Ann Thorac Surg 1997;64:86-93
© 1997 The Society of Thoracic Surgeons
Original Articles: Cardiovascular
Intramural Blood Flow of Skeletal Muscle Ventricles Functioning as Aortic Counterpulsators
Catharina A. M. van Doorn, FRCS,
Hans Degens, PhD,
Moninder S. Bhabra, FRCS,
Christopher B. W. Till, FRCA,
Trudi E. Shaw,
Jonathan C. Jarvis, PhD,
Stanley Salmons, PhD,
Timothy L. Hooper, MD
Department of Cardiothoracic Surgery, Wythenshawe Hospital, Manchester, and Department of Human Anatomy and Cell Biology, University of Liverpool, United Kingdom
Accepted for publication January 11, 1997.
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Abstract
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Background. Skeletal muscle ventricles (SMVs) working as aortic counterpulsators have provided long-term left ventricular assistance under experimental conditions. However, gradual deterioration of SMV pump function and rupture have been observed, and this may be related to compromised intramural blood flow during synchronized counterpulsation under systemic working conditions.
Methods. Transformed, double-layered SMVs in 6 sheep were stimulated for 3-minute periods (5 V, 30 Hz, burst duration and delay from QRS both 40% of the cardiac cycle) to work as diastolic counterpulsators in the systemic circulation at a 1:2 (SMV:heart) and 1:1 ratio, and on a mock circulation with low-pressure loading conditions at a 1:2 ratio. Thoracodorsal artery blood flow was monitored by ultrasonic flow probe, and intramural blood flow distribution was investigated by fluorescent microspheres. Thoracodorsal venous lactate concentrations were measured before and after each period of stimulation.
Results. Thoracodorsal artery blood flow increased significantly (p < 0.001) after stimulation. The magnitude of augmentation (89%; 95% confidence interval, 36% to 163%) was similar for all working conditions studied. Reactive hyperemia was observed after most 1:1 regimens but was rare after 1:2 regimens. A significant (p < 0.05) 15% increase in serum lactate levels was present after 1:1 regimens only. All regimens of stimulation resulted in a significant increase (p < 0.01) in blood flow to sections in the outer wall of the SMV, but a significant increase (p < 0.05) in blood flow to sections in the inner wall was observed only under low loading conditions.
Conclusions. Skeletal muscle ventricles subjected to 1:1 systemic counterpulsation regimens work under partly anaerobic conditions. High loading conditions may compromise SMV inner wall blood flow.
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Introduction
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In recent years there has been interest in the use of skeletal muscle ventricles (SMVs), constructed from the latissimus dorsi (LD) muscle, for circulatory assistance. Various experimental designs and configurations have been evaluated in the pulmonary and systemic circulations [1]. One of the more promising options for future clinical application, proposed by Stephenson and co-workers, is aortic diastolic counterpulsation generated by an SMV connected to the thoracic aorta. That group has reported significant left ventricular assistance in dogs [2, 3], and has also confirmed the capacity of these SMVs to function in the circulation for 2 years or more without significant thromboembolic complications [4]. However, problems have been observed in some animals, including SMV dilatation, rupture, and occasionally a gradual deterioration in function over time [4, 5].
There are two concerns about the adequacy of blood supply to the muscular wall of SMVs when they function as aortic counterpulsators. First, it has been suggested that a counterpulsation configuration is well suited to muscle perfusion because SMVs contract during cardiac diastole and relax during systole, when physiologic blood flow to the muscle is greatest. However, this suggestion neglects the high intraluminal pressure fluctuations to which SMVs are continuously exposed when connected to the aorta, which follow those within the nutrient arteries supplying the SMV wall. Moreover, although the action of the aortic valve results in a "low-pressure" diastolic phase for the native left ventricle during which myocardial perfusion predominates, the SMV is not afforded the same protection. Second, we [6] have recently demonstrated in a cardiomyoplasty model that a 1:1 muscle:heart synchronization ratio leads to some impairment of LD muscle perfusion. Although muscle contraction in this case occurred during systole, the effect was seen with stimulus bursts appreciably shorter than those employed for diastolic counterpulsation.
The purpose of this study was to examine blood flow in the muscular wall of the SMV during aortic counterpulsation in sheep.
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Material and Methods
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Six castrated male Dorset sheep with body weights in the range of 50 to 64 kg were operated on and maintained in accordance with the regulations of the United Kingdom Government's Animal (Scientific Procedures) Act 1986. All animals underwent a preliminary procedure for construction of the SMV, followed 15 weeks later by a terminal experiment for SMV blood flow measurements.
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Anesthetic Techniques
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General anesthesia was induced and maintained with halothane (1% to 2%) in a mixture of equal volumes of oxygen and nitrous oxide. Anesthesia was supplemented with morphine (0.1 mg/kg) intravenously as an initial bolus followed by 0.025-mg/kg increments as required. The animals were intubated and mechanically ventilated (Blease Volume Divider, Chesham, UK) to maintain arterial blood gasses and pH within physiologic limits. A rumen tube was inserted. Fluid loss was replaced with warmed crystalloid solution (glucose 4%/NaCl 0.18%) and colloid solution (Gelofusine; Braun Medical Ltd, Aylesbury, UK) to maintain the hematocrit between 25% and 30%. Pharyngeal temperature was maintained with a heating blanket between 38° and 40°C, within the normal range for sheep. Before construction of the SMVs a single 1.5-g dose of cefuroxime sodium (Glaxo Laboratories Ltd, Uxbridge, UK) was given intravenously for antimicrobial prophylaxis and 1.5 mg/kg of diclofenac sodium (Geigy Pharmaceuticals, Horsham, UK) was given intramuscularly for postoperative analgesia.
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Skeletal Muscle Ventricle Construction
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Under aseptic conditions the left flank was incised from the axilla toward the tip of the 11th rib. The LD muscle was dissected from the chest wall with ligation of all collateral vessels but with careful preservation of the thoracodorsal neurovascular pedicle. A bipolar nerve cuff electrode (Medtronic Inc, Minneapolis, MN) was placed around the thoracodorsal nerve. The electrode was connected to a bipolar nerve stimulator (Itrel SP 4721; Medtronic), which was positioned behind the left rectus sheath. The broad base of the LD muscle was folded, so that the costal border was placed over the spinal border. An SMV was then constructed by wrapping this double layer of LD muscle from one to one and a quarter times around a silicone rubber bladder (capacity, 30 mL; pressurized with saline solution to 10 mm Hg) of an implantable mock circulation system (IMC) (Medtronic Inc) (Fig 1
). The free upper border of the LD wrap was sutured progressively to a Dacron felt (Bard, Billerica, MA) sewing ring around the neck of the IMC. The IMC has been described in detail before [7]. Briefly, it consists of two silicone rubber bladders interconnected by silicone tubing and filled with saline solution; the SMV is formed around one bladder and compresses it against the compliance provided by the other bladder. The SMV and IMC were placed subcutaneously. After skin closure, additional saline solution was injected into the IMC via a subcutaneous port, generating a measured pressure of 30 mm Hg within the IMC, to cause some passive stretch of the muscle.
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Fig 1. . Construction of skeletal muscle ventricle (SMV) from the left latissimus dorsi (LD) muscle. (IMC = implantable mock circulation; x = spinal border; xx = costal border.)
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Muscle Transformation
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The muscle was conditioned with an escalating protocol of burst stimulation (Table 1). This protocol represented an attempt to condition the muscle in a progressive way to reduce the risk of stimulation-induced damage, but its effectiveness in this regard could not be tested within the confines of this experimental design. In the current state of knowledge any such protocol will necessarily be intuitively based and it is not presented here as an optimal scheme. After a 3-week vascular delay period, contractions were induced by delivering a 30-Hz burst to the SMV at two to three times threshold intensity (amplitude, 1 to 3 V; pulse width, 210 µs). Stimulation was commenced at 14 times per minute (duty cycle on, 0.19 seconds; off, 4 seconds) initially for 1 hour a day, and then increased progressively to 24 hours per day over the next 3 weeks. The off time of the duty cycle was then shortened at 2-week intervals until an SMV contraction rate of 35 per minute was achieved. Stimulation at this rate was continued for a further 5 weeks. During transformation the pressure in the SMV was gradually increased by adding more saline solution, both to provide a degree of muscle stretch and to provide a smooth transition to the eventual use of the SMV as a systemic counterpulsator.
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Skeletal Muscle Ventricle Blood Flow Studies
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After a 3-week vascular delay period and 12 weeks of muscle conditioning, a terminal procedure was performed. The left carotid artery was cannulated with a 14-gauge cannula (Vygon, Cirencester, UK) to allow for monitoring of arterial blood pressure, sampling for blood gas measurements, and withdrawal of reference blood samples during microsphere injections. Central venous pressure was measured via a cannula in the left internal jugular vein. The neurovascular bundle of the SMV was dissected and a 2-mm ultrasonic flow probe (Transonic Systems Inc, Ithaca, NY) was placed around the thoracodorsal artery (TDA). The thoracodorsal vein was cannulated with a 22-gauge cannula (Vygon) to allow sampling for serum lactate measurements. A left thoracotomy and pericardotomy were performed and the left atrial appendage was cannulated with a 14-gauge cannula for injection of fluorescent microspheres. Two epicardial electrodes (SP 6500; Medtronic) were placed on the left ventricle. The bipolar nerve electrode was retrieved from the rectus sheath and connected, together with the epicardial electrodes, to an R-wave–synchronized pulse-train generator (Prometheus, model 6101; Medtronic). The base of the SMV was exposed, the IMC was removed, and the SMV was then connected to the descending thoracic aorta with a purpose-built plastic Y connector (Fig 2). The aorta was ligated between the ascending and descending limbs of the connector, diverting all aortic blood flow through the SMV. A 20-mm ultrasonic flow probe (Transonic) was placed around the main pulmonary artery for monitoring of cardiac output. The animal was systemically heparinized with 5,000 IU of heparin sodium (CP Pharmaceuticals Ltd, Wrexham, UK) to help to maintain patency of the vascular lines and conduit.
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Fig 2. . Experimental preparation (see text for description). (SMV = skeletal muscle ventricle; TDA = thoracodorsal artery; TDV = thoracodorsal vein.)
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Protocol of Investigation
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To investigate the effects of aortic counterpulsation on SMV wall blood flow, we stimulated the SMV with supramaximal 30-Hz bursts, synchronized with cardiac diastole (amplitude, 5V; onset, delayed after the R wave by 40% of the R-R interval; duration, 40% of the R-R interval). Each period of stimulation lasted for 3 minutes and was followed by 15 minutes of rest. These periods were chosen on the basis of previous experiments in our laboratory [6] in which we had shown that stimulation-induced augmentation of TDA blood flow reaches a plateau within 1.5 minutes of the onset of burst stimulation and returns to baseline within 10 minutes of cessation of stimulation.
The following protocol was followed for each animal.
- Measurements at rest, with the SMV cavity exposed to the systemic circulation.
- Aortic counterpulsation at a 1:2 (SMV:heart) ratio.
- Aortic counterpulsation at a 1:1 ratio.
- Counterpulsation at a 1:2 ratio, but with the SMV lumen exposed to low loading conditions on a mock circulation (preload, 30 mm Hg; afterload, 30 mm Hg) to assess the effect of reduced intraluminal pressure on SMV intramural blood flow.
At the end of the experiment, the animals were killed by anesthetic overdose and the SMVs were removed for analysis of microsphere content and histologic studies.
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Hemodynamic Data Collection and Analysis
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All hemodynamic parameters were recorded continuously on an IBM-compatible personal computer with the use of CODAS data acquisition software (Dataq Instruments Inc, Akron, OH), and were analyzed with WINDAQ/EX (Dataq) postacquisition software.
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Intramural Blood Flow Measurements
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The use of microspheres for measurement of regional blood flow has been extensively validated for radioactive [8] and recently also for fluorescent dye-labeled microspheres [9]. Baseline measurements for distribution of SMV intramural blood flow were obtained by injection of 20 million yellow-green, 15-µm-diameter, fluorescent microspheres (Triton Technology Inc, San Diego, CA) into the left atrium with the SMV at rest but exposed to aortic pressure. This was followed by a further injection of 10 million microspheres (blue-green, orange, and blue, respectively) during each period of stimulation. Injections commenced 2 minutes after the onset of stimulation, when stimulation-induced hyperemia had reached a plateau, and were administered over 20 to 30 seconds. With each injection, a reference blood sample was withdrawn from the left carotid artery at a rate of 12 mL/min, starting 5 seconds before injection, and lasting for a total of 120 seconds. For microsphere analysis, each SMV was transected twice at right angles to its long axis, dividing it into three sections of equal length. The basal section, which included the sewing ring, and the apical section, were discarded. The middle section, whose wall comprised an inner and outer ring of muscle, was further divided into six samples (four outer wall and two inner wall) (Fig 3), with a minimum weight of 6 g for each sample. The recovery of microspheres from blood and skeletal muscle, the extraction of dye from the spheres, and the measurement of emission intensity of the fluorescent dye have been described in detail recently [9, 10]. Blood flow was calculated as follows [9]: Blood flow (mL•min-1•g-1) = [Reference withdrawal rate (mL•min-1) x Intensity of emission (g-1)]/Intensity of emission in reference withdrawal sample. Samples with an emission intensity corresponding to less than 400 microspheres were discarded to avoid inaccurate blood flow estimates [11].
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Fig 3. . Regions of the wall of the skeletal muscle ventricle used for measuring distribution of intramural blood flow.
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Lactate Measurements
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One-milliliter samples of blood were taken from the thoracodorsal vein for serum lactate measurements immediately before the onset of each period of stimulation, and again within 15 seconds of cessation of stimulation. The blood samples were immediately centrifuged at 2,500 g for 3 minutes and the supernatant was removed and stored at -20°C. Serum lactate analysis was performed with the Cobas Bio centrifugal analyzer with a fluorimetric attachment (Roche Products Ltd, Welwyn Garden City, UK) [12].
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Skeletal Muscle Ventricle Performance
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The diastolic pressure–time index (DPTI) was calculated by integrating the area under the carotid artery pressure waveform bounded by the dicrotic notch and the beginning of the systolic pressure rise (Fig 4). Baseline DPTI was calculated with the stimulator switched off. With the stimulator switched on, diastolic augmentation was determined as the mean percentage increase in DPTI in cycles with SMV stimulation compared with baseline, calculated over ten consecutive stimulated cycles.
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Fig 4. . Representative hemodynamic tracings taken before and after the onset of 1:2 aortic counterpulsation. In cycles with skeletal muscle ventricle stimulation (*) there was a marked change in thoracodorsal artery (TDA) blood flow pattern and an increase in the diastolic pressure–time index (DPTI). (ECG = electrocardiogram.)
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Histologic Analysis
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MORPHOLOGY.
Two full-thickness specimens were taken from the middle section of each SMV. Each specimen was separated into its inner and outer layer, stored in 10% formalin, embedded in paraffin wax, and cut into 10-µm sections, which were stained with Masson's trichrome. In each layer, 15 consecutive 5.668-mm2 fields were examined for their contents of muscle, fat, and fibrous tissue with an automated quantitative histologic analyzer (Seescan, Cambridge, UK). In 1 sheep a full-thickness specimen from the unconditioned contralateral muscle was also examined.
HISTOCHEMISTRY.
After sacrifice of the animal a small full-thickness sample was taken from the middle section of the SMV, quickly frozen in melting isopentane above liquid nitrogen, and stored at -77°C pending analysis. The sample was subjected to gel electrophoresis for analysis of myosin heavy chain composition as described in detail in a recent publication [13]. Control LD sheep muscles with known isoform compositions were included in the gels as an aid to identification of the bands.
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Statistical Analysis
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The TDA flow and microsphere data were found to be log-normally distributed and were converted to natural logarithmic values for analysis. After analysis the results were transformed back into the original units and presented as geometric means with 95% confidence intervals; the latter were used to illustrate dispersion of data, as standard deviations and standard errors cannot be transformed back directly from natural logarithms. The changes in each experiment were evaluated using repeated-measures analysis of variance, and results were expressed as absolute values together with proportional changes from baseline as appropriate. For the morphometric studies, the measurements of fibrous tissue, muscle, and fat were analyzed separately. For each, a two-factor nested analysis of variance was performed, considering the factors animal and layer. The adequacy of the analysis was tested on each occasion by examination of the model residuals. GLIM 3.77 statistical software (Royal Statistical Society, London, UK) was used for the computations. A probability level of less than 5% was used as the criterion for significance.
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Results
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All sheep tolerated the construction of the SMV well and were fully ambulatory without apparent discomfort. During the terminal experiment, the animals were hemodynamically stable with average heart rates of 100 to 200 beats/min. Mean carotid arterial blood pressure ranged from 75 to 105 mm Hg and cardiac output was between 2.5 and 4.0 L•min-1 but did not change significantly within an animal during the course of the final experiment.
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Thoracodorsal Artery Blood Flow
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Mean baseline TDA blood flows, measured with the SMV at rest, were stable during the course of the experiment. All protocols of counterpulsation resulted in a significant (p < 0.001) increase in TDA blood flow from the immediately preceding baseline value (Table 2). There was no statistical difference in the magnitude of augmentation of blood flow produced by the various counterpulsation regimens. However, reactive hyperemia was observed in 1 of 6 animals after cessation of 1:2 systemic counterpulsation and in 5 of 6 after stimulation with a 1:1 regimen; it did not occur after 1:2 counterpulsation on the mock circulation.
Skeletal muscle ventricle stimulation profoundly affected the pattern of TDA blood flow (see Fig 4
). Cycle-by-cycle analysis of TDA blood flow during 1:2 systemic counterpulsation showed a significant 57% (49% to 65%; p < 0.001) reduction in blood flow during cycles with SMV stimulation compared with those without stimulation. Counterpulsation on the mock circulation at a 1:2 ratio resulted in a similar reduction in TDA blood flow (56% [49% to 64%]; p < 0.001) in cycles with SMV stimulation.
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Skeletal Muscle Ventricle Intramural Blood Flow
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Distribution of blood flow within the SMV wall was calculated for each of the six (A to F) samples in 4 animals. In the remaining 2 animals, thrombus formed in the reference withdrawal sample, and this precluded analysis.
With the SMV at rest and its lumen exposed to the systemic circulation, blood flows in the two samples for the inner wall of the SMV (E and F) were significantly greater (p < 0.01) than those in any of the samples of the outer wall (A-D) (Table 3). All regimens of counterpulsation resulted in a significant increase (p < 0.01) in blood flow in the 4 outer areas of the SMV wall. The magnitude of this increase was similar for the different regimens of stimulation (Fig 5). Blood flow did not increase significantly in either of the inner areas of the SMV during counterpulsation under systemic pressures, but it did to a small but significant (p < 0.05) extent under low-pressure working conditions on the mock circulation.
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Fig 5. . Distribution of intramural blood flow relative to resting flow in area A. All regimens of counterpulsation resulted in a significant increase in blood flow to areas of the outer wall of the skeletal muscle ventricle. A small but significant increase in blood flow to the inner areas of the skeletal muscle ventricle was seen only after counterpulsation on the mock circulation (see Table 3 for absolute blood flow measurements). (mock circ = mock circulation; sys circ = systemic circulation.)
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Thoracodorsal Vein Serum Lactate Level
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A gradual rise in arterial and venous baseline lactate levels was observed over the 1- to 1.5-hour course of the experiment. Stimulation for 3 minutes at a 1:2 ratio under systemic or low-pressure working conditions did not significantly alter venous lactate levels. However, a significant 15% (5% to 26%; p < 0.05) rise in thoracodorsal vein lactate levels was seen after 1:1 systemic counterpulsation.
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Skeletal Muscle Ventricle Diastolic Counterpulsation
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There was considerable variation in the hemodynamic performance between the individual SMVs. At 1:2 diastolic counterpulsation a significant (p < 0.01) increase in DPTI was observed in 4 of 6 SMVs, ranging from 7% to 20% (for example, see Fig 4). Diastolic augmentation was maintained at the same level throughout the 3-minute stimulation period. Stimulation at a 1:1 ratio initially resulted in a significant (p < 0.001) increase in DPTI (8% to 16%) in 3 SMVs, but this could not be sustained in 2 SMVs due to fatigue. In 2 of 6 SMVs, no significant diastolic augmentation was achieved during any regimen of aortic counterpulsation, in spite of palpable muscle contractions and characteristic changes in TDA blood flow pattern with stimulation. There were no apparent correlations between SMV performance and blood flow or lactate levels.
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Histology
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The SMVs were surrounded by a thick layer of subcutaneous fat, and could easily be separated from the chest wall. There were no apparent collateral vessels or dense adhesions between the SMV and the surrounding tissues. Histologic examination of the inner SMV wall showed that the SMV cavity was lined by a thick layer of fibrous connective tissue. The muscular component of this layer consisted of muscle fibers of small diameter with signs of segmental necrosis. The outer SMV wall also showed evidence of focal degeneration and repair but contained areas of well-preserved muscle. In both layers muscle fasciculi were infiltrated with fat. The intramural blood vessels appeared normal.
The inner layer of the SMV showed a significantly larger proportion of fibrous tissue than the outer layer (20% [16% to 22%] and 6% [3% to 8%], respectively; p < 0.05) and contained less muscle (27% [24% to 30%] and 50% [48% to 53%], respectively; p < 0.01). There was no significant difference in the amount of fat between the two layers (inner, 53% [50% to 56%]; outer; 44% [41% to 47%]). The unconditioned contralateral LD muscle showed quite a different composition (fibrous tissue, 3% [2% to 4%]; muscle, 96% [94% to 97%]; fat, 1% [0.3% to 2%]).
Gel electrophoresis of myosin heavy chains from the SMV samples revealed only the slow isoform of the myosin heavy chain, confirming that the muscle was fully transformed.
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Comment
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The results of this study confirm that SMV blood flow may be compromised under certain conditions of counterpulsation. Although the augmentation of TDA blood flow did not differ between the various working conditions, the reactive hyperemia and the rise in thoracodorsal vein lactate levels after 1:1 systemic counterpulsation indicate that the muscle was working under partly anaerobic conditions. There was, in contrast, little evidence of this after 1:2 regimens. Because the SMVs in this study were transformed to the extent that they contained only the slow form of the myosin heavy chain, we would expect them also to have had a high aerobic capacity [14]. The increased lactate production may partly reflect the increased metabolic demands of 1:1 stimulation, but it seems likely that it is also due to insufficient oxygen delivery, the result of insufficient blood flow for this stimulation regimen.
In an animal model of cardiomyoplasty that used LD muscle conditioned in situ, we recently demonstrated [6] that muscle blood flow during synchronized systolic stimulation at 1:1 ratios is inadequate to maintain aerobic metabolism. Furthermore, ischemia was more pronounced when the burst stimulus occupied a larger proportion of the R-R interval. No evidence of muscle ischemia was observed with 1:2 regimens. Using a similar setup but performing asynchronous stimulation over a range of burst durations and stimulation rates, Gealow and colleagues [15] found that for each burst duration there is a rate limit above which TDA blood flow declines. Thus in these models of linear muscle contraction, developed muscle tension can prevent adequate muscle perfusion, probably when the duty cycle exceeds a critical level. However, with the SMV configuration there is the additional component of intraluminal pressure, which may further prejudice perfusion of the SMV wall. In the aortic counterpulsation model, intraluminal pressure follows systemic pressure, and one might anticipate a substantial impairment of blood flow to the muscle from this cause.
The effect of intraluminal SMV pressure on SMV blood flow has been studied previously. Mock circulation experiments with SMVs subjected to a range of loading conditions showed that SMV blood flow decreased with increasing preload [16, 17]. In SMVs working in the systemic circulation but under restricted preloads, it has been shown that the inner muscle wall received less blood flow than the outer wall [18]. In the present study we report on the distribution of intramural blood flow in SMVs that are continuously exposed to systemic arterial pressures, the conditions one would encounter in clinical practice. The finding that the inner wall of the SMV received approximately 4 times more blood flow at rest than the outer wall is surprising. On theoretical grounds it was expected that blood flow to the inner wall would, if anything, be compromised. Regional muscle blood flow (Q) depends on the gradient between driving pressure from the TDA (PTDA) and intramuscular pressure (PIM), and is inversely related to the regional resistance (R) [Q = (PTDA - PIM)/R]. Intramuscular pressure has been shown to be higher at the inner than the outer radius of a ventricle [19]. At the inner lining of the SMV pouch, PIM is equal to systemic pressure, which is in turn very similar to PTDA; flow to the inner part of the SMV wall should therefore be reduced. Reduction of PIM toward the outer layer of the SMV results in a sufficient pressure difference to ensure adequate perfusion of the muscle. At rest, these effects can be offset to some extent by regional differences in vascular tone, which may produce less resistance to flow in the inner layer. During stimulation-induced vasodilatation, however, perfusion becomes more dependent on pressure gradients, allowing increased blood supply to the outer layer of the SMV. In our study, vascular autoregulation at rest may have contributed to the relatively high baseline blood flow in the inner wall. There is, however, also a possible methodologic explanation for this finding. The microspheres were injected centrally into the heart, and thus the inner layer of the SMV was exposed to microspheres both from its feeding artery and from direct contact of the inner surface with the aortic circulation, with possible infiltration of the SMV lining by microspheres under the high systemic pressure. The importance of pressure gradients for muscle perfusion during stimulation is supported by our observation that only during mock circulation testing, when SMV intraluminal pressure was at subsystemic levels, was a significant increase in inner wall blood flow achieved.
The distribution of SMV intramural blood flow is, however, based not only on a physiologic mechanism but also dependent on the tissues of which the SMV is composed. Our experimental design was based on the assumption that both the inner and the outer wall of the conditioned SMV would consist predominantly of muscle tissue. The significant loss of muscle, which was more extensive in the inner wall than the outer wall, was an unexpected finding, which complicates the interpretation of the blood flow data: the lack of stimulation-induced hyperemia in the inner wall may be related not only to high intramural pressures but also to the lower proportion of muscle in this layer. The possibility that the more extensive structural degeneration of the inner SMV wall may be related to local ischemia needs to be investigated in future studies.
In conclusion, SMVs subjected to 1:1 systemic counterpulsation regimens under the heart rates and burst durations tested in this study work under partly anaerobic conditions. In addition, blood flow to the inner wall of SMVs connected as counterpulsators could be compromised by sustained high intraluminal pressures.
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Acknowledgments
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Doctor Catharina A. M. van Doorn was a British Heart Foundation Research Fellow. Doctor Hans Degens was supported by grants from the British Heart Foundation and the European Community. Doctor Jonathan C. Jarvis was supported by a Beit Memorial Research Fellowship. We thank Dr Philip Hasselton, pathologist at the Wythenshawe Hospital, for his help with the histologic studies, and Mr. E. Brian Faragher, statistician at the University of Manchester, for his help with the statistical analysis.
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Footnotes
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Address reprint requests to Dr Hooper, Department of Cardiothoracic Surgery, Wythenshawe Hospital, Southmoor Rd, Manchester M23 9LT, UK.
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I. R. Ramnarine, M. Capoccia, Z. Ashley, H. Sutherland, M. Russold, N. Summerfield, S. Salmons, and J. C. Jarvis
Counterpulsation From the Skeletal Muscle Ventricle and the Intraaortic Balloon Pump in the Normal and Failing Circulations
Circulation,
July 4, 2006;
114(1_suppl):
I-10 - I-15.
[Abstract]
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A. T.M Tang, J. C Jarvis, T. L Hooper, and S. Salmons
Observation and basis of improved blood flow to the distal latissimus dorsi muscle: a case for electrical stimulation prior to grafting
Cardiovasc Res,
October 1, 1998;
40(1):
131 - 137.
[Abstract]
[Full Text]
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Abstract
Introduction
