus dorsi muscle (in the absence of cardiomyoplasty). In seven mongrel dogs, a nerve cuff electrode (Medtronic 6901) was placed around the left thoracodorsal nerve (TDN). This was attached to a pulse generator (Medtronic, Itrel 7420), delivering a 4.0 volt, 0.19 second on, 0.81 second off, 33 Hz, 210 microsecond pulse width, cyclic bursts similar to that used in DCM. Stroke volume index (SVI) and other hemodynamic parameters as well as plasma norepinephrine (NE) levels were measured at five stages: baseline, stimulator on at 0, 2, and 5 minutes, and stimulator off at 30 minutes after. The animals were then subjected to 4 weeks of rapid pacing at 240 beats/min (Medtronic 8329) to induce heart failure, and as the rapid pacing was discontinued, measurements were repeated as above. After rapid pacing, cardiac function was significantly depressed, and NE was elevated (133 +/- 69 versus 500 +/- 353 pg/mL, p < 0.05). In the normal hearts, TDN stimulation increased SVI, heart rate, systemic pressure, and NE levels. In heart failure, however, no significant changes in cardiac function and NE levels were noted. In conclusion, our data indicate that in the normal hearts, afferent impulses from TDN stimulation alone may augment cardiac function by means of a neurohumoral effect that is not seen in severe heart failure. The implications of these findings in DCM are discussed.     

Functional MRI study of the cognitive generation of affect

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.     

Targeted disruption of the TGA3 locus in Arabidopsis thaliana

BACKGROUND: Severe latissimus dorsi muscle damage may compromise cardiomyoplasty performance. We analyzed factors underlying the damage produced in 20 sheep latissimus dorsi muscles by isolating the influences of electrical stimulation, mobilization (with some loss of vascular supply), loss of normal resting tension, or a combination of these. METHODS: In group I (n = 3), the muscle was mobilized except for its neurovascular pedicle and reattached at normal resting length. In group II (n = 3), the muscle was mobilized and reattached at about 80% of resting length. Groups III (n = 6) and IV (n = 4) were as groups I and II except that continuous indirect stimulation at 2 Hz was added after 2 weeks. In group V (n = 4), the undisturbed muscle received stimulation alone. After 10 to 12 weeks, muscle samples were taken for morphometric analysis. RESULTS: Loss of resting muscle tension appeared to be the single most damaging intervention, though mobilization and stimulation had further deleterious effects. The worst damage was seen when all three factors were combined, when 60% of the muscle cross section was occupied by connective tissue and fat. The changes were significantly more severe in the distal than in the proximal part of the muscle, implicating ischemia as a contributory factor. CONCLUSIONS: Fiber damage reduces the effectiveness of muscle grafts used for cardiac assistance and merits further systematic investigation.     

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.     

Linear epitope mapping of humoral responses induced by vaccination with recombinant HIV-1 envelope protein gp160

Ischemic preconditioning of the myocardium with repeated brief periods of ischemia and reperfusion prior to prolonged ischemia significantly reduces subsequent myocardial infarction. Following ischemic preconditioning, two "windows of opportunity" (early and late) exist, during which time prolonged ischemia can occur with reduced infarction size. The early window occurs at approximately 4 hours and the late window at 24 hours following ischemic preconditioning of the myocardium. We investigated if ischemic preconditioning of skeletal muscle prior to flap creation improved subsequent flap survival and perfusion immediately or 24 hours following ischemic preconditioning. Currently, no data exist on the utilization of ischemic preconditioning in this fashion. The animal model used was the latissimus dorsi muscle of adult male Sprague-Dawley rats. Animals were assigned to three groups, and the right or left latissimus dorsi muscle was chosen randomly in each animal. Group 1 (n = 12) was the control group, in which the entire latissimus dorsi muscle was elevated acutely without ischemic preconditioning. Group 2 (n = 8) investigated the effects of ischemic preconditioning in the early window. In this group, the latissimus dorsi muscle was elevated immediately following preconditioning. Group 3 (n = 8) investigated the effects of ischemic preconditioning in the late window, with elevation of the latissimus dorsi muscle 24 hours following ischemic preconditioning. The preconditioning regimen used in groups 2 and 3 was two 30-minute episodes of normothermic global ischemia with intervening 10-minute episodes of reperfusion. Latissimus dorsi muscle ischemia was created by occlusion of the thoracodorsal artery and vein and the intercostal perforators, after isolation of the muscle on these vessels. Muscle perfusion was assessed by a laser-Doppler perfusion imager. One week after flap elevation, muscle necrosis was quantified in all groups by means of computer-assisted digital planimetry. Our results show that ischemic preconditioning resulted in a significant reduction (p < 0.05) in muscle-flap necrosis immediately and 24 hours following ischemic preconditioning. Perfusion changes after flap elevation were similar among the three groups. Ischemic preconditioning of skeletal muscle prior to flap creation significantly reduces subsequent muscle-flap necrosis caused by the ischemia of flap creation immediately and 24 hours following ischemic preconditioning. Further elaboration of the mechanisms of ischemic preconditioning may allow pharmacologic preconditioning to be used in the augmentation of skeletal muscle-flap survival in the clinical setting.     

Right latissimus dorsi cardiomyoplasty augments left ventricular systolic performance

We hypothesized that the right latissimus dorsi cardiomyoplasty augments left ventricular performance. Five dogs underwent staged right latissimus dorsi cardiomyoplasty. Ventricular function was studied 1 to 3 weeks later. Left ventricular pressure was measured with a micromanometer and left ventricular dimensions with piezoelectric crystals. Inferior vena caval occlusion was used to vary preload. Pressure-volume data were collected with the muscle unstimulated and stimulated at 1:2 and 1:1 muscle/heart ratios. The end-systolic pressure-volume relation (mm Hg/mL), stroke work, preload recruitable stroke work, left ventricular end-diastolic volume, and the diastolic relaxation constant were calculated and expressed as mean +/- standard deviation. Stimulated beats at a 1:2 ratio showed an increase in stroke work of 42.1% (978 +/- 381 to 1,390 +/- 449 g.cm; p < 0.01) and preload recruitable stroke work of 28.8% (59.4 +/- 20.7 to 76.6 +/- 11.0 g.cm/cm3; p = 0.05) compared with the unstimulated beats. With the stimulator on at 1:1, smaller changes occurred: stroke work increased 9% (1,167 +/- 390 to 1,273 +/- 363 g.cm; not significant) and preload recruitable stroke work increased 27% (63.9 +/- 22.7 to 80.9 +/- 23.1 g.cm/cm3; p = 0.05). There were no significant changes in the end-systolic pressure-volume relation. The diastolic relaxation constant did not change at 1:1 (36 +/- 9.7 to 37 +/- 6.4 ms; not significant) or 1:2 (36 +/- 9.3 to 39 +/- 8.2 ms; not significant). Left ventricular end-diastolic volume was unchanged at 1:1 (34 +/- 10.7 to 32 +/- 10.3 mL) and at 1:2 (31 +/- 9.0 to 32 +/- 8.7 mL).(ABSTRACT TRUNCATED AT 250 WORDS)