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Notes: CHEKANOV, V., et al.: Transplantation of Autologous Endothelial Cells Induces Angiogenesis. This study examined the feasibility and efficacy of autologous endothelial cell (EC) transplantation using a fibrin matrix in the ischemic myocardium of sheep. Four weeks after placing an ameroid constrictor in the circumflex artery of 12 adult sheep, four animals (EC group) were subjected to EC transplantation. In four others (saline [SAL] group) saline with added inactivated cells was injected and four animals served as controls. Eight weeks after treatment the animals were sacrificed to assess histology and ultrastructure. Eight weeks after injection, ventricular function was markedly improved in the EC transplant group, but had deteriorated in the SAL and control groups. Myocardial blood flow was also increased in the EC group. Histology and electron microscopy revealed extensive neovascularization after EC transplantation and improved myocardial appearance. Heterotopic transplantation of EC within a fibrin matrix enhances neovascularization, increases myocardial blood flow, and improves left ventricular function. (PACE 2003; 26[Pt. II]:496–499)

Notes: Abstract Local stimulation of angiogenesis is a new approach for the treatment of critical limb ischemia. Our investigation tested intramuscular (IM) injection of a modified fibrin meshwork in a rabbit model. Methods: The left external iliac and femoral arteries were excised in 24 rabbits that were divided into four groups: control; IM saline injection; fibrin meshwork plus low dose (2.5 mg) fibrinogen IM; fibrin meshwork plus high-dose (5.0 mg) fibrinogen IM. Angiography was performed before surgery, immediately after surgery, and one month postoperatively. Lower limb-calf blood pressure was measured immediately after surgery and at postoperative days 10, 20, and 30. On day 30, conventional indirect immunostaining was performed to determine the percentage of the area occupied by capillaries. Results: Immediately after surgery, in all four groups, the number of contract-opacified arteries (COA) crossing a specific segment of a grid decreased from 5.3 ± 1.3 to 3.2 ± 1.0 (p 〈 0.05) ; the number of grid intersections decreased from 30.2 ± 6.5 to 19.3 ± 4.8 (p 〈 0.05) ; and the total number of grids with COA decreased from 18.3 ± 3.8 to 12.2 ± 2.5 (p 〈 0.05) . One month after surgery, in the control group, these parameters were 6.2 ± 1.1, 33.2 ± 5.7 and 20.3 ± 1.5 , respectively; in the saline-treated group, these parameters were 6.1 ± 0.8, 28.3 ± 6.9 and 19.8 ± 1.1 , respectively ( p 〉 0.05 versus control and versus baseline data). When fibrin containing 5.0 mg fibrinogen was used, these parameters increased to 8.5 ± 0.9, 48.3 ± 5.1 , and 27.1 ± 0.9 , respectively ( p 〈 0.001 versus immediately after surgery and p 〈 0.05 versus control). In all four series, no Doppler flow signal was detected from the posterior tibial artery by day 10. By day 30, the lower limb-calf blood pressure ratio had improved in all four series, but was significantly improved in only the two groups treated with fibrin sealant ( 0.3 ± 0.05 control; 0.3 ± 0.08 saline; 0.6 ± 0.06 fibrinogen 2.5; 0.7 ± 0.05 fibrinogen 5.0). Conclusion: Intramuscular injection of a fibrin meshwork considerably increased angiogenesis in the severely ischemic hind limb and may be strongly recommended for clinical use in patients with limb-threatening ischemia.(J Card Surg 2002;17:502-511)

Notes: Abstract Background: In our previous investigations we showed that electrical impulses (EI) can prevent the development of atherosclerosis if they began simultaneously with high cholesterol diet (HCD) or in the early stages of atherosclerosis (after three weeks of HCD only). In this investigation we demonstrated the slow progression or elimination of atherosclerosis by low-frequency EI in case of moderate atherosclerosis (after eight weeks of HCD). Methods: Series I rabbits (control group) were fed HCD for eight weeks. Series II rabbits were fed HCD for eight weeks and were then switched to normal diet for eight weeks (no EI). Series III rabbits were fed HCD for eight weeks and then switched to a normal diet with simultaneous EI (applied near the abdominal aorta) for eight weeks (3 V, 30 single impulses per minute, 24 hours/day). After euthanization, the level of atherosclerosis, percentage of surface area involved in the atherosclerosis process, and an atherosclerosis score were calculated in the aortic arch, thoracic and abdominal aorta. Results: Statistically significant differences were seen in the level of atherosclerosis in the abdominal aorta between series III animals (0.4 ± 0.2) and the other two groups: 1.5 ± 0.4 in series I (HCD only), 1.2 ± 0.3 in series II (HCD then normal diet). Gross examination of the surface also revealed statistically significant differences (p 〈 0.05) in the percentage of atherosclerosis between the control series I (30.1 ± 4.1%) and series II (21.3 ± 3.6%), compared with series III (5.5 ± 5.4%). In addition, the atherosclerosis score was also significantly different: 45.8 ± 3.9 in series I, 25.2 ± 6.9 in series II, and 2.2 ± 2.0 in series III (p 〈 0.05). Conclusion: Our study showed that, when applied near the abdominal aorta, low-frequency electrical impulses decrease atherosclerotic deposition in the abdominal aorta. (J Card Surg 2003; 18:47-58)

Notes: Abstract Still a controversial procedure, cardiomyoplasty (CMP) improves the failing heart's ability to contract by using a latissimus dorsi muscle (LDM), but to date, hemodynamic results correlate poorly with clinical improvement. The following two causes for apprehension bar attempting to change the conventional electrical stimulation (ES) protocol to improve CMP results: (1) fear of beginning ES for LDM-assisted contraction immediately postmobilization and CMP and (2) fear of stopping or slowing ES during sleep periods. Methods: In ten different experimental series, I used animal models of CMP to determine how to apply ES to newly mobilized LDM, how to begin partial cardiac assist immediately post-CMP, and how to suspend ES for 12 hours daily. Results: From my experimental series I noted the following three results. (1) Different ES regimens applied 1 hour postmobilization changed the contractile force (CF). After a 30-minute fatigue test, CF decreased by 34%± 3% with continuous ES at 30 contractions per minute (cpm), by 23%± 2% with continuous ES at 15 cpm, by 25%± 5% with ES in a work-rest regimen at 30 cpm, and by 8%± 3% with ES in a work-rest regimen at 15 cpm. (2) Imitation of partial cardiac assist immediately postmobilization slightly decreased CF. Sixteen days postmobilization, during a 30-minute fatigue test in animals in which ES had been started immediately after mobilization, CF decreased by only 6%± 3% and did not change when ES was combined with imitation of cardiac assist for 30 minutes twice daily (work-rest regimen). (3) ES cessation for 24 hours daily or 12 hours daily in CMP model created no difference in ejection fraction (EF) with ES (54%± 4% vs 53%± 5%, respectively (or in left ventricular end-diastolic volume (LVEDV, 234.3 ml ± 1.0 ml vs 24.8 mL ± 0.6 mL, respectively) or in LV end-systolic volume (LVESV; 12.1 mL ± 0.7 mL vs 12.8 mL ± 0.7 mL, respectively). Conclusion: For improving angiographic potential in the LDM, ES can be started safely immediately post-CMP at 15 cpm (a 1:4 or 1:5 regimen) and single impulses per burst. For partial cardiac assist and for improving LDM performance, cardiac assist can be used for 30 minutes twice daily immediately post-CMP. To rest the muscle and save it from overuse, muscle contraction can be either stopped or slowed down during hours of sleep.

Notes: Abstract We investigated the possibility of preventing further aggravation of muscle ischemia and necrosis in newly mobilized, unconditioned latissimus dorsi muscle (LDM) by utilizing short increments of stimulation with intervening rest periods. Adult St. Croix sheep (N = 12) weighing 30 ± 8 kg were used in this study. Fatigue tests (30 min) using different stimulation regimens before and after LDM mobilization were performed on all animals; the length of time to return to baseline levels was also measured. Our investigation yielded results that contradict the conventional wisdom that any electrical stimulation damages newly mobilized LDM and will cause a considerable decrease in contractile force (CF). Stimulation regimens using continuous contractions at 30 and 60 contractions per minute (CPM) for 30 minutes were damaging to the LDM. CF also dropped significantly and returned slowly to baseline values: at 60 CPM, CF dropped to 50 ± 4% and did not return to baseline even after 90 minutes of rest; at 30 CPM, CF dropped to 61 ± 4% and baseline was restored after 80 minutes of rest. Electrical stimulation using continuous contractions at a slower rate (15 CPM) was tolerable, although a 23% decrease in CF was noted (p 〈 0.05 when compared to 60 CPM). These results did not satisfy us that such a regimen would be useful for cardiac assistance immediately after cardiomyoplasty. The work-rest regimen at 30 CPM also gave poor results: CF decreased to 75 ± 2% and baseline was restored after 80 minutes of rest. Promising results were seen when utilizing a work-rest regimen at 15 CPM. The newly mobilized LDM showed no visible signs of fatigue: CF decreased minimally to 92 ± 3% (p 〈 0.05 when compared to 30 CPM), and light microscopic analysis of biopsies revealed no morphological damage exceeding that typically seen after subtotal mobilization. Such results open avenues for future investigations: beginning electrical stimulation immediately after cardiomyoplasty (using a single impulse and a slow rate of contraction); decreasing the length of time necessary to obtain full cardiac assistance; and beginning partial cardiac assistance immediately after cardiomyoplasty (if needed) for approximately 30 minutes several times a day.

Notes: Abstract In adult organisms, when stimulation of skeletal muscle is stopped, all changes revert to control after 10–14 days. This is the reason that training of the skeletal muscle before cardiomyoplasty is not done. We hypothesized that the muscle of a growing organism would not revert during a delay. Four lambs received 8 weeks of electrical stimulation of the left latissimus dorsi muscle (LDM) with the right LDM as control. Contractility force and positive and negative dF/dt were measured after 8 weeks conditioning, 2 weeks delay, and control. Conditioned muscle during a 30-minute fatigue test had decreased contractile force on an average of 7±2%; control muscle had decreased contractile force on an average of 39±4%; and after 2 weeks delay, there was a decrease in the contractile force of 12±2%. A stronger fatigue test was performed after 10 minutes of rest. Conditioned muscle lost an average of 15±5% of their contractile force, 16±2% positive dF/dt, and 14±2% negative dF/dt. Control muscle lost 40±3%, 39±4%, and 42±5%, respectively. After 2 weeks delay, previously conditioned muscle showed the following decreases: contractile force 21±3%, positive dF/dt 19±3%, and negative dF/dt 16±3%. Skeletal muscle biopsies were also taken and levels of lactate dehydrogenase (LDH) fractions were measured. LDH fractions one and two (LDH-1 + 2) after 8 weeks conditioning consisted of 6.7±1.9% (p〈0.05 vs control) of total LDH, 7.2±1.5% (p〈0.05 vs control) after 2 weeks delay, and 2.5±0.9% in control muscle. LDH-5 levels decreased to 77±8%, 68±3%, and 91±5%, respectively. Percent of mitochondrial area on conditioned muscle increased and remained elevated after the delay. There was good correlation between fatigue resistance in conditioned and delay muscles with decreasing total units LDH, decreasing LDH-5, and increasing LDH-1 + 2 levels (compared with control muscle). Contractile force, LDH, and mitochondrial data in the delay muscle more closely resemble conditioned muscle than control. This may be very useful for clinical congenital heart surgery.