Skeletal muscle for heart repair or assistance.
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Animals↗
Biomedical subjects
M A Acker
Publications and source records attributed to M A Acker.
An autologous biologic pump motor.
Latissimus dorsi skeletal muscle ventricles were constructed in six beagles. They first underwent a period of vascular delay and of electrical preconditioning over several weeks. The skeletal muscle ventricles were then connected to a totally implantable mock circulation that allowed for the chronic measurement of pressures and flows produced by the muscle. The skeletal muscle ventricles were actuated by stimulation of the motor nerve with an implanted generator that delivered brief pulse trains. The skeletal muscle ventricles pumped continuously against an afterload of 80 mm Hg with a preload of 40 to 50 mm Hg at a rate of 54 times per minute. At initiation of pumping, systolic pressure was 135 +/- 24 mm Hg and flow was 464 +/- 116 ml/min. After 2 weeks of continuous pumping, the systolic pressure was 104 +/- 1 mm Hg and continuous flow was 206 +/- 16 ml/min. Two of the skeletal muscle ventricles pumped continuously for 5 and 9 weeks, respectively. At the end of that time one was still capable of generating pressure up to 205 mm Hg and the other, 160 mm Hg. These results suggest that a chronic auxiliary skeletal muscle ventricle is a feasible approach to the treatment of end-stage cardiac failure.
Animals↗
Generalized imitative affection: relationship to prior kinds of imitation training.
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Affect↗
Acute systolic and diastolic indices of left ventricular function after cardiomyoplasty in a chronic model of heart failure.
Recent experimental studies have suggested that the initial nonstimulated stage of dynamic cardiomyoplasty acutely impairs ventricular function. Those investigations were performed on normal hearts and primarily examined diastolic alterations as a result of the passive muscle wrap. The purpose of this study was to assess the acute systolic and diastolic effects of a nonstimulated muscle wrap in chronic heart failure induced by rapid ventricular pacing in canines. Pressure-volume analysis of ventricular function based on conductance catheter volume and micromanometer pressure data was used. Each animal was studied before rapid pacing, before cardiomyoplasty, and immediately after wrap. By the end of the pacing period and before wrap, left ventricular dysfunction developed in all dogs, manifested by significant deterioration of both systolic and diastolic indices of ventricular function, as well as progressive increases in left ventricular volumes. However, no further deterioration with load insensitive indices of systolic or diastolic indicators of ventricular function was found as a result of the passive muscle wrap. These results suggest that the cardiomyoplasty procedure can be safely performed on failing hearts without prohibitive acute impairment of ventricular function.
Animals↗
Determination of global function and regional mechanics of dynamic cardiomyoplasty using magnetic resonance imaging.
This study used tissue tagged magnetic resonance (MR) to assess regional strain and generate pressure-volume (PV) loops in a canine model of cardiomyoplasty (CMP). Three dogs with rapid ventricular pacing induced heart failure underwent dynamic CMP chronic cardiac assistance for 1 year. At the end of the study period, we performed a MR study with the myostimulator "on" and "off" and recording of left ventricular (LV) pressure. We determined the short axis displacement (D) and maximal and minimal principal strains (lambda1 and lambda2) by quantitative two-dimensional regional spatial modulation of magnetization visualization utility image analysis. LV PV loops were generated by combining the LV volume data from the MR images with the LV pressure recorded during imaging. Muscle stimulation produced a leftward shift of the LV PV loops in two of the three dogs, and an increase in LV peak pressure and dp/dt max. In contrast, short axis lambda1 and lambda2 did not change significantly (p = NS). D increased significantly in the anterolateral, posterolateral, and posteroseptal regions (p < 0.05) but did not change for the septal region (p = NS). Flap stimulation augments LV function in the absence of short axis strain change; this suggests that dynamic CMP exerts its main action along the long axis of the heart.
Animals↗
Dynamic cardiomyoplasty decreases myocardial workload as assessed by tissue tagged MRI.
The effects of dynamic cardiomyoplasty (CMP) on global and regional left ventricular (LV) function in end-stage heart failure still remain unclear. MRI with tissue-tagging is a novel tool for studying intramyocardial motion and mechanics. To date, no studies have attempted to use MRI to simultaneously study global and regional cardiac function in a model of CMP. In this study, we used MRI with tissue-tagging and a custom designed MR compatible muscle stimulating/pressure monitoring system to assess long axis regional strain and displacement variations, as well as changes in global LV function in a model of dynamic cardiomyoplasty. Three dogs underwent rapid ventricular pacing (RVP; 215 BPM) for 10 weeks; after 4 weeks of RVP, a left posterior CMP was performed. After 1 year of dynamic muscle stimulation, the dogs were imaged in a 1.5 T clinical MR scanner. Unstimulated and muscle stimulated tagged long axis images were acquired. Quantitative 2-D regional image analysis was performed by dividing the hearts into three regions: apical, septal, and lateral. Maximum and minimum principal strains (lambda, and lambda2) and displacement (D) were determined and pooled for each region. MR LV pressure-volume (PV) loops were also generated. Muscle stimulation produced a leftward shift of the PV loops in two of the three dogs, and an increase in the peak LV pressure, while stroke volume remained unchanged. With stimulation, lambda1 decreased significantly (p<0.05) in the lateral region, whereas lambda2 increased significantly (p<0.05) in both the lateral and apical regions, indicating a decrease in strain resulting from stimulation. D only increased significantly (p<0.05) in the apical region. The decrease in strain between unassisted and assisted states indicates the heart is performing less work, while maintaining stroke volume and increasing peak LV pressure. These findings demonstrate that the muscle wrap functions as an active assist, decreasing the workload of the heart, while preserving total pump performance.
Animals↗
Assessment of synchronized direct mechanical ventricular actuation in a canine model of left ventricular dysfunction.
Direct mechanical ventricular actuation (DMVA) is an experimental procedure that provides biventricular cardiac assistance by intracorporeal pneumatic compression of the heart. The advantages this technique has over other assist devices are biventricular assistance, no direct blood contact, pulsatile blood flow, and rapid, less complicated application. Prior studies of nonsynchronized DMVA support have demonstrated that a subject can be maintained for up to 7 days. The purpose of this study was to determine the acute hemodynamic effects of cardiac synchronized, partial DMVA support in a canine model (RVP) of left ventricular (LV) dysfunction. The study consisted of rapidly pacing seven dogs for 4 weeks to create LV dysfunction. At the conclusion of the pacing period, the DMVA device was positioned around the heart by means of a median sternotomy. The animals were then imaged in a 1.5 T whole body high speed clinical MR system, with simultaneous LV pressure recording. Left ventricular pressure-volume (PV) loops of the nonassisted and DMVA assisted heart were generated and demonstrated that DMVA assist shifted the loops leftward. In addition, assist significantly improved pressure dependent LV systolic parameters (left ventricular peak pressure and dp/dt max, p < 0.05), with no diastolic impairment. This study demonstrates that DMVA can provide synchronized partial assist, resulting in a decrease in the workload of the native heart, thus having a potential application for heart failure patients.
Animals↗
Arterial delivery of genetically labelled skeletal myoblasts to the murine heart: long-term survival and phenotypic modification of implanted myoblasts.
The ability to replace damaged myocardial tissue with new striated muscle would constitute a major advance in the treatment of diseases that irreversibly injure cardiac muscle cells. The creation of focal grafts of skeletal muscle has been reported following the intramural injection of skeletal myoblasts into both normal and injured myocardium. The goals of this study were to determine whether skeletal myoblast-derived cells can be engrafted into the murine heart following arterial delivery. The murine heart was seeded with genetically labeled C2C12 myoblasts introduced into the arterial circulation of the heart via a transventricular injection. A transventricular injection provided access to the coronary and systemic circulations. Implanted cells were characterized using histochemical staining for beta-galactosidase, immunofluorescent staining for muscle-specific antigens, and electron microscopy. Initially the injected cells were observed entrapped in myocardial capillaries. One week after injection myoblasts were present in the myocardial interstitium and were largely absent from the myocardial capillary bed. Implanted cells underwent myogenic development, characterized by the expression of a fast-twitch skeletal muscle sarcoendoplasmic reticulum calcium ATPase (SERCA1) and formation of myofilaments. Four months following injection myoblast-derived cells began to express a slow-twitch/cardiac protein, phospholamban, that is normally not expressed by C2C12 cells in vitro. Most surprisingly, regions of close apposition between LacZ labeled cells and native cardiomyocytes contained structures that resembled desmosomes, fascia adherens junctions, and gap junctions. The cardiac gap junction protein, connexin43, was localized to some of the interfaces between implanted cells and cardiomyocytes. Collectively, these findings suggest that arterially delivered myoblasts can be engrafted into the heart, and that prolonged residence in the myocardium may alter the phenotype of these skeletal muscle-derived cells. Further studies are necessary to determine whether arterial delivery of skeletal myoblasts can be developed as treatment for myocardial dysfunction.
Animals↗
Use of theophylline for treatment of prolonged sinus node dysfunction in human orthotopic heart transplantation.
Sinus node dysfunction may complicate heart transplantation in over 50% of cases, leading to prolonged bradyarrhythmias in 20% of recipients. Permanent pacemaker implantation, the standard treatment for such persistent rhythm disturbances, can result in significant complications in this setting. A protocol with theophylline, a methylxanthine known to reverse the sinus node electrophysiologic abnormalities observed in transplant patients, was initiated at our institution in October 1989 to treat posttransplantation bradyarrhythmias and to reduce the need for pacemaker implantation. Patients with sinus or nodal bradycardia or sinus arrest were given theophylline orally; the drug was initiated in 15 of 38 patients (39.5%), 3 to 24 days after transplantation. Mean duration of treatment was 57.4 days (range, 20 to 105 days). Normal sinus rhythm with a rate of more than 90 beats/min was restored in 14 of 15 patients (93.3%). Permanent pacing was required in one patient. Transplant recipients before October 1989 (group 1, n = 112) were compared with subsequent transplant recipients (group 2, n = 38). These groups did not differ significantly in incidence of bradyarrhythmias or potential risk factors for posttransplantation sinus node dysfunction, though a greater preoperative use of amiodarone occurred in group 2. Permanent pacemaker requirement was significantly reduced from 16.1% in group 1 to 2.6% in group 2 (p < 0.05) with the introduction of theophylline. Theophylline is effective treatment for posttransplantation bradyarrhythmias, thereby resulting in a reduced need for pacemaker implantation.
Adult↗
Modified rapid ventricular pacing: a chronic model of heart failure for evaluation of new surgical therapies.
Rapid ventricular pacing (RVP) in dogs creates a well characterized model of dilated cardiomyopathy. Standard pacing protocols use RVP at 240-260 beats/min for 2-4 weeks, and result in high mortality rates if continued longer. The authors describe a modification of RVP that results in significant heart failure by 4 weeks, but can be continued for up to 10 weeks with low mortality. Nineteen mongrels underwent RVP at 215 beats/min for 10 weeks. Serial pressure-volume analysis and echocardiography were performed in this model to assess longitudinally changes in left ventricular (LV) function and volumes. The mortality rate was 10%. Significant progressive LV dysfunction with concomitant LV enlargement was observed throughout the pacing period. Finally, norepinephrine levels were elevated at the end of pacing, consistent with an activated sympathetic system. This modified RVP protocol permits long-term pacing with a low mortality rate and results in progressive heart failure throughout the pacing period. This model would be useful in the long-term evaluation of newer surgical and medical therapies of the failing heart.
Animals↗