Race L. Kao

Right latissimus dorsi cardiomyoplasty for left ventricular failure

Recent experimental studies have shown that cardiomyoplasty using the right latissimus dorsi provides excellent hemodynamic augmentation. Based on these experimental findings, this procedure was performed in a 40-year-old man with a dilated cardiomyopathy after a large myocardial infarction. The patient tolerated the procedure well and has had marked functional improvement. Examination 6 months after operation demonstrated decreases in right atrial pressure, pulmonary capillary wedge pressure, and left ventricular end-diastolic volume. In addition, increases were noted in cardiac output, stroke volume, left ventricular stroke-work, right ventricular ejection fraction, and left ventricular ejection fraction. Because of this promising clinical result, we have started a series of right latissimus dorsi cardiomyoplasties for left ventricular failure.

Bilateral latissimus dorsi cardiomyoplasty

This study was undertaken to test the hypothesis that a bilateral latissimus dorsi cardiomyoplasty provides greater hemodynamic augmentation than a unilateral procedure. Two types of bilateral procedure and a left posterior cardiomyoplasty were tested in each of 8 mongrel dogs. R-wave synchronous muscle pacing was achieved with a programmable burst stimulator. Hemodynamic variables of stimulated beats were compared with those of a nonstimulated baseline using paired t tests. The effects of a double anterior muscle wrap were equal to a right anterior/left posterior configuration. Therefore, the data on the two types of bilateral procedure were combined and compared with the left wrap. Stimulation of the bilateral cardiomyoplasty resulted in significant increases in right ventricular pressure (44 +/- 3.1 versus 26 +/- 1.8), first derivative of right ventricular pressure (595 +/- 117 versus 196 +/- 14), pulmonary artery pressure (34 +/- 1.9 versus 23 +/- 1.6), left ventricular pressure (90 +/- 5.9 versus 69 +/- 5.3), first derivative of left ventricular pressure (1454 +/- 141 versus 1072 +/- 107), aortic pressure (80 +/- 5.4 versus 67 +/- 4.9), and peak aortic flow (9.4 +/- 1.1 versus 7.7 +/- 0.8) (p less than 0.05). Significant increases in all of these variables also occurred with stimulation of the left cardiomyoplasty, but the increases in right ventricular pressure, first derivative of right ventricular pressure, pulmonary artery pressure, and aortic pressure were larger for the bilateral than the left cardiomyoplasty. The bilateral and the left procedure can each augment systolic ventricular function. The bilateral procedure appears to have greater effects, especially on right ventricular function.

Fatigue resistant muscle with preserved force and mass for cardiac assist.

Sheep under general anesthesia had their left and right latissimus dorsi muscles mobilized for paraneuroelectrode and pulse generator implantation. After a 10‐day recovery period, the left‐side muscles were stimulated with a gradually increasing duration and rate over 3 months. At 4 months after operation, the tendinous end of each latissimus dorsi muscle was freed from its humeral insertion and attached to a strain gauge force transducer. Both left and right latissimus dorsi muscles, from each animal, were stimulated to contract for 2 hours for the fatigue study before being isolated, trimmed, and weighed. Frozen tissue biopsies were used to determine creatine phosphate, adenosine triphosphate, lactate, and glycogen content and muscle myosine ATPase, and succinate dehydrogenase activities. The arterial diameter in the conditioned muscle was 30% larger than that of the control muscle and had a 40% higher blood flow at rest. A three‐ to fivefold increase in blood flow during the fatigue test was observed. The force decreased 47% for the conditioned muscle and 91% for the control muscle. The mass and cross‐sectional area of conditioned and unconditioned muscles were similar. Electric conditionIng increased fatigue resistant fiber content from 33% to 92%, as evidenced by myosine ATPase activity. During the early phase of the fatigue test, higher glucose uptake but significantly lower lactate production were found for the conditioned muscle. This study indicates that it is possible to produce fatigue resistant muscle with preserved force and mass. In addition to skeletal muscle fiber transformation, metabolic adaptations appear to be important factors for fatigue resistance of skeletal muscle.

Isolated biventricular working rat heart preparation

The isolated perfused heart from small animals has been used extensively for hemodynamic and metabolic studies. The left working heart preparation proved superior to the Langendorff model for functional evaluations but has not allowed study of right heart function. A simple and inexpensive biventricular working heart preparation has been developed by modifying the left working rat heart model. Under general anesthesia the heart was removed surgically leaving sufficient vessels attached to it. Cannulation of the aorta, left atrium, right atrium, and pulmonary artery was completed in 10 minutes. A pressurized compliance chamber allowed rapid and reliable regulation of aortic impedance. For the 7 hearts that were subjected to 3-hour biventricular perfusion (their end points expressed as percent of their initial values), the aortic output (95% +/- 3%), pulmonary flow (88% +/- 9%), mean aortic pressure (109% +/- 5%), mean pulmonary pressure (100% +/- 2%), heart rate (106% +/- 8%), myocardial adenosine triphosphate level (85% +/- 8%), and creatine phosphate level (89% +/- 4%) were all maintained at physiologic levels. For the 11 hearts that were converted from left working heart preparation to biventricular working mode, significant improvement in stroke volume, aortic and cardiac output, and pressure development were observed. Experimental results indicate that the biventricular working model for isolated perfused rat hearts is superior to the left working preparation for studying the function of the total heart. Further study of the biventricular perfused working rat heart appears warranted.

Resuscitation of injured myocardium with adenosine and biventricular assist

Recovery of energy metabolism and contractility in stunned myocardium requires several days, even when mechanical circulatory support is employed. This double-blind study was undertaken to determine if myocardial recovery could be accelerated by intracoronary infusion of adenosine during reperfusion. Ten mongrel dogs were subjected to 45 minutes of global normothermic ischemia while on biventricular support with centrifugal pumps. During initial reperfusion, 20 minutes later, and at hourly intervals for 4 hours, dogs received 100 mL/min of unaltered blood or blood enriched with adenosine (0.2 mmol/L) into the coronary arteries for 5 minutes. Circulatory support was discontinued after 4 hours or sooner if the first time derivative of left ventricular pressure exceeded 2,000 mm Hg/s. Animals that received adenosine were weaned sooner (72 +/- 27 versus 216 +/- 54 minutes) and had higher systolic pressure (110 +/- 21 versus 57 +/- 36 mm Hg), lower left ventricular end-diastolic pressure (23.8 +/- 4.8 versus 34.0 +/- 7.2 mm Hg), and higher first time derivative of left ventricular pressure (3,407 +/- 812 versus 1,510 +/- 1376 mm Hg/s) than controls at the completion of the experiment (p less than 0.05). Final myocardium adenosine triphosphate levels were higher in the adenosine group (20.0 +/- 3.6 versus 14.2 +/- 4.0 mumol/g protein; p less than 0.05). Determination of infusion and coronary sinus blood concentrations demonstrated a 90% uptake of adenosine. All adenosine animals survived, but 2 of 5 control animals died within 1 hour of weaning. Reperfusion with adenosine-enriched blood accelerated recovery of ischemic myocardium and should be considered for patients requiring mechanical circulatory support after a heart operation.

Cellular Cardiomyoplasty Using Skeletal Muscle Stem Cells

Skeletal muscle satellite cells (myoblasts) are the primary stem cells of skeletal muscle which contribute to growth, maintenance, and repair of the muscle. Satellite cells offer several advantages for cellular cardiomyoplasty: can be easily obtained without affecting ones function, vastly proliferated in culture, have high resistance to ischemic and hypoxic conditions, no identified risk for tumor generation, and more commitment to myogenic differentiation. Cellular cardiomyoplasty is a developing new therapy that use stem cells or progenitor cells for injured heart to improve cardiac function and mitigate heart failure. Since we first published cellular cardiomyoplasty in 1989, this procedure became one of the innovative methods to treat damaged myocardium other than heart transplantation. A significant improvement in cardiac function, metabolism, and perfusion is generally observed in experimental and clinical studies, but the improvement is mild and incomplete. Although safety, feasibility, and efficacy have been well documented for the procedure, the beneficial mechanisms remain unclear and optimization of the procedure requires further study. This paper briefly reviews the skeletal muscle stem cells used for cellular cardiomyoplasty and their clinical outcomes with possible improvements in future studies.

Autologous Stem Cells and Transmyocardial Laser Revascularization for Ischemic Heart

Myogenic stem cells and transmyocardial laser revascularization (TMR) have been used independently to treat patients with coronary heart disease. We assessed the hypothesis that implantation of autologous myogenic stem cells dur- ing TMR will augment ventricular function by new muscle formation and will improve perfusion by neovascularization. Thirty two mini-swine were subjected to myocardial ischemia by applying an ameroid constrictor on the left anterior de- scending coronary artery. Pigs were randomly assigned into four equal size groups of Ischemia, Ischemia+TMR, Ische- mia+Cell and Ischemia+TMR+Cell. Myocardial blood flow was estimated using colored microspheres, 12 lead ECG was recorded, and ventricular function was determined by the hemodynamic system coupled with sonomicrometry. Three weeks after ameroid constrictor application, ECG changes indicated myocardial infarction of left anterior and apical areas in all pigs. Significant decreases (P<.01) in systolic % wall thickening fraction and % segmental shortening fraction were also observed. At 9 weeks after initial surgery a dramatic decrease (P<.01) in scar areas, a marked improvement (P<.05) in myocardial perfusion and significant better hemodynamic functions were observed for cell implantation groups. Labeled muscle tissue was observed at the implantation sites. Systolic % wall thickening fraction and % segmental shortening fraction were also clearly improved in the cell implanted groups. Stem cells alone or TMR+Cell significantly reduced scar areas, developed new muscle tissue, improved myocardial perfusion, and enhanced contractile function after myocardial infarction.

Laser-assisted vascular anastomosis

The milliwatt CO2 laser and a thermal activated binding compound (20% serum albumin) were used for microvascular anastomoses. Under general anesthesia, the femoral arteries (0.7 to 1.0 mm diameter) of 6 rats were isolated. After the left femoral artery in each rat was clamped and transected, the vessel was held together with 3 equidistant 10-0 Xomed sutures. The cut edges were coated 3 to 4 times with the albumin solution and sealed with the CO2 laser (power density = 120 W/cm2). The binding compound solidified to a translucent tensile substance which supported the anastomosis until self healing and repair were achieved. The right femoral artery was used as sham operated control. Complete hemostasis and patency were observed in every case immediately and at 1, 3, and 6 months following surgery. The binding compound absorbed most of the laser energy thus minimizing thermal injury to the underlying tissue. Mongrel dogs weighing 28 to 33 kg were anesthetized and prepared for sterile surgical procedures. In 5 dogs, the femoral and jugular veins were exposed, transected, and anastomosed using a CO2 laser (Sharplan 1040) with the binding compound. In another 12 dogs, cephalic veins were isolated and used for aortocoronary artery bypass procedures. The Sharplan 1040 CO2 laser and 20% albumin solution were utilized to complete the coronary anastomoses in 6 dogs, and 6 dogs were used as controls by suturing the vessels. Again, hemostasis, patency, and minimal tissue damage were observed immediately and 6 weeks after the procedures. Improved surgical results, reduced operating time, minimized tissue damage, and enhanced anastomotic integrity are the advantages of laser assisted vascular anastomosis with a thermal activated binding compound.