hERGAPDbase: a database documenting hERG channel inhibitory potentials and APD-prolongation activities of chemical compounds.

Drug-induced QT interval prolongation is one of the most common reasons for the withdrawal of drugs from the market. In the past decade, at least nine drugs, i.e. terfenadine, astemizole, grepafloxacin, terodiline, droperidol, lidoflazine, sertindole, levomethadyl and cisapride, have been removed from the market or their use has been severely restricted because of drug-induced QT interval prolongation. Therefore, this irregularity is a major safety concern in the case of drugs submitted for regulatory approval. The most common mechanism of drug-induced QT interval prolongation may be drug-related inhibition of the human ether-á-go-go-related gene (hERG) channel, which subsequently results in prolongation of the cardiac action potential duration (APD). hERGAPDbase is a database of electrophysiological experimental data documenting potential hERG channel inhibitory actions and the APD-prolongation activities of chemical compounds. All data entries are manually collected from scientific papers and curated by a person. With hERGAPDbase, we aim to provide useful information for chemical and pharmacological scientists and enable easy access to electrophysiological experimental data on chemical compounds. Database URL: http://www.grt.kyushu-u.ac.jp/hergapdbase/.

Muscular ventricular septal defect visualized as nonreversible perfusion abnormality on myocardial perfusion SPECT and confirmed on cardiac computed tomography angiography images.

A 47-year-old woman with no history of CAD presented with an episode of left-sided atypical chest pain. Her work-up was negative for acute MI. She underwent a myocardial perfusion Tc-99m tetrofosmin SPECT study to rule out myocardial ischemia. The SPECT images revealed a small nonreversible mid-anteroseptal perfusion defect. For additional evaluation coronary computed tomography angiography was performed. This revealed normal coronary arteries and demonstrated a small muscular ventricular septal defect which corresponded to the location of the fixed perfusion defect on the SPECT images. The presence of the ventricular septal defect should be considered in differential diagnosis of an isolated fixed septal perfusion abnormality on SPECT images in patients with no history of prior MI.

Cardiac assistance from skeletal muscle: a reappraisal.

Cardiac assistance from skeletal muscle offers an attractive surgical solution to the problem of end-stage heart failure, yet it is widely regarded as a failed approach. I argue here that this is an outdated assessment. Systematic progress has been made over the last 25 years in understanding the relevant basic science. In the light of these advances we should be reconsidering the place of skeletal muscle assist in the surgical armamentarium.

Is skeletal muscle ventricle chronic stability dependent on wall stress? Design implications.

Chronic skeletal muscle ventricle (SMV) stability is essential for clinical implementation. SMVs in animal models have chronically expanded or collapsed when exposed to physiologic pressures. SMV wall stress is a more appropriate indicator than pressure or geometry to compare SMVs between studies. SMV wall tensions during conditioning were determined for SMVs that collapsed, expanded, or were isovolumetric in a previous study. Wall stresses in SMVs that expanded (2.76 +/- 0.803 N/cm(2)) were significantly greater than isovolumetric SMVs (0.89 +/- 0.450) and SMVs that collapsed (0.88 +/- 0.451). These data support the existence of minimum and maximum wall stresses for SMV volume stability and provide empiric estimates for SMV design. Scaling SMV designs from animal models with smaller volumes and similar pressures may result in greater wall stresses in clinical designs. Therefore, the use of volume limiting implants or an isovolumetric conditioning phase to increase the wall stress expansion threshold may be required.

The functional and histological effects of clenbuterol on the canine skeletal muscle ventricle.

BACKGROUND: We investigated the anabolic effects of the sympatho-mimetic drug clenbuterol upon pumping chambers constructed from latissimus dorsi muscle (LDM). METHODS AND RESULTS: In control and treatment groups (n = 4 dogs each), skeletal muscle ventricles (SMVs) were constructed followed by a 3-week recuperative delay and 6-7 weeks of electrical conditioning at 2 Hz to induce phenotypic expression of fatigue resistant slow muscle fibers. The treatment group received oral administration of clenbuterol (8 microg/kg, 2x/day) during this period. The clenbuterol group increased significantly in body weight as compared with the control group (P < 0.05). In a terminal experiment, the SMVs were assessed with a mock circulation device to determine pumping performance and also were examined with regard to fiber type distribution and area in the SMVs and their contralateral in situ LDMs. Initially the clenbuterol group performed better than the control group, but by the end of a 60-min fatigue test, there were no significant differences. With regard to fiber type distribution and areas, the SMVs of the clenbuterol group exhibited a fast fiber distribution similar to unconditioned muscles (28% +/- 4%), whereas the control group showed complete transformation (100%) to slow fibers. The fast fibers of the clenbuterol group were larger than control (P < 0.05), but the slow fibers were not significantly different. CONCLUSIONS: At the dose given, clenbuterol does induce hypertrophy and preserves the normal percentages of fiber types, possibly by hyperplasia, but it does not affect chronic pumping performance of skeletal muscle ventricles in the canine model.

Monitoreo de vancomicina administrada intraventricularmente en lactantes durante el tratamiento de ventriculitis / Monitoring of intraventricularly administered vancomycin in infants in the treatment of ventriculitis

El objetivo de este estudio fue establecer pautas para el monitoreo de Vancomicina cuando la misma es administrada intraventricularmente en lactantes. En este estudio se incluyeron once pacientes con derivaciones ventrículo-peritoneal. Todos los pacientes recibieron una dosis de Vancomicina intraventricular (IVT). Las muestras de líquido cefalorraquídeo (LCR) fueron analizadas y se calcularon los parámetros farmacocinéticos: constante de velocidad de eliminación (ke) y volumen de distribución (Vd) para poder llevar a cabo un ajuste posológico. Las medias referidas al Vd y a la semivida de eliminación para estos pacientes fueron de 244(±162) mL y 37.1(±23.3) horas respectivamente. En algunos pacientes se observó una gran variabilidad en el Vd. Este cambio en Vd se correlacionó con problemas en el tamaño ventricular o con ventrículos septados. En todos los casos, se propuso una nueva dosis de acuerdo a los parámetros calculados. Debido a variaciones en el sistema a lo largo de la terapia, se propuso un protocolo para la recolección de muestras de LCR de forma tal de individualizar la dosis de Vancomicina con los parámetros farmacocinéticos obtenidos

The objective of this study was to establish guidelines for the monitoring of intraventricularly administered Vancomycin in infants. Eleven patients with ventriculo-peritoneal shunts who developed ventriculitis were included in the study. All patients were given an intraventricular (IVT) dose of Vancomycin. Cerebrospinal fluid (CSF) samples were analysed and pharmacokinetic parameters: elimination rate constant (ke) and distribution volume (Vd) were calculated in order to adjust the dose. Mean values of Vd and elimination half-life for these patients were 244 (± 162) mL and 37.1 (±23.3) hours respectively. A great variability in the Vd was observed in some patients. This change in Vd correlates with problems in the ventricle size or with septated ventricles. In all cases a new dose was suggested according to the calculated parameters. Due to variations in the system throughout therapy, a protocol for CSF samples collection was proposed in order to individualise Vancomycin dosage according to pharmacokinetic parameters

Diabetes-induced alterations in latissimus dorsi muscle properties impair effectiveness of dynamic cardiomyoplasty in rats.

Short-term diabetes was induced in male Wistar rats with streptozotocin injection. The effects of diabetes on latissimus dorsi (LD) muscle contractile and biochemical properties and acute cardiomyoplasty (CDM) were assessed and compared with data from 16 control rats. Isometric force, contractile properties, and fatigue were measured in electrically stimulated muscles (0.3 ms, 1-256 Hz), and Na+K+ and Ca2+ATPase activities were quantified in muscle membrane preparations. Systolic arterial pressure and aortic blood flow were recorded at rest and during LD muscle stimulation. Compared with control muscle, diabetic muscle showed smaller maximum specific tetanic tension and lower rates of rise and fall in force. Diabetic LD muscle also showed lower muscle enzyme activities. Twitch tension and fatigue did not differ between groups. Smaller increases in aortic flow and systolic pressure after CDM were found in diabetic rats compared to controls. The marked decrease in CDM effectiveness in diabetic rats likely reflected the alterations in muscle properties associated with diabetes.

[The hemodynamic and myostimulation regimens parallels of the extraaortic counterpulsation and skeletal ventricle in the experiment]. / Ekstraaortines kontrapulsacijos ir skeleto raumens skilvelio hemodinamikos bei miostimuliacijos rezimo paraleles eksperimente.

OBJECTIVE: Our investigation was aimed to evaluate the effect of extraaortic counterpulsation to central hemodynamics during the two modes of latissimus dorsi muscle electrostimulation. MATERIAL AND METHODS: Two groups of experimental dogs were divided into two subgroups and affected with continuous and work-rest regimens of stimulation. In one group latissimus dorsi muscle was mobilized and left in situ. The contraction force was measured before and during experiment, until it decreased till 50%. Recovery time needed to completely restore contraction force was calculated. In the second group latissimus dorsi muscle was stimulated just after aortomyoplasty and skeletal muscle ventricle by using LD PACE II electrostimulator (ventricle - muscle delay 290 ms). RESULTS: By using continuous stimulation in the first group the contraction force decreased till 50% of pre-assist level after 52+/-8 minutes and returned to baseline after 84+/-16 minutes of rest. Under the work-rest regimen this decrease lasted 105+/-8 minutes and returned to baseline after 25+/-6 minutes (p<0.05). After this regimen light microscopy did not revealed significant changes of muscle tissue. After continuous stimulation increased basophilic degeneration and wavy fibrils were revealed. Thoracic aortic counterpulsation by using continuous stimulation increased hemodynamic parameters from pre-assisted level in 40 minutes. The hemodynamic parameters during work-rest regimen became better after 20 minutes and lasted 100 minutes (p<0.05). When counterpulsation was completed, recovery time to baseline in case of continuous electrostimulation was 96+/-9 minutes; in case of work-rest electrostimulation, it was only 43+/-6 minutes. CONCLUSIONS: Work-rest regimen using LD PACE II electrostimulator may be used safely immediately post cardiac assist procedure.

Skeletal muscle ventricles with a single-limb conduit: the importance of hemodynamic design.

BACKGROUND: Skeletal muscle ventricles (SMVs) connected to the descending thoracic aorta have the potential for providing long-term diastolic augmentation. A successful existing design employs a bifurcated conduit, but aortic constriction between the limbs of the conduit is required to ensure obligatory flow-through. Here we evaluate an alternative approach in which connection to the aorta is made by a single-limb conduit. METHODS: In two groups of dogs SMVs were constructed from the left latissimus dorsi muscle and connected to the circulation via a single-limb conduit of length 110-120 mm (Group 1, n = 5) or 70 mm (Group 2, n = 5). The animals were followed over 10 weeks. RESULTS: Although all animals showed significant augmentation of diastolic aortic pressure at the outset, substantial thrombus developed in the SMVs of both groups. The results were analyzed by reference to design criteria for a single-limb conduit SMV, developed from empirical, in-vitro flow studies and formulated mathematically. CONCLUSION: The SMVs constructed in this experiment appeared to meet the criteria for adequate mixing of blood within the ventricle. They did not, however, achieve adequate exchange of blood with the circulation. Thrombosis was therefore attributable to excessive residence time of blood in the SMV and conduit. Both the experimental study and the mathematical analysis point to the need for SMVs of this configuration to be constructed closer to the aorta. Preliminary results are reported for such an experiment in the pig, in which the SMV was thrombus-free when terminated electively after 1 week.

Pathological changes of the myonuclear fibrous lamina and internal nuclear membrane in two cases of autosomal dominant limb-girdle muscular dystrophy with atrioventricular conduction disturbance (LGMD1B).

Mutations in the lamin A/C gene have been reported in a variety of disorders including autosomal dominant Emery-Dreifuss muscular dystrophy and autosomal dominant limb girdle muscular dystrophy with cardiac conduction block or limb girdle muscular dystrophy type 1B (LGMD1B). However, how these mutations are involved in developing these diseases is not known. We examined morphological changes of the skeletal muscle in two cases of LGMD1B in a family, directing our attention to the nuclear envelope and its underlying structures where lamin A/C is located. Although conventional fluorescence microscope revealed no discernible abnormality in the distribution of emerin and lamin A/C, a serial multi-layer scanning with confocal laser scanning microscope showed an attenuated and uneven distribution of lamin A/C. Furthermore, under an electron microscope, the nuclear fibrous lamina and inner nuclear membrane were relatively indistinct compared to controls. These changes in the myonuclei may be related to pathomechanisms of the present cases.

Haemodynamic considerations in the design of a skeletal muscle ventricle.

Skeletal muscle ventricles (SMVs) configured to operate as diastolic counterpulsators show promise as cardiac assist devices. In four pigs, SMVs were connected to the aorta by a single-limbed conduit and activated during every third cardiac diastole. During the assisted beats, mean diastolic aortic pressure increased by 30.3 +/- 2.2%, peak diastolic aortic pressure increased by 38.5 +/- 2.7%, the endocardial viability ratio increased by 42.3 +/- 3.4%, and mean left anterior descending coronary artery flow increased by 61.6 +/- 4.5%. Although there are major advantages to making the connection to the aorta by a single-limb conduit, the lack of separation between inlet and outlet means that such devices must be designed carefully to avoid thrombogenesis under chronic conditions. Design rules were developed for this configuration, based on earlier in vitro studies. They addressed the problem of stasis by promoting the development of a propagating vortex that travels the length of the ventricle and ensured proper exchange of blood with the circulation by limiting the volume of the connecting conduit. An SMV compatible with these rules was connected in a pig. At elective termination 1 week later, activation of the SMV increased peak diastolic pressure by 20.1% and reduced left-ventricular stroke work in the post-assisted beat by 10.1%. The SMV was free from thrombus.

Skeletal muscle ventricle pressure-volume properties conform to dynamic and static conditioning.

BACKGROUND: Chronic changes in skeletal muscle ventricle (SMV) size and strength can directly affect performance and stability. These changes may depend on the conditioning protocol or implant system. Therefore the effects of conditioning protocols on SMV geometry and contractility must be identified for optimal SMV design and application. METHODS: Skeletal muscle ventricles were constructed in 14 goats using the left latissimus dorsi muscle. The SMVs were conditioned with a 40 mL constant-volume isovolumetric implant (n = 5, IsoVol group) or a compliant pneumatic system that allowed dynamic shortening and direct exposure to resting pressures. Dynamic SMV resting pressure was either progressively increased from 40 to 100 to 120 mm Hg (n = 5, high pressure [HiP] group) or maintained at 40 mm Hg (n = 4, low pressure [LowP] group) during conditioning. The SMV pressure and volume characteristics were monitored daily. RESULTS: All HiP SMVs expanded in volume during conditioning after exposure to physiologic pressures. Three of 4 LowP SMVs decreased in volume during conditioning. Skeletal muscle ventricle passive and active (isovolumetric evoked pressure) pressure-volume curves shifted toward the increasing, stable, and decreasing volumes in HiP, IsoVol, and LowP SMVs respectively. CONCLUSIONS: Frequent monitoring of SMV characteristics during conditioning enabled progressive pressure training and is a valuable tool to evaluate SMV conformation. Chronic SMV adaptation is dependent on the conditioning protocol or implant system utilized. Demonstration of SMV expansion at physiologic pressures suggests that clinical sized SMVs may be chronically unstable unless a supporting implant system is utilized or SMV compliance is reduced. Therefore the mechanisms effecting chronic expansion should be further defined to optimally design SMVs for clinical implementation.

Contractile response of different segments of the latissimus dorsi muscle to chronic stimulation.

OBJECTIVE: This study was planned to investigate if there is any difference in terms of the muscle force between the distal and proximal segments of the latissimus dorsi muscle. SUBJECTS AND METHODS: An inplantable mock circulation system was placed around the latissimus dorsi muscle. The wrapping procedure around the implantable mock circulation was performed by using two different latissimus dorsi muscle segments. In group 1, the very proximal and in group 2, very distal part of the latissimus dorsi were wrapped. The main difference is the blood supply to the distal part of the latissimus dorsi that was interrupted during dissection. During the stimulation period which lasted 120 minutes, the pressure developed in this system and adenosine triphosphate (ATP) levels were measured. RESULTS: The stimulation at 20 Hz did not result in any change in pressure and metabolic data. When it was switched to 43 and 85 Hz, ATP levels decreased with a resultant drop in pressure in group 2. However ATP levels were 15.9 +/- 2.2 micromol/gr and 14.8 +/- 2.5 micromol/gr in group 1, 12.0 +/- 1.4 micromol/gr and 6.1 +/- 1.2 micromol/gr in group 2 at 43 and 85 Hz respectively (p < 0.05) at the end of the 90 minutes. The pressures at the same time interval were 89 +/- 11 and 102 +/- 7 mmHg in group 1, 61 +/- 7 and 65 +/- 8 mmHg in group 2 (p < 0.05). CONCLUSION: In this study, we demonstrated that changes in the distal segment of the latissimus dorsi muscle affects its performance in terms of metabolic and pressure changes during high frequency electrical stimulation at 43 and 85 Hz.

Capturing in situ skeletal muscle power for circulatory support: a new approach to device design.

Efforts to harness in situ skeletal muscle for circulatory support have been extensive, but implants designed to tap this power source have yet to meet the strict performance standards incumbent upon such devices. A fourth generation muscle energy converter (MEC4) is described that represents a significant departure from previous hydraulic muscle pump designs, all of which have assumed a long cylindrical profile. The MEC4, in contrast, features a puck shaped metallic bellows oriented so that its end fittings lie parallel to the chest wall. The fixed end is centered over a fluid port that passes into the thoracic cavity across one resected rib. The opposite end of the bellows supports a roller bearing that moves beneath a linear cam fixed to a reciprocating shaft. The shaft exits the housing through a spring loaded seal and is attached to a sintered anchor pad for muscle tendon fixation. This configuration was chosen to improve bellows durability, lower device profile, and reduce tissue encumbrance to actuator recoil. Bench tests show that modest actuation forces can effect full actuator displacement in 0.25 seconds against high pressure loads, transmitting up to 0.9 J/stroke at 60% efficiency. In vitro tests also confirm that key device performance parameters can be computed from pressure readings transmitted via radiotelemetry, clearing the way for long-term implant studies in conscious animals.

A durable load bearing muscle to prosthetic coupling.

Skeletal muscles have been successfully linked to power mechanical support devices acutely. However, the required load bearing muscle to prosthetic interfaces have not been consistently durable. Tissue simply may not tolerate the repetitive pressure generated, ranging to 40,000 mm Hg, when necessary forces meet the crosssectional areas accessible by suture or clamp fixation. Dramatically increasing the force transfer surface by dispersing ultrafine polymer fibers in the distal muscle substance is the principle of a coupling device termed the MyoCoupler. Earlier, effective force transfer was computationally projected and confirmed in a pilot 30 day rabbit trial, with pull-out strength several times need. This investigation tested bonding strength after longer periods and examined the postulated fiber tissue integration. Devices and controls (buttressed suture fixation alone) were implanted contralaterally in the posterior tibial muscles of 28 rabbits for up to 90 days. Of the 28 rabbits, 21 were used for bond strength testing, and 3 were used for histology. Infection or procedural error disqualified 4 of the rabbits. Pull-out strength levels at 10-30 days (n = 7), 31-60 days (n = 10), 61-90 days (n=4), and all (n=21) were, respectively, 107.1 +/- 58.1, 111.4 +/- 42.7, 97.0 +/- 21.3, and 107.2 +/- 43.9 for MyoCouplers and 58.4 +/- 19.4, 52.3 +/- 34.7, 40.5 +/- 13.0, and 52.1 +/- 26.9 for the control animals. Differences were statistically significant (one-tailed t-test for paired data) and at progressively higher standards of probability for each successive period (p < 0.05 at 10-30 days, p < 0.01 at 31-60 days, p < 0.001 at 90 days, and p < 0.00001 for all). Histology showed fibrous tissue insinuation. Of 360 random fiber surface sites, 88% were closer to fibrous tissue structures than to other fibers. These findings support the aggressive pursuit of muscle powered mechanisms for artificial hearts, assist devices, and heart wall actuators.

A review of the concept of circulatory bioassist focused on the "new" demand dynamic cardiomyoplasty: the renewal of dynamic cardiomyoplasty?

After the initial enthusiasm, the dynamic cardiomyoplasty lost its reputation owing to the poor long-term results, caused by the muscular degeneration subsequent to chronic continuous electrical stimulation of the latissimus dorsi. An activity-rest stimulation protocol that avoids full transformation of the skeletal muscle, maintaining muscular properties over time, has been successfully tried. This "demand" stimulation protocol showed in humans good results improving NYHA class, ejection fraction value, and survival. The discussion about the capability of this and a unique kind of cardiocirculatory bioassist is due to be reopened. In fact, heart transplant, percutaneous circulatory-supporting device, multisites stimulation therapy, and total artificial heart have some drawbacks, one of which is the economic cost. In developing countries the more economic demand dynamic cardiomyoplasty may still play a role.

Growth factors improve latissimus dorsi muscle vascularization and trophicity after cardiomyoplasty.

BACKGROUND: Dynamic cardiomyoplasty consists of wrapping the electrostimulated latissimus dorsi muscle (LDM) around the failed heart. Partial ischemia followed by atrophy of the middle and distal part of the LDM were observed in 30% of clinical cases after LDM flap elevation from its origin. In the current study, we hypothesized that local administration of growth factors at the LDM/epicardial interface could improve muscle vascularization and trophicity. METHODS: In 24 sheep, dynamic cardiomyoplasty was performed using the left LDM. A multiperforated catheter was positioned at the LDM/epicardial interface for a weekly administration, during a 1-month period, of the following factors: basic fibroblast growth factor (bFGF, n = 6), vascular endothelial growth factor (VEGF, n = 6), and regenerating agent (RGTA, n = 6). Six sheep injected with phosphate-buffered saline (used for dilution of the growth factors) were used as a control group. At 3 months, angiographic, histologic, and histomorphometric studies were performed. RESULTS: Angiographic studies of the animals treated with growth factors demonstrated hypervascularization due to the development of new vessels. Histomorphometric and histologic studies showed a significant increase in the number of capillaries and arterioles (100 fields/muscle) in the groups treated with bFGF (443.0 +/- 101.2, p < 0.01), RGTA (293.2 +/- 29.3, p < 0.05), and VEGF (246.5 +/- 45.9, p < 0.05), as compared with the control group (81.5 +/- 11.4). A significantly lower atrophy score was observed in the groups treated with bFGF (1.4 +/- 0.18, p < 0.05), RGTA (1.59 +/- 0.17, p < 0.05), and VEGF (1.96 +/- 0.14, NS), as compared with the control group (2.48 +/- 0.16). CONCLUSIONS: Local administration at the heart/muscle interface of growth factors increases muscle vascularization and avoids muscle atrophy in an experimental cardiomyoplasty model, both of which are advantageous to the contracting LDM. The local growth factors delivery system used in this study appears efficient, easy to implant, and manipulate and safe.

Maintained benefits and improved survival of dynamic cardiomyoplasty by activity-rest stimulation: 5-year results of the Italian trial on "demand" dynamic cardiomyoplasty.

OBJECTIVE: Latissimus dorsi (LD) muscular degeneration caused by continuous electrical stimulation has been the main cause of the poor results of dynamic cardiomyoplasty (DCMP) and its exclusion from the recent international guidelines on heart failure. To avoid full transformation of the LD and to improve results, a new stimulation protocol was developed; fewer impulses per day are delivered, providing the LD wrap with daily periods of rest ("demand" stimulation), based on a heart rate cut-off. The aim of this work is to report the results at 5 years of follow-up of the Italian Trial of Demand Dynamic Cardiomyoplasty and to discuss their impact on the destiny of this type of cardiac assistance. METHODS: Twelve patients with dilated myocardiopathy (M/F=11/1, mean age 58.2+/-5.8 years, sinus rhythm/atrial fibrillation=11/1) were submitted during the period 1993-1996 to DCMP and at different intervals to demand protocol. Clinical, echocardiographic, mechanographic and cardiac invasive assessments were scheduled before initiating the demand protocol and during the follow-up at 0, 6 and every 12 months. RESULTS: The mean duration of follow-up was 40.2+/-13.8 months (range 18-64). There were no perioperative deaths. The demand stimulation protocol showed a decrease in 5 years in New York Health Association (NYHA) class (3.17+/-0.38-1.67+/-0.77, P=0.0001), an improvement of left ventricular ejection fraction (22.6+/-4.38-32.0+/-7.0, P<0.001), a 5-year actuarial survival of 83.3% (one patient was switched to heart transplantation programme due to clinical worsening and another one died of massive pulmonary embolism). CONCLUSIONS: Demand DCMP maintains over time LD muscular properties, enhances clinical benefits and improves survival of DCMP, thus reopening the debate whether this type of treatment should be considered in patients with end-stage heart failure.

Effects of acute dynamic cardiomyoplasty in a goat model of chronic ventricular dilatation: part 1.

BACKGROUND: The acute effects of cardiomyoplasty in an experimental model of chronic dilated heart have not been thoroughly investigated. Therefore, a model of chronic left ventricular (LV) dilatation was created to accurately determine actual changes shortly after passive and active wrapped skeletal muscle. METHODS: A carotid-jugular shunt model in 8 goats was used to induce progressive dilatation of the cardiac ventricles. Geometric modifications induced by the arteriovenous shunt were monitored by transthoracic echocardiography. After 8 weeks, cardiomyoplasty was performed, and the acute hemodynamic changes obtained with static cardiomyoplasty soon after the wrapping procedure were determined. Hence, hemodynamic variables recorded during assisted cardiac beats were then compared with data collected with unassisted cardiac beats using the conductance catheter method to generate pressure-volume loops. RESULTS: During electrical stimulation of the unconditioned skeletal muscle wrapped around the dilated left ventricle, a significant increase in stroke volume (117 +/- 48 mL versus 87 +/- 38 mL; p < 0.05) was observed. Early wrapped latissimus dorsi muscle activation also induced a reduction in LV end-systolic volume (from 51 +/- 28 mL to 27 +/- 14 mL; p < 0.05) when compared with unassisted LV contraction. CONCLUSIONS: In a chronic model of cardiac dilatation, acute dynamic cardiomyoplasty was shown to increase LV contractile performance and reduce LV volume. Further evaluation is necessary to show the effects of a conditioned wrapped muscle on LV systolic function and dimensions in the long-term.