Effect of short pulsed nonablative infrared laser irradiation on vascular cells in vitro and neointimal hyperplasia in a rabbit balloon injury model.

BACKGROUND: Neointimal hyperplasia after PTCA is an important component of restenosis. METHODS AND RESULTS: Cultures of rabbit endothelial cells and smooth muscle cells (SMCs) were irradiated with different doses of nonablative infrared (1064-nm) radiation. Normalized viability index detected with nondestructive Alamar Blue assay and direct cell count were studied. Our experiments demonstrated dose-dependent cytostatic or cytotoxic effects of laser irradiation. We also evaluated the long-term effect of endoluminal nonablative infrared laser irradiation on neointimal hyperplasia in a rabbit balloon injury model. PTCA of both iliac arteries of 23 New Zealand White rabbits was performed. One iliac artery was subjected to intra-arterial subablative infrared irradiation via a diffuse tip fiber. The contralateral vessel served as control. The diet was supplemented with 0.25% cholesterol and 2% peanut oil for 10 days before and 60 days after PTCA. Morphometry after 60 days showed that intimal areas were 0.76+/-0.18 and 1.85+/-0.30 mm(2) in the laser and control arteries, respectively (P=2.2x10(-11)). CONCLUSIONS: We conclude that nonablative infrared laser inhibited neointimal hyperplasia after PTCA in cholesterol-fed rabbits for up to 60 days.

Cardiomyoplasty after implantation of a pacemaker and cardioverter/defibrillator.

Presently, a combination of two surgical methods improves the survival of patients with advanced ventricular dysfunction: implantable cardioverter/defibrillator implantation (which prevents sudden cardiac death) and cardiomyoplasty (which prevents further dilatation of the heart and provides additional cardiac assistance). We report the clinical course of a patient who had cardiomyoplasty after cardioverter/defibrillator implantation and pacemaker insertion. It is a rare case in which three different devices cardioverter/defibrillator, pacemaker, and cardiomyostimulator) are functioning together without crosstalk.

Skeletal muscle used as experimental cardiac assist: Russian experience.

This manuscript presents experimental data in the area of biomechanical cardiac support obtained at the Bakulev Institute for Cardiovascular Surgery in Moscow, Russia. After creation of the left ventricular aneurysm and subsequent cardiomyoplasty, active functioning of the muscle-heart complex was observed. In the late postoperative stages (3-6 months) hemodynamic parameters did not reach original preoperative values, but were satisfactory to support decreasing heart function: Cardiac index was decreased by 9.8%, the pumping coefficient of the left heart (KLH) by 24.7%, and left ventricular stroke work index (LVSWI) fell by 25%. Acute aneurysm of the left ventricle is a good model to study the effectiveness of cardiomyoplasty. Determination of parameters for stimulation of the muscle autograft showed that from the point of view of hemodynamic parameters of the muscle-heart complex, the optimal initial training schedule is a burst of seven pulses, each from 0.07 to 0.6 ms in duration, with a frequency of 30-50 Hz an amplitude of 6 V, and a burst following frequency of 15-30 per minute.

Age related skeletal muscle response to electrical stimulation.

We hypothesized that the conditioned muscles of elderly and growing organisms have different responses to electrical stimulation from that of young adult organisms. Five day old lambs, 1 year old sheep, and 8 year old elderly sheep were used for this investigation. The latissimus dorsi muscle (LDM) was partially mobilized and left in situ. Two electrodes were implanted and electrical stimulation (ES) was begun for 8 weeks; it was then stopped for 2 weeks. Biopsies were taken before ES, after 8 weeks of ES, and after the 2 week delay period. The LDM of old sheep has less fatigue resistance than the LDM of younger animals. Conditioned LDM of the lamb continued to be fatigue resistant after a 2 week delay compared with adult sheep. In all animals, lactate dehydrogenase (LDH) fraction five decreased and LDH-1 + 2 fractions increased after ES. After a 2 week delay, the data returned to baseline values only in adult animals. The percentage area occupied by mitochondria in old sheep was less after ES than in younger animals. In all animals, the mitochondrial area increased after ES and reverted to baseline values after the delay. The number of nuclei and fibers considerably increased after ES. Only in the lamb did the number of nuclei and fibers continue to be elevated after the delay. There are more changes in young skeletal muscle than in adult (1 year or 8 year old) muscle during ES, and they "remember" these properties. Elderly skeletal muscle does not convert to a fatigue resistant state as completely as adult skeletal muscle during a conventional 8 week ES protocol. It is necessary to change and prolong the ES protocol for elderly patients.

Angiogenesis in the latissimus dorsi muscle using different regimens of electrical stimulation and pharmaceutical support.

It is our contention that the prevention of ischemia-reperfusion injuries immediately after latissimus dorsi muscle (LDM) mobilization and enhancement of angiogenesis will be effective in improving cardiomyoplasty results. The investigations were performed on adult sheep. Three hours after LDM mobilization, various stages of leukocyte-endothelium interaction were revealed: leukocytes binding to the endothelium, leukocyte destruction of endothelium, and leukocytes leaving capillaries through gaps in the endothelium. Fifty-six days after mobilization various stages of necrosis were discernible. The area occupied by capillaries was 3.45 +/- 0.26% vs. 3.99 +/- 0.24% in control muscle; most of the endothelial cells exhibited morphologic degeneration. Electrical stimulation with 60 CPM actually decreased the capillary density to 2.15 +/- 0.7%, and most of the endothelial cells were damaged, with disrupted plasma membranes. Muscle subjected to 15 CPM increased the percent of capillaries to 5.01 +/- 0.56%, and endothelial cells appeared normal in ultrastructure. Pharmaceutical support prevented muscle damage and accelerated revascularization. After 56 days of autologous biological glue (ABG) application, the area occupied by capillaries was 5.57 +/- 0.24%. This increased to 8.47 +/- 0.72% when aprotinin (proteinase inhibitor) was added to ABG, and to 9.40 +/- 1.24% with pyrrolostatin (free radical scavenger). Both ABG application with aprotinin and electrical stimulation at 15 CPM prevent the LDM from postmobilization damage, and increase angiogenic potential.

Biologic glue increases capillary ingrowth after cardiomyoplasty in an ischemic cardiomyopathy model.

The authors investigated the multi-step mechanism of healing after cardiomyoplasty, focusing on the process of angiogenesis. The authors contend that enhancement of angiogenesis and prevention of ischemia-reperfusion injuries immediately after muscle mobilization will be effective in improving cardiomyoplasty results. After cardiomyoplasty, autologous biologic glue (ABG) was administered between the latissimus dorsi muscle (LDM) and myocardium. By 2 months, a new pseudo interlayer was present that bridged the gap between the LDM and myocardium. Neovascularization was visible in the form of numerous small capillaries. Marked degeneration of the LDM was noted, possibly caused by muscle ischemia-reperfusion damage after mobilization. Pockets were created of ischemic and nonischemic LDM to test for angiogenesis. One was left free of ABG (control); one received ABG only; one received ABG and pyrrolostatin. Some of the capillaries were large and had erythrocytes inside. biopsy samples showed 9.4 +/- 1.9% of the sample was occupied by blood vessels (compared with 3.6 +/- 0.7% in control muscle). These preliminary studies prove the feasibility of the authors' concept and provide evidence that angiogenesis can accelerate the healing process and provide an organic bridge between the LDM and myocardium after cardiomyoplasty.

Is it possible to perform immediate cardiac assist using untrained latissimus dorsi muscle in a work-rest regimen?

The authors investigated what contractile force (CF) could be obtained from unconditioned latissimus dorsi muscle immediately after mobilization and for the 2 week vascular period of recovery. Latissimus dorsi muscle mobilization was performed on seven adult (4 experimental and 3 control) sheep leaving only the pedicle and the peripheral muscle intact. Telectronics stimulators (Myostim 7220; Teletronics Pacing Systems, Inc, Englewood, CO) were implanted. Immediately after mobilization 11-35% of the initial CF was lost. A 30 min fatigue test was performed 1 hr after mobilization (20 g/kg preload, 10 V, 10 Hz, 15 BPM, 6 impulses per burst) using a 1 min work-1 min rest regimen. Two sheep lost 2-12% of initial CF; two increased CF by 14-24%. At the end of the fatigue test, CF consisted of 74-89% of immobilized CF. Electrical stimulation training of the muscle was then initiated with the following regimen in the experimental animals only: 15 BPM, single impulses, 5 V, 10 Hz. Every day the muscle was exercised using a work-rest regimen to mimic cardiac assist, starting with 20 min on day 2, and increasing by 2 min per day until a total of 50 min was reached on day 16. All animals were retested for CF using a 42 min fatigue test on days 6, 11, and 16. On day 6, there was no fatigue evident in the experimental group during the 42 min test. CF after testing was 59-81% (mean 67%) of initial data. In the control group (animals with no electrical stimulation training protocol), CF decreased by 11% (from 64 to 53%). On day 11, there was no fatigue evident in the experimental group; CF in all animals increased by 2-8%. On day 16, there was also no fatigue evident in the experimental group; CF increased by 0-9%. An additional 20 min of continuous contraction (15 BPM) fatigue testing was performed on the muscle without rest between the tests. No fatigue was evident at the end of testing. Light microscopic analysis of latissimus dorsi muscle biopsy specimens taken on the days of testing showed no evidence of necrotic damage. Our investigations suggest that it may be possible to start muscle transformation immediately after mobilization and use the untrained latissimus dorsi muscle for cardiac assist immediately after surgery for short periods.

Skeletal muscle of a growing organism has a greater transformation after electrical stimulation than adult skeletal muscle.

Six adult sheep and four newborn lambs (5 days old) were implanted with stimulator leads into the latissimus dorsi muscle and connected to a Myostim 7220 pacing system (Telectronics Pacing Systems, Inc., Englewood, CO). Electrical stimulation was started immediately after the operation. After 8 weeks of electrical stimulation, contractile force (CF) in adult sheep decreased to 76-81%, and to 78-82% in lambs. After 2 weeks' delay, CF in adults was 96-98%, and only 89-93% in lambs. After a 30 min intensive stress test, unconditioned control muscle lost 39% in lambs and 43% in adults. Muscle conditioned for 8 weeks lost 7-8% CF. However, after 2 weeks' delay, CF in adult muscle lost 33%, but only 12% in lambs. After cessation of electrical stimulation, the LDH-5 and LDH-1 + 2 fractions reverted to initial levels in adults, whereas in lambs, these levels continued to follow trends established during electrical stimulation. In both adults and lambs, the percent area occupied by the mitochondria increased during electrical stimulation by 6.9% in adults and 6.5% in lambs. After electrical stimulation cessation, the percent area in adults returned to baseline levels, whereas it continued to be elevated in lambs (3.3% vs 5.1%, respectively). The transformed muscle of the lamb did not revert to baseline levels after a delay period.

Force enhancement of skeletal muscle used for dynamic cardiomyoplasty and as a skeletal muscle ventricle.

Some patients with pre end-stage congestive heart disease do not receive a significant hemodynamic benefit from dynamic cardiomyoplasty because, during prolonged preoperative immobilization, their latissimus dorsi muscle (LDM) becomes extremely weak. It is the authors' hypothesis that the local administration of an anabolic steroid into an electrically stimulated LDM will produce a thicker and stronger muscle with significant resistance to fatigue. The electrical stimulation training protocol of sheep continued for 8 weeks. For localized anabolic steroid administration an osmotic pump was placed in a subcutaneous pocket and the catheter was introduced into the LDM. The contractile force of electrically stimulated and unstimulated control muscle was studied. Control data were calculated as 100% and all other data were corrected to control. After 4 weeks there was no decrease in contractile force. The change seen was from 88 to 100% with different preloads (10, 15, and 20 g/kg) and amplitudes of impulses (5 and 10 V). After 8 weeks, the LDM was more powerful than before electrical stimulation, with a change of 97-133%. Usually after 8 weeks of electrical stimulation alone, contractile force decreases to 70-75%. During a fatigue test (30 min, 100 bursts per minute, 10-25 Hz, ripple frequency, 10 V impulse amplitude) after 4 and 8 weeks of our protocol, the LDM lost only 12% of its initial force, whereas control muscle lost 40%. Thus local anabolic steroid administration makes the LDM stronger and more useful for cardiomyoplasty.

LD-PACE II: a new cardiomyostimulator for cardiac bioassist.

The LD-PACE II was designed for use in cardiomyoplasty, aortomyoplasty, and skeletal muscle ventricles. All parameters specified as programmable can be changed in a noninvasive manner (using a programming interface wand connected to a computer using the Windows 95/98 environment). Two new functions may be very useful clinically, based on experimental research. 1. Work-rest regimen. The LD-PACE II is able to deliver alternating periods of muscle contractions and rest. Work and rest periods may be programmed independently between 1 and 120 minutes in increments of 1 minute. The work-rest regimen may be useful clinically if muscle contractions are needed for cardiac assist postoperatively. 2. Night/day regimen. This feature allows for a change in the ratio of muscle contractions according to a patient's activity level. During the day the cardiosynchronization ratio may be set from 1:1 to 1:4, and during the night it may be set for 1:8 to 1:16. This allows the muscle to have a long rest period, prevents overuse, and prolongs battery life. These two new features make this cardiomyostimulator very attractive for cardiomyoplasty in particular. The addition of the work-rest and night-day regimens allow the muscle to rest for periods during the day to prevent overuse, subsequent damage, and potential atrophy.

LD Pace II, an easily programmable device for cardiomyoplasty.

The efficacy of programmable devices depends heavily on being able to select parameter values matched to the individual patient's needs. In many cases, physicians fail to make use of all of the features of a device because of programming complexities. This paper presents a new cardiomyostimulator, "LD Pace II", emphasising in particular its novel features and the steps taken to make the behaviour of the device easy for the physician to program.

Angiogenesis in a patient with ischemic limb induced by intramuscular injection of vascular endothelial growth factor and fibrin platform.

Direct revascularization of critical ischemia of the limb is often unsuccessful due to the anatomic extent and distribution of arterial occlusive disease, and no pharmacologic treatment has proved effective in treating this condition. Patients with ischemic limb may eventually require amputation and may develop serious morbidity and mortality. The goal of limb salvage in these patients has stimulated research into alternative treatment methods, including angiogenesis. Attempts have been made to apply growth factors directly or to encode DNA for such factors, but it is unknown whether these factors remain at the target site long enough to be effective. We report our strategy of using vascular endothelial growth factor in a fibrin network, which enables the sustained release of biologic material at the target site.

[Electrocardiographic diagnosis of patent ductus atrio-ventricularis]. / Elektrokardiograficheskaia diagnostika otkrytogo atrio-ventrikuliarnogo kanala

The paper deals with the diagnosis of defective development of the patent ductus atrioventricularis. Electrocardiographic changes in 81 patients with firmly established hemodynamic form of the patent ductus atrioventricularis, ascertained during surgery and catheterization, are summarized. Characteristic electrocardiographic signs of the defect distinguishing it from other congenital diseases and differential-diagnostic symptoms of diverse anatomo-hemodynamic forms of the patent ductus atrioventricularis were educed.

[Electro- and phonocardiographic changes in cases of a common arterial trunk]. / Elektro- i fonokardiograficheskie izmeneniia pri obshchem arterial'nom stvole

Analysing the data of the examination of 27 patients with a common arterial duct the authors studied the phono- and electrocardiographic changes observed in this cardiac defect. The probable phono- and electrocardiographic signs of this pathology are described the criteria that permit to suspect the presence of a common arterial duct are presented.

[Study of hemodynamics after creation of a new experimental outflow tract for the left heart ventricle]. / Izuchenie gemodinamiki posle sozdaniia v éksperimente novogo vyvodnogo trakta iz levogo zheludochka serdtsa.

Experimental analysis was made of hemodynamic changes occurring in the left heart and systemic circulation after making an aorto-left-ventricular shunt while simulating the complete obstruction of an outflow segment in the left ventricle. The hemodynamics of the left cardiac cavities in a "new operation" was studied. Analysis of the recording of pressure curves in the aorta, large arteries, and left ventricle, of electromagnetic flowmetric, echo-, and Doppler cardiographic findings suggested good results of the operations in the periods up to 12 months. The proposed model of an experimentally induced artificial aorto-left-ventricular shunt with conduit allows one to test and study the functional state of various types of prosthetic valves (biological and artificial) in long periods after surgery.

[Construction of left ventricle-aorta conduits (review of the literature)]. / Konstruktsii levozheludochkovo-aortal'nykh konduitov. (Obzor literatury).

The development prospectives of the design problem for extracardial conduits, which lies in creation of different sizes series of conduits design for left and right part of the heart relating to the age of the patient, type of obstruction lesion and anatomic peculiarities of its heart is discussed.

[Hydrodynamic criteria in the choice of surgical tactics in implanting pulmonary artery trunk prosthesis]. / Gidrodinamicheskie kriterii vybora khirurgicheskoi taktiki pri implantatsii proteza stvola legochnoi arterii.

The paper is concerned with the present-day problem of modern medicine, namely with surgical correction of the diseases of the initial part of the pulmonary circulation. The authors suggest hemohydrodynamic simulation of the right heart complicated by extracardial conduit. The simulation was performed at the high theoretical, practical and methodological level to obtain highly significant information which is likely to have paramount importance for clinical practice.