Cardiomyoplasty (CMP), a surgical treatment for heart failure, has several advantages: skeletal muscle requires no external power source; each patient serves as his/her """"""""donor;"""""""" and rejection is not a problem. CMP prevents systolic bulging and inhibits progressive ventricular enlargement. Both mechanisms probably contribute to subjective decrease in symptoms and may explain phase II clinical CMP trials, in which, progressive left ventricular (LV) enlargement was inhibited. However, experimentally and clinically, systolic augmentation of LV function by latissimus dorsi muscle (LDM) is rarely observed. This is a major problem. Our view is that CMP will not thrive as a viable approach without physiologically important large increases in LV pressure and outflow with LDM stimulation. Our goal is to achieve these large pressure and flow increases. Our approach is to systematically examine this problem by sequentially measuring the effects of different interventions. Typically, CMP studies try some intervention, and only examine the effects after LDM training. We believe that this has been a major mistake, and has actually slowed progress. Important improvements may have been missed. Our approach is to maximize the response at 2 weeks after surgery (already accomplished). Then from this foundation, obtain the best results at 1, 2, and 3 months. This grant will examine preconditioning (for revascularization) and daily rest periods (intermittent stimulation).
Our aims are for little, if any, LDM damage and a strong, yet fatigue resistant, muscle. With this muscle, LDM stimulation should increase LV pressure by 15 to 20 mmHg and stroke volume by 20 to 30 percent. We will test these interventions in 2 sections. In both, LV function will be depressed by intra-coronary microsphere injections. In preconditioning studies, vascular delay (dividing part of vascular supply prior to surgery) and/or injections of bFGF will be tested to stimulate revascularization and decrease LDM damage. Dogs will be randomly divided into control, standard CMP, CMP with vascular delay, and CMP with vascular delay plus bFGF groups. Revascularization will be assessed histologically and by measuring regional LDM blood flow and vascular growth factors. At 2 weeks, 1, 2, and 3 months, LV function will be assessed. In intermittent stimulation studies, after preconditioning, dogs will be randomly divided into continuous (24 hours/day) vs intermittent LDM stimulation groups (stimulator off 8 hrs/day). At 2 weeks, 1, 2, and 3 months, LV function will be assessed. The mechanisms will be examined by immuno-histochemical techniques and by experiments to assess LDM mechanical performance. In preliminary experiments, the results have reached our goals: 19 mmHg increases in peak LV pressure and 40 percent increases in stroke volume. These very large increases are consistent with our hypothesis and show that significant increases in LV pressure and stroke volume can occur with LDM stimulation.
| Kashem, A; Santamore, W P; Hassan, S et al. (2001) Can latissimus dorsi muscle stimulation benefit heart during training period after vascular delay? ASAIO J 47:655-61 |
| Kashem, A; Santamore, W P; Chiang, B et al. (2001) Vascular delay and intermittent stimulation: keys to successful latissimus dorsi muscle stimulation. Ann Thorac Surg 71:1866-73 |
