Left ventricular full-thickness cardiomyoplasty with pericardial neoendocardium: experimental development of a surgical procedure

Cardiomyoplasty, a surgical procedure using stimulated skeletal muscle graft to replace or repair damaged myocardium, has been successfully performed in experimental animals and clinical patients. Whenever feasible, endocardium of the damaged myocardial segment is retained and partial-thickness cardiomyoplasty should be carried out. However, if this procedure were to be applied to enlarge a hypoplastic ventricle or to maintain normal dimensions of the ventricular cavity in some repairs in adults, full-thickness replacement of the ventricular wall with contractile skeletal muscle mass would be required. To develop such a technique, several canine experiments were carried out. In 7 dogs, "simple full-thickness cardiomyoplasty" was performed by using a latissimus dorsi muscle graft to repair a full-thickness left ventricular wall defect. We found it was difficult to obtain adequate hemostasis between the nonscarred myocardial tissue and the skeletal muscle graft, and excessive suturing to obtain hemostasis resulted in strangulation of the muscle grafts. The skeletal muscle-blood interface in the left ventricle was found to be highly thrombogenic. The perioperative hemorrhage and the risk of muscle graft strangulation by excessive sutures were avoided by using a pericardial patch as neoendocardium in 5 dogs that underwent similar full-thickness cardiomyoplasty procedures. Although the pericardial neoendocardium was not fully antithrombogenic in this canine model, endothelialization of the endocardium occurred within several weeks after operation. Thus, when combined with an implantable synchronized burst stimulator, this technique may in the future provide an effective "full-thickness dynamic cardiomyoplasty" to enlarge the ventricles and augment myocardial function in select patients.     

Transforming skeletal muscle for myocardial assist: a feasibility study

Canine experiments were undertaken to determine the feasibility of transforming skeletal muscle for myocardial assistance. Initially, a rectus-muscle pedicle flap was used to power a ventricular assist conduit. A specially designed "pulse-train" stimulator produced skeletal muscle contractions capable of augmenting myocardial function. Statistically significant increases in either systolic or diastolic pressures were achieved by appropriate synchronization and signal delays of the stimulator. Then, the left rectus muscle was conditioned by stimulating it at low frequencies (2 to 10 Hz) for 6 to 12 weeks. The degree of transformation from type II (fast) to type I (slow) fibres was examined and the resultant tolerance to fatigue studied. Preliminary data show that a greater proportion of type I fibres is associated with increased resistance to fatigue. Such transformed skeletal muscle should therefore be more suited to power the cardiac assist devices.     

A skeletal muscle ventricle made from rectus abdominis muscle in the dog

This study examined the ability of a skeletal muscle-powered assist ventricle to augment cardiac output in 10 dogs with experimentally induced heart failure. Heart failure was induced with the use of the beta-blocking agents atenolol and propranolol. A "skeletal muscle ventricle" was then surgically constructed by wrapping the rectus abdominis muscle, with an intact neurovascular supply, around a double open-ended compressible pouch. The skeletal muscle ventricle was then interposed in a left ventricular apicoaortic conduit. The motor nerves to the skeletal muscle ventricle were stimulated by a custom designed pulse generator and caused tetanic contraction of the ventricle during diastole of every fourth natural heart beat. Stimulation was continued for 60 min. Cardiac output, systolic and diastolic blood pressures, mean blood pressure, left ventricular end diastolic pressure, and central venous pressure were then monitored prior to, during, and several times after skeletal muscle ventricle stimulation to evaluate assist ventricle function. There was an increased cardiac output in all 10 dogs at all recording times during skeletal muscle ventricle assistance compared to the cardiac output prior to stimulation of the assist ventricle. The mean increase in cardiac output after 30 min of assist ventricle stimulation was 31.0 +/- 14% (P less than 0.01), and at 60 min was 8.0 +/- 1% (P less than 0.05). The mean diastolic blood pressure after 1 and 30 min of skeletal muscle ventricle assistance (50.0 +/- 2.9 and 48.6 +/- 2.2 mm Hg, respectively) was increased (P less than 0.05) vs the preassistance value (44.9 +/- 2.8 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental aortic replacement with a vascularized tissue graft

Prosthetic graft infection in the aortic position remains a catastrophic complication of aortic replacement. In an effort to incorporate the advantages of vascularized tissue into aortic replacement, the practionally of infrarenal aortic replacement was investigated in dogs by a vascularized, musculofascial, pedicle graft. Eight dogs underwent laparotomy, and the left rectus abdominus muscle, its posterior rectus sheath, and underlying peritoneum were used to construct a tube graft based on the inferior epigastric vascular pedicle. A 2- to 4-cm section of the infrarenal aorta was resected, and the tube graft was interposed. Aortography documented graft patency immediately and at 1,6, and 10 months. Gross and histologic examination of the grafts at one month revealed viable skeletal muscle in the pedicle graft, with a thin layer of fibrin deposition on the luminal surface. Ten months after insertion, the microscopic examination against revealed patent vessels in the graft and a neoendothelial layer that lined the luminal surface of the graft. Successful replacement of the dog infrarenal aorta can be performed using a tube graft as part of a vascularized, musculofascial, pedicle flap. The potential for its use in the infected field is intriguing and deserves further study.     

Implantable extra-aortic balloon assist powered by transformed fatigue-resistant skeletal muscle

The hypothesis tested in this study was whether a skeletal muscle could be transformed to be fatigue resistant, to be used to power an implantable extra-aortic balloon assist device, and therefore to provide dynamically significant cardiac assistance. Eight dogs underwent implantation of an Itrel pacemaker to stimulate the thoracodorsal nerve over 8 to 18 weeks and transform the latissimus dorsi muscle. Biopsies of these muscles confirmed near complete (up to 98%) transformation into fatigue-resistance type I muscle fibers, identified by the adenosinetriphosphatase histochemical stains. Biochemical assays showed conversion of myosin isoforms to that of myocardial V3 phenotype, decreased activity of anaerobic glycolytic marker, and increased activity of aerobic enzyme marker, which indicated greater resemblance of such muscle to the myocardial fibers. In four dogs, the optimal stimulation parameters of such muscles in response to a burst stimulator, which synchronizes and summates the muscle contraction, were studied and compared with the contralateral, nontransformed muscle. Fatigue tests confirmed the marked fatigue resistance of the transformed muscle. In four dogs, a 100 ml balloon was placed beneath the transformed latissimus dorsi muscle and connected to the thoracic aorta with a Dacron graft. By means of the optimal burst-stimulating parameters identified above, the latissimus dorsi muscle was stimulated to contract during diastole, compressing the balloon to achieve diastolic augmentation while allowing the balloon to fill during systole. A 39% increase (p less than 0.001) in the "subendocardial viability index" (diastolic pressure-time index/tension-time index) was obtained as calculated from the left ventricular and ascending aortic pressure tracings. We conclude that the skeletal muscle can be transformed to resemble myocardium, which can generate sufficient force to provide hemodynamically significant and clinically relevant counterpulsation.     

After a cardiomyoplasty, collaterals from skeletal muscle form to chronic ischemic myocardium

We measured the collateral formation between skeletal muscle and the heart after a latissimus dorsi cardiomyoplasty in an animal model that contained normal, chronic ischemic, and infarcted myocardium. The area at risk for ischemia was 27.0 +/- 3.2% of the left ventricular mass (n = 10, mean +/- SE). In five animals the risk area developed predominantly into chronic ischemic myocardium; in five others the risk area became an infarct. The collateral blood flow from the skeletal muscle to chronic ischemic myocardium (6.05 +/- 1.36 ml/100 g/min, n = 5) was higher than flow to the infarct (0.46 +/- 0.31 ml/100 g/min, n = 5). The collateral blood flow to normal myocardium was minimal (0.04 +/- 0.01 ml/100 g/min). The collateral blood flow appeared to be concentrated in the outer half of the left ventricular wall, with the epicardium having a higher skeletal muscle derived collateral blood flow than endocardium (p < 0.05). We conclude that after a cardiomyoplasty a collateral blood flow, which approaches clinical significance, is preferentially established between skeletal muscle and chronic ischemic myocardium. Enhancement of this collateral blood flow might provide a means to revascularize patients with presently inoperable coronary disease.     

Implantable rate-responsive counterpulsation assist system

To apply the potential energy source available from skeletal muscle in cardiac assistance, we developed an implantable counterpulsation assist system. This study reports the results using this implantable counterpulsation assist system in an acute in vivo animal model. Twelve dogs had a dual-chambered, extraaortic counter-pulsation pump anastomosed in parallel to the thoracic aorta. The left latissimus dorsi muscle was used to power the pump. A newly developed implantable stimulator was used to make the muscle contract in synchrony with the diastolic phase. The unique feature of this stimulator is its ability to adjust timing of muscle contraction according to changing heart rates. The stimulator is also able to detect arrhythmias, and as a safety measure, shuts down until a normal rhythm is resumed. During counterpulsation assist with the implantable counterpulsation assist system, diastolic pressure increased an average of 34 mm Hg from baseline, equivalent to a 69% augmentation. Systolic peak pressure decreased an average of 10 mm Hg, equivalent to an 11% unloading. With induced heart rate changes, the implantable counterpulsation assist system readjusted its timing, maintaining optimal counterpulsation without systolic interference. Induced ventricular tachycardia resulted in immediate shutdown of the stimulator until resumption of a normal rhythm. The feasibility of using an intraaortic balloon pump console as back-up was also demonstrated. Excellent counterpulsation was obtained with either muscle power or balloon pump console. We conclude that the implantable counterpulsation assist system can provide effective counterpulsation assist and has the potential for continuous cardiac support.     

Comparison of the effects of halothane on newborn and adult rabbit myocardium

The effect of halothane on myocardial contractility was studied in isolated right ventricular muscle preparations from newborn and adult rabbits. Right ventricular strips were mounted in oxygenated Krebs' solution and stimulated with supramaximal voltages at 1.0 Hz, while isometric force of contraction was continuously recorded. Halothane (0.4, 0.7, and 1.1%) caused a significant dose-dependent depression of both peak developed tension (42, 61, and 70%, respectively) and maximum rate of rise of isometric tension (40, 56, and 64%, respectively) of newborn myocardium. Newborn myocardial preparations exhibited approximately 20% greater depression of contractility than adult myocardium at each concentration studied (P less than 0.05), thus a parallel shift of the dose-response curves was observed. It was concluded that halothane exerts a potent depressant effect on newborn myocardium that is greater than that on adult myocardium. The depression effect of halothane on the newborn myocardium may contribute to its hypotensive effect in newborn infants.     

The influence of timing on the functional and morphological result after nerve grafting: an experimental study in rabbits.

Clinical experience and experimental work in sheep have shown that a two-stage approach to restoring muscle function with a long nerve graft and free muscle grafting seems to be more beneficial than a one-stage approach. Based on a standardised experimental protocol, one-stage and two-stage nerve grafting approaches in rabbits were compared, and the actual differences in muscle force, together with morphological data, were calculated. In 20 rabbits the saphenous nerve was used as a 7 cm nerve graft. Animals were separated into two groups. In group 1, 10 rabbits underwent a one-stage approach to reinnervate the rectus femoris muscle. In the left hindlimb, the proximal end of the graft was coapted to the cut motor nerve branch of the vastus medialis muscle, and the distal end was coapted to the nerve branch of the rectus femoris muscle. In group 2, 10 rabbits underwent a two-stage approach, leaving the distal end of the nerve graft unconnected to the rectus femoris muscle in the first stage. In the second stage, this end was coapted to the freshly cut motor nerve branch of the rectus femoris muscle. After 15 months, the maximum tetanic tensions in the reinnervated rectus femoris muscle and the contralateral unoperated muscle were determined. The graft and the motor branch distal to the graft were biopsied in order to count the number of regenerated myelinated nerve fibres. The mean+/-s.d. maximum tetanic tensions in the reinnervated rectus femoris muscles were 10.6+/-4.9 N in group 1 and 21.4+/-1.1 N in group 2. Compared with the unoperated side, the muscle force following denervation and reinnervation was 38.3% in group 1 and 58.9% in group 2 (P=0.01). The mean+/-s.d. numbers of regenerated myelinated nerve fibres distal to the graft in the rectus femoris muscle branch were 737+/-340 in group 1 and 1487+/-1004 in group 2 (P=0.05). These results show that the neurotrophic effect of an immediately connected target organ is far outweighed by the adverse effect of the longer period of muscle denervation. Therefore, nerve grafting and muscle transplantation should not be performed in the same operation.     

Effects of abdominal left ventricular assist device (ALVAD) on myocardial contractility during acute coronary occlusion

Experiments were designed to investigate the effects of ALVAD pumping on myocardial contractility and performance during acute coronary occlusion. Calculation of local changes in contractile function provided a method of quantitating these effects.The Maxwell-Hill two-component model of muscular contraction was utilized for the calculation of the Vce. Directly measured rate of lengthening of the series elastic component and the velocity of muscle shortening were used for these calculations.During periods of induced myocardial ischemia, ALVAD assistance decreased peak wall tension from a mean of 179 ± 5.8 to 36 ± 4.1 gm/cm² (P < 0.01) and increased ejection fraction 77% (P < 0.01). During assistance, peak Vce increased 46% from acute occlusion levels.The results of the current study suggest that mechanical left ventricular assistance increases the oxygen supply: demand ratio in acutely ischemic myocardium by reducing the oxygen demands of tension development. This reduction in ventricular wall tension and oxygen demand allows the depressed contractile function of the ischemic segment to increase to normal control levels.     

Effects of Ketamine on the Contractility of Failing and Nonfailing Human Heart Muscles In Vitro

Background: Induction of anesthesia with ketamine may decrease cardiac output in critically ill patients. The direct effects of ketamine on the failing human myocardium are unknown. This study examined the effects of ketamine on contractility of human failing and nonfailing myocardium in vitro.

Methods: Trabecular muscles were obtained from the left ventricles and right atria of 10 patients with heart failure undergoing transplantation and from the right atria of 14 patients undergoing coronary artery bypass surgery. Muscles were dissected and mounted in a 37 [degree sign]C bath and stimulated at 1 Hz. Isometric contraction variables were recorded before and after addition of ketamine (concentrations between 0.44 and 440.0 micro Meter) to the bath. The effects of ketamine were compared with those of buffer. To test muscle contractility, at the end of each experiment, 1 micro Meter isoproterenol was added.

Results: Ketamine caused a significant dose-dependent decrease in developed tension in nonfailing atrial and failing atrial and ventricular muscles (P < 0.01 for all). In vehicle-treated muscles, developed tension remained stable, and isoproterenol increased developed tension 136% (nonfailing atrial muscles) and 178% (failing atrial and ventricular muscles; P < 0.01). In nonfailing atrial muscle, isoproterenol restored the ketamine-induced decrease in developed tension toward the baseline value. In failing atrial and ventricular muscles exposed to ketamine, isoproterenol did not counteract the ketamine.     

Functional outcome of new blood vessel growth into ischemic skeletal muscle

PURPOSE: The administration of angiogenic growth factors and the transfer of well-vascularized tissues have been shown to induce development of new blood vessels in ischemic muscle. The functional significance of these new vessels is unknown. The hypothesis of this study is that the transfer of vascularized muscle and the local infusion of basic fibroblast growth factor (bFGF) synergistically improve contractile function of ischemic skeletal muscle. METHODS: Twenty-six rabbits were divided into four groups. An ischemic hindlimb was created in each by ligating the right common iliac artery. The flap + bFGF group (n = 6) had transposition of a contralateral rectus muscle flap onto the thigh. Additionally, bFGF (3 ng/h) was continuously infused at the flap-thigh interface. In the flap group (n = 6), a similar muscle flap was created, but carrier solution was infused at the interface. In the bFGF group (n = 6), no muscle flap was created; instead, bFGF (3 ng/h) was infused into the external iliac artery of the ischemic limb. In the control group (n = 8), carrier solution was infused into the external iliac artery (no flap, no bFGF). After 1 week, the soleus muscle was isolated and stimulated. Maximum twitch tension, the fatigue index (force of contraction after 2 minutes of continuous stimulation/initial force of contraction), maximum recovery, and the number of limbs recovered (ie, limbs that achieve a force of contraction during the recovery period of > 75% of the force of the initial contraction at the start of continuous stimulation) were recorded. Blood vessel density (number of vessels per ***) was determined by immunostaining the soleus muscle with anti-alpha-actin antibody. RESULTS: All values were indexed to the contralateral normal limb. The flap + bFGF group showed significant improvement versus the control group in maximum twitch tension (1.07 +/- 0.13 vs 0.63 +/- 0.12, P < .05), maximum recovery (0.94 +/- 0.05 vs 0.58 +/- 0.05, P < .05), and the number of limbs recovered (5/5 vs 0/6, P < .05). This improved function correlated with increased vessel density (flap + bFGF group, 1.44 +/- 0.11 vs control group, 0.72 +/- 0.01, P < .05). CONCLUSION: Reperfusion of an ischemic limb with a well-vascularized muscle flap and local bFGF infusion promoted increased blood vessel density in distal ischemic muscle. This increased vascularity was associated with restoration of otherwise impaired muscle function. Improved function occurred rapidly (1 week). A transposed muscle flap provided a functional blood supply to the site of maximum ischemia; this could be used to salvage otherwise nonreconstructible ischemic limbs.     

Dynamic reconstruction of large abdominal defects using a free rectus femoris musculocutaneous flap with normal motor function

Reconstruction of large abdominal wall defects with conventional reconstruction including the component separation technique is difficult because of strong transverse tension and loss or weakness of the rectus abdominis muscle. To overcome this problem, dynamic reconstruction of the abdominal wall using a free innervated rectus femoris musculocutaneous flap was performed for large defects with separation of the bilateral rectus abdominis muscles. The intact motor nerve of the rectus femoris muscle was transferred without transection, and only the pedicle vessels were anastomosed to the omental vessels. Four and one-half years after surgery, the rectus femoris muscle had voluntary strong muscle contraction and there was no abdominal protrusion, herniation, or donor morbidity. This new method with dynamic function can replace conventional techniques for large abdominal defects without rectus muscle function.     

Single fibers of skeletal muscle as a novel graft for cell transplantation to the heart

OBJECTIVE: Skeletal myoblast transplantation is a promising alternative to treat heart failure. A single fiber, the minimal functional unit of skeletal muscle, retains skeletal myoblasts beneath the basal lamina. When surrounding muscle is injured, myoblasts migrate from the fiber into the damaged area to regenerate muscle. We hypothesized that such isolated fibers could be used as an efficient vehicle to deliver myoblasts into damaged myocardium, resulting in improved cardiac function. METHODS: Living single fibers of rat skeletal muscle were isolated, and their behavior was characterized in vitro. Single fibers were injected into the myocardium (at 4 sites, each receiving a single fiber) of rats in 2 models of heart failure induced either by means of doxorubicin administration or left coronary artery occlusion. RESULTS: Skeletal myoblasts dissociated from an isolated single fiber, proliferated, and differentiated into multinucleated myotubes in vitro. Within 3 days after grafting in vivo, original fibers provided putative myoblasts and disappeared. At 4 weeks, discrete loci consisting of several multinucleated myotubes were observed. Furthermore, single-fiber transplantation significantly improved cardiac function compared with the control treatment in either doxorubicin-treated hearts (maximum dP/dt, 4013.9 +/- 96.1 vs 3603.1 +/- 102.3 mm Hg/s; minimum dP/dt, -2313.7 +/- 75.1 vs. -2057.1 +/- 52.4 mm Hg/s) or ischemic hearts (maximum dP/dt, 3905.6 +/- 103.0 vs 3572.6 +/- 109.7 mm Hg/s; minimum dP/dt, -2336.1 +/- 69.7 vs -2106.4 +/- 74.2 mm Hg/s). CONCLUSION: Single-fiber transplantation acts as a vehicle for delivering putative skeletal myoblasts that appear to differentiate into myotubes within the myocardium. This was associated with improved function of failing hearts, suggesting its efficacy as a novel graft for cellular cardiomyoplasty.     

Phrenic nerve conduction disorder after open heart surgery--electrophysiological study

In 32 consecutive adult patients undergoing heart surgery, the induced diaphragmatic muscle action potential was measured. Phrenic nerve conduction disorder was defined as disappearance of muscle action potential (Edi) and conduction time (CT). Phrenic nerve conduction disorder was observed in 10 patients (31%); 8 patients on the left side and 2 patients on both sides. In non-conduction disorder group (22 patients), Edi and CT were measured. Edi of the right side decreased significantly from preoperative value of 705 +/- 318 microV to 445 +/- 285 microV at 1-3 days after operation (stage I) and to 559 +/- 314 microV at 7-10 days after operation (stage II) (p less than 0.05). CT of the right side prolonged significantly from 7.1 +/- 0.7 msec before operation to 7.44 +/- 0.97 msec at postoperative stage I and to 7.40 +/- 0.21 msec at postoperative stage II (p less than 0.05). For the left phrenic nerve, Edi showed significant (p less than 0.05) decrease from 803 +/- 338 microV before operation to 429 +/- 251 microV at the postoperative stage I and 620 +/- 350 microV at the postoperative stage II. In the conduction disorder group, incidence of atelectasis, diaphragm elevation and pleural effusion as documented by chest roentgenographic findings were higher than those of non-conduction disorder group (p less than 0.01). Moreover, the lowest temperature of the myocardium during operation was significantly (p less than 0.05) lower for conduction disorder group as compared to non-conduction disorder group. We believed that it is necessary to develop a innovative method for preventing the phrenic nerve from cold injury.     

Skeletal muscle ventricle used for right ventricle assistance

There are a number of advantages in using an electrically stimulated autogenous skeletal muscle to construct an auxiliary ventricle to assist a heart. The purpose of this study was to determine the feasibility of biological right ventricular assistance using long-term electrically stimulated skeletal muscle grafts. In fourteen dogs, the latissimus dorsi muscles and the right thoracodorsal nerves were exposed and unipolar pulse generator was implanted. The initial rate of 70 cycle/min. was increased to a rate of 100 cycle/min. Six or 12 months later, the latissimus dorsi was wrapped around a latex pouch equipped with inflow and outflow valved conduit (skeletal muscle ventricles; SMVs). The SMVs were connected to main pulmonary artery and right atrium. These SMVs were stimulated 20 Hz for 200 msec at a fixed rate of 90 cycle/min, the hemodynamic changes with or without skeletal muscle ventricular assistance (SMVA) were measured. In as animals the circulation failed after total right ventricular bypass without SMVA. But the SMVA increased aortic blood pressure, aortic blood flow, left atrial pressure and peak pulmonary pressure significantly. There was a linear correlation between central venous pressure and skeletal muscle ventricular assist flow. Histologic studies showed the conditioned muscles had a greater percentage of slow-twitch, fatigue resistant fibers on ATPase stain. These results suggested the long-term electrical conditioning skeletal muscle could be possible to use SMVs in humans to provide support in children with some types of congenital heart disease.     

A treatment of intractable sternal osteomyelitis--significant use of pedicle muscular flaps

In recent years, the greater omentum of pedicle muscular flap has been used to treat chest wall infection and Sternal Osteomyelitis following cardiac or respiratory surgery. In Japan, however, there has been an increasing number of cases in which neither the greater omentum Nor the rectus muscle can be used due to the comparatively young age of the patient. There are also many cases undergoing abdominal surgery for malignant tumor and bypass surgery of the coronary artery in which the internal thoracic artery (ITA) and gastroepiploic artery (GEA) are used. We studied three such cases; a case of coronary aortic bypass graft (CABG) where ITA from both the right and left sides were used following stomach resection; a case in which CABG and gallbladder resection were carried out simultaneously; and a case of sternal osteomyelitis is years following surgery for ventricular septal defect. All three cases had undergone reconstructive surgery using the pectoralis major muscle or a pedicle muscular flap from the latissimus dorsi muscle. It is estimated that cases of CABG using both the right and left sides of ITA and GEA, cases of the elderly as well as cases of children will continue to increase. Consequently, cases of sternal osteomyelitis in which neither the omentum nor rectus muscle can be used will also increase. Therefore, it is considered that treatment using pedicle muscular flaps from the breast or dorsal area may be very effective. Herein, we report on the choice of treatment and its results.     

Skeletal muscle ventricles as left atrial-aortic pumps: short-term studies.

In 5 dogs, skeletal muscle ventricles (SMVs) were constructed from the latissimus dorsi muscle and placed in the left hemithorax. After a 3-week vascular delay period, SMVs were electrically preconditioned with 2-Hz stimulation for 6 weeks. At a second operation, SMVs were connected between the left atrium and thoracic aorta by afferent and efferent aortic root homografts, and stimulated to contract in a 1:2 diastolic mode. At a mean left atrial pressure of 12.4 +/- 1.3 mm Hg and a burst stimulation frequency of 33 Hz, SMV stroke volume was initially 43% of that of the native left ventricle, achieving a flow equivalent to 21% of cardiac output (194 +/- 38 versus 902 +/- 85 mL/min). At 50-Hz stimulation, this figure rose to 27% (246 +/- 41 mL/min; p less than 0.05). Skeletal muscle ventricle power output (the product of stroke work and contraction rate) at 33 Hz was 0.016 +/- 0.003 W, increasing to 0.024 +/- 0.004 W at 50 Hz (p less than 0.05), corresponding to 14% and 22%, respectively, of left ventricular power output (0.11 +/- 0.012 W). After 4 hours of continuous pumping, four of the SMVs were still generating flows of more than 70% of starting values and more than 60% of initial power output. This study demonstrates that SMVs can function in the systemic circulation at physiologic left atrial preloads.     

Effects of dynamic cardiomyoplasty on left ventricular performance and myocardial mechanics in dilated cardiomyopathy

We tested the hypothesis that dynamic cardiomyoplasty produces beneficial changes in the functional mechanics of the dilated, failing left ventricle. Chronic dilated cardiomyopathy was induced in seven mongrel dogs by rapid ventricular pacing (260 beats/min) for 3 to 4 weeks. After completion of the induction period, dynamic cardiomyoplasty was performed with the left latissimus dorsi muscle, paced synchronously with the R waves of the electrocardiogram (Medtronic SP1005). Instruments included an aortic flow probe, a left ventricular Millar pressure catheter, and piezoelectric sonomicrometric crystals on the left ventricle for measurements of wall thickness and minor and major axis dimensions. Data were obtained with the stimulator off and on. Statistical comparisons were made with Student's t test for paired data. Dynamic cardiomyoplasty increased the cardiac output of the failing heart (966 +/- 124 versus 1166 +/- 112 ml/min; p less than 0.01). Systolic shortening of both minor and major axis dimensions increased (3.1 +/- 0.3 versus 4.7 +/- 0.3 mm, p less than 0.01, and 4.6 +/- 0.3 versus 7.3 +/- 0.9 mm, p less than 0.05, respectively). Left ventricular end-diastolic pressure decreased by 16% (18 +/- 1 versus 15 +/- 1 mm Hg, p less than 0.01). Although skeletal muscle contraction increased the pressure development in the left ventricular chamber, mean systolic wall stress was diminished by concomitant changes in left ventricular dimensions (116,144 +/- 11,530 versus 101,268 +/- 7464 dynes/cm2, p less than 0.05). At end-systole, wall thickness increased (11.8 +/- 1.1 versus 12.7 +/- 1.1 mm, p less than 0.01), minor axis dimension decreased (51.3 +/- 1.4 versus 49.2 +/- 1.8 mm, p less than 0.01), and major axis dimension also decreased (85.6 +/- 3.3 versus 79.0 +/- 2.3 mm, p less than 0.05). Our detailed evaluation of left ventricular chamber mechanics suggests that dynamic cardiomyoplasty may have a role in ameliorating the functional and mechanical derangements associated with progression of dilated cardiomyopathy both by augmenting cardiac performance and by diminishing determinants of myocardial oxygen consumption. (All values are expressed as mean +/- standard error of the mean.)     

Comparison of the effects of fetal cardiomyocyte and skeletal myoblast transplantation on postinfarction left ventricular function

OBJECTIVES: Transplantation of fetal cardiomyocytes improves function of infarcted myocardium but raises availability, immunologic, and ethical issues that justify the investigation of alternate cell types, among which skeletal myoblasts are attractive candidates. METHODS: Myocardial infarction was created in rats by means of coronary artery ligation. One week later, the animals were reoperated on and intramyocardially injected with culture growth medium alone (controls, n = 15), fetal cardiomyocytes (5 x 10(6) cells, n = 11), or neonatal skeletal myoblasts (5 x 10(6) cells, n = 16). The injections consisted of a 150-microL volume and were made in the core of the infarct, and the animals were immunosuppressed. Left ventricular function was assessed by echocardiography immediately before transplantation and 1 month thereafter. Myoblast-transplanted hearts were then immunohistologically processed for the expression of skeletal muscle-specific embryonic myosin heavy chain and cardiac-specific connexin 43. RESULTS: The left ventricular ejection fraction markedly increased in the fetal and myoblast groups from 39.3% +/- 3.9% to 45% +/- 3.4% (P =.086) and from 40.4% +/- 3.6% to 47.3% +/- 4.4% (P =.034), respectively, whereas it decreased in untreated animals from 40.6% +/- 4% to 36.7% +/- 2.7%. Transplanted myoblasts could be identified in all animals by the positive staining for skeletal muscle myosin. Conversely, clusters of connexin 43 were not observed on these skeletal muscle cells. CONCLUSIONS: These results support the hypothesis that skeletal myoblasts are as effective as fetal cardiomyocytes for improving postinfarction left ventricular function. The clinical relevance of these findings is based on the possibility for skeletal myoblasts to be harvested from the patient himself.